Comparison of Activity and Safety of DSPAα1 and Its N-Glycosylation Mutants.

DSPAα1 is a potent rude thrombolytic protein with high medicative value. DSPAα1 has two natural N-glycan sites (N153Q-S154-S155, N398Q-K399-T400) that may lead to immune responses when administered in vivo. We aimed to study the effect of its N-glycosylation sites on DSPAα1 in vitro and in vivo by mutating these N-glycosylation sites. In this experiment, four single mutants and one double mutant were predicted and expressed in Pichia pastoris. When the N398Q-K399-T400 site was mutated, the fibrinolytic activity of the mutant was reduced by 75%. When the N153Q-S154-S155 sites were inactivated as described above, the plasminogen activating activity of its mutant was reduced by 40%, and fibrin selectivity was significantly reduced by 21-fold. The introduction of N-glycosylation on N184-G185-A186T and K368N-S369-S370 also considerably reduced the activity and fibrin selectivity of DSPAα1. The pH tolerance and thermotolerance of all mutants did not change significantly. In vivo experiments also confirmed that N-glycosylation mutations can reduce the safety of DSPAα1, lead to prolonged bleeding time, non-physiological reduction of coagulation factor (α2-AP, PAI) concentration, and increase the risk of irregular bleeding. This study ultimately demonstrated the effect of N-glycosylation mutations on the activity and safety of DSPAα1.

Analysis of appendicitis management during COVID-19 pandemic: A study of Chinese adult cohorts.

Background: Healthcare seeking behavior has been widely impacted due to the restricted movements of individuals during the Coronavirus disease-19 (COVID-19) pandemic. This study aims to perform risk stratification in patients requiring timely intervention during the recovery periods. Methods: Operation notes of acute appendicitis (AA) patients within a hospital were analyzed during three six-month periods (23 January-23 July in 2019, 2020, and 2021, respectively). Patient data were collected retrospectively including demographics, pre-emergency status, perioperative information, postoperative outcomes, and follow-up results. Results: 321 patients were included in this study, with 111, 86, and 124 patients in 2019, 2020, and 2021 groups, respectively. The median age of patients decreased by 4 years in 2020 as compared to that in 2019. The proportion of pre-hospitalization symptoms duration of more than 48 h in the 2020 group was higher (36.05% in 2020 vs. 22.52% in 2019). Length of hospital stay (LOS) in 2020 was shorter than it was during the same period in 2019 (4.77 vs. 5.64) and LOS in 2021 was shorter than in 2019 (4.13 vs. 5.64). Compared to the lockdown period, the proportion of patients with recurrent AA was higher in the post-lockdown period (15.1% vs. 27.4%). The median age was 34 years (vaccinated) vs. 37 years (unvaccinated). Logistic regression suggests that elevated C-reactive protein (CRP) (OR = 1.018, CI = 1.010-1.028), white cell count (WBC) (OR = 1.207, CI = 1.079-1.350), female (OR = 2.958, CI = 1.286-6.802), recurrent (OR = 3.865, CI = 1.149-12.997), and fecalith (OR = 2.308, CI = 1.007-5.289) were associated with complicated appendicitis (CA). Conclusion: The lockdown measures during the COVID-19 epidemic are shown to be correlated with a reduction in the proportion of AA patients who underwent surgery, particularly in older adults. Risk factors for CA include elevated CRP, WBC, female, recurrent, and fecalith.

Consistency of the relationship between air pollution and the urban form: Evidence from the COVID-19 natural experiment.

The lockdown measures enacted to control the COVID-19 pandemic in Wuhan, China, resulted in a suspension of nearly all non-essential human activities on January 23, 2020. Nevertheless, the lockdown provided a natural experiment to understand the consistency of the relationship between the urban form and air pollution with different compositions of locally or regionally transported sources. This study investigated the variations in six air pollutants (PM2.5, PM10, NO2, CO, O3, and SO2) in Wuhan before and during the lockdown and in the two same time spans in 2021. Moreover, a hierarchical agglomerative cluster analysis was conducted to differentiate the relative levels of pollutants and to detect the relationships between the air pollutants and the urban form during these four periods. Several features depicting the urban physical structures delivered consistent impacts. A lower building density and plot ratio, and a higher porosity always mitigated the concentrations of NO2 and PM2.5. However, they had inverse effects on O3 during the non-lockdown periods. PM10, CO, and SO2 concentrations have little correlation with the urban form. This study improves the comprehensive understanding of the effect of the urban form on ambient air pollution and suggests practical strategies for mitigating air pollution in Wuhan.

Large-scale integration of meta-QTL and genome-wide association study discovers the genomic regions and candidate genes for yield and yield-related traits in bread wheat.

KEY MESSAGE: Based on the large-scale integration of meta-QTL and Genome-Wide  Association Study, 76 high-confidence MQTL regions and 237 candidate genes that affected wheat yield and yield-related traits were discovered. Improving yield and yield-related traits are key goals in wheat breeding program. The integration of accumulated wheat genetic resources provides an opportunity to uncover important genomic regions and candidate genes that affect wheat yield. Here, a comprehensive meta-QTL analysis was conducted on 2230 QTL of yield-related traits obtained from 119 QTL studies. These QTL were refined into 145 meta-QTL (MQTL), and 89 MQTL were verified by GWAS with different natural populations. The average confidence interval (CI) of these MQTL was 2.92 times less than that of the initial QTL. Furthermore, 76 core MQTL regions with a physical distance less than 25 Mb were detected. Based on the homology analysis and expression patterns, 237 candidate genes in the MQTL involved in photoperiod response, grain development, multiple plant growth regulator pathways, carbon and nitrogen metabolism and spike and flower organ development were determined. A novel candidate gene TaKAO-4A was confirmed to be significantly associated with grain size, and a CAPS marker was developed based on its dominant haplotype. In summary, this study clarified a method based on the integration of meta-QTL, GWAS and homology comparison to reveal the genomic regions and candidate genes that affect important yield-related traits in wheat. This work will help to lay a foundation for the identification, transfer and aggregation of these important QTL or candidate genes in wheat high-yield breeding.