EEG biomarkers analysis in different cognitive impairment after stroke: an exploration study.

Stroke is a cerebrovascular illness that brings about the demise of brain tissue. It is the third most prevalent cause of mortality worldwide and a significant contributor to physical impairment. Generally, stroke is triggered by blood clots obstructing the brain's blood vessels, or when these vessels rupture. And, the cognitive impairment's evaluation and detection after stroke is crucial research issue and significant project. Thus, the objective of this work is to explore an potential neuroimage tool and find their EEG biomarkers to evaluate and detect four cognitive impairment levels after stroke. In this study, power density spectrum (PSD), functional connectivity map, and one-way ANOVA methods were proposed to analyze the EEG biomarker differences, and the number of patient participants were thirty-two human including eight healthy control, mild, moderate, severe cognitive impairment levels, respectively. Finally, healthy control has significant PSD differences compared to mid, moderate and server cognitive impairment groups. And, the theta and alpha bands of severe cognitive impairment groups have presented consistent superior PSD power at the right frontal cortex, and the theta and beta bands of mild, moderated cognitive impairment (MoCI) groups have shown significant similar superior PSD power tendency at the parietal cortex. The significant gamma PSD power difference has presented at the left-frontal cortex in the mild cognitive impairment (MCI) groups, and severe cognitive impairment (SeCI) group has shown the significant PSD power at the gamma band of parietal cortex. At the point of functional connectivity map, the SeCI group appears to have stronger functional connectivity compared to the other groups. In conclusion, EEG biomarkers can be applied to classify different cognitive impairment groups after stroke. These findings provide a new approach for early detection and diagnosis of cognitive impairment after stroke and also for the development of new treatment options.

Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Broadband nonlinear modulation of incoherent light using a transparent optoelectronic neuron array.

Nonlinear optical processing of ambient natural light is highly desired for computational imaging and sensing. Strong optical nonlinear response under weak broadband incoherent light is essential for this purpose. By merging 2D transparent phototransistors (TPTs) with liquid crystal (LC) modulators, we create an optoelectronic neuron array that allows self-amplitude modulation of spatially incoherent light, achieving a large nonlinear contrast over a broad spectrum at orders-of-magnitude lower intensity than achievable in most optical nonlinear materials. We fabricated a 10,000-pixel array of optoelectronic neurons, and experimentally demonstrated an intelligent imaging system that instantly attenuates intense glares while retaining the weaker-intensity objects captured by a cellphone camera. This intelligent glare-reduction is important for various imaging applications, including autonomous driving, machine vision, and security cameras. The rapid nonlinear processing of incoherent broadband light might also find applications in optical computing, where nonlinear activation functions for ambient light conditions are highly sought.

Diagnostic Value of Dual-Energy CT Virtual Noncalcium for the Assessment of Bone Marrow Edema of Wrist in Patients with Rheumatoid Arthritis.

RATIONALE AND OBJECTIVES: To evaluate the value of dual-energy CT (DECT) virtual noncalcium (VNCa) images in the diagnosis of wrist bone marrow edema (BME) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 43 patients with wrist involvement in active RA prospectively underwent DECT and MRI. Functional DECT images reconstruction yielded VNCa images. MRI served as the reference standard for diagnosing BME. BME diagnosis differences between VNCa images and MRI were compared. Differences in CT values between BME and normal bone marrow were assessed. The optimal CT value for detecting BME in VNCa images was determined through ROC curve analysis. The correlation between VNCa images scores and RA disease activity was evaluated. RESULTS: There was a high agreement between VNCa images and MRI in diagnosing BME (Kappa=0.831). VNCa images showed a significant difference in CT values between BME and normal bone marrow (P < 0.001). A cut-off value of - 54.8 HU yielded a sensitivity, specificity, and accuracy of 90.72%, 94.30%, and 93.33%, respectively, for detecting BME on VNCa images. The area under the ROC curve was 0.937 for distinguishing BME from normal bone marrow. Conventional CT images showed no statistically significant difference (P = 0.174) in CT values between BME and normal bone marrow. The VNCa images BME scores were positively correlated with RA disease activity (r = 0.399). CONCLUSION: The DECT VNCa technique demonstrates its potential for diagnosing wrist BME in patients with RA and provides a valuable tool for assessing disease activity in RA. IMPORTANT FINDINGS: The DECT VNCa technique has the ability to distinguish between BME and normal bone marrow. The VNCa images BME scores were positively correlated with the disease activity in RA.

