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2.
Health Secur ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38815144

ABSTRACT

The purpose of this study was to investigate the feasibility and effectiveness of COVID-19 throat swab samples delivered by medical drones in epidemic prevention and control. This study was carried out in both southern and northern hospital districts of the Affiliated Hospital of Jiangnan University from May to October 2022. The main participants were the Affiliated Hospital of Jiangnan University and Zhejiang Antwork Technology Co., Ltd. We first constructed an urban medical unmanned aerial vehicle (UAV) delivery system and developed a UAV-specific storage box for COVID-19 samples. The UAV system was used to transport COVID-19 throat swab samples from the northern hospital district to the southern hospital district, and the following indexes were obtained: (1) flight time of COVID-19 samples delivered by UAV, (2) real-time temperature of COVID-19 nucleic acid samples during transportation, and (3) the time of distribution of COVID-19 nucleic acid samples by road traffic as measured using the Baidu Maps application, compared with the flight time of UAV. The COVID-19 sample delivery system for urban medical UAV mainly consists of intelligent logistics UAV, low-temperature COVID-19 throat swab sample storage box, unmanned logistics hub, and cloud operation control platform. The flight distance between the northern and southern districts of the Affiliated Hospital of Jiangnan University was 10 km, and the ground distance was 24 km. From May 11 to October 28, 2022, a total of 1,190 UAV flights occurred. The average flight time was 13 minutes, which was 40 to 70 minutes faster than the average road travel time required for manual delivery of COVID-19 throat swab samples. At different time points in the day, UAV delivery efficiency increased by 67.5% to 82%. The use of 5G with the Internet of Things and UAV technology to deliver nucleic acid samples has the characteristics of fast speed, being unaffected by ground traffic conditions, and the ability to ensure the safety of nucleic acid samples in the transportation process, which is worthy of further study.

3.
Parasit Vectors ; 17(1): 239, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802961

ABSTRACT

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.


Subject(s)
Antigens, Protozoan , Collagen Type I , Fibroblasts , Plasmodium vivax , Signal Transduction , Spleen , Plasmodium vivax/genetics , Plasmodium vivax/immunology , Fibroblasts/parasitology , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Antigens, Protozoan/metabolism , Animals , Collagen Type I/metabolism , Collagen Type I/genetics , Spleen/immunology , Spleen/parasitology , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Mice , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/immunology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/immunology , Tryptophan/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Computational Biology
5.
Photochem Photobiol ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634423

ABSTRACT

Excessive exposure to blue light can cause retinal damage. Hydrogen-rich saline (HRS), one of the hydrogen therapies, has been demonstrated to be effective in eye photodamage, but the effect on the expression of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) is unknown. In this study, we used a rat model of light-induced retinal injury to observe the expression of melanopsin after HRS treatment and to determine the effect of HRS on retinal ganglion cell protection. Adult SD rats were exposed to blue light (48 h) and treated with HRS for 0, 3, 7, and 14 days. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were performed to find the expression of genes and proteins, respectively. The function of retinal ipRGCs was measured by pattern-evoked electroretinography (pERG). The number and morphological changes of melanopsin-positive ganglion cells in the retina were observed by immunofluorescence (IF). Acute blue light exposure caused a decrease in ipRGC function, decreased expression of melanopsin protein and the melanopsin-positive RGCs, and diminished immunoreactivity in dendrites. However, over time, melanopsin showed a tendency to self-recovery, with an increase in melanopsin protein expression and the number of melanopsin-positive RGCs, with incomplete recovery of function within two weeks. HRS treatment accelerated the recovery process, with a significant increase in melanopsin expression and the number of melanopsin-positive RGCs, and an improvement in the pERG waveform within two weeks.

