Causal role of immune cells on risk of Parkinson’s disease: a Mendelian randomization study

BackgroundPrevious observational studies have suggested a correlation between immune cells and Parkinson’s disease (PD), yet specific investigations into the causal relationship between the two remain limited. This study aims to explore this potential causal relationship.MethodsWe utilized genome-wide association study (GWAS) data on immune cells and Parkinson’s Disease, conducting a two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms (SNPs). To estimate causality, we employed inverse variance weighting (IVW), MR-Egger, and weighted median (WM) methods. For sensitivity analysis, we used Cochran’s Q-test, MR-Egger intercept, leave-one-out analysis, and funnel plots.ResultsAfter false discovery rate (FDR) correction, the effects of PD on immune cells, and vice versa, were not statistically significant. These include CX3CR1 on CD14+ CD16-monocyte (OR = 0.91, 95% CI = 0.86–0.96, p = 0.0003 PFDR = 0.152), CD62L-CD86+ myeloid DC AC (OR = 0.93, 95% CI = 0.89–0.97, p = 0.0005, PFDR = 0.152),CD11b on Mo (OR = 1.08, 95% CI = 1.03–1.13, p = 0.001, PFDR = 0.152), CD38 on igd+ cd24− (OR = 1.14, 95% CI = 1.06–1.23, p = 0.001, PFDR = 0.152), D14+ cd16+ monocyte %monocyte (OR = 1.10, 95% CI = 1.04–1.17, p = 0.001, PFDR = 0.159). Additionally, PD may be causally related to the immune phenotype of CM CD8br %T cell (beta = 0.10, 95% CI = 1.14–1.16, p = 0.0004, PFDR = 0.151), SSC-A on monocyte (beta = 0.11, 95% CI = 1.15–1.18, p = 0.0004, PFDR = 0.1 SSC-A on monocyte). No pleiotropy was determined.ConclusionThis study suggested a potential causal link between immune cells and Parkinson’s Disease through the MR method, which could provide a new direction for the mechanistic research and clinical treatment of PD

Detection and Mitigation of Position Spoofing Attacks on Cooperative UAV Swarm Formations

Detecting spoofing attacks on the positions of unmanned aerial vehicles (UAVs) within a swarm is challenging. Traditional methods relying solely on individually reported positions and pairwise distance measurements are ineffective in identifying the misbehavior of malicious UAVs. This paper presents a novel systematic structure designed to detect and mitigate spoofing attacks in UAV swarms. We formulate the problem of detecting malicious UAVs as a localization feasibility problem, leveraging the reported positions and distance measurements. To address this problem, we develop a semidefinite relaxation (SDR) approach, which reformulates the non-convex localization problem into a convex and tractable semidefinite program (SDP). Additionally, we propose two innovative algorithms that leverage the proximity of neighboring UAVs to identify malicious UAVs effectively. Simulations demonstrate the superior performance of our proposed approaches compared to existing benchmarks. Our methods exhibit robustness across various swarm networks, showcasing their effectiveness in detecting and mitigating spoofing attacks. {\blue Specifically, the detection success rate is improved by up to 65\%, 55\%, and 51\% against distributed, collusion, and mixed attacks, respectively, compared to the benchmarks.Comment: accepted by IEEE TIFS in Dec. 202

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Detecting spoofing attacks on the positions of unmanned aerial vehicles (UAVs) within a swarm is challenging. Traditional methods relying solely on individually reported positions and pairwise distance measurements are ineffective in identifying the misbehavior of malicious UAVs. This paper presents a novel systematic structure designed to detect and mitigate spoofing attacks in UAV swarms. We formulate the problem of detecting malicious UAVs as a localization feasibility problem, leveraging the reported positions and distance measurements. To address this problem, we develop a semidefinite relaxation (SDR) approach, which reformulates the non-convex localization problem into a convex and tractable semidefinite program (SDP). Additionally, we propose two innovative algorithms that leverage the proximity of neighboring UAVs to identify malicious UAVs effectively. Simulations demonstrate the superior performance of our proposed approaches compared to existing benchmarks. Our methods exhibit robustness across various swarm networks, showcasing their effectiveness in detecting and mitigating spoofing attacks. Specifically, the detection success rate is improved by up to 65%, 55%, and 51% against distributed, collusion, and mixed attacks, respectively, compared to the benchmarks.info:eu-repo/semantics/publishedVersio

