Hyperforin Promotes Post-stroke Neuroangiogenesis via Astrocytic IL-6-Mediated Negative Immune Regulation in the Ischemic Brain

Hyperforin has been shown to be capable of promoting angiogenesis and functional recovery after ischemic stroke in our previous study. However, the exact mechanisms involved are not fully elucidated. In this study, adult male mice were subjected to 60-min transient middle cerebral artery occlusion followed by reperfusion for 28 days. Hyperforin was administrated to MCAO mice every 24 h for 2 weeks starting at 14 days post-ischemia (dpi). Then flow cytometry, quantitative Real-time PCR (RT-qPCR), western blotting, immunohistochemistry, and functional assays were performed to explore the molecular mechanisms in vivo and in vitro. Our data showed that hyperforin increased astrocytic interleukin (IL)-6 in the ischemic hemisphere via TLR4 at 28 dpi. The astrocytic IL-6 was essential to the promoting effects of hyperforin on the neural precursor cells proliferation, neuronal differentiation, angiogenesis, and functional recovery after stroke. Furthermore, hyperforin promoted the infiltration of regulatory T cells (Tregs) to the ischemic hemisphere and increased Tregs-derived cytokine IL-10 and transforming growth factor-β (TGF-β) in a manner that was dependent on astrocytic IL-6. Astrocytic IL-6 was critical to the role of hyperforin in promoting the infiltration of T-helper (Th) type 2 cells to the ischemic hemisphere and Th2-derived cytokine IL-4, relative to Th1 and Th1-derived cytokine interferon-γ (IFN-γ), which decreased during stroke recovery. After depletion of CD25+ Tregs, the promoting effects of hyperforin on post-stroke neurogenesis was attenuated. Moreover, blockade of IL-4 and TGF-β abrogated the promoting role of hyperforin in post-stroke neurogenesis, angiogenesis and functional recovery. Our results reveal a previously uncharacterized role of astrocytic IL-6-mediated negative immune regulation in the promoting effects of hyperforin on post-stroke neurovascular regeneration and functional recovery

BML-111 Reduces Neuroinflammation and Cognitive Impairment in Mice With Sepsis via the SIRT1/NF-κB Signaling Pathway

Sepsis is a life-threatening state of organ dysfunction caused by infection and which can induce severe neurological disorders that lead to neuroinflammation and cognitive impairment. Inflammation has been reported to cause neuronal apoptosis in sepsis, which can finally lead to cognitive impairment. Previous studies have suggested that BML-111 can exhibit anti-inflammatory and proresolution activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the NF-κB signaling pathway in an inflammation state. However, the role of the SIRT1/NF-κB signaling pathway in the protective effects of BML-111 against sepsis-induced neuroinflammation and cognitive impairment remains unclear. This study aimed to determine the effects of BML-111 on neuroinflammation and cognitive impairment induced by sepsis. Male C57BL/6J mice were subjected to cecal ligation and puncture (CLP) or a sham operation. BML-111 was administered via intracerebroventricular injection (0.1 mg/kg) immediately after CLP. Boc-2 (50 μg/kg) was administered intracerebroventricularly 30 min before CLP, and EX527 (10 μg) was administered every 2 days for a total of three times before CLP, also intracerebroventricularly. Some of the surviving mice underwent open-field, novel-object-recognition, and fear-conditioning behavioral tests at 7 days after surgery. Some of the other surviving mice were killed at 24 h after surgery to assess synaptic damage (PSD95 and Synapsin1), markers of inflammation [tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β], cytoplasmic p65, nuclear p65, Ac- NF-κB and SIRT1. At 48 h after CLP, TUNEL and glia-activation by immunofluorescence investigations were performed on a separate cohort of surviving animals. The results suggested that sepsis resulted in cognitive impairment, which was accompanied by the decreased the expression of PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation of glias, increased production of TNF-α and IL-1β, increased expression of nuclear p65, Ac- NF-κB, and decreased expression of SIRT1 and cytoplasmic p65. It is especially notable that these abnormalities could be reduced by BML-111 treatment. EX527, an SIRT1 inhibitor, abolished the effects of BML-111. These results demonstrate that BML-111 can reduce the neuroinflammation and cognitive impairment induced by sepsis via SIRT/NF-κB signaling pathway

ARHGAP44-mediated regulation of the p53/C-myc/Cyclin D1 pathway in modulating the malignant biological behavior of osteosarcoma cells