6.
Food Microbiol ; 121: 104497, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38637068

ABSTRACT

Daqu is a saccharification agent required for fermenting Baijiu, a popular Chinese liquor. Our objective was to investigate the relationships between physicochemical indices, microbial community diversity, and metabolite profiles of strong-flavor Jinhui Daqu during different storage periods. During different storage periods of Jinhui Daqu, we combined Illumina MiSeq sequencing and non-target sequencing techniques to analyze dynamic changes of the microbial community and metabolite composition, established a symbiotic network and explored the correlation between dominant microorganisms and differential metabolites in Daqu. Fungal community diversity in 8d_Daqu was higher than that in 45d_Daqu and 90d_Daqu, whereas bacterial community diversity was higher in 90d_Daqu. Twelve bacterial and four fungal genera were dominant during storage of Daqu. Bacillus, Leuconostoc, Kroppenstedtia, Lactococcus, Thermomyces and Wickerhamomyces decreased as the storage period increased. Differences of microbiota structure led to various metabolic pathways, and 993 differential metabolites were found in all Daqu samples. Differential microorganisms were significantly related to key metabolites. Major metabolic pathways involved in the formation of amino acids and lipids, such as l-arogenate and hydroxyproline, were identified. Interactions between moisture, acidity, and microbes may drive the succession of the microbial community, which further affects the formation of metabolites.


Subject(s)
Bacillus , Microbiota , Fermentation , Bacteria , Metabolome
7.
Brain Res Bull ; 212: 110968, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38679110

ABSTRACT

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.


Subject(s)
Cerebral Cortex , Chronic Pain , Low Back Pain , Magnetic Resonance Imaging , Humans , Female , Male , Low Back Pain/diagnostic imaging , Low Back Pain/pathology , Adult , Magnetic Resonance Imaging/methods , Middle Aged , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Chronic Pain/diagnostic imaging , Chronic Pain/pathology , Nerve Net/diagnostic imaging , Nerve Net/pathology
8.
Infect Immun ; 92(5): e0011324, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38624215

ABSTRACT

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.


Subject(s)
Antigens, CD , Antigens, Protozoan , Macrophages , Malaria , Plasmodium yoelii , Animals , Female , Humans , Mice , Antigens, CD/metabolism , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/metabolism , Antigens, Differentiation, Myelomonocytic/immunology , Antigens, Protozoan/immunology , Antigens, Protozoan/metabolism , Antigens, Surface/immunology , Antigens, Surface/metabolism , Cell Membrane/metabolism , Cell Membrane/immunology , Inflammation/immunology , Inflammation/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/parasitology , Malaria/immunology , Malaria/parasitology , NF-kappa B/metabolism , NF-kappa B/immunology , Plasmodium yoelii/immunology , Protein Binding , Signal Transduction
9.
J Biol Chem ; 300(5): 107285, 2024 May.
Article in English | MEDLINE | ID: mdl-38636656

ABSTRACT

The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.


Subject(s)
Antigens, CD , Plasmodium vivax , Protozoan Proteins , Receptors, Transferrin , Reticulocytes , Plasmodium vivax/metabolism , Plasmodium vivax/genetics , Reticulocytes/metabolism , Reticulocytes/parasitology , Humans , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Antigens, CD/metabolism , Antigens, CD/genetics , Receptors, Transferrin/metabolism , Receptors, Transferrin/genetics , Anion Exchange Protein 1, Erythrocyte/metabolism , Anion Exchange Protein 1, Erythrocyte/genetics , Protein Binding , Merozoite Surface Protein 1/metabolism , Merozoite Surface Protein 1/genetics , Malaria, Vivax/parasitology , Malaria, Vivax/metabolism , Animals
10.
Front Neurol ; 15: 1351335, 2024.
Article in English | MEDLINE | ID: mdl-38606278

ABSTRACT

Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.

