The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and Nb-021) that target non-overlapping epitopes in SARS-CoV-2 S-RBD. Both nanobodies could efficiently neutralize diverse viruses of SARS-CoV-2. The neutralizing mechanisms for the two nanobodies are further delineated by high-resolution nanobody/S-RBD complex structures. In addition, an Fc-based tetravalent nanobody format is constructed by combining Nb-015 and Nb-021. The resultant nanobody conjugate, designated as Nb-X2-Fc, exhibits significantly enhanced breadth and potency against all-tested SARS-CoV-2 variants, including Omicron sub-lineages. These data demonstrate that Nb-X2-Fc could serve as an effective drug candidate for the treatment of SARS-CoV-2 infection, deserving further in-vivo evaluations in the future.
The biosynthesis of antioxidant pigments, namely, betalains, has predominantly been found in Caryophyllales. The potential betalains biosynthesis was firstly explored in Aspergillus sydowii H-1 under controlled culture conditions. This study identified, knocked out, and overexpressed genes involved in the betanin biosynthesis and assessed the activities of tyrosinase, 4'5-DOPA dioxygenase and LigB. The results indicated these betanin biosynthesis pathway was crucial for colony morphology, conidiogenesis, stress response, and violet pigment synthesis. Moreover, AsDODA and AsLigB catalyzed the conversion of L-DOPA into 4'5-seco-DOPA, a key intermediate in the formation of betalamic acid in vitro. Additionally, transcription factors such as AsbHLH, AsMYB1R, and AsWD40 positively regulated the expression of betalain biosynthesis genes. This research provides new insights into the evolutionary origins of betalain-producing species, expanding the scope of betalain biosynthesis to include Aspergillus species.
Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MemP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: one with MPL as the interface of lipid droplets (RE-1), one with membrane protein concentrate (MPC; RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analysis. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was (mean ± SD; n = 3) 255.00 ± 3.54 µmol, 328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more UFA during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of UFA, and the presence of MPC increased the release of FFA. These results show that both MPL and MemP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods.
Background: To investigate whether a real-time visual feedback device could improve the quality of chest compression (CC), and, if so, whether the mechanism is associated with dynamic indexes such as velocity and acceleration. Methods: A self-control trial of 2-minutes CC on a manikin by trained rescuers compared the quality of CC without or with a visual feedback device. Demographic characteristics were recorded and CC metrics for the two tests were computed. Multivariable linear regression analyses were performed to examine the impact of variables on rate of qualified chest compression (RQCC). Multivariable logistic regression was performed to determine independent risk factors for achieving qualified chest compression (QCC) in the second test. Results: A total of 159 participants (average age: 29.36±9.0 years, 80 (50.3%) men) were recruited. RQCC of the second test was significantly greater than that of the baseline test. Multivariable linear regression analysis showed that maximum compression velocity (V compression ) and maximum compression velocity (a compression ) were independent risk factors for RQCC for both tests. The mean V compression and a compression of the second test were significantly greater than those of the baseline test. However, V compression was the only independent risk factor predicting QCC achievement during the second test. ROC curve analysis showed the area under curve (AUC) was0.84,and the optimal cut-offvalue ofV compression was 39.48 cm/s. Conclusions: Increasing the V compression and a compression might improve the quality of simulated CC and should be recommended to improve QCC. Only V compression was an independent risk factor for achieving QCC during CC with a visual feedback device.
Background:The Barthel index (BI) is a widely used assessment tool for evaluating physical performance in activities of daily living (ADL).The association between BI scores and mortality in hospital and during follow-up of acute coronary syndrome (ACS) patients remains unclear.The present study investigated whether the BI score could be used as a predictor for mortality of ACS.Methods: We investigated ACS patients from the multi-center Retrospective Evaluation of Acute Chest Pain (REACP) study.The association between BI scores and all-cause mortality of patients with ACS was analyzed by Cox proportional hazards models.The primary endpoint was all-cause death and the secondary endpoint was cardiac death during follow-up.Results: Among 2908 patients with ACS enrolled, 277 (9.5%) patients died within a median follow-up time of 10.6 months.Patients with lower BI had higher risks of mortality, compared with those with higher BI in ACS patients.Kaplan-Meier analysis revealed that patients with lower BI had worse survival rates than patients with higher BI (P < 0.001).After adjustment for potential influencing factors, multivariate Cox regression analysis showed that the BI was independently associated with all-cause mortality and cardiac mortality, respectively. Conclusion:The BI at admission has the powerful potential to provide useful prognostic information of early risk stratification, and routine recording of the BI at the ED visit may help in decision-making and health care planning for patients with ACS.
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