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Background: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). Methods: CD4+CD45RA1T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutaminetreated iTregs in vivo. Results: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutaminetreated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. Conclusion: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS. [ABSTRACT FROM AUTHOR]

The monocular 6D pose estimation of a noncooperative satellite is essential in various on-orbit automatic operations. Nevertheless, the application of this technology still faces challenges, such as heavy model parameters and high latency. In this study, we comprehensively explored the critical components of satellite pose estimation, including landmark description, localisation, and the PnP algorithm, and we introduce a high-precision, real-time, and robust pipeline. Existing methods adopt external convex landmarks, such as 11 landmarks for the SPEED dataset, which are insufficient to describe the geometric structure of the satellite. This study adopted a wireframe-based landmark description, encompassing all visually prominent satellite joints connected directly into the satellite's wireframe model. In addition, unlike most existing methods that rely on heatmap-based landmark localisation, which incurs high computational costs and quantisation errors, we adopt direct coordinate classification for satellite landmark localisation, which is lightweight, fast, and accurate. Experimental results on the SPEED dataset demonstrate that our method outperforms the current state-of-the-art technique, with an accuracy increase of 28% and parameter number decrease of 78%. In particular, our method is very lightweight and robust, and it runs in real-time, making it well-suited for on-orbit real-time satellite pose estimation. • A lightweight monocular satellite pose estimation method is very important for resource-constrained in-orbit platforms. • The three key processes of satellite pose estimation are studied to achieve the balance between accuracy and efficiency. • A High-accuracy, real-time, and robust pipeline for noncooperative satellite pose estimation is proposed. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial hydroxychloroquine (HCQ) as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 mM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and sitedirected mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum immunoglobulin E and inflammatory factors such as tumor necrosis factor-a and interleukin-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels. [ABSTRACT FROM AUTHOR]

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle–induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles–induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α–XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle–induced osteolysis and highlight the IRE1α–XBP1s pathway as a potential therapeutic target for preventing aseptic loosening. [ABSTRACT FROM AUTHOR]