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Introduction: The prognosis for glioma is generally poor, and the 5-year survival rate for patients with this disease has not shown significant improvement over the past few decades. Parkinson's disease (PD) is a prevalent movement disorder, ranking as the second most common neurodegenerative disease after Alzheimer's disease. Although Parkinson's disease and glioma are distinct diseases, they may share certain underlying biological pathways that contribute to their development. Objective: This study aims to investigate the involvement of genes associated with Parkinson's disease in the development and prognosis of glioma. Methods: We obtained datasets from the TCGA, CGGA, and GEO databases, which included RNA sequencing data and clinical information of glioma and Parkinson's patients. Eight machine learning algorithms were used to identify Parkinson-Glioma feature genes (PGFGs). PGFGs associated with glioma prognosis were identified through univariate Cox analysis. A risk signature was constructed based on PGFGs using Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) method. We subsequently validated its predictive ability using various methods, including ROC curves, calibration curves, KM survival analysis, C-index, DCA, independent prognostic analysis, and stratified analysis. To validate the reproducibility of the results, similar work was performed on three external test datasets. Additionally, a meta-analysis was employed to observe the heterogeneity and consistency of the signature across different datasets. We also compared the differences in genomic variations, functional enrichment, immune infiltration, and drug sensitivity analysis based on risk scores. This exploration aimed to uncover potential mechanisms of glioma occurrence and prognosis. Results: We identified 30 PGFGs, of which 25 were found to be significantly associated with glioma survival. The prognostic signature, consisting of 19 genes, demonstrated excellent predictive performance for 1-, 2-, and 3-year overall survival (OS) of glioma. The signature emerged as an independent prognostic factor for glioma overall survival (OS), surpassing the predictive performance of traditional clinical variables. Notably, we observed differences in the tumor microenvironment (TME), levels of immune cell infiltration, immune gene expression, and drug resistance analysis among distinct risk groups. These findings may have significant implications for the clinical treatment of glioma patients. Conclusion: The expression of genes related to Parkinson's disease is closely associated with the immune status and prognosis of glioma patients, potentially regulating glioma pathogenesis through multiple mechanisms. The interaction between genes associated with Parkinson's disease and the immune system during glioma development provides novel insights into the molecular mechanisms and targeted therapies for glioma.
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Atherosclerosis, a chronic inflammatory disease, is the most relevant cause of carotid artery stenosis. Vascular endothelial cells (ECs) play a significant role in the development of atherosclerosis. In this chronic inflammatory environment, we aimed to investigate whether PCSK9 could mitigate atherosclerosis progression by reducing tissue factor expression in ECs via in vivo and in vitro assays. In vivo, we investigated the effect of PCSK9 inhibition on preventing atherosclerotic lesion formation in ApoE-/- mice fed a western diet. The results showed that inhibiting PCSK9 could significantly downregulate the protein expression of tissue factor (TF) in ECs to reduce the area of atherosclerotic plaques. In vitro, we incubated human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). We found that LPS-induced TF elevation was suppressed by a PCSK9 inhibitor at both the mRNA and protein levels and that the TLR4/NF-κB pathway was also suppressed by a PCSK9 inhibitor. With respect to plasma samples from patients with carotid artery stenosis, we also demonstrated that the expression of TF was positively correlated with that of PCSK9. Thus, in addition to regulating lipid metabolism, the regulation of endothelial cell TF expression through the TLR4/NF-κB pathway may be a potential mechanism of PCSK9 in promoting atherosclerotic carotid stenosis.
Subject(s)
Apolipoproteins E , Carotid Stenosis , Human Umbilical Vein Endothelial Cells , Mice, Inbred C57BL , NF-kappa B , Proprotein Convertase 9 , Signal Transduction , Thromboplastin , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Mice , NF-kappa B/metabolism , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , Humans , Carotid Stenosis/metabolism , Male , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Apolipoproteins E/deficiency , Human Umbilical Vein Endothelial Cells/metabolism , Thromboplastin/metabolism , Thromboplastin/genetics , Thromboplastin/biosynthesis , Signal Transduction/physiology , Mice, Knockout, ApoE , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Mice, Knockout , PCSK9 Inhibitors , FemaleABSTRACT
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Fibroblast Growth Factor 7 , Islets of Langerhans , Organoids , Animals , Humans , Male , Mice , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , COVID-19/pathology , Fibroblast Growth Factor 7/genetics , Fibroblast Growth Factor 7/metabolism , Human Embryonic Stem Cells/metabolism , Insulin Secretion/genetics , Islets of Langerhans/metabolism , Islets of Langerhans/virology , Islets of Langerhans/pathology , Organoids/virology , Organoids/metabolism , Organoids/pathology , SARS-CoV-2/geneticsABSTRACT
How to construct a new electrode/electrolyte interface structure in solid-state batteries (SSBs), enhance interface stability, and improve the cycling performance of SSBs is a great challenge for the development of SSBs. Here, an all-in-one "interface-free" structure was developed. This interfacial structure constructs a full-interface hydrogen bonding network through the abundant hydrogen bond donors and acceptors in the cathode and electrolyte to enhance the interfacial stability and avoid interfacial failure during charging and discharging, and generates cathode-electrolyte interface (CEI) in-situ to effectively regulate zinc ion transport. Square cells assembled in this structure are stabilized for 100 cycles at a current density of 0.1 mA cm-2. This integrated electrode provides a new idea for the long stable cycle of SSBs.
