JAML promotes the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function in human lung cancer.

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

Inflammatory dendritic cells restrain CD11b+CD4+ CTLs via CD200R in human NSCLC.

CD4+ cytotoxic T lymphocytes (CD4+ CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non-small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor-infiltrating CD11b+CD4+ CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4+ regulatory T (Treg) cells restrain the anti-tumor role of CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1ß (IL-1ß). Finally, we demonstrate that CD200 blockade can revive the tumor-killing role of CD11b+CD4+ CTLs and prolong the survival of tumor-bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.

Toxicity and potential underlying mechanism of Karenia selliformis to the fish Oryzias melastigma.

Karenia selliformis can produce toxins such as gymnodimines, and form microalgal blooms causing massive mortality of marine life such as fish and shellfish, and resulting in serious economic losses. However, there are a few of studies on the toxic effects of K. selliformis on marine organisms and the underlying mechanisms, and it is not clear whether the toxins produced by K. selliformis affect fish survival through the food chain. In this study, a food chain was simulated and composed by K. selliformis-brine shrimp-marine medaka to investigate the possibility of K. selliformis toxicity transmission through the food chain, in which fish behavior, histopathology and transcriptomics changes were observed after direct or indirect exposure (through the food chain) of K. selliformis. We found that both direct and indirect exposure of K. selliformis could affect the swimming behavior of medaka, manifested as decreased swimming performance and increased "frozen events". Meanwhile, exposure to K. selliformis caused pathological damage to the intestine and liver tissues of medaka to different degree. The effect of direct exposure to K. selliformis on swimming behavior and damage to fish tissues was more severe. In addition, K. selliformis exposure induced significant changes in the expression of genes related to energy metabolism, metabolic detoxification and immune system in medaka. These results suggest that toxins produced by K. selliformis can be transferred through the food chain, and that K. selliformis can destroy the intestinal integrity of medaka and increase the absorption of toxins, leading to energy metabolism disorders in fish, affecting the metabolic detoxification capacity of the liver. Our finding provides novel insight into the toxicity of K. selliformis to marine fish.

Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis.

Background: Radical cystectomy and removal of pelvic lymph nodes (RC-PLND) is a recommended treatment for high-risk non-muscle-invasive and muscle-invasive non-metastatic bladder cancer (BC). However, 50% of patients relapse after RC-PLND. This study aimed to evaluate the effect of programmed cell death ligand-1 (PD-L1) on the prognosis of bladder urothelial carcinoma (BUC) after RC-PLND. Methods: We present this meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Guidelines. The main outcomes were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) of 3 and 5 years after RC-PLND. Results: Overall, 11 studies and 1393 BUC cases were included in our meta-analysis. In tumor cells (TCs), the PD-L1 negative group had statistically significant advantage in 5-year OS (risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.74-0.97, P = 0.02), RFS (RR: 0.76, 95% CI: 0.58-0.99, P = 0.04), and CSS (RR: 0.73, 95% CI: 0.58-0.92, P = 0.009) compared with the PD-L1 positive group. But, no statistically significant difference in 5-year OS and RFS was observed between the PD-L1 negative and positive groups in tumor-infiltrating immune cells. Conclusions: Our study found that patients with BUC who tested positive for PD-L1 in TCs had a poor prognosis after RC-PLND. PD-1 or PD-L1 inhibitors could be used as a adjuvant medication for patients with BUC after RC-PLND who exhibit PD-L1 overexpression in TCs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022301424.

Synthetic augmentation for semantic segmentation of class imbalanced biomedical images: A data pair generative adversarial network approach.

In recent years, deep learning (DL) has been recognized very useful in the semantic segmentation of biomedical images. Such an application, however, is significantly hindered by the lack of pixel-wise annotations. In this work, we propose a data pair generative adversarial network (DPGAN) for the purpose of synthesizing concurrently the diverse biomedical images and the segmentation labels from random latent vectors. First, a hierarchical structure is constructed consisting of three variational auto-encoder generative adversarial networks (VAEGANs) with an extra discriminator. Subsequently, to alleviate the influence from the imbalance between lesions and non-lesions areas in biomedical segmentation data sets, we divide the DPGAN into three stages, namely, background stage, mask stage and advanced stage, with each stage deploying a VAEGAN. In such a way, a large number of new segmentation data pairs are generated from random latent vectors and then used to augment the original data sets. Finally, to validate the effectiveness of the proposed DPGAN, experiments are carried out on a vestibular schwannoma data set, a kidney tumor data set and a skin cancer data set. The results indicate that, in comparison to other state-of-the-art GAN-based methods, the proposed DPGAN shows better performance in the generative quality, and meanwhile, gains an effective boost on semantic segmentation of class imbalanced biomedical images.

EVs delivery of miR-1915-3p improves the chemotherapeutic efficacy of oxaliplatin in colorectal cancer.

PURPOSE: Oxaliplatin is a crucial component of the combinatorial chemotherapeutic standard of care for advanced colorectal cancer (CRC). Unfortunately, a serious barrier to effective oxaliplatin treatment is drug resistance due to epithelial-mesenchymal transitioning (EMT). Interestingly, stable oxaliplatin-resistant CRC cell lines show differential expression of miR-1915-3p; thus, this microRNA may represent a potential modifier of oxaliplatin resistance in CRC cells. METHODS: miR-1915-3p was over-expressed in oxaliplatin-resistant CRC cells and a non-tumorigenic intestinal cell line (FHC) via lentiviral transduction. Extracellular vesicles (EVs) were purified from transduced FHC cells and co-incubated with CRC cells. Expression levels of miR-1915-3p and other RNA species were assessed by RT-qPCR, while protein expression levels were assessed by Western blotting. The effects of miR-1915-3p on CRC viability were evaluated by proliferation, apoptosis assays, and Transwell assays. Effects of miR-1915-3p over-expression on in vivo oxaliplatin sensitivity was tested via murine xenograft models. RESULTS: miRNA-1915-3p decreased EMT marker expression in oxaliplatin-resistant CRC cell lines and in vivo. FHC cells were able to produce and secrete miR-1915-3p-containing EVs, which we employed to mediate miR-1915-3p delivery to oxaliplatin-resistant CRC cells and increase their oxaliplatin sensitivity in vivo and in vitro. Mechanistically, miR-1915-3p overexpression downregulated the EMT-promoting oncogenes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and ubiquitin carboxyl-terