Leucine-Mediated SLC7A5 Promotes Milk Protein and Milk Fat Synthesis through mTOR Signaling Pathway in Goat Mammary Epithelial Cells.

The SLC7A5 gene encodes a Na+ and pH-independent transporter protein that regulates cell growth by regulating the uptake of AA. This study, utilizing RNA-seq, aimed to explore the effect of SLC7A5 on the synthesis of milk proteins and fats in goat mammary epithelial cells (GMECs) through gene interference and overexpression techniques. The results demonstrated that the overexpression of SLC7A5 resulted in a significant increase in the expression of CSN1S1, SCD, CEBPB, ACACA, αS1-casein, p-S6K, and p-S6. The levels of p-S6K and p-S6 gradually increased as the AA/Leu stimulation time lengthened. The overexpression of SLC7A5 rescued the role of Torin1 in GMECs. In conclusion, SLC7A5 plays a crucial role in promoting the synthesis of milk proteins and milk fats through the mTOR signaling pathway in GMECs, providing a theoretical foundation for improving the quality of goat milk.

The persistence and antitumor efficacy of CAR-T cells are modulated by tonic signaling within the CDR.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable clinical efficacy, but challenges related to relapse and CAR-T cell exhaustion persist. One contributing factor to this exhaustion is CAR tonic signaling, where CAR-T cells self-activate without antigen stimulation, leading to reduced persistence and impaired antitumor activity. To address this issue, we conducted a preclinical study evaluating tonic signaling using nanobody-derived CAR-T cells. Our investigation revealed that specific characteristics of the complementary determining regions (CDRs), including low solubility, polarity, positive charge, energy, and area of ionic and positive CDR patches of amino acids, were associated with low antigen-independent tonic signaling. Significantly, we observed that stronger tonic signaling directly impacted CAR-T cell proliferation in vitro, consequently leading to CAR-T cell exhaustion and diminished persistence and effectiveness in vivo. Our findings provide compelling preclinical evidence and lay the foundation for the clinical assessment of CAR-T cells with distinct tonic signaling patterns. Understanding the role of CDRs in modulating tonic signaling holds promise for advancing the development of more efficient and durable CAR-T cell therapies, thereby enhancing the treatment of cancer and addressing the challenges of relapse in CAR-T cell therapy.

Elastic Restraint Induced by Carbon Coating Enhances Potassium-Ion Batteries' Performance via Phase Transition.

Potassium-ion batteries (PIBs) possess great potential in the next generation of large-scale energy storage due to their abundant sources and suitable operating voltage. However, the serious volume expansion resulting from the large radius of K+ makes it difficult to insert and extract, which greatly limits the development of PIBs. Herein, tin phosphide coated with carbon (Sn4P3@C) is designed for the PIB anode material by in situ construction of robust physical barriers of carbonaceous materials to accommodate the strain induced by volume expansion. Furthermore, the unique elastic restraint induced by the carbon coating in Sn4P3@C blocks the phase transition of α-Sn to ß-Sn during the process of potassiation. Meanwhile, the existence of α-Sn facilitates K+ diffusion dynamics, endowing the Sn4P3@C electrode with high reversible discharge ability, good circularity, and a low discharge plateau. Moreover, the electrode can maintain a capacity of 187 mAh g-1 over repeated 1500 cycles at 1 A g-1. This work not only explores the chemical kinetics of K+ in Sn4P3 but also provides a new idea for basic research of tin-based anode materials.

Machine learning-based surrogate model assisting stochastic model predictive control of urban drainage systems.

Quantifying the uncertainty of stormwater inflow is critical for improving the resilience of urban drainage systems (UDSs). However, the high computational complexity and time consumption obstruct the implementation of uncertainty-addressing methods for real-time control of UDSs. To address this issue, this study developed a machine learning-based surrogate model (MLSM) that maintains high-fidelity descriptions of drainage dynamics and meanwhile diminishes the computational complexity. With stormwater inflow and controls as inputs and system overflow as the output, MLSM is able to fast evaluate system performance, and therefore stochastic optimization becomes feasible. Thus, a real-time control strategy was built by combining MLSM with the stochastic model predictive control. This strategy used stochastic stormwater inflow scenarios as input and aimed to minimize the expected overflow under all scenarios. An ensemble of stormwater inflow scenarios was generated by assuming the forecast errors follow normal distributions. To downsize the ensemble, representative scenarios with their probabilities were selected using the simultaneous backward reduction method. The proposed control strategy was applied to a combined UDS of China. Results are as follows. (1) MLSM fit well with the original high-fidelity urban drainage model, while the computational time was reduced by 99.1%. (2) The proposed strategy consistently outperformed the classical deterministic model predictive control in both magnitude and duration dimensions of system resilience, when the consumed time compatible is with the real-time operation. It is indicated that the proposed control strategy could be used to inform the real-time operation of complex UDSs and thus enhance system resilience to uncertainty.

Optimization of in-pipe storage capacity use in urban drainage systems with improved DP considering the time lag of flow routing.

The active control of urban drainage systems (UDSs) is playing an increasingly important role in the world threatened by urban flooding and associated disasters caused by insufficient drainage capacity. However, little research has recognized the importance of the optimal use of in-pipe storage space. To address this issue, the use of the in-pipe storage capacity was optimized in this study. A novel approach, that is, dynamic programming with successive approximation considering the time lag of flow routing (DPSA-TL), was developed to determine the control policies, in addition to the commonly used passive, rule-based control (RBC), and evolutionary algorithm (EA) strategies. A real-life urban catchment considering flooding control and combined sewer overflow (CSO) reduction was used as the case study. First of all, the potential benefit of maximizing the use of in-pipe storage space was tested using the four control strategies in three storm events, including a 3-year, 2-hour design (46.5 mm), a 5-year, 2-hour design (56.0 mm) and a 7-h historical (152.5 mm) storm events. Results indicate that DPSA-TL performed best in all cases. Without compromising the goal of flooding control, it provided 16.5%, 12.6%, and 3.0% reductions in CSO volume for the three storm events when compared with the passive strategy. Due to the limited capacity of in-pipe storage, the relative improvement diminished as the total rainfall depth increased. Then, control strategies were further applicated to the real-time operation. DPSA-TL was found to be the best alternative for CSO control, with the CSO volume reduced by 14.7%, 11.4%, and 2.5% in the three storm events, respectively. The findings suggest that the performance of UDS can be significantly improved by optimizing the use of in-pipe storage capacity, and the proposed method is effective in the offline optimization and real-time control of UDSs.

Glaesserella parasuis induces inflammatory response in 3D4/21 cells through activation of NLRP3 inflammasome signaling pathway via ROS.

Glaesserella parasuis (G. parasuis) is an important pathogenic bacterium that can cause Glässer's disease, and it has resulted in tremendous economic losses to the global swine industry. The intensive pulmonary inflammatory response caused by G. parasuis infection is the main cause of lung injury and death in pigs. However, the exact mechanism by which it causes severe pulmonary inflammation is not fully understood yet. In this study, severe pneumonia was observed in piglets infected with G. parasuis; and an infection cell model was established using porcine alveolar macrophages cell line 3D4/21, which was determined to be susceptible to G. parasuis infection in vitro. G. parasuis infection of 3D4/21 cells induced upregulation of proinflammatory cytokines TNF-α, IL-1ß, IL-18 and production of intracellular reactive oxygen species (ROS). The expression of IL-1ß related to activation of the NLRP3 inflammasome signaling pathway, which had not been shown before in G. parasuis infection. Furthermore, it was first found that release of intracellular ROS, which was mediated by NADPH oxidase in 3D4/21 cells, was found crucial for the activation of the NLRP3 signaling pathway and promoted the expression of proinflammatory cytokines, such as TNF-α and IL-1. In general, this study explored the specific mechanism of severe pulmonary inflammation caused by G. parasuis infection, and provides a foundation for further elucidating the pathogenic mechanism of G. parasuis.

Fabrication of Superhydrophobic and Luminescent Rare Earth/Polymer complex Films.

The motivation of this work is to create luminescent rare earth/polymer films with outstanding water-resistance and superhydrophobicity. Specifically, the emulsion polymerization of styrene leads to core particles. Then core-shell-structured polymer nanoparticles are synthesized by copolymerization of styrene and acrylic acid on the core surface. The coordination reaction between carboxylic groups and rare earth ions (Eu(3+) and Tb(3+)) generates uniform spherical rare earth/polymer nanoparticles, which are subsequently complexed with PTFE microparticles to obtain micro-/nano-scaled PTFE/rare earth films with hierarchical rough morphology. The films exhibit large water contact angle up to 161° and sliding angle of about 6°, and can emit strong red and green fluorescence under UV excitation. More surprisingly, it is found that the films maintain high fluorescence intensity after submersed in water and even in aqueous salt solution for two days because of the excellent water repellent ability of surfaces.

Heat-Resistant Crack-Free Superhydrophobic Polydivinylbenzene Colloidal Films.

Highly cross-linked poly(divinylbenzene) (PDVB) spherical colloidal particles with nano-, submicron-, and micron-sizes of 157.2 nm, 602.1 nm, and 5.1 µm were synthesized through emulsion and dispersion polymerization methods. The influences of particle size on the surface morphology, roughness, superhydrophobicity, and critical cracking thickness of colloidal films were studied in detail. The results show that PDVB colloidal films possess large water contact angle (CA) over 151°, belonging to superhydrophobic materials. Moreover, it is interesting to observe that the highly cross-linked network structure leads to PDVB film's excellent heat-resistance. The CA and rough surface morphology remain nearly unchanged after thermal-treatment of films at 150 °C for 24 h. In addition, no cracks were observed in films with thicknesses up to 8.1 µm, exceeding most of polymer and inorganic particle films reported in the literature. The simple and scalable preparation method, low-cost, superhydrophobicity, and excellent thermal stability endow the PDVB colloidal films with promising applications in advanced coating fields, especially when employed in the high-temperature service environment.