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Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of coactivators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1-/- mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T-cell activation-induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and antitumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell-mediated antitumor immune responses.

T cell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 recruited by c-Myc enhances CD4+ T cell activation to stimulate immune responses via upregulation of amino acid transporter Slc7a5. Mice deficient of SRC2 in T cells (SRC2fl/fl/CD4Cre) are resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and susceptible to Citrobacter rodentium (C. rodentium) infection. Adoptive transfer of naive CD4+ T cells from SRC2fl/fl/CD4Cre mice fails to elicit EAE and colitis in Rag1/ recipients. Further, CD4+ T cells from SRC2fl/fl/CD4Cre mice display defective T cell proliferation, cytokine production, and differentiation both in vitro and in vivo. Mechanically, SRC2 functions as a coactivator to work together with c-Myc to stimulate the expression of amino acid transporter Slc7a5 required for T cell activation. Slc7a5 fails to be up-regulated in CD4+ T cells from SRC2fl/fl/CD4Cre mice, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability of SRC2fl/fl/CD4Cre CD4+ T cells to induce EAE. Therefore, SRC2 is essential for CD4+ T cell activation and, thus, a potential drug target for controlling CD4+ T cell-mediated autoimmunity.

RORγt is known to instruct the differentiation of T helper 17 (TH17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORγt plays a distinct role in the differentiation and effector function of TH17 cells. Here, we show that mutation of RORγt lysine-256, a ubiquitination site, to arginine (K256R) separates the RORγt role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORγt-dependent thymocyte development, and TH17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORγt to bind to and activate Runx1 expression critical for TH17-mediated EAE. Thus, RORγt regulates the effector function of TH17 cells in addition to TH17 differentiation. This work informs the development of RORγt-based therapies that specifically target the effector function of TH17 cells responsible for autoimmunity.

Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. While SRC1 inhibits the differentiation of regulatory T cells (Tregs) critical for establishing immune tolerance, we show here that SRC2 stimulates Treg differentiation. SRC2 is dispensable for the development of thymic Tregs, whereas naive CD4+ T cells from mice deficient of SRC2 specific in Tregs (SRC2fl/fl/Foxp3YFP-Cre) display defective Treg differentiation. Furthermore, the aged SRC2fl/fl/Foxp3YFP-Cre mice spontaneously develop autoimmune phenotypes including enlarged spleen and lung inflammation infiltrated with IFNγ-producing CD4+ T cells. SRC2fl/fl/Foxp3YFP-Cre mice also develop severer experimental autoimmune encephalomyelitis (EAE) due to reduced Tregs. Mechanically, SRC2 recruited by NFAT1 binds to the promoter and activates the expression of Nr4a2, which then stimulates Foxp3 expression to promote Treg differentiation. Members of SRC family coactivators thus play distinct roles in Treg differentiation and are potential drug targets for controlling immune tolerance.

Rural domestic sewage treatment is crucial for improving rural living environment, controlling agricultural and rural pollution, and implementing the rural revitalization strategy. In this paper, we evaluated the achievements of rural domestic sewage treatment from the aspects of regulations and standards, treatment scale and technology, and environmental protection education, and analyzed the problems associated with treatment capacity, technology, standards, and operation and maintenance. Rural domestic sewage treatment should adapt to local conditions, focus on resource utilization, and be economical, convenient, and scientifically planned. Key tasks were proposed from the perspectives of treatment mode, technical process, resource utilization, and operating mechanism. The development path we proposed emphasizes systematic treatment and integration of all parties. Moreover, several countermeasures are suggested. Discharge standards should be formulated scientifically for rural domestic sewage as nitrogen and phosphorus in rural sewage needs to be reused for irrigation. Ecological and simple treatment of the rural domestic sewage should be promoted based on the economical and feasible principles. The market mechanism needs to be improved to promote the specialized trusteeship of rural sewage treatment.