11.
BMC Complement Med Ther ; 24(1): 133, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38539165

ABSTRACT

BACKGROUND: Ethyl acetate extracts from Tetrastigma hemsleyanum (Sanyeqing) (EFT), a member of the Vitaceae plant family, have been shown to exhibit efficacy against a variety of cancers. In this light, our current study seeks to examine the mechanism of efficacy between EFT extracts and human pancreatic cancer PANC-1 cells. METHODS: The chemical components of EFT were analyzed by gas chromatography-mass spectrometry. The cytotoxicity of EFT on PANC-1 cells was measured using an MTT assay. In order to investigate EFT induction of cell cycle arrest, changes in cell-cycle distribution were monitored by flow cytometry. Wound healing and transwell assays were employed to investigate whether migration and invasion of PANC-1 cells were inhibited by EFT. Relative protein expression was detected using Western blot. RESULTS: GC-MS analysis of the chemical composition of EFT revealed that the majority of constituents were organic acids and their corresponding esters. EFT exhibits measurable cytotoxicity and inhibition of PANC-1 invasion. Growth inhibition was primarily attributed to downregulation of CDK2 which induces cell cycle arrest in the S-phase. Inhibition of metastasis is achieved through downregulation of mesenchymal-associated genes/activators, including ZEB1, N-cadherin, Vimentin, and Fibronectin. Meanwhile, the expression of E-cadherin was significantly increased by EFT treatment. Furthermore, downregulation of MMP-2 and MMP-9 were observed. CONCLUSION: Treatment of PANC-1 with EFT demonstrated measurable cytotoxic effects. Furthermore, EFT evoked S phase arrest while inhibiting the migration and invasion of PANC-1 cells. Additionally, EFT inhibited the epithelial to mesenchymal transition and MMPs expression in PANC-1 cells. This study serves to confirm the strong therapeutic potential of EFT while identifying the mechanisms of action.


Subject(s)
Pancreatic Neoplasms , Vitaceae , Humans , Cell Line, Tumor , S Phase , Epithelial-Mesenchymal Transition , Pancreatic Neoplasms/drug therapy , Vitaceae/chemistry
12.
ACS Appl Mater Interfaces ; 16(11): 13773-13785, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38442348

ABSTRACT

Conventional ocean wave observation instruments are powered by batteries, limiting the continuous observation time. Besides, the waste of batteries brings environmental contaminations. Triboelectric nanogenerators (TENGs) can reveal ocean wave information through their electrical output, taking the triboelectric charge as the information carrier. However, charge amplification is necessary, consuming additional energy. Herein, taking the photons rather than electrons as the information carrier, we developed a fully self-powered natural light-enabled sensing system for ocean wave monitoring by coupling two rotary-freestanding sliding TENGs (RFS-TENGs) and a polymer network liquid crystal (PNLC)-triggered optical system. The natural light is modulated by the PNLC driven by ocean wave-induced friction. With the assistance of a one-way bearing, the rise and fall of the wave will trigger different RFS-TENGs to power the PNLC in different voltage drops, leading to different transmitted natural light intensities. The wave height information can be obtained through the number of pulse signals with the same trough light intensity, while the wave period can be obtained through the duration between the same two sets of pulse signals. The effectiveness of the developed sensing paradigm in practical applications was verified by flume-based experiments, with the highest accuracies of 90.7% in wave height and 99.8% in wave period.

13.
Eur Radiol ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38528135

ABSTRACT

OBJECTIVES: To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). MATERIALS AND METHODS: This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. RESULTS: All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). CONCLUSION: Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. CLINICAL RELEVANCE STATEMENT: Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. KEY POINTS: • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

14.
Talanta ; 274: 125994, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38547841

ABSTRACT

Since the outbreak of corona virus disease 2019 (COVID-19), this pandemic has caused severe death and infection worldwide. Owing to its strong infectivity, long incubation period, and nonspecific symptoms, the early diagnosis is essential to reduce risk of the severe illness. The electrochemical biosensor, as a fast and sensitive technique for quantitative analysis of body fluids, has been widely studied to diagnose different biomarkers caused at different infective stages of COVID-19 virus (SARS-CoV-2). Recently, many reports have proved that nanomaterials with special architectures and size effects can effectively promote the biosensing performance on the COVID-19 diagnosis, there are few comprehensive summary reports yet. Therefore, in this review, we will pay efforts on recent progress of advanced nanomaterials-facilitated electrochemical biosensors for the COVID-19 detections. The process of SARS-CoV-2 infection in humans will be briefly described, as well as summarizing the types of sensors that should be designed for different infection processes. Emphasis will be supplied to various functional nanomaterials which dominate the biosensing performance for comparison, expecting to provide a rational guidance on the material selection of biosensor construction for people. Finally, we will conclude the perspective on the design of superior nanomaterials-based biosensors facing the unknown virus in future.