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The accurate perception of multiple flight parameters, such as the angle of attack, angle of sideslip, and airflow velocity, is essential for the flight control of micro air vehicles, which conventionally rely on arrays of pressure or airflow velocity sensors. Here, we present the estimation of multiple flight parameters using a single flexible calorimetric flow sensor featuring a sophisticated structural design with a suspended array of highly sensitive vanadium oxide thermistors. The proposed sensor achieves an unprecedented velocity resolution of 0.11 mm·s-1 and angular resolution of 0.1°. By attaching the sensor to a wing model, the angles of attack and slip were estimated simultaneously. The triaxial flight velocities and wing vibrations can also be estimated by sensing the relative airflow velocity due to its high sensitivity and fast response. Overall, the proposed sensor has many promising applications in weak airflow sensing and flight control of micro air vehicles.
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This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/genetics , Anoikis/genetics , Endothelial Cells , Phosphatidylinositol 3-Kinases , AlgorithmsABSTRACT
Liquid phase exfoliation (LPE) of graphene is a potentially scalable method to produce conductive graphene inks for printed electronic applications. Among LPE methods, wet jet milling (WJM) is an emerging approach that uses high-speed, turbulent flow to exfoliate graphene nanoplatelets from graphite in a continuous flow manner. Unlike prior WJM work based on toxic, high-boiling-point solvents such as n-methyl-2-pyrollidone (NMP), this study uses the environmentally friendly solvent ethanol and the polymer stabilizer ethyl cellulose (EC). Bayesian optimization and iterative batch sampling are employed to guide the exploration of the experimental phase space (namely, concentrations of graphite and EC in ethanol) in order to identify the Pareto frontier that simultaneously optimizes three performance criteria (graphene yield, conversion rate, and film conductivity). This data-driven strategy identifies vastly different optimal WJM conditions compared to literature precedent, including an optimal loading of 15 wt% graphite in ethanol compared to 1 wt% graphite in NMP. These WJM conditions provide superlative graphene production rates of 3.2 g hr-1 with the resulting graphene nanoplatelets being suitable for screen-printed micro-supercapacitors. Finally, life cycle assessment reveals that ethanol-based WJM graphene exfoliation presents distinct environmental sustainability advantages for greenhouse gas emissions, fossil fuel consumption, and toxicity.
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Wide-bandgap metal halide perovskites have demonstrated promise in multijunction photovoltaic (PV) cells. However, photoinduced phase segregation and the resultant low open-circuit voltage (Voc) have greatly limited the PV performance of perovskite-based multijunction devices. Here, a alloying strategy is reported to achieve uniform distribution of triple cations and halides in wide-bandgap perovskites by doping Rb+ and Cl- with small ionic radii, which effectively suppresses halide phase segregation while promoting the homogenization of surface potential. Based on this strategy, a Voc of 1.33 V is obtained from single-junction perovskite solar cells, and a VOC approaching 3.0 V and a power conversion efficiency of 25.0% (obtained from reverse scan direction, certified efficiency: 24.19%) on an 1.04 cm2 photoactive area can be achieved in a perovskite/perovskite/c-Si triple-junction tandem cell, where the certification efficiency is by far the greatest performance of perovskite-based triple-junction tandem solar cells. This work overcomes the performance deadlock of perovskite-based triple-junction tandem cells by setting a materials-by-design paradigm.
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BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.
Subject(s)
Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/epidemiology , Male , Female , Middle Aged , Risk Factors , Retrospective Studies , Adult , Aged , Sex Factors , Intracranial Aneurysm/epidemiology , Incidence , Propensity ScoreABSTRACT
The objective of this study is to preliminarily investigate the surgical safety, efficacy, techniques, and clinical value of fully neuroendoscopic surgery for the resection of cerebellopontine angle (CPA) tumors via a retrosigmoid approach. The clinical data of 47 cerebellopontine angle area (CPA) tumors that were treated by full neuroendoscopic surgery from June 2014 to June 2023 were retrospectively analyzed. The efficacy and advantages of the surgical techniques were evaluated based on indicators such as duration of the surgery, neuroendoscopic techniques, intraoperative integrity of nerves and blood vessels, extent of tumor resection, outcomes or postoperative symptoms, and incidence of complications. The 47 cases of cerebellopontine angle tumors include 34 cases of epidermoid cysts, 7 cases of vestibular schwannomas, and 6 cases of meningiomas. All patients underwent fully neuroendoscopic surgery. Twenty tumors were removed using the one-surgeon two-hands technique, and 27 tumors were removed using the two-surgeons four-hands technique. The anatomical integrity of the affected cranial nerves was preserved in all 47 cases. None of the patients suffered a postoperative hemorrhage, cerebrospinal fluid leak, and aseptic or septic meningitis, or died. The rate of total tumor resection was 72.3% (34/47), and the symptom improvement rate was 89.4% (42/47). All patients were followed up for 2 to 12 months, and none died nor showed any signs of tumor recurrence. By analyzing 47 fully neuroendoscopic resections of CPA tumors using the posterior sigmoid sinus approach in our center, we believe that such method allows complete, safe, and effective resection of CPA tumors and is thereby worthy of clinical promotion.