Staphylococcus aureus and biofilms: transmission, threats, and promising strategies in animal husbandry.

Staphylococcus aureus (S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts (meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.

Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.

BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

Significant hydrogen generation via photo-mechanical coupling in flexible methylammonium lead iodide nanowires.

The flexoelectric effect, which refers to the mechanical-electric coupling between strain gradient and charge polarization, should be considered for use in charge production for catalytically driving chemical reactions. We have previously revealed that halide perovskites can generate orders of higher magnitude flexoelectricity under the illumination of light than in the dark. In this study, we report the catalytic hydrogen production by photo-mechanical coupling involving the photoflexoelectric effect of flexible methylammonium lead iodide (MAPbI3) nanowires (NWs) in hydrogen iodide solution. Upon concurrent light illumination and mechanical vibration, large strain gradients were introduced in flexible MAPbI3 NWs, which subsequently induced significant hydrogen generation (at a rate of 756.5 µmol g-1 h-1, surpassing those values from either photo- or piezocatalysis of MAPbI3 nanoparticles). This photo-mechanical coupling strategy of mechanocatalysis, which enables the simultaneous utilization of multiple energy sources, provides a potentially new mechanism in mechanochemistry for highly efficient hydrogen production.

Combined Placental Mesenchymal Stem Cells with Guided Nanoparticles Effective Against Diabetic Nephropathy in Mouse Model.

Background: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of cell therapies in treating DN. Methods: We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. Results: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. Conclusion: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.

The effect of EEG and fNIRS in the digital assessment and digital therapy of Alzheimer's disease: a systematic review.

In the context of population aging, the growing problem of Alzheimer's disease (AD) poses a great challenge to mankind. Although there has been considerable progress in exploring the etiology of AD, i.e., the important role of amyloid plaques and neurofibrillary tangles in the progression of AD has been widely accepted by the scientific community, traditional treatment and monitoring modalities have significant limitations. Therefore novel evaluation and treatment modalities for Alzheimer's disease are called for emergence. In this research, we sought to review the effectiveness of digital treatment based on monitoring using functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). This work searched four electronic databases using a keyword approach and focused on journals focusing on AD and geriatric cognition. Finally, 21 articles were included. The progress of digital therapy and outcome monitoring in AD was reviewed, including digital therapy approaches on different platforms and different neuromonitoring techniques. Because biomarkers such as theta coherence, alpha and beta rhythms, and oxyhemoglobin are effective in monitoring the cognitive level of AD patients, and thus the efficacy of digital therapies, this review particularly focuses on the biomarker validation results of digital therapies. The results show that digital treatment based on biomarker monitoring has good effectiveness. And the effectiveness is reflected in the numerical changes of biomarker indicators monitored by EEG and fNIRS before and after digital treatment. Increases or decreases in the values of these indicators collectively point to improvements in cognitive function (mostly moderate to large effect sizes). The study is the first to examine the state of digital therapy in AD from the perspective of multimodal monitoring, which broadens the research perspective on the effectiveness of AD and gives clinical therapists a "reference list" of treatment options. They can select a specific protocol from this "reference list" in order to tailor digital therapy to the needs of individual patients.

Investigation on the fault monitoring of high-voltage circuit breaker using improved deep learning.

Mechanical faults are the main causes of abnormal opening, refusal operation, or malfunction of high-voltage circuit breakers. Accurately assessing the operational condition of high-voltage circuit breakers and delivering fault evaluations is essential for the power grid's safety and reliability. This article develops a circuit breaker fault monitoring device, which diagnoses the mechanical faults of the circuit breaker by monitoring the vibration information data. At the same time, the article adopts an improved deep learning method to train vibration information of high-voltage circuit breakers, and based on this, a systematic research method is employed to identify circuit breaker faults. Firstly, vibration information data of high-voltage circuit breakers is obtained through monitoring devices, this vibration data is then trained using deep learning methods to extract features corresponding to various fault types. Secondly, using the extracted features, circuit breaker faults are classified and recognized with a systematic analysis of the progression traits across various fault categories. Finally, the circuit breaker's fault type is ascertained by comparing the test set's characteristics with those of the training set, using the vibration data. The experimental results show that for the same type of circuit breaker, the accuracy of this method is over 95%, providing a more efficient, intuitive, and practical method for online diagnosis and fault warning of high-voltage circuit breakers.

