De novo glomerular osteopontin expression in rat crescentic glomerulonephritis

De novo glomerular osteopontin expression in rat crescentic glomerulonephritis. Osteopontin (OPN) is a secreted acidic glycoprotein that has potent monocyte chemoattractant and adhesive properties. Up-regulation of tubular OPN expression is thought to promote interstitial macrophage infiltration in experimental nephritis; however, the role of OPN in glomerular lesions, particularly crescent formation, is unknown. The present study used Northern blotting, in situ hybridization and immunohistochemistry to examine OPN expression in a rat model of accelerated anti-GBM glomerulonephritis. Osteopontin mRNA and protein is expressed by some parietal epithelial cells, thick ascending limbs of Henle and medullary tubules and collecting ducts in normal rat kidney. De novo OPN mRNA and protein expression was evident in glomerular visceral and parietal epithelial cells in anti-GBM glomerulonephritis. Glomerular OPN expression preceded and correlated with macrophage infiltration in the development of hypercellularity, focal and segmental lesions and, notably, crescent formation. There was marked up-regulation of OPN expression by tubular epithelial cells that also preceded and correlated with interstitial macrophage (r = 0.93, P < 0.001) and T-cell infiltration (r = 0.85, P < 0.001). Both glomerular and tubular OPN expression correlated significantly with proteinuria (P < 0.001) and a reduction in creatinine clearance (P < 0.01). In addition, double immunohistochemistry showed co-expression of osteopontin and one of its ligands, CD44, in intrinsic renal cells. CD44 and OPN expression by parietal epithelial cells was evident in crescent formation, while virtually all OPN-positive tubules expressed CD44. Infiltrating macrophages and T-cells were CD44-positive, but only a small proportion of T-cells and few macrophages showed OPN expression. Interestingly, strong OPN mRNA and protein expression was seen in macrophage multinucleated giant cells. In summary, this study suggests that OPN promotes macrophage and T-cell infiltration in the development of renal lesions in rat anti-GBM glomerulonephritis, including glomerular crescent and multinucleated giant cell formation

TIGIT regulates CD4+ T cell immunity against polymicrobial sepsis

BackgroundSepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.MethodAn experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT-/-) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.ResultsThe expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4+ T cells from TIGIT-/- mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT-/- mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT-/- mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.ConclusionTIGIT modulates CD4+ T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis

DLPformer: A Hybrid Mathematical Model for State of Charge Prediction in Electric Vehicles Using Machine Learning Approaches

Accurate mathematical modeling of state of charge (SOC) prediction is essential for battery management systems (BMSs) to improve battery utilization efficiency and ensure a good safety performance. The current SOC prediction framework only considers battery-related features but ignores vehicle information. Additionally, in light of the emergence of time-series Transformers (TSTs) that harness the power of multi-head attention, developing a SOC prediction model remains a significant challenge. Therefore, we introduce a new framework that integrates laboratory battery data with mathematical vehicle model features to improve the accuracy of the SOC and propose a prediction model named DLPformer, which can effectively capture variations in the SOC attributed to both trend and seasonal patterns. First, we apply Matlab/Simulink to simulate a mathematical model of electric vehicles and process the generated vehicle data with Spearman correlation analysis to identify the most relevant features, such as the mechanical losses of the electric motor, differential, and aerodynamic drag. Then, we employ a data fusion method to synchronize the heterogeneous datasets with different frequencies to capture the sudden changes in electric vehicles. Subsequently, the fused features are input into our prediction model, DLPformer, which incorporates a linear model for trend prediction and patch-input attention for seasonal component prediction. Finally, in order to effectively evaluate the extrapolation and adaptability of our model, we utilize different driving cycles and heterogeneous battery datasets for training and testing. The experimental results show that our prediction model significantly improves the accuracy and robustness of SOC prediction under the proposed framework, achieving MAE values of 0.18% and 0.10% across distinct driving cycles and battery types

