Label-Free, High-Throughput, Sensitive, and Logical Analysis Using Biomimetic Array Based on Stable Luminescent Copper Nanoclusters and Entropy-Driven Nanomachine.

The development of an array for high-throughput and logical analysis of biomarkers is significant for disease diagnosis. DNA-templated copper nanoclusters (CuNCs) have a strong potential to serve as a label-free photoluminescence source in array platforms, but their luminescent stability and sensitivity need to be improved. Herein, we report a facile, sensitive, and robust biomimetic array assay by integrating with stable luminescent CuNCs and entropy-driven nanomachine (EDN). In this strategy, the luminescent stability of CuNCs was improved by adding fructose in CuNCs synthesis to offer a reliable label-free signal. Meanwhile, the DNA template for CuNCs synthesis was introduced into EDN with excellent signal amplification ability, in which the reaction triggered by target miRNA would cause the blunt/protruding conformation change of 3'-terminus accompanied by the production or loss of luminescence. In addition, a biomimetic array fabricated by photonic crystals (PCs) physically enhanced the emitted luminescent signal of CuNCs and achieved high-throughput signal readout by a microplate reader. The proposed assay can isothermally detect as low as 4.5 pM of miR-21. Moreover, the logical EDN was constructed to achieve logical analysis of multiple miRNAs by "AND" or "OR" logic gate operation. Therefore, the proposed assay has the advantages of label-free property, high sensitivity, flexible design, and high-throughput analysis, which provides ideas for developing a new generation of facile and smart platforms in the fields of biological analysis and clinical application.

Improved Electrochemical Alkaline Seawater Oxidation over Cobalt Carbonate Hydroxide Nanowire Array by Iron Doping.

Constructing efficient and low-cost oxygen evolution reaction (OER) catalysts operating in seawater is essential for green hydrogen production but remains a great challenge. In this study, we report an iron doped cobalt carbonate hydroxide nanowire array on nickel foam (Fe-CoCH/NF) as a high-efficiency OER electrocatalyst. In alkaline seawater, such Fe-CoCH/NF demands an overpotential of 387 mV to drive 500 mA cm-2, superior to that of CoCH/NF (597 mV). Moreover, it achieves excellent electrochemical and structural stability in alkaline seawater.

The reference ranges and characteristics of lymphocyte parameters and the correlation between lymphocyte parameters and routine health indicators in adults from China.

BACKGROUND: Assessment of immune function is of key importance in recognition of disease or healthy status, which still faces challenge in clinical practice. We conducted a 10-center study to investigate lymphocyte parameters including the number, phenotype and IFN-γ-producing ability, and routine laboratory indicators by using the standard method. RESULTS: Although the heterogeneity of lymphocyte parameters was widely found, we have established the normal ranges of these parameters by using pooled data which showed no significant difference among centers. Cluster analysis of 35 parameters found 3 interesting clusters which represented different immunological status. Cluster 1 (parameters: IFN-γ+CD4+ T cell percentage and IFN-γ+CD8+ T cell percentage) represented current lymphocyte function, which was associated with indicators such as body mass index and red blood cell; Cluster 2 (parameters: NK cell number and CD45RA+CD4+ T cell percentage) represented potential of lymphocytes, which was associated with indicators such as albumin and high-density lipoprotein. Cluster 3 (parameters: HLA-DR+CD8+ T cell percentage) represented inflammatory status, which was associated with indicators such as low-density lipoprotein, globulin and age. Correlation analysis found that nutritional indicator albumin is significantly positively correlated with lymphocyte potential. Triglyceride and body mass index were positively correlated with current lymphocyte function rather than lymphocyte potential. The loss of CD8+ T cells was extremely pronounced with increasing age and was one of the most important factors to cause immunosenescence, which may be associated with increased glucose. CONCLUSIONS: We have established the normal ranges of lymphocyte parameters in different areas. This study elucidates the key indicators used to reflect the current function or potential of lymphocytes, which may provide a valuable clue for how to keep immunity healthy.

Clinical and laboratory characteristics of severe and non-severe patients with COVID-19: A retrospective cohort study in China.

BACKGROUND: Patients diagnosed with the novel coronavirus disease (COVID-19) who develop severe symptoms need to be determined in advance so that appropriate treatment strategies are in place. METHODS: To determine the clinic features of patients diagnosed definitely with COVID-19 and evaluate risk factors for severe outcome, the medical records of hospitalized patients were reviewed retrospectively by us and data were compiled. Laboratory data from 90 cases were analyzed, and COVID-19 patients were classified into two groups (severe and non-severe) based on the severity. RESULTS: Severe COVID-19 cases on admission had higher leukocyte and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), D-dimer, fibrinogen, C-reactive protein levels, and lower lymphocyte counts compared with those of non-severe cases (p < 0.05). The area under the curve (AUC) for leukocyte counts, neutrophil counts, and levels of C-reactive protein was 0.778, 0.831, and 0.800, respectively. The thresholds were 7.70 × 109 /L for leukocyte counts, 5.93 × 109/L for neutrophil counts, and 75.07 mg/L for C-reactive protein, respectively. Logistic regression analyses indicated that higher white blood cell (WBC) counts (OR, 1.34; 95% CI, 1.05-1.71), neutrophil counts (OR, 1.35; 95% CI, 1.06-1.73), and C-reactive protein levels (OR, 1.02; 95% CI, 1.0-1.04) were several predictive factors for severe outcome. Severe COVID-19 patients had a reduction in WBC counts, D-dimer, C-reactive protein, and fibrinogen upon discharge from hospital, while lymphocyte counts increased (p < 0.05). CONCLUSION: Counts of WBC, neutrophil, and lymphocyte, NLR, and levels of C-reactive protein, D-dimer, and fibrinogen are helpful for prediction of the deterioration trend in patients diagnosed with COVID-19.

Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer's disease.

Objectives: This study aimed to make a systematic analysis of cuproptosis-related genes (CRGs) in immunological characterization and predictive drugs in Alzheimer's disease (AD) through bioinformatics and biological experiments. Methods: The molecular clusters related to CRGs and associated immune cell infiltrations in AD were investigated. The diagnostic models were constructed for AD and different AD subtypes. Moreover, drug prediction and molecular docking were also performed. Subsequently, a molecular dynamics (MD) simulation was conducted to further verify the findings. Finally, RT-qPCR validation was performed. Results: The characterization of 12 AD-related CRGs was evaluated in AD, and a diagnostic model for AD showed a satisfying discrimination power based on five CRGs by LASSO regression analysis. The dysregulated CRGs and activated immune responses partially differed between patients with AD and healthy subjects. Furthermore, two molecular subtypes (clusters A and B) with different immune infiltration characteristics in AD were identified. Similarly, a diagnostic model for different AD subtypes was built with nine CRGs, which achieved a good performance. Molecular docking revealed the optimum conformation of CHEMBL261454 and its target gene CSNK1D, which was further validated by MD simulation. The RT-qPCR results were consistent with those of the comprehensive analysis. Conclusion: This study systematically elucidated the complex relationship between cuproptosis and AD, providing novel molecular targets for treatment and diagnosis biomarkers of AD.

[Diagnostic value of salivary cortisol in Cushing's syndrome].

OBJECTIVE: To evaluate the usefulness of the measurement of midnight salivary cortisol (SC) in the initial diagnosis of Cushing's syndrome (CS). METHODS: A total of 18 patients with pathologically confirmed CS were recruited in the study. Thirteen patients with pure obesity and 36 healthy people served as controls. Salivary samples at 8:00, 16:00, 24:00 and 8:00 the next day after the 1 mg dexamethasone suppression test(DST) were collected by a commercially-available saliva collection device, and assayed by Electro Chemiluminescence Immuno Assay (ECLIA). RESULTS: There were highly significant correlations between salivary cortisol and plasma cortisol (PTC) at the 4 time points. The correlation coefficient was 0.73 (0.71, 0.74, 0.78 and 0.61 at the four time points, respectively) (P < 0.05). Midnight salivary cortisol level in Cushing's Syndrome [(10.58 +/- 5.17) nmol/L] was significantly higher than healthy people [(1.55 +/- 0.60) nmol/L]. The receiver operating characteristics curve (ROC) analysis showed a sensitivity of 100.00% and specificity of 84.00% at 8:00 with the cut-off point of 6.21 nmol/L. CONCLUSION: The measurement of midnight salivary cortisol is a convenience and noninvasive screening test for the initial diagnosis of Cushing's Syndrome.