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Summary ParagraphDespite effective countermeasures, SARS-CoV-2 persists worldwide due to its ability to diversify and evade human immunity1. This evasion stems from amino-acid substitutions, particularly in the receptor-binding domain of the spike, that confer resistance to vaccines and antibodies2–16. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different receptor binding domain (RBD) sites17,18into multispecific antibodies. Here, we describe multispecific antibodies, including a trispecific that prevented virus escape >3000-fold more potently than the most effective clinical antibody or mixtures of the parental antibodies. Despite being generated before the evolution of Omicron, this trispecific antibody potently neutralized all previous variants of concern and major Omicron variants, including the most recent BA.4/BA.5 strains at nanomolar concentrations. Negative stain electron microscopy revealed that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated inter-spike binding. An optimized trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2 and BA.5, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. Such multispecific antibodies decrease the likelihood of SARS-CoV-2 escape, simplify treatment, and maximize coverage, providing a strategy for universal antibody therapies that could help eliminate pandemic spread for this and other pathogens.

Breast milk samples were collected in Shanghai, and classified into four groups according to mothers' age and dietary habits. No major difference was found in the saturated fatty acids among the four groups. The percentage relative to total palmitic acid of palmitic acid in sn-2 position ranged from 71.5 to 77.8% and was not affected by the mothers’ age. The content of vitamins D and E were very low, and vitamins K, B1, B2, and B12 were not detected in all the groups. For the same age group, the group with regular vitamin and mineral supplements intake with higer content of calcium, zinc and iron, and with higer Ca/P ratio. Sufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) were found and the daily supplementation may be not necessary. Vitamin D, vitamin K and vitamin B supplementation is needed for breastfed babies.

To explore the role of histone H3 acetylation in cleft palate induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice, and its mechanism.On gestation day 10 (GD10), 36 pregnant mice were randomly divided into two groups as the treated group(n = 18) and the control group( n = 18). The mice in the treated group received intragastric administration with TCDD 28 μg/kg, while the mice in the control group received equivalent corn oil. The pregnant mice were sacrificed on GD13. 5, GD14. 5 and GD15. 5, collecting fetal palates to determine the activities of histone acetyltransferases (HATs) by Colorimetric and the expression level of acetylated histone H3 (Acetylated histone H3, Ac-H3) by Western-blot.The activity of HATs was 0.409 7 ± 0.0147, 0.522 3 ± 0.017 1 and 0.643 5 ± 0.013 9 in control group on GD13.5, GD14.5 and GD15.5; 0.865 0 ± 0.0129, 0.719 1 ± 0.017 8 and 0.551 2 ± 0.016 8 in TCDD group. The activity of HATs in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference between the two groups (t = - 56. 932, t = - 19. 516, P0.01); however, the activity of HATs in TCDD group was significantly lower than that in control group on GD15. 5 (t = 10. 382, P0.01). The expression level of Ac-H3 was 0.745 0 ± 0.113 5, 1.055 9 ± 0.249 4 and 1.795 5 ± 0.081 9 in control group on GD13. 5, GD14. 5 and GD15. 5; while 1.4490 ± 0. 1460, 1. 641 8 ± 0.099 7 and 1. 512 1 ± 0. 150 2 in TCDD group. The expression of Ac-H3 in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference( t = -6. 593, -3. 779, P0. 01, P0.05) ; However, the expression of Ac-H3 in TCDD group was statistically lower than that in control group (t = 2. 870, P0. 05).The acetylation of histone H3 was involved in the cleft palate of C57BL/6J mice induced by TCDD, which may be one of the mechanisms in TCDD-induced cleft palate.

According to solid annealing physics phenomenon and based on simulated annealing applying in combinational optimization problem, this paper puts forward a method that could use simulated annealing algorithm (SABA) to solve broadcast path in wireless sensor network. The broadcast transmission link formed by this algorithm not only can absorb local optimum solution, but also can jump out of the wrong local optimum. Furthermore, at first it absorbs the inferior solution, with temperature decreased, it will get rid of the inferior solution step by step to get global optimal solution. The simulation shows that comparing to 2-opt algorithm, this algorithm can decrease the length of transmission, and save energy consumption.