Combining Porous Se@SiO2 Nanocomposites and dECM Enhances the Myogenic Differentiation of Adipose-Derived Stem Cells.

Background: Volumetric Muscle Loss (VML) denotes the traumatic loss of skeletal muscle, a condition that can result in chronic functional impairment and even disability. While the body can naturally repair injured skeletal muscle within a limited scope, patients experiencing local and severe muscle loss due to VML surpass the compensatory capacity of the muscle itself. Currently, clinical treatments for VML are constrained and demonstrate minimal efficacy. Selenium, a recognized antioxidant, plays a crucial role in regulating cell differentiation, anti-inflammatory responses, and various other physiological functions. Methods: We engineered a porous Se@SiO2 nanocomposite (SeNPs) with the purpose of releasing selenium continuously and gradually. This nanocomposite was subsequently combined with a decellularized extracellular matrix (dECM) to explore their collaborative protective and stimulatory effects on the myogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The influence of dECM and NPs on the myogenic level, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) activity of ADSCs was evaluated using Western Blot, ELISA, and Immunofluorescence assay. Results: Our findings demonstrate that the concurrent application of SeNPs and dECM effectively mitigates the apoptosis and intracellular ROS levels in ADSCs. Furthermore, the combination of dECM with SeNPs significantly upregulated the expression of key myogenic markers, including MYOD, MYOG, Desmin, and myosin heavy chain in ADSCs. Notably, this combination also led to an increase in both the number of mitochondria and the respiratory chain activity in ADSCs. Conclusion: The concurrent application of SeNPs and dECM effectively diminishes ROS production, boosts mitochondrial function, and stimulates the myogenic differentiation of ADSCs. This study lays the groundwork for future treatments of VML utilizing the combination of SeNPs and dECM.

Evaluation of popular science tourism in Guangzhou HEMC based on PLS-SEM.

Science popularization is not only a prerequisite for national development, but also an effective means of enhancing citizens' personal quality. All sectors of society, represented by colleges and universities, bear the responsibility of promoting popular science. The integration of popular science and tourism in popular science tourism serves to advance both the field of popular science and the tourism industry simultaneously. The Guangzhou Higher Education Mega Center (HEMC) possesses abundant resources for science popularization and has the potential to develop popular science tourism, yet its current development in this area remains insufficient. This study utilizes Guangzhou HEMC as a case study and modifies the American Customer Satisfaction Index model by incorporating relevant questions pertaining to popular science tourism. A total of 280 valid questionnaires were collected through surveying, which were then analyzed to measure tourist satisfaction using the Tourist Satisfaction Index. The partial least squares structural equation model was employed for analysis, and on the basis of calculation results, the IPA map was constructed. The research revealed that tourists' satisfaction with popular science tourism at Guangzhou HEMC was suboptimal. Among the factors correlating to satisfaction, expectations, quality, and price are all important factors to consider when making a purchase decision; however, prioritizing expectations and quality can lead to greater satisfaction in the long run. Therefore, there is still ample room for improvement in the popular science tourism of HEMC Guangzhou. This can be achieved by intensifying publicity efforts, enhancing infrastructure, improving the quality and safety of catering services, strengthening the introduction and construction of popular science content, as well as appropriately reducing the price of popular science products and services.

SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Cardiovascular complications significantly augment the overall COVID-19 mortality, largely due to the susceptibility of human cardiomyocytes (CMs) to SARS-CoV-2 virus. SARS-CoV-2 virus encodes 27 genes, whose specific impacts on CM health are not fully understood. This study elucidates the deleterious effects of SARS-CoV-2 genes Nsp6, M, and Nsp8 on human CMs. METHODS: CMs were derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, using 2D and 3D differentiation methods. We overexpressed Nsp6, M, or Nsp8 in hPSCs and then applied whole mRNA-seq and mass spectrometry for multi-omics analysis. Co-immunoprecipitation mass spectrometry was utilized to map the protein interaction networks of Nsp6, M, and Nsp8 within host hiPSC-CMs. RESULTS: Nsp6, Nsp8, and M globally perturb the transcriptome and proteome of hPSC-CMs. SARS-CoV-2 infection and the overexpression of Nsp6, Nsp8, or M coherently upregulated genes associated with apoptosis and immune/inflammation pathways, whereas downregulated genes linked to heart contraction and functions. Global interactome analysis revealed interactions between Nsp6, Nsp8, and M with ATPase subunits. Overexpression of Nsp6, Nsp8, or M significantly reduced cellular ATP levels, markedly increased apoptosis, and compromised Ca2+ handling in hPSC-CMs. Importantly, administration of FDA-approved drugs, ivermectin and meclizine, could restore ATP levels, thereby mitigating apoptosis and dysfunction in hPSC-CMs overexpressing Nsp6, Nsp8, or M. CONCLUSION: Overall, our findings uncover the extensive damaging effects of Nsp6, Nsp8, and M on hPSC-CMs, underlining the crucial role of ATP homeostasis in CM death and functional abnormalities induced by these SARS-CoV-2 genes, and reveal the potential therapeutic strategies to alleviate these detrimental effects with FDA-approved drugs.

MicroRNA transcriptome analysis for elucidating the immune mechanism of the redclaw crayfish Cherax quadricarinatus under Decapod iridescent virus 1 infection.

Redclaw crayfish (Cherax quadricarinatus) is a large, tropical freshwater crustacean species with considerable potential of commercial production. In recent years, infection with DIV1 in redclaw crayfish is being reported in aquaculture industries, causing high mortality and huge economic losses. However, many characteristics of this virus, including pathogenesis, transmission mechanism, and host immunity, remain largely unknown.MicroRNAs are known to play important roles in numerous biological processes, and many microRNAs are reported to be involved in the regulation of immune responses. In this study, nine-small RNA libraries were constructed using hemocytes of redclaw crayfish to characterize the differentially expressed miRNAs (DE-miRNAs) at 24 and 48 h postinfection (hpi). A total of 14 and 22 DE-miRNAs were identified in response to DIV1 infection at 24 and 48 hpi, respectively. Further, functional annotation of the predicted host target genes using GO and KEGG pathway enrichment analyses indicated that relevant biological processes and signal pathways underwent miRNA-mediated regulation after DIV1 infection. Our results enhanced the understanding of the mechanisms of miRNA-mediated regulation of immune responses under DIV1 infection in crustaceans.

A Photosensitizer-Loaded Polydopamine Nanomedicine Agent for Synergistic Photodynamic and Photothermal Therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising non-invasive approaches to cancer treatment. However, the development of multifunctional nanomedicines is necessary to enhance these approaches' effectiveness and safety. In this study, we investigated a polydopamine-based nanoparticle (PDA-ZnPc+ Nps) loaded with the efficient photosensitizer ZnPc(4TAP)12+ (ZnPc+) through in vitro and in vivo experiments to achieve synergistic PDT and PTT. Our results demonstrated that PDA-ZnPc+ Nps exhibited remarkable efficacy due to its ability to generate reactive oxygen species (ROS), induce photothermal effects, and promote apoptosis in cancer cells. Moreover, in both MCF-7 cells and MCF-7 tumor-bearing mice, the combined PDT/PTT treatment with PDA-ZnPc+ Nps led to synergistic effects. Subcellular localization analysis revealed a high accumulation of ZnPc+ in the cytoplasm of cancer cells, resulting in cellular disruption and vacuolation following synergistic PDT/PTT. Furthermore, PDA-ZnPc+ Nps exhibited significant antitumor effects without causing evident systemic damage in vivo, enabling the use of lower doses of photosensitizer and ensuring safer treatment. Our study not only highlights the potential of PDA-ZnPc+ Nps as a dual-functional anticancer agent combining PDA and PTT but also offers a strategy for mitigating the side effects associated with clinical photosensitizers, particularly dark toxicity.

Mechanism of Accelerated Deterioration of High-Temperature Vulcanized Silicone Rubber under Multi-Factor Aging Tests Considering Temperature Cycling.