A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson’s disease

Abstract Biomarkers play important roles in the diagnosis and differential diagnosis of Parkinson’s disease (PD). Thus, we carried out a systematic review and meta-analysis evaluating the diagnostic utility of cerebrospinal fluid (CSF) biomarkers to distinguish PD from atypical parkinsonian syndromes (APSs) and controls. Data for PD and APS and controls were extracted from 123 studies that reported the concentration of CSF biomarkers. Comparisons were presented using pooled Hedges’ g. Sources of heterogeneity were evaluated using meta-regression, and subgroup and sensitivity analyses. We found that compared with controls, PD patients had lower levels of amyloid beta 1-42, phosphorylated tau, total tau, total α-synuclein, Zn, DJ-1, and YKL-40, and higher levels of oligomeric and phosphorylated α-synuclein. Moreover, lower CSF levels of neurofilament light chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of Aβ42 compared with patients with progressive supranuclear palsy. Reduced levels of p-tau and t-tau and higher Aβ42 levels were found in PD patients compared with patients with dementia with Lewy bodies. Finally, reduced NFL levels were found in patients with PD compared with patients with cortical basal degeneration. Therefore, we believe that the combinations of t-α-syn, Aβ42, and NFL could be promising biomarkers for the differential diagnosis of PD and APSs

Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies

Polyglutamine (polyQ) diseases are hereditary neurodegenerative disorders caused by an abnormal expansion of a trinucleotide CAG repeat in the coding region of their respective associated genes. PolyQ diseases mainly display progressive degeneration of the brain and spinal cord. Nine polyQ diseases are known, including Huntington’s disease (HD), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA), and six forms of spinocerebellar ataxia (SCA). HD is the best characterized polyQ disease. Many studies have reported that transcriptional dysregulation and post-translational disruptions, which may interact with each other, are central features of polyQ diseases. Post-translational modifications, such as the acetylation of histones, are closely associated with the regulation of the transcriptional activity. A number of groups have studied the interactions between the polyQ proteins and transcription factors. Pharmacological drugs or genetic manipulations aimed at correcting the dysregulation have been confirmed to be effective in the treatment of polyQ diseases in many animal and cellular models. For example, histone deaceylase inhibitors have been demonstrated to have beneficial effects in cases of HD, SBMA, DRPLA, and SCA3. In this review, we describe the transcriptional and post-translational dysregulation in polyQ diseases with special focus on HD, and we summarize and comment on potential treatment approaches targeting disruption of transcription and post-translation processes in these diseases

Clinical characteristics and short-term prognosis of LGI1 antibody encephalitis: a retrospective case study

Abstract Background Recently, most reports of Leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis are from Europe and the US, while the short term outcome and clinical characteristics of Chinese patients are rarely reported,we study the clinical manifestations, laboratory results and brain magnetic resonance images (MRI) of eight patients who were recently diagnosed with LGI1 antibody encephalitis in our hospital to improve the awareness and knowledge of this disease. Methods Eight patients (five males and three females; mean age, 63.4) with LGI1 antibody encephalitis who were diagnosed and treated in the Department of Neurology of Shengjing Hospital of China Medical University from September 2016 to June 2017 were recruited for the current study. Their general information, clinical manifestations, treatment regimens, and short-term prognoses were retrospectively analyzed, as were the results from MRI and laboratory findings. Results Overall, patient symptoms included cognitive impairment, which manifested primarily as memory deficits (8/8), seizures (including faciobrachial dystonic seizure, (FBDS)) (8/8), psychiatric and behavioral disorders (7/8), sleep disorders (4/8), and autonomic abnormalities (3/8). Five patients also had abnormal findings on brain MRI, mainly involving the hippocampus, basal ganglia and insula. Hyponatremia occurred in six cases. All patients tested positive for LGI1 antibodies in their serum/cerebrospinal fluid (CSF)and patients were negative for tumors. Symptoms rapidly improved after treatment with immunoglobulin and/or steroid therapy. The patients were followed up for 4–13 months after discharge, and two patients relapsed. Conclusion Primary symptoms of LGI1 antibody encephalitis include memory impairments, seizures, FBDS, and mental and behavioral abnormalities. Increased titers of LGI1 antibodies are also present in the serum/CSF of patients. Patients often have hyponatremia, and MRIs show abnormalities in various brain regions. Finally, immunotherapy shows good efficacy and positive benefits, although patients may relapse in the short-term