Abstract Objective Osteosarcoma is a rare primary malignant tumor of the bone characterized by poor survival rates, owing to its unclear pathogenesis. Rho GTPase-activating protein 44 (ARHGAP44), which belongs to the Rho GTPase-activating protein family, has promising applications in the targeted therapy of tumors. Therefore, this study aimed to investigate the biological function of ARHGAP44 in osteosarcoma and its possible application as a therapeutic target. Methods The expression level of ARHGAP44 in osteosarcoma and its relationship with tumor prognosis were detected using Gene Expression Omnibus database analysis and immunohistochemical staining of clinical specimens. The cell model of ARHGAP44 knockdown was constructed, and the effects of this gene on the malignant biological behavior of osteosarcoma cells were investigated using CCK-8, clone formation, transwell invasion, wound healing, and flow cytometry assays. Western blotting was performed to detect the expression of ARHGAP44, p53, C-myc, and Cyclin D1 in osteosarcoma. Results Biogenic analysis showed that ARHGAP44 was highly expressed in osteosarcoma. This result was associated with poor tumor prognosis and negatively correlated with the expression of the tumor suppressor gene p53. Immunohistochemistry and western blotting revealed significantly upregulated expression of ARHGAP44 in osteosarcoma tissues. Additionally, Kaplan–Meier analysis of clinical specimens suggested that ARHGAP44 was negatively correlated with tumor prognosis. CCK-8, clone formation, transwell invasion, wound healing, and flow cytometry assays showed that downregulation of ARHGAP44 expression significantly reduced the malignant biological behavior of osteosarcoma cells. Furthermore, western blotting showed that the expression level of p53 in osteosarcoma cells was significantly increased after the downregulation of ARHGAP44 expression, whereas the expression of C-myc and Cyclin D1 was significantly decreased compared with that in the control group. Conclusion ARHGAP44 was highly expressed in osteosarcoma and was negatively correlated with its prognosis. The downregulation of ARHGAP44 expression reduced the malignant biological behavior of osteosarcoma cells. These findings suggest that the downregulation of ARHGAP44 expression inhibits the malignant progression of osteosarcoma by regulating the p53/C-myc/Cyclin D1 pathway, demonstrating the potential of ARHGAP44 as a therapeutic target for osteosarcoma

Spatial structure of turbulent mixing of an anticyclonic mesoscale eddy in the northern South China Sea

Upper turbulent mixing in the interior and surrounding areas of an anticyclonic eddy in the northern South China Sea (SCS) was estimated from underwater glider data (May 2015) in the present study, using the Gregg-Henyey-Polzin parameterization and the Thorpe-scale method. The observations revealed a clear asymmetrical spatial pattern of turbulent mixing in the anticyclonic eddy area. Enhanced diffusivity (in the order of 10(-3) m(2)/s) was found at the posterior edge of the anticyclonic mesoscale eddy; on the anterior side, diffusivity was one order of magnitude lower on average. This asymmetrical pattern was highly correlated with the eddy kinetic energy. Higher shear variance on the posterior side, which is conducive to the triggering of shear instability, may be the main mechanism for the elevated diffusivity. In addition, the generation and growth of sub-mesoscale motions that are fed by mesoscale eddies on their posterior side may also promote the occurrence of strong mixing in the studied region. The results of this study help improve our knowledge regarding turbulent mixing in the northern SCS

Efficient Removal of Hexavalent Chromium from Wastewater with Electro-Reduction

Removal of hexavalent chromium had attracted much attention as it is a hazardous contaminant. An electrocoagulation-like technology electro-reduction was applied. The chromium (VI) in the wastewater was reduced to chromium (III) by the electron supplied by electricity power and Fe2+, formed from corrosion of steel electrodes in acidic conditions. The mechanism and parameters affecting the reaction were investigated. The results optimized by response surface methodology indicated that the influence of single factor on the reduction efficiency followed the order: A: dosage of H2SO4 > C: reaction time > D: reaction temperature > B: current intensity. The reduction efficiency was hardly affected by current intensity, while it was increased with the increasing of reaction time and acid concentration. The reducing agent, Fe2+ an and extra free electron, acted as a reducing agent and could easily reduce hexavalent chromium to trivalent chromium at high temperatures in an acidic medium

Development and comparison of machine learning-based models for predicting heart failure after acute myocardial infarction

Abstract Aims Heart failure (HF) is one of the common adverse cardiovascular events after acute myocardial infarction (AMI), but the predictive efficacy of numerous machine learning (ML) built models is unclear. This study aimed to build an optimal model to predict the occurrence of HF in AMI patients by comparing seven ML algorithms. Methods Cohort 1 included AMI patients from 2018 to 2019 divided into HF and control groups. All first routine test data of the study subjects were collected as the features to be selected for the model, and seven ML algorithms with screenable features were evaluated. Cohort 2 contains AMI patients from 2020 to 2021 to establish an early warning model with external validation. ROC curve and DCA curve to analyze the diagnostic efficacy and clinical benefit of the model respectively. Results The best performer among the seven ML algorithms was XgBoost, and the features of XgBoost algorithm for troponin I, triglycerides, urine red blood cell count, γ-glutamyl transpeptidase, glucose, urine specific gravity, prothrombin time, prealbumin, and urea were ranked high in importance. The AUC of the HF-Lab9 prediction model built by the XgBoost algorithm was 0.966 and had good clinical benefits. Conclusions This study screened the optimal ML algorithm as XgBoost and developed the model HF-Lab9 will improve the accuracy of clinicians in assessing the occurrence of HF after AMI and provide a reference for the selection of subsequent model-building algorithms

Results of the Multi-Resolution Decomposition for the FTIR Spectra with DWT.

<p><i>Rhodobryum roseum</i> collected from different areas (a): <i>Rhodobryum roseum</i> 1; (b): <i>Rhodobryum roseum</i> 2; Two Replicates of <i>Rhodobryum roseum</i>; (c): <i>Rhodobryum roseum</i> 2.1; (d): <i>Rhodobryum roseum</i> 2.2.</p