cholesterol-stearamide-mediate-lymphocyte-apoptosis-cytokine

Cholesterol and Stearamide Mediate Lymphocyte Apoptosis and Cytokine Secretion in Systemic Lupus Erythematosus

Alterations in serum metabolite composition have been increasingly associated with systemic lupus erythematosus (SLE), yet the direct effects of these ...

Anhui University of Science & Technology

Recently, nanoluminophores with the potential-resolved multicolor electrochemiluminescence (PRMCECL) property have emerged and shown promising applications in sensitive, selective, and accurate bioassays, bioimaging, and multicolor emitting devices. However, only limited PRMCECL nanoluminophores and their applications in ratiometric biosensors eliminating proportional errors have been reported. Herein, a novel PRMCECL nanoluminophore was synthesized by encapsulating CdS quantum dots (CdSQDs) into MOF-5 (CdSQDs@MOF-5). Using KSO as a coreactant, two electrochemiluminescence (ECL) peaks, ECL-1 centered at 685 nm and ECL-2 centered at 475 nm, were observed at -1.4 and -1.8 V, respectively. Related ECL mechanisms have been proposed. Based on the potential-resolved ECL signals, a label-free differential ECL immunosensor for the determination of cardiac troponin I (cTnI) was established by assembly of poly(diallyldimethylammonium chloride), CdSQDs@MOF-5, and cTnI antibody-functionalized silver nanoparticles on the surface of the fluorine-doped tin oxide electrode subsequently. In the presence of cTnI, cTnI was captured by the sensing interface, leading to an increase in ECL-1 and ECL-2 intensity. cTnI could be determined in the range of 0.01-1000 pg/mL with a detection limit of 5.01 fg/mL using the intensity difference between ECL-1 and ECL-2. This work provides a new family member of PRMCECL nanoluminophores. The proposed label-free differential ECL immunosensor provides a new strategy based on potential-resolved ECL signals, which could effectively eliminate the additive error and show better sensitivity, selectivity, and accuracy for the detection of cTnI than the single-signal strategy and ratiometric strategy.

Potential-Resolved Differential Electrochemiluminescence Immunosensor for Cardiac Troponin I Based on MOF-5-Wrapped CdS Quantum Dot Nanoluminophores.

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

Label-free electrochemiluminescence (ECL) immunoassays (-ECLIA), based on biomarker-induced ECL signal changes, have attracted increasing attention due to the simple, rapid, and low-cost detection of biomarkers without secondary antibodies and complicated labeling procedures. However, the interaction rule and mechanism between analytical interfaces and biomarkers have rarely been explored. Herein, the interactions between biomarkers and analytical interfaces constructed by assembly of a nanoluminophore and antibody-functionalized gold nanoparticles on an indium tin oxide electrode were studied. The nanoluminophore was synthesized by mixing Cu/l-cysteine chelate and N-(4-Aminobutyl)-N-ethylisoluminol-bifunctionalized gold nanoparticles with chitosan. It was found that positively charged biomarkers increased the ECL intensity, whereas negatively charged biomarkers decreased the ECL intensity. The assembly pH influenced the biomarker charges, which determined the ECL enhancement or inhibition. The detection pH only affected the ECL intensity but not the ECL changing trends. Based on the ECL signal changes, a charge-dependent -ECLIA was established, which exhibited inhibition responses to negatively charged human immunoglobulin G and copeptin and enhancement responses to positively charged cardiac troponin I, heart-type fatty acid binding protein, brain natriuretic peptide, and SARS-CoV-2 N protein. The linear range was 0.1-1000 pg/mL, and the detection limits were distributed in 0.024-0.091 pg/mL. Besides, a mechanism of the charge-dependent ECL enhancement and inhibition effects is proposed, which is very important for the development of new -ECLIA methodologies.

Charge-Dependent Signal Changes for Label-Free Electrochemiluminescence Immunoassays.

Acute myocardial infarction (AMI) represents a leading cause of death globally. Key to AMI recovery is timely diagnosis and initiation of treatment, ideally within 3 h of symptom onset. Cardiac troponin T (cTnT) is the gold standard yet a low cTnT result cannot rule out AMI at early times. Here, we develop a three-biomarker joint strategy for early and accurate diagnosis of AMI via an electrochemiluminescence (ECL) immunoarray coupled with robust machine learning. The ECL immunoarray is based on an array microchip with a single-electrode and chemiluminescent immuno-Gold (ciGold) nanoassemblies. The ciGold immunoarray was obtained by successively assembling nanocomposites of Cu/cysteine complexes and N-(aminobutyl)-N-(ethylisoluminol) bifunctionalized gold nanoparticles combined with chitosan and antibody conjugated gold nanoparticles on the surface of a microchip. Three biomarkers, including cardiac troponin I, heart type fatty acid binding protein, and copeptin, were simultaneously detected in 260 serum samples from patients presenting with chest pain by an innovative multiplexed ECL immunoarray, and classified via the three-biomarker joint assessment model using support vector machines. The model achieved perfect discrimination (100% sensitivity and specificity) for AMI vs non-AMI patients, substantially higher than cTnT alone. Within 12 h of symptom onset, high-sensitivity cardiac troponin T (hs-cTnT) misclassified >20% of patients, while the joint biomarker assessment model retained perfect accuracy. As the time between symptom onset and testing became shorter, the degree to which the joint assessment model outperformed hs-cTnT increased. The proposed three-biomarker joint strategy is obviously superior to hs-cTnT for early and accurate diagnosis of AMI, hopefully reducing AMI mortality and saving limited medical resources.