High-temperature vulcanized silicone rubber (HTV-SR) employed for composite insulators is continuously subjected to a complex environment of alternating heat, corona discharge, humidity, etc. These stresses (especially alternating heat) complicate the aging mechanism of HTV-SR, which lacks systematic investigation. In this paper, a multi-factor aging platform considering temperature cycling, moisture, and corona discharge is established. Specifically, four temperature-cycling settings are employed, each of which lasts for 15 cycles. The surface morphology, hydrophobicity, and chemical, mechanical, and electrical properties of aged samples are methodically characterized. Experimental results show that the aging degree is correlated to the range of temperature cycling, which is attributed to diverse crosslink-degradation degrees with different temperature differences. Under a large temperature difference (70 °C), HTV-SR possesses a high crosslinking degree and a low degradation degree, making the material hard but easy to crack with alternating thermal stress. Then, severe defects and water condensation emerge on the HTV-SR surface, which promote the diffusion of corona products and water molecules into the material. The subsequent rise in crosslinking density caused by in-depth oxidation further exacerbates the aging of the material. Consequently, it brings about poor hydrophobicity, high interfacial polarization, and shallow trap energy levels in HTV-SR. This work provides a detailed analysis of the aging mechanism of HTV-SR in a simulated on-site environment.

AI-Driven Discovery of Amorphous Fluorinated Polymer Electret with Improved Charge Stability for Energy Harvesting.

Electret materials are promising dielectric materials with trapped charges for various applications such as vibration energy harvesters and acoustic transducers. In the present work, ionization potential is discovered as the descriptor to quantify the charging performance for amorphous fluorinated polymer electrets. Using this descriptor, high-throughput computations, and graph neural network models, 1 176 591 functional groups are screened on the cyclic transparent optical polymers (CYTOP), and 3 promising electrets are identified. The electrets are synthesized experimentally as 15 µm-thick films. The films are able to keep their both bipolar surface potentials above ±3.1 kV for over 1500 h and are estimated to have longevity of 146 years under 80 °C, achieving significant improvements on charging stability among CYTOP-based polymer electrets. The excellent bipolar charging performance can greatly enhance power generation capacity of electret-based vibration energy harvesters. This work also demonstrates the use of deep learning as a new paradigm for accelerating practical materials discovery.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus 10398A>G.

Mitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer's disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT heteroplasmy was present throughout the entire MT genome for blood samples, we detected MT heteroplasmy only within the MT control region for brain samples. We observed that an MT variant 10398A>G (rs2853826) was significantly associated with overall MT heteroplasmy in brain tissue while also being linked with the largest number of distinct disease phenotypes of all annotated MT variants in MitoMap. Using gene-expression data from our brain samples, our modeling discovered several gene networks involved in mitochondrial respiratory chain and Complex I function associated with 10398A>G. The variant was also found to be an expression quantitative trait loci (eQTL) for the gene MT-ND3. We further characterized the effect of 10398A>G by phenotyping a population of lymphoblastoid cell-lines (LCLs) with and without the variant allele. Examination of RNA sequence data from these LCLs reveal that 10398A>G was an eQTL for MT-ND4. We also observed in LCLs that 10398A>G was significantly associated with overall MT heteroplasmy within the MT control region, confirming the initial findings observed in post-mortem brain tissue. These results provide novel evidence linking MT SNPs with MT heteroplasmy and open novel avenues for the investigation of pathomechanisms that are driven by this pleiotropic disease associated loci.

Comparison of peripheral blood T, B, and NK lymphocytes between frontline medical workers for treating patients of COVID-19 and normal outpatient and emergency medical workers in China.

The outbreak of the novel coronavirus disease 2019 (COVID-19) has led to significant mental stress for frontline medical workers treating patients with confirmed COVID-19 in China. Psychological stress has an impact on the immune system. The number and percentage of lymphocyte subsets are standard indicators of cellular immune detection. Here, we reported the differences in CD3, CD4, CD8, CD19, and CD56 lymphocytes between 158 frontline medical workers and 24 controls from medical staffs of the outpatient and emergency departments. We found that frontline medical workers had significantly lower absolute values and percentages of CD19+ B cells, especially in the female and the aged ≥40 years subgroup. Stratification analysis showed that the absolute values of CD4+ T cells were significantly lower in the aged <40 years subgroup, while percentages of CD8+ T cells were lower and percentages of CD56+ NK cells were higher in the aged ≥40 years subgroup. In summary, this study suggests paying more attention to frontline medical workers' mental health and immune function, and properly providing them with psychological interventions and measures of care.