Fc galactosylation follows consecutive reaction kinetics and enhances immunoglobulin G hexamerization for complement activation

Fc galactosylation is a critical quality attribute for anti-tumor recombinant immunoglobulin G (IgG)-based monoclonal antibody (mAb) therapeutics with complement-dependent cytotoxicity (CDC) as the mechanism of action. Although the correlation between galactosylation and CDC has been known, the underlying structure–function relationship is unclear. Heterogeneity of the Fc N-glycosylation produced by Chinese hamster ovary (CHO) cell culture biomanufacturing process leads to variable CDC potency. Here, we derived a kinetic model of galactose transfer reaction in the Golgi apparatus and used this model to determine the correlation between differently galactosylated species from CHO cell culture process. The model was validated by a retrospective data analysis of more than 800 historical samples from small-scale and large-scale CHO cell cultures. Furthermore, using various analytical technologies, we discovered the molecular basis for Fc glycan terminal galactosylation changing the three-dimensional conformation of the Fc, which facilitates the IgG1 hexamerization, thus enhancing C1q avidity and subsequent complement activation. Our study offers insight into the formation of galactosylated species, as well as a novel three-dimensional understanding of the structure–function relationship of terminal galactose to complement activation in mAb therapeutics

Shewanella oneidensis arcA Mutation Impairs Aerobic Growth Mainly by Compromising Translation

Arc (anoxic redox control), one of the most intensely investigated two-component regulatory systems in γ-proteobacteria, plays a major role in mediating the metabolic transition from aerobiosis to anaerobiosis. In Shewanella oneidensis, a research model for respiratory versatility, Arc is crucial for aerobic growth. However, how this occurs remains largely unknown. In this study, we demonstrated that the loss of the response regulator ArcA distorts the correlation between transcription and translation by inhibiting the ribosome biosynthesis. This effect largely underlies the growth defect because it concurs with the effect of chloramphenicol, which impairs translation. Reduced transcription of ArcA-dependent ribosomal protein S1 appears to have a significant impact on ribosome assembly. We further show that the lowered translation efficiency is not accountable for the envelope defect, another major defect resulting from the ArcA loss. Overall, our results suggest that although the arcA mutation impairs growth through multi-fold complex impacts in physiology, the reduced translation efficacy appears to be a major cause for the phenotype, demonstrating that Arc is a primary system that coordinates proteomic resources with metabolism in S. oneidensis

CSR strategy composition and leaf traits for herbaceous plants in garden design

Low community stability and sustainability, accompanied by high maintenance cost was an important ecological problem in planted herbaceous communities in many cities. Investigation showed that the overwhelmingly majority of garden designers ignored the subtle interactions between plants and plants in community itself, as well as the fitness of plants to certain environment. Fortunately, CSR strategy methodology based on leaf traits could be a useful tool for reflecting plant functional groups, thus we can have a deeper understanding of the characteristics of various herbaceous plants. In this study, we used 318 common herbaceous plants in Shaanxi as experimental material to investigate leaf area (LA), leaf fresh weight (LFW) and leaf dry weight (LFW) of them. Their CSR strategies were determined using the 'StrateFy' analysis tool and were presented in a triangular distribution. The results showed that S-selection was responsible for the vast majority of herbaceous plants in garden design, C- selection took second place, and R- selection was the least. Sub-strategy (CS, S/CS, CR, CS/CSR, S/CSR and so on) also played a vital role in garden plants, which together accounted for 90.88% from all plant strategies. In terms of the representative families, the strategies of Labiatae and Asteraceae distributed widely, and the trade-off appeared in C-S axes of Gramineae and Liliaceae. Among three leaf traits, LA was of great importance to C- strategy, LDMC to S- strategy, and SLA was important to R-strategy. CSR strategy composition indicates the power of artificial selection, and reasonable collocation of different CSR strategies can create a better community. Thus, we propose that future investigations on CSR strategies in different regions all over the world should provide a reliable database for garden herbaceous species selection

On the diodicity enhancement of multistage Tesla valves

Tesla valve is a particular check valve that can be used as a fluidic diode, but has no moving parts, and shows promising applications in macro- and microfluidic systems. Fluidic diode indicates that the inflow direction of a Tesla valve affects the pressure drop, allowing fluid to pass easily in one direction while presenting higher resistance in the reverse direction. Although previous studies have shown that the diode performance of such valves can be significantly improved by placing a series of valve units in a compact cascade, the reason is still unclear. In this study, the effect of the internal flow, especially the inflow status of each valve unit, on the diode characteristics of a multistage Tesla valve is investigated numerically and experimentally. Through a proper mathematic treatment, we derived the limiting diodicity in terms of the number of units and demonstrated that the diodicity enhancement of a multistage Tesla valve with its number of units was mainly due to the distorted inflow from subsequent units. To further verify this hypothesis, we elongated the space between subsequent units and found as expected the diodicity declined. The results indicate that distorted inflow can enhance the diodicity of a Tesla valve.info:eu-repo/semantics/publishe

Piceatannol Ameliorates Hepatic Oxidative Damage and Mitochondrial Dysfunction of Weaned Piglets Challenged with Diquat

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis