Discovering a Dihydrofluorescein Analogue as a Promising Fluorescence Substrate to HRP

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP;however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models.

The association between COVID-19 pandemic and maternal isolated hypothyroxinemia in first and second trimesters.

BACKGROUND: The outbreak of COVID-19 epidemic has induced entire cities in China placed under 'mass quarantine'. The majority of pregnant women have to be confined at home may be more vulnerable to stressors. In our study, we aimed to explore the effects of the epidemic on maternal thyroid function, so as to provide evidence for prevention and intervention of sustained maternal and offspring's health impairment produced by thyroid dysfunction. METHODS: The subjects were selected from an ongoing prospective cohort study. we included the pregnant women who receive a thyroid function test during the COVID-19 epidemic and those receiving the test during the corresponding lunar period of 2019. A total of 7148 pregnant women with complete information were included in the final analysis. Multivariate linear and logistic regression models were used for analyzing the association of COVID-19 pandemic with FT4 levels and isolated hypothyroxinemia. RESULTS: We found a decreased maternal FT4 level during the period of the COVID-19 pandemic in first and second trimesters (ß = -0. 131, 95%CI = -0.257,-0.006，p = 0.040) and in first trimester (ß = -0. 0.176, 95%CI = -0.326,-0.026，p = 0.022) when adjusting for 25 (OH) vitamin D, vitamin B12, folate and ferritin and gestational days, maternal socio-demographic characteristics and health conditions. The status of pandemic increased the risks of isolated hypothyroxinemia in first and second trimesters (OR = 1.547, 95%CI = 1.251,1.913, p < 0.001) and first trimester (OR = 1.651, 95%CI = 1.289,2.114, p < 0.001) when adjusting for the covariates. However, these associations disappeared in the women with positive TPOAb (p > 0.05). Additionally, we found associations between daily reported new case of COVID-19 and maternal FT4 for single-day lag1, lag3 and multi-day lag01 and lag04 when adjusting for the covariates (each p < 0.05). CONCLUSIONS: Mass confinement as a primary community control strategy may have a significant cost to public health resources. Access to health service systems and adequate medical resources should be improved for pregnant women during the COVID-19 pandemic.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.