Three-Biomarker Joint Strategy for Early and Accurate Diagnosis of Acute Myocardial Infarction via a Multiplex Electrochemiluminescence Immunoarray Coupled with Robust Machine Learning.

Biomarkers, including proteins, nucleic acids, and metabolites, are the molecules that can provide insightful information about biological processes and pathological developments. Identification and quantification of biomarkers are highly beneficial for disease diagnosis, progression monitoring, and treatment supervision. However, disease development often involves the complex interplay of molecular networks that limits the utility of individual biomarkers in reaching reliable diagnostic and therapeutic decisions. Thus, recent developments of bioassays have turned the focus to analysis of a collection of biomarkers simultaneously, aiming to improve precision in diagnosis. To achieve the demanded throughput in multiplex detection while keeping the excellent analytical performance in speed, sensitivity, and selectivity, nanomaterials stand out to be the proper enabling tools, with their unique but highly diversified physical and chemical properties and the much advanced synthesis strategies. Herein, this review highlights the recent (2020-2024) developments in the nanomaterial-enabled, optical multiplex sensing techniques. Four key approaches to achieve multiplexity were discussed: spatial coding, signal coding, biocarriers, and data deconvolution using machine learning. We believe these advancements have driven forward the applications of multiplex detection in clinical settings by improving the throughput of biomarker analysis.

Multiplex Detection of Biomarkers Empowered by Nanomaterials.

Single-algorithm machine learning models for acute myocardial infarction (AMI) often struggle with heterogeneous clinical data and lack transparency, limiting their clinical adoption.

Interpretable hybrid-ensemble acute myocardial infarction diagnosis with clinical transparency.

The brain is the core of the central nervous system, responsible for regulating and integrating various physiological and psychological functions. Abnormal disruptions in genes during brain development can lead to a range of neurodevelopmental disorders. In this study, we performed a systematic investigation of human fetal brain tissue from miscarriages between 8 and 17 weeks of gestation using integrated single-cell RNA sequencing (scRNA-seq) and single-cell transposase-accessible chromatin sequencing (scATAC-seq). We constructed single-cell transcriptomic and epigenomic maps of neurodevelopment, revealing key signaling pathways involved in neural cell proliferation, differentiation, and functional maturation. Through pseudotime analysis, we reconstructed the developmental trajectory of neuronal differentiation and its dynamic regulatory mechanisms. Additionally, we identified cell type-specific chromatin accessibility regions during neurogenesis and, through integrated analysis, predicted potential regulatory elements involved in the process. Overall, the single-cell multi-omics integration map constructed in this study provides valuable resources for a deeper understanding of fetal brain development, cellular heterogeneity, lineage relationships, and transcriptional regulatory networks during neurogenesis.

Article	Year
Potential-Resolved Differential Electrochemiluminescence Immunosensor for Cardiac Troponin I Based on MOF-5-Wrapped CdS Quantum Dot Nanoluminophores. Analytical chemistry\| PubMed ID: 32962342	2020
Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19. Cell discovery\| PubMed ID: 34103487	2021
Charge-Dependent Signal Changes for Label-Free Electrochemiluminescence Immunoassays. Analytical chemistry\| PubMed ID: 36377666	2022
Three-Biomarker Joint Strategy for Early and Accurate Diagnosis of Acute Myocardial Infarction via a Multiplex Electrochemiluminescence Immunoarray Coupled with Robust Machine Learning. Chemical & biomedical imaging\| PubMed ID: 39474620	2023
Multiplex Detection of Biomarkers Empowered by Nanomaterials. Precision chemistry\| PubMed ID: 40574998	2025
Interpretable hybrid-ensemble acute myocardial infarction diagnosis with clinical transparency. International journal of cardiology\| PubMed ID: 40623633	2025
Integrative Single-Cell Analysis Decodes Gene Expression and Chromatin Accessibility in the Developing Human Fetal Brain. Molecular neurobiology\| PubMed ID: 40663269	2025

Mingquan Guo

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