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

Abstract Background NLRP3 inflammasome is involved in the inflammatory responses during acute lung injury (ALI). RIP3 triggered NLRP3 inflammasome activation independent of necroptosis induction has recently been documented. In this study, the role of RIP3 in the activation of NLRP3 inflammasome in the development of ALI was investigated. Methods A selective RIP3 inhibitor GSK872 was used to investigate the roles of RIP3 in NLRP3 inflammasome activation in the lipopolysaccharide (LPS) induced ALI mouse model. The mechanism of NLRP3 inflammasome activation was investigated in the human monocytic cell line THP-1. NLRP3 inflammasome and necroptosis were measured by flow cytometry or western blot. RIP3–NLRP3 interaction was interrogated using immunoprecipitation and the Duolink® In situ detection. Results Significant upregulation of both necroptosis and NLRP3 inflammasome pathways were observed in the lungs of mice with LPS induced ALI. GSK872 significantly suppressed the activation of necroptosis and NLRP3 activation with reduction of IL-1β and IL-18 production and inflammatory cells infiltration, resulting in a significant amelioration of lung injury. These two processes were shown to be active in interstitial macrophages and CD11b+ monocyte–macrophages/dendritic cells. In THP-1 cells, RIP3 and NLRP3 interaction was enhanced by LPS/ATP stimulation resulting in IL-1β and IL-18 production. This RIP3–NLRP3 interaction was significantly inhibited by GSK872. Conclusion Taking together, these results show that RIP3 participates in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. This process plays a significant pathogenic role in LPS-induced lung injury

SASEGAN-TCN: Speech enhancement algorithm based on self-attention generative adversarial network and temporal convolutional network

Traditional unsupervised speech enhancement models often have problems such as non-aggregation of input feature information, which will introduce additional noise during training, thereby reducing the quality of the speech signal. In order to solve the above problems, this paper analyzed the impact of problems such as non-aggregation of input speech feature information on its performance. Moreover, this article introduced a temporal convolutional neural network and proposed a SASEGAN-TCN speech enhancement model, which captured local features information and aggregated global feature information to improve model effect and training stability. The simulation experiment results showed that the model can achieve 2.1636 and 92.78% in perceptual evaluation of speech quality (PESQ) score and short-time objective intelligibility (STOI) on the Valentini dataset, and can accordingly reach 1.8077 and 83.54% on the THCHS30 dataset. In addition, this article used the enhanced speech data for the acoustic model to verify the recognition accuracy. The speech recognition error rate was reduced by 17.4%, which was a significant improvement compared to the baseline model experimental results

DataSheet_1_TIGIT regulates CD4+ T cell immunity against polymicrobial sepsis.docx

BackgroundSepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.MethodAn experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT-/-) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.ResultsThe expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4+ T cells from TIGIT-/- mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT-/- mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT-/- mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.ConclusionTIGIT modulates CD4+ T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis.</p

An Oxa[5]helicene-Based Racemic Semiconducting Glassy Film for Photothermally Stable Perovskite Solar Cells

Attaining the durability of high-efficiency perovskite solar cells (PSCs) operated under concomitant light and thermal stresses is still a serious concern before large-scale application. It is crucial to maintain the phase stability of the organic hole-transporting layer for thermostable PSCs across a range of temperatures sampled during device operation. To address this issue, we propose a racemic semiconducting glassy film with remarkable morphological stability, exemplified here by a low-molecular symmetry oxa[5]helicene-centered organic semiconductor (O5H-OMeDPA). The helical configuration of O5H-OMeDPA confers the trait of multiple-dimension charge transfer to the solid, resulting in high hole mobility of 6.7 x 10(-4) cm(2) V-1 s(-1) of a solution-processed glassy film. O5H-OMeDPA is combined with a triple-cation dual-halide lead perovskite to fabricate PSCs with power conversion efficiencies of 21.03%, outperforming the control cells with spiro-OMeTAD (20.44%). Moreover, the cells using O5H-OMeDPA exhibit good long-term stability during full-sunlight soaking at 60 degrees C

Stable and Efficient Organic Dye-Sensitized Solar Cell Based on Ionic Liquid Electrolyte

Dye-sensitized solar cells (DSCs) for outdoor applications must show both high efficiency and long-term stability. Here we introduce a co-sensitized, ionic liquid electrolyte-based DSC meeting these requirements. A key feature of our embodiment is the concerted action of two judiciously designed organic dyes, whose co-adsorption at the surface of a mesoscopic TiO(2 )scaffold results in the formation of a compact and highly robust self-assembled monolayer, harvesting sunlight across the whole visible region and converting the photons into charges with near-unity quantum efficiency. Apart from producing a high photocurrent, the dense dye layer blocks the back electron transfer from TiO2 to the redox electrolyte, increasing the photovoltage. This allows for the first time to attain a solar to electric power-conversion efficiency of 10% with an ionic liquid-based DSC Remarkably, the co-sensitized cell is stable under both full-sunlight soaking at 60 degrees C and heat stress at 85 degrees C for 1,000 hr