Subject(s)
Biosensing Techniques , COVID-19 , Electrochemical Techniques , Nanostructures , SARS-CoV-2 , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , COVID-19/diagnosis , COVID-19/virology , Humans , Nanostructures/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , SARS-CoV-2/isolation & purification , COVID-19 Testing/methods , COVID-19 Testing/instrumentation
15.
Sci Rep ; 14(1): 5487, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38448556

ABSTRACT

This study addresses the escalating risk of high-speed railway (HSR) infrastructure in China, amplified by climate warming, increased rainfall, frequent extreme weather, and geohazard events. Leveraging a georeferenced dataset of recent HSR defects obtained through an extensive literature review, we employ machine learning techniques for a quantitative multi-defect risk assessment. Climatic, geomorphological, geohydrological, and anthropogenic variables influencing HSR subgrade safety are identified and ranked. Climatic factors significantly impact frost damage and mud pumping, while geomorphological variables exhibit greater influence on settlement and uplift deformation defects. Notably, frost damage is prevalent in the northeast and northwest, mud pumping along the southeast coast, and settlement and uplift deformation in the northwest and central areas. The generated comprehensive risk map underscores high-risk zones, particularly the Menyuan Hui Autonomous and Minle County sections of the Lanzhou-Urumqi HSR, emphasizing the need for focused attention and preventive actions to mitigate potential losses and ensure operational continuity.

16.
J Neuroinflammation ; 21(1): 50, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38365833

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain's resident immune cells, are an attractive target for potentially more effective therapeutic strategies. However, there is no current in vitro model system that captures AD patient-specific microglial characteristics using physiologically relevant and experimentally flexible culture conditions. METHODS: To address this shortcoming, we developed novel 3D Matrigel-based monocyte-derived microglia-like cell (MDMi) mono-cultures and co-cultures with neuro-glial cells (ReNcell VM). We used single-cell RNA sequencing (scRNAseq) analysis to compare the transcriptomic signatures of MDMi between model systems (2D, 3D and 3D co-culture) and against published human microglia datasets. To demonstrate the potential of MDMi for use in personalized pre-clinical strategies, we generated and characterized MDMi models from sixteen AD patients and matched healthy controls, and profiled cytokine responses upon treatment with anti-inflammatory drugs (dasatinib and spiperone). RESULTS: MDMi in 3D exhibited a more branched morphology and longer survival in culture compared to 2D. scRNAseq uncovered distinct MDMi subpopulations that exhibit higher functional heterogeneity and best resemble human microglia in 3D co-culture. AD MDMi in 3D co-culture showed altered cell-to-cell interactions, growth factor and cytokine secretion profiles and responses to amyloid-ß. Drug testing assays revealed patient- and model-specific cytokine responses. CONCLUSION: Our study presents a novel, physiologically relevant and AD patient-specific 3D microglia cell model that opens avenues towards improving personalized drug development strategies in AD.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/pathology , Microglia/metabolism , Neuroglia/metabolism , Amyloid beta-Peptides/metabolism , Cytokines/metabolism
18.
Genet Epidemiol ; 48(3): 114-140, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38317326

ABSTRACT

Advancements in high-throughput genomic technologies have revolutionized the field of disease biomarker identification by providing large-scale genomic data. There is an increasing focus on understanding the relationships among diverse patient groups with distinct disease subtypes and characteristics. Complex diseases exhibit both heterogeneity and shared genomic factors, making it essential to investigate these patterns to accurately detect markers and comprehensively understand the diseases. Integrative analysis has emerged as a promising approach to address this challenge. However, existing studies have been limited by ignoring the adjacency structure of genomic measurements, such as single nucleotide polymorphisms (SNPs) and DNA methylations. In this study, we propose a structured integrative analysis method that incorporates a spline type penalty to accommodate this adjacency structure. We utilize a fused lasso type penalty to identify both heterogeneity and commonality across the groups. Extensive simulations demonstrate its superiority compared to several direct competing methods. The analysis of The Cancer Genome Atlas melanoma data with DNA methylation measurements and GENEVA diabetes data with SNP measurements exhibit that the proposed analysis lead to meaningful findings with better prediction performance and higher selection stability.


