Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles.

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use ß-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.

Deep Compressed Communication and Application in Multi-Robot 2D-Lidar SLAM: An Intelligent Huffman Algorithm.

Multi-robot Simultaneous Localization and Mapping (SLAM) systems employing 2D lidar scans are effective for exploration and navigation within GNSS-limited environments. However, scalability concerns arise with larger environments and increased robot numbers, as 2D mapping necessitates substantial processor memory and inter-robot communication bandwidth. Thus, data compression prior to transmission becomes imperative. This study investigates the problem of communication-efficient multi-robot SLAM based on 2D maps and introduces an architecture that enables compressed communication, facilitating the transmission of full maps with significantly reduced bandwidth. We propose a framework employing a lightweight feature extraction Convolutional Neural Network (CNN) for a full map, followed by an encoder combining Huffman and Run-Length Encoding (RLE) algorithms to further compress a full map. Subsequently, a lightweight recovery CNN was designed to restore map features. Experimental validation involves applying our compressed communication framework to a two-robot SLAM system. The results demonstrate that our approach reduces communication overhead by 99% while maintaining map quality. This compressed communication strategy effectively addresses bandwidth constraints in multi-robot SLAM scenarios, offering a practical solution for collaborative SLAM applications.

USP7 inhibition inhibits proliferation and induces megakaryocytic differentiation in MDS cells by upregulating gelsolin.

Myelodysplastic syndrome (MDS), a largely incurable hematological malignancy, is driven by complex genetic and epigenetic alterations from an aberrant clone of hematopoietic stem/progenitor cells (HSPCs). Ubiquitin-specific protease 7 (USP7) has been demonstrated to have an important oncogenic role in the development of several cancer types, but its role in MDS is unknown. Here, we demonstrate that USP7 expression is elevated in MDS cell lines and patient samples. The USP7-selective small-molecule inhibitors P5091 and P22077 inhibited cell proliferation and induced megakaryocytic differentiation in both cell lines and primary cells. Furthermore, pharmacological inhibition of USP7 markedly suppressed the growth of MDS cell lines in xenograft mouse models. To explore the mechanisms underlying the observed phenotypic changes, we employed RNA-seq to compare the differences in genes after USP7 inhibitor treatment and found that gelsolin (GSN) expression was increased significantly after USP7 inhibitor treatment. Furthermore, knockdown of GSN attenuated the proliferation inhibition, apoptosis induction and megakaryocyte differentiation induced by USP7 inhibitors in MDS cells. Collectively, our findings identify previously unknown roles of USP7 and suggest that the USP7/GSN axis may be a potential therapeutic target in MDS.

Deubiquitylase USP7 regulates human terminal erythroid differentiation by stabilizing GATA1.

Ubiquitination is an enzymatic post-translational modification that affects protein fate. The ubiquitin-proteasome system (UPS) was first discovered in reticulocytes where it plays important roles in reticulocyte maturation. Recent studies have revealed that ubiquitination is a dynamic and reversible process and that deubiquitylases are capable of removing ubiquitin from their protein substrates. Given the fact that the UPS is highly active in reticulocytes, it is speculated that deubiquitylases may play important roles in erythropoiesis. Yet, the role of deubiquitylases in erythropoiesis remains largely unexplored. In the present study, we found that the expression of deubiquitylase USP7 is significantly increased during human terminal erythroid differentiation. We further showed that interfering with USP7 function, either by short hairpin RNA-mediated knockdown or USP7-specific inhibitors, impaired human terminal erythroid differentiation due to decreased GATA1 level and that restoration of GATA1 levels rescued the differentiation defect. Mechanistically, USP7 deficiency led to a decreased GATA1 protein level that could be reversed by proteasome inhibitors. Furthermore, USP7 interacts directly with GATA1 and catalyzes the removal of K48-linked poly ubiquitylation chains conjugated onto GATA1, thereby stabilizing GATA1 protein. Collectively, our findings have identified an important role of a deubiquitylase in human terminal erythroid differentiation by stabilizing GATA1, the master regulator of erythropoiesis.

Hyperthermia inhibits the progression of gastric cancer by downregulating PLEK2/PD-L1 and possibly participates in immunomodulation.