Image-guided Pro-angiogenic Therapy in Diabetic Stroke Mouse Models Using a Multi-modal Nanoprobe

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2014.04.28; Accepted: 2014.04.29; Published: 2014.05.25 Purpose: The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. Methods: A home-made ανβ 3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. Results: The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in bot

Key technologies for complex surface seismic acquisition in the Sichuan Basin and their application effect

The earth surface in the Sichuan Basin and its periphery is geologically complex, which causes low signal-to-noise ratio of seismic data, poor imaging quality of seismic profiles and great difficulty in data acquisition. In order to ensure high-quality operation of the seismic survey project in the complex surface of the Sichuan Basin, researchers have been working continuously to solve the bottleneck problems in the seismic acquisition technology for complex surface in recent years. In addition, the upgrading of acquisition technology and operation capacity is promoted effectively by means of technical innovation, and a series of key technologies for seismic acquisition are developed. And the following application results of this series of technologies are obtained. First, the optimization design technology of the geometry based on wave equation forward modeling and actual data, combined with prestack migration imaging can show the influence of different acquisition schemes on the prestack imaging effect of complex targets more directly, which makes the seismic acquisition scheme more economic and effective. Second, by extracting landform risks and surface obstacle information intelligently, combined with field fine reconnaissance, landform risk identification and hierarchical evaluation and indoors intelligent optimization of well-shot physical point deployment are conducted, and thus the GIS+ intelligent deployment technology of shot point in complex surface is formed, which effectively reduces the risks of operation. Third, the cavity excitation technology which reduces the initial pressure of explosive pulse and extends the explosive action time of explosives can increase the conversion rate of rock excitation energy into effective elastic wave energy and the reflected energy and improve the quality of seismic single shot data. Fourth, combination of the automatic evaluation technology for field seismic data acquired in mountainous regions and the KL-GMLiveQC1.0 software can improve the evaluation efficiency, reduce the evaluation cost and ensure the high-quality acquisition of seismic data in complex surface. In conclusion, this series of key seismic acquisition technologies greatly improve the signal-to-noise ratio and resolution of seismic data, lay a foundation for fine reservoir prediction, and ensure the continuous important breakthrough of three-dimensional natural gas exploration and development in the gas fields of marine carbonate rock, shale gas, volcanic rock and shallow tight sandstone gas in the Sichuan Basin

Overcoming the Blood–Brain Barrier for Delivering Drugs into the Brain by Using Adenosine Receptor Nanoagonist

The extremely low permeability of the blood–brain barrier (BBB) poses the greatest impediment in the treatment of central nervous system (CNS) diseases. Recent work indicated that BBB permeability can be up-regulated by activating A_2A adenosine receptor (AR), which temporarily increases intercellular spaces between the brain capillary endothelial cells. However, due to transient circulation lifetime of adenosine-based agonists, their capability to enhance brain delivery of drugs, especially macromolecular drugs, is limited. In this work, a series of nanoagonists (NAs) were developed by labeling different copies of A_2A AR activating ligands on dendrimers. <i>In vitro</i> transendothelial electrical resistance measurements demonstrated that the NAs increased permeability of the endothelial cell monolayer by compromising the tightness of tight junctions, the key structure that restricts the entry of blood-borne molecules into the brain. <i>In vivo</i> imaging studies indicated the remarkably up-regulated brain uptake of a macromolecular model drug (45 kDa) after intravenous injection of NAs. Autoradiographic imaging showed that the BBB opening time-window can be tuned in a range of 0.5–2.0 h by the NAs labeled with different numbers of AR-activating ligands. By choosing a suitable NA, it is possible to maximize brain drug delivery and minimize the uncontrollable BBB leakage by matching the BBB opening time-window with the pharmacokinetics of a therapeutic agent. The NA-mediated brain drug delivery strategy holds promise for the treatment of CNS diseases with improved therapeutic efficiency and reduced side-effects