Subject(s)
Genomics , Models, Genetic , Humans , Genomics/methods , DNA Methylation/genetics
19.
J Virol ; 98(3): e0189723, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38411946

ABSTRACT

Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, has recently gained considerable attention in the field of cancer therapy. There is significant crosstalk between ferroptosis and several classical signaling pathways, such as the Hippo pathway, which suppresses abnormal growth and is frequently aberrant in tumor tissues. Yes-associated protein 1 (YAP), the core effector molecule of the Hippo pathway, is abnormally expressed and activated in a variety of malignant tumor tissues. We previously proved that the oncolytic Newcastle disease virus (NDV) activated ferroptosis to kill tumor cells. NDV has been used in tumor therapy; however, its oncolytic mechanism is not completely understood. In this study, we demonstrated that NDV exacerbated ferroptosis in tumor cells by inducing ubiquitin-mediated degradation of YAP at Lys90 through E3 ubiquitin ligase parkin (PRKN). Blocking YAP degradation suppressed NDV-induced ferroptosis by suppressing the expression of Zrt/Irt-like protein 14 (ZIP14), a metal ion transporter that regulates iron uptake. These findings demonstrate that NDV exacerbated ferroptosis in tumor cells by inducing YAP degradation. Our study provides new insights into the mechanism of NDV-induced ferroptosis and highlights the critical role that oncolytic viruses play in the treatment of drug-resistant cancers.IMPORTANCEThe oncolytic Newcastle disease virus (NDV) is being developed for use in cancer treatment; however, its oncolytic mechanism is still not completely understood. The Hippo pathway, which is a tumor suppressor pathway, is frequently dysregulated in tumor tissues due to aberrant yes-associated protein 1 (YAP) activation. In this study, we have demonstrated that NDV degrades YAP to induce ferroptosis and promote virus replication in tumor cells. Notably, NDV was found to induce ubiquitin-mediated degradation of YAP at Lys90 through E3 ubiquitin ligase parkin (PRKN). Our study reveals a new mechanism by which NDV induces ferroptosis and provides new insights into NDV as an oncolytic agent for cancer treatment.


Subject(s)
Ferroptosis , Neoplasms , Newcastle disease virus , Oncolytic Virotherapy , YAP-Signaling Proteins , Animals , Humans , Adaptor Proteins, Signal Transducing , Cell Line, Tumor , Iron , Neoplasms/therapy , Oncolytic Viruses/physiology , Transcription Factors/genetics , Ubiquitin-Protein Ligases , Ubiquitins
20.
J Am Chem Soc ; 146(7): 4822-4829, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38329466

ABSTRACT

The construction of function-oriented covalent organic frameworks (COFs) remains a challenge as it requires simultaneous consideration of diversified structures, robust linkage, and tailorable functionalities. Herein, we report the rational synthesis of functionalized COFs via a four-component reaction strategy. Through the four-component Debus-Radziszewski reaction, 11 N-substituted imidazole-based COFs with diversified structures were facilely constructed from readily available building blocks. By forming the N-substituted imidazole linkage, these synthesized COFs displayed ultrastability toward strong acids and base. Moreover, the four components reaction allows the rational synthesis of COFs with tailorable functionalities. As an example, the phosphonate-functionalized COF (LZU-530) was rationally constructed for the efficient adsorption of uranium(VI). The uranium(VI) uptake of LZU-530 reaches up to 95 mg·g-1 in 2 M HNO3, which is the highest uptake of the existing organic porous materials under such harsh conditions. Our results highlight the use of multicomponent reaction for the rational synthesis of robust and functionalized COFs toward targeted applications.

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