2D Zn-Porphyrin-Based Co(II)-MOF with 2-Methylimidazole Sitting Axially on the Paddle-Wheel Units: An Efficient Electrochemiluminescence Bioassay for SARS-CoV-2.

High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin-based heterobimetallic 2D metal organic framework (MOF), [(ZnTCPP)Co2(MeIm)] (1), is successfully self-assembled from the zinc(II) tetrakis(4-carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2-methylimidazole (MeIm) by a facile one-pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle-wheel [Co2(-CO2)4] secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive [Co2(-CO2)4] SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS-CoV-2 with an extremely low limit of detection (≈30 aM).

PLR and IL-8 were Potential Markers in Differential Diagnosis and Disease Activity in Ulcerative Colitis Patients.

BACKGROUND: At present, the most direct method to evaluate mucosal healing in patients with ulcerative colitis (UC) is endoscopy, but it is costly and invasive. Therefore, it is necessary to find a biomarker with low cost, easy access, high sensitivity and specificity as an indicator of UC activity. This study aimed to examine the level of platelet to lymphocyte ratio (PLR) and interleukin-8 (IL-8) in UC patients and evaluate their roles in differential diagnosis and disease activity assessment. METHODS: A retrospective study involving 130 UC patients and 141 irritable bowel syndrome (IBS) patients was performed. The UC patients were divided into remission group and active group according to the Modified Mayo score. The receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cutoff value of PLR and IL-8 in differential diagnosis between UC patients and IBS patients. RESULTS: The levels of WBC, PLR, and IL-8 in UC patients were higher than those compared with IBS controls. The optimal cutoff to differentiate UC and IBS patients was 6.76 109/L, 114.70, and 19.42 pg/mL for WBC, PLR, and IL-8, respectively (sensitivity, 36.9% vs. 83.8% vs. 72.3%; specificity, 83.0% vs. 65.2% vs. 94.3%; AUC, 0.601 vs. 0.815 vs. 0.859). IL-8 had the highest AUC and specificity. Among 130 patients, 75 patients (57.6%) had mucosal inflammation. The cutoff value of IL-8 for predicting disease severity of UC patients was 22.21 pg/mL (AUC: 0.861). The sensitivity, specificity, and Youden index of IL-8 for predicting severe UC were 92.0%, 81.8%, and 0.702, respectively. CONCLUSIONS: PLR and IL-8 showed great performance in distinguishing UC from IBS patients. Moreover, elevated IL-8 level indicated mucosal inflammation, reflecting disease severity in UC patients.

Diagnostic Utility of CD64 and CD38 Biomarkers for the Differential Diagnosis of Infections.

Purpose: Identification of infection type in patients with fever is particularly important in the emergency departments (EDs) of hospitals. This study was designed to evaluate the performance of two biomarkers, the modified neutrophil CD64 (nCD64) index and CD38 presence on T cells, using flow cytometry. Methods: A total of 305 potentially infected patients with fever were admitted to the ED of Zhongda Hospital (Nanjing, China) between March 2021 and August 2021. This study included three groups of patients: bacterial (N = 180), viral (N = 30) , and uninfected (N = 65) based on their final diagnostic outcomes and clinical records. Results: The expression level of traditional/modified nCD64 was significantly increased in the bacterial infection group, especially in case of patients infected with Gram-negative bacteria. The most prevalent species were Staphylococcus spp. and Escherichia coli. In contrast, CD3+CD38+ cell percentages were elevated in patients with viral infections, which were mostly caused by Epstein-Barr virus and cytomegalovirus. CD38 expression is age dependent, and higher percentages of CD3+CD38+ cells were observed in children with viral infections. For the prediction of bacterial infections, the area under the curve (AUC) of modified nCD64 (AUC: 0.800) was significantly higher than that of C-reactive protein and heparin-binding protein but slightly lower than that of traditional nCD64 (AUC: 0.831). The AUC, specificity, and sensitivity values for the prediction of viral infections using CD3+CD38+ cells percentages in children were 0.899 (0.785-1.000), 96.2%, and 85.9%, respectively. Conclusion: nCD64 levels and CD3+CD38+ cell percentage are potential biomarkers that facilitate identification of patients with bacterial and viral infections.

Increased formation of neutrophil extracellular traps is associated with gut leakage in patients with type 1 but not type 2 diabetes.

BACKGROUND: The aim of this study was to investigate the association of the formation of neutrophil extracellular traps (NETs) with gut leakage in type 1 (T1D) and type 2 diabetes (T2D). METHODS: In all, 105 subjects (56 T1D, 49 T2D) were included in the study. Eight biomarkers of NET formation and gut leakage (ie, protein arginine deiminase type 4 [PAD4], neutrophil elastase [NE], proteinase 3 [PR3], complement 5a [C5a], α1 -antitrypsin [AAT], DNase I, zonulin, and lipopolysaccharide [LPS]) were measured in serum samples by ELISA. Neutrophils were isolated and stimulated by phorbol myristate acetate to form NETs in vitro. Neutrophil intracellular contents were then collected and used as antigens to detect anti-neutrophil cytoplasmic antibodies (ANCA) in the serum. RESULTS: There was an increase in NET-associated proteins (PAD4, NE, PR3, C5a, AAT and DNase I) in new-onset T1D patients but not in those with T2D. Of PAD4, NE, and PR3, PAD4 was found to be the most sensitive biomarker for the diagnosis of T1D. Furthermore, circulating levels of zonulin and LPS were not only increased, but were also strongly correlated with NET formation and ANCA generation in T1D patients. CONCLUSIONS: This study provides evidence that increased formation of NETs, particularly PAD4, is closely associated with gut leakage in T1D but not T2D, and suggests that microorganisms and the release of neutrophil cytoplasmic antigen during the formation of NETs may be involved in the pathogenesis of T1D.

Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source.

Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.