Deficient O-GlcNAc Glycosylation Impairs Regulatory T Cell Differentiation and Notch Signaling in Autoimmune Hepatitis

Post-translational modifications such as glycosylation play an important role in the functions of homeostatic proteins, and are critical driving factors of several diseases; however, the role of glycosylation in autoimmune hepatitis is poorly understood. Here, we established an O-GlcNAc glycosylation-deficient rat model by knocking out the Eogt gene by TALEN-mediated gene targeting. O-GlcNAc glycosylation deficiency overtly aggravated liver injury in concanavalin-A induced autoimmune hepatitis, and delayed self-recovery of the liver. Furthermore, flow cytometry analysis revealed increased CD4+ T cell infiltration in the liver of rats with O-GlcNAc glycosylation deficiency, and normal differentiation of regulatory T cells (Tregs) in the liver to inhibit T cell infiltration could not be activated. Moreover, in vitro experiments showed that O-GlcNAc glycosylation deficiency impaired Treg differentiation to inhibit the Notch signaling pathway in CD4+ T cells. These finding indicate that O-GlcNAc glycosylation plays a critical role in the activation of Notch signaling, which could promote Treg differentiation in the liver to inhibit T cell infiltration and control disease development in autoimmune hepatitis. Therefore, this study reveals a regulatory role for glycosylation in the pathogenesis of autoimmune hepatitis, and highlights glycosylation as a potential treatment target

A hierarchical framework for improving ride comfort of autonomous vehicles via deep reinforcement learning with external knowledge

Ride comfort plays an important role in determining the public acceptance of autonomous vehicles (AVs). Many factors, such as road profile, driving speed, and suspension system, influence the ride comfort of AVs. This study proposes a hierarchical framework for improving ride comfort by integrating speed planning and suspension control in a vehicle-to-everything environment. Based on safe, comfortable, and efficient speed planning via dynamic programming, a deep reinforcement learning-based suspension control is proposed to adapt to the changing pavement conditions. Specifically, a deep deterministic policy gradient with external knowledge (EK-DDPG) algorithm is designed for the efficient self-adaptation of suspension control strategies. The external knowledge of action selection and value estimation from other AVs are combined into the loss functions of the DDPG algorithm. In numerical experiments, real-world pavements detected in 11 districts of Shanghai, China, are applied to verify the proposed method. Experimental results demonstrate that the EK-DDPG-based suspension control improves ride comfort on untrained rough pavements by 27.95% and 3.32%, compared to a model predictive control (MPC) baseline and a DDPG baseline, respectively. Meanwhile, the EK-DDPG-based suspension control improves computational efficiency by 22.97%, compared to the MPC baseline, and performs at the same level as the DDPD baseline. This study provides a generalized and computationally efficient approach for improving the ride comfort of AVs

Enhancing Sugarcane Growth and Improving Soil Quality by Using a Network-Structured Fertilizer Synergist

High usage and low efficiency of fertilizers not only restrict sugarcane production but also destroy the soil environment in China. To solve this problem, a network-structured nanocomposite as a fertilizer synergist (FS) was prepared based on attapulgite (ATP) and polyglutamic acid (PGA). Field demonstrations were conducted from 2020 to 2021. Leaching tests and characterization were used to evaluate the ability of the network structure to control nutrient loss. The effects of FS on sugarcane growth and field soil quality were also investigated. The results showed FS could effectively reduce nitrogen loss by 20.30% and decrease fertilizer usage by at least 20%. Compared to fertilizer with the same nutrition, fertilizer with FS could enhance sugarcane yield and brix by 20.79% and 0.58 percentage points, respectively. Additionally, FS improved the soil physicochemical properties, including reducing the soil bulk density and increasing the contents of nitrogen, phosphorus, potassium, and organic matter. FS also altered the diversity of the bacteria and improved the bacterial richness. Our study shows this FS has a good ability to control nutrient loss, advance sugarcane agronomic traits, and improve soil quality. This work offers an option for the sustainable development of sugarcane through the novel FS

Study on Microwave Deicing Efficiency of Microwave-Absorbing Concrete Pavements and Its Influencing Factors