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are integral to T cell biology, influencing immune responses and associated diseases. This review explores the interplay between the UPR and T cell immunity, highlighting the role of these cellular processes in T cell activation, differentiation, and function. The UPR, mediated by IRE1, PERK, and ATF6, is crucial for maintaining ER homeostasis and supporting T cell survival under stress. However, the precise mechanisms by which ER stress and the UPR regulate T cell-mediated immunity remain incompletely understood. Emerging evidence suggests that the UPR may be a potential therapeutic target for diseases characterized by T cell dysfunction, such as autoimmune disorders and cancer. Further research is needed to elucidate the complex interactions between ER stress, the UPR, and T cell immunity to develop novel therapeutic strategies for T cell-associated diseases. [ABSTRACT FROM AUTHOR]

To solve to the problems of long planning times and low success rates in automatic parking in constrained parking lanes, a modified approach to path planning was proposed, which could improve the hybrid A* algorithm. Firstly, the parking path was divided into two parts : a forward pose adjustment segment and a reverse parking segment. A linear-arc constrained optimization model was established to plan the pose adjustment segment, while finding a suitable starting point for reverse parking. Subsequently, collision risk cost was introduced as an additional factor in the hybrid A* algorithm. The node expansion process was improved by checking whether the vehicle contour intersects with obstacle lines, enhancing the real-time performance and safety of the reverse parking segment. Finally, a cost function was designed with criteria such as path length, smoothness, and deviation, taking into account the vehicle's kinematic constraints. A quadratic programming approach was used to smooth the initial path, resulting in the final path. Simulation analysis was conducted using MATLAB to compare the modified algorithm with the original algorithm. The results showed that, in constrained parking lanes, the improved algorithm could produce a smooth, collision-free parking path with a reduced search time of 23.8% compared with the hybrid A* algorithm. Additionally, the obtained path was safer and more suitable for tracking control. [ABSTRACT FROM AUTHOR]

Purpose: One-hole Split Endoscopy (OSE) is a newer surgical modality that can be applied to posterior cervical foraminotomy (PCF), lumbar discectomy, laminectomy, and decompression. It incorporates intervertebral foraminotomy, open surgery, and other lumboendoscopic techniques with a wide observation field, free space, and compatibility with various spinal surgical techniques and instruments. This study investigated the clinical efficacy of minimally invasive posterior cervical nucleus pulposus removal for cervical spondylotic radiculopathy (CSR) by OSE-Keyhole technique. Patients and Methods: This was a retrospective study of 63 patients treated with OSE keyhole treatment for CSR between May 2021 and September 2023 at Qilu Hospital of Shandong University, Qilu Hospital of Shandong University (Qingdao, China), and Second Hospital of Shandong University, respectively. Clinical outcomes included patients' preoperative and postoperative visual analogue scale (VAS) - arm and neck, Japanese Orthopaedic Association Assessment Treatment Score (JOA) - cervical spine, which were collected at baseline, two days postoperatively, one month postoperatively, and three months postoperatively after the last follow-up visit for evaluation, and perioperative indicators, including intraoperative bleeding, length of hospital stay, postoperative complications, and reoperations, which were also collected. Results: Statistical analyses were performed for the baseline data and follow-up results of 63 patients. Compared to the preoperative baseline values, the follow-up results two days, one month and three months after surgery showed significant improvements in vas-arm, neck and JOA scores in the operated patients (P< 0.05) as well as a reduction in all perioperative-related indices. Conclusion: In the treatment of cervical pain and disability due to radiculopathy, OSE keyhole removal of the posterior cervical nucleus pulposus is a better clinical option as it is less invasive and recovers better postoperatively. [ABSTRACT FROM AUTHOR]

Accurate estimation of the State of Health (SOH) of batteries is important for intelligent battery management in energy storage systems. To solve the problems of poor quality of data features as well as the difficulty of model parameter adjustment, this study proposes a method for estimating the SOH of lithium batteries based on denoising battery health features and an improved Long Short-Term Memory (LSTM) neural network. First, in this study, three health features related to SOH decrease were selected from the battery charge/discharge data, and the singular value decomposition technique was applied to the noise reduction of the features to improve their correlation with the SOH. Then, the whale optimization algorithm is improved using cubic chaotic mapping to enhance its global optimization-seeking capability. Then, the Improved Whale Optimization Algorithm (IWOA) is used to optimize the model parameters of LSTM, and the IWOA-LSTM model is applied to the battery SOH estimation. Finally, the model proposed in this research is validated against the Center for Advanced Life Cycle Engineering (CALCE) battery dataset. The experimental results show that the prediction error of battery SOH by the method proposed in this study is less than 0.96%, and the prediction error is reduced by 49.42% compared to its baseline model. The method presented in the article achieves accurate estimation of the SOH, providing a reference for practical engineering applications. [ABSTRACT FROM AUTHOR]