BACKGROUND: Hyperthermia is used as an adjunctive treatment for gastric cancer; however, the corresponding antitumor mechanism remains unclear. OBJECTIVE: To investigate the expression of PLEK2 in gastric cancer and the mechanism by which hyperthermia inhibits gastric cancer progression and participating in immunomodulation. METHODS: PLEK2 was screened by combining microarray analysis with gene knockdown and proliferation assays. Analysis based on the TCGA database, GEPIA website, and detection of clinical samples was employed to investigate the expression and correlation of PLEK2 and PD-L1. Knockdown of the expression PLEK2, subsequent experiments including western blotting, RT-qPCR, cell functional assays, and flow cytometry were used to assess the effects on cell migration, invasion, viability, and apoptosis. Intervention with hyperthermia to explore its effects. To evaluate the impact on immunity by detecting T cell proliferation and the release of IFNγ, activated T cells were co-cultured with the target cells. RESULTS: Hyperthermia significantly reduced the expression of PLEK2 and PD-L1, while both were increased in gastric cancer. Knockdown of PLEK2 inhibited PD-L1 expression and significantly inhibited the proliferation, invasion, migration, and viability of gastric cancer cells. A decrease in PLEK2 expression promotes cell apoptosis. Although it cannot affect the proliferation of activated T cells, it can partially reverse IFNγ suppression. CONCLUSION: PLEK2 plays a promoting role in gastric cancer, and hyperthermia downregulates PLEK2/PD-L1, which further inhibits cell proliferation, invasion, and migration, promotes cell apoptosis, and possibly participates in immune regulation.

Review and Assessment of Fatigue Delamination Damage of Laminated Composite Structures.

Fatigue delamination damage is one of the most important fatigue failure modes for laminated composite structures. However, there are still many challenging problems in the development of the theoretical framework, mathematical/physical models, and numerical simulation of fatigue delamination. What is more, it is essential to establish a systematic classification of these methods and models. This article reviews the experimental phenomena of delamination onset and propagation under fatigue loading. The authors reviewed the commonly used phenomenological models for laminated composite structures. The research methods, general modeling formulas, and development prospects of phenomenological models were presented in detail. Based on the analysis of finite element models (FEMs) for laminated composite structures, several simulation methods for fatigue delamination damage models (FDDMs) were carefully classified. Then, the whole procedure, range of applications, capability assessment, and advantages and limitations of the models, which were based on four types of theoretical frameworks, were also discussed in detail. The theoretical frameworks include the strength theory model (SM), fracture mechanics model (FM), damage mechanics model (DM), and hybrid model (HM). To the best of the authors' knowledge, the FDDM based on the modified Paris law within the framework of hybrid fracture and damage mechanics is the most effective method so far. However, it is difficult for the traditional FDDM to solve the problem of the spatial delamination of complex structures. In addition, the balance between the cost of acquiring the model and the computational efficiency of the model is also critical. Therefore, several potential research directions, such as the extended finite element method (XFEM), isogeometric analysis (IGA), phase-field model (PFM), artificial intelligence algorithm, and higher-order deformation theory (HODT), have been presented in the conclusions. Through validation by investigators, these research directions have the ability to overcome the challenging technical issues in the fatigue delamination prediction of laminated composite structures.

Preoperative computer tomography-guided indocyanine green injection is associated with successful localization of small pulmonary nodules.

BACKGROUND: Localization of small pulmonary nodules (SPNs) is challenging in minimally invasive pulmonary resection, and it is unknown whether computer tomography (CT) guided by indocyanine green (ICG) can provide accurate localization with minimal complications. METHODS: We performed a retrospective study of patients who underwent thoracoscopic resection of pulmonary nodules after CT-guided preoperative localization with ICG from May 2019 to May 2020. Demographics, procedural data, postoperative complications, and pathologic information, were collected, and an analysis of the accuracy and complications after surgery was conducted. RESULTS: In 471 patients, there was a total of 512 peripheral pulmonary nodules that were ≤2 cm in size. The average time for CT-guided percutaneous ICG injection for localization was 18 minutes, and 98.4% (504/512) of the nodules were successfully localized. The average size of the nodules was 9.1 mm, and the average depth from the pleural surface was 8.9 mm. Overall, 5.9% (28/471) of the patients had asymptomatic pneumothorax after localization, but none needed a tube thoracostomy. All the nodules were resected using video-assisted thoracoscopy technique. CONCLUSIONS: Preoperative CT-guided transthoracic ICG injection is safe and feasible for localization of small lung nodules for minimally invasive pulmonary resection. This technique should be considered for preoperative CT-guided localization of small lung nodules.

Effects of individual and combined zinc oxide nanoparticle, norfloxacin, and sulfamethazine contamination on sludge anaerobic digestion.

This work investigated the individual and combined effects of zinc oxide, norfloxacin, and sulfamethazine on sludge anaerobic digestion-associated methane production, protein and carbohydrate metabolism, and microbial diversity. Norfloxacin and sulfamethazine (500 mg/kg) did not inhibit methane production, but inhibited its production rate. Zinc oxide nanoparticles with antibiotics inhibited hydrolysis, fermentation, and methanogenesis over varying digestion periods. Complex pollution had a greater impact on methane production than zinc oxide alone, with acute, synergistic toxicity to methanogenesis over short periods. Complex pollution also had varying effects on bacterial and archaeal communities during digestion. These results aid understanding of the toxicity of emerging contaminants in sludge digestion, with the potential to improve pollution removal and reduce associated risks.

Glasses-free 3D versus 2D video-assisted thoracoscopic thymectomy: a single-center short-term comparative study.

BACKGROUND: Thymectomy is widely used to for the treatment of thymomas, thymic cysts, thymic adenocarcinomas, and other thymic diseases. The development of video-assisted thoracoscopic surgery (VATS) thymectomy by our team offers the advantages of a glasses-free 3D thoracoscopic system for pulmonary surgery. The aim of the present retrospective study was to compare the advantages and short-term outcomes of glasses-free 3D VATS vs. 2D VATS for the treatment of thymic diseases. METHODS: The medical records of patients who underwent traditional 2D and glasses-free 3D video-assisted thoracoscopic thymectomy at the First Affiliated Hospital of Guangzhou Medical University from May 2015 to December 2018 were retrospectively reviewed, while focusing on the collection, evaluation, and comparison of clinical data and perioperative manifestations. RESULTS: A total of 152 patients were included, of which 71 patients underwent glasses-free 3D VATS and 81 underwent 2D VATS. There were no significant differences in demographic characteristics and baseline variables between the two groups (P>0.05). The overall surgical duration was significantly shorter in the 3D group than the 2D group (105.08±4.08 vs. 119.93±4.81 min, respectively, P=0.022). Further intergroup comparisons revealed that the median estimated intraoperative blood loss volume (10 vs. 20 mL, respectively, P=0.038) was less, postoperative thoracic tube indwelling rate (43/71 vs. 64/81, respectively, P=0.013) was lower, and the median duration of postoperative hospitalization (3 vs. 4 days, respectively, P=0.034) was shorter in the 3D group than the 2D group. Although no patient had died, complications occurred in 5 (7.0%) patients in the 3D group and 9 (11.1%) in the 2D group (P=0.387). CONCLUSIONS: As compared with traditional 2D thoracoscopy, glasses-free 3D VATS thymectomy is both safe and effective, and can shorten the surgical duration, reduce blood loss, decrease the indwelling rate of thoracic tube, and shorten the postoperative length of hospitalization.

Nanomaterials for treating emerging contaminants in water by adsorption and photocatalysis: Systematic review and bibliometric analysis.

Emerging contaminants in the aquatic environment have become a worldwide problem. Conventional wastewater treatment processes are ineffective for eliminating the emerging contaminants at trace concentrations. Nanomaterials possessing novel size-dependent properties, however, have shown great potential for removing these contaminants. Herein we reviewed nanomaterials reported for removing emerging contaminants by adsorption and/or photocatalysis, and their removal capacity, mechanism, and influencing factors are discussed. Meanwhile, a large-scale bibliometric analysis is conducted on the trends of the emerging contaminants, nanoadsorbents, nanophotocatalysts, and related research topics from the literature during 1998-2017.