Microwave deicing technology, as a new environmentally friendly deicing technology, can effectively solve the problem of the frequent icing of road surfaces in the winter, which affects the safety of traffic. To improve the efficiency of microwave deicing on cement concrete pavement, this study proposed the use of magnetite, iron sulfide slag, steel slag, lead–zinc slag, and graphite as microwave-absorbing materials, and conducted microwave deicing tests under the influence of five factors, namely the form of the pavement surface structure, the content of the microwave-absorbing material, microwave power, the shielding state, and dry and wet conditions. Layer by layer, we selected the combination of pavement surface structure, microwave-absorbing material content, microwave power, shielding state, and dry and wet conditions on the bottom surface of the concrete slab with the optimal deicing effect. The results showed that the 2 cm scattered microwave-absorbing surface concrete structure has the fastest heating rate; the higher the magnetite content and microwave power, the higher the deicing efficiency; the maximum heating rate can be increased by 17.6% when the shielding layer is set at the bottom of the cement concrete slab; and the heating rate of the microwave-absorbing concrete slab in the wet state is increased by 20.8% relative to the dry state. In summary, 7000 W of power, a magnetite content of 60 vol % in the scattered microwave-absorbing surface, a shielding layer set at the bottom surface, and wet conditions can greatly improve the efficiency of microwave deicing compared with the microwave ice melting effects of plain cement concrete and other microwave-absorbing materials mixed into the concrete. In addition, the temperature uniformity of the microwave-absorbing materials is essential to improve the deicing efficiency of microwave-absorbing concrete, so it is essential to explore it further

The transcriptional factor Clr-5 is involved in cellulose degradation through regulation of amino acid metabolism in Neurospora crassa

Abstract Background Filamentous fungi are efficient degraders of plant biomass and the primary producers of commercial cellulolytic enzymes. While the transcriptional regulation mechanisms of cellulases have been continuously explored in lignocellulolytic fungi, the induction of cellulase production remains a complex multifactorial system, with several aspects still largely elusive. Results In this study, we identified a Zn2Cys6 transcription factor, designated as Clr-5, which regulates the expression of cellulase genes by influencing amino acid metabolism in Neurospora crassa during growth on cellulose. The deletion of clr-5 caused a significant decrease in secreted protein and cellulolytic enzyme activity of N. crassa, which was partially alleviated by supplementing with yeast extract. Transcriptomic profiling revealed downregulation of not only the genes encoding main cellulases but also those related to nitrogen metabolism after disruption of Clr-5 under Avicel condition. Clr-5 played a crucial role in the utilization of multiple amino acids, especially leucine and histidine. When using leucine or histidine as the sole nitrogen source, the Δclr-5 mutant showed significant growth defects on both glucose and Avicel media. Comparative transcriptomic analysis revealed that the transcript levels of most genes encoding carbohydrate-active enzymes and those involved in the catabolism and uptake of histidine, branched-chain amino acids, and aromatic amino acids, were remarkably reduced in strain Δclr-5, compared with the wild-type N. crassa when grown in Avicel medium with leucine or histidine as the sole nitrogen source. These findings underscore the important role of amino acid metabolism in the regulation of cellulase production in N. crassa. Furthermore, the function of Clr-5 in regulating cellulose degradation is conserved among ascomycete fungi. Conclusions These findings regarding the novel transcription factor Clr-5 enhance our comprehension of the regulatory connections between amino acid metabolism and cellulase production, offering fresh prospects for the development of fungal cell factories dedicated to cellulolytic enzyme production in bio-refineries

Effects of Exercise on Blood Glucose and Glycemic Variability in Type 2 Diabetic Patients with Dawn Phenomenon

Background. The dawn phenomenon (DP) is the primary cause of difficulty in blood glucose management in type 2 diabetic (T2D) patients, and the use of oral hypoglycemic agents has shown weak efficacy in controlling DP. Thus, this study is aimed at investigating the effect of moderate-intensity aerobic exercise before breakfast on the blood glucose level and glycemic variability in T2D patients with DP. Methods. A total of 20 T2D patients with DP confirmed via continuous glucose monitoring (CGM) participated in the current study. After collecting baseline measurements by CGM as a control, CGM was reinstalled and 30 minutes of moderate-intensity aerobic exercise was performed prior to breakfast. Dawn blood glucose increase, blood glucose levels, and glycemic variability were measured before and after exercise. Results. Dawn blood glucose increase (ΔGlu, 1.25±0.84vs.2.15±1.07, P=0.005), highest blood glucose value before breakfast (Gmax, 8.01±1.16vs. 8.78±1.09, P=0.005), and mean blood glucose (MBG, 7.80±0.97vs. 8.37±0.95, P=0.001) were all lower, and time in range (TIR, 90.75±12.27vs. 83.5±15.41, P=0.015) was higher after exercise than before exercise. Among the glycemic variability indicators, blood glucose standard deviation (SD, 1.1±0.5vs. 1.48±0.63, P=0.001), coefficient of variation (CV, 14.14±5.94vs.17.69±7.46, P=0.006), mean amplitude of glucose excursion (MAGE, 2.71±1.52vs.3.73±1.98, P=0.006), and largest amplitude of glucose excursion (LAGE, 4.97±2.07vs.6.41±2.36, P=0.002) were all decreased following exercise. Conclusions. Acute moderate-intensity aerobic exercise before breakfast reduced the morning rise of blood glucose in T2D patients, partially counteracting DP. Furthermore, exercise significantly reduced blood glucose fluctuations and improved blood glucose control throughout the day. We recommend that T2D patients with DP take moderate-intensity aerobic exercise before breakfast to improve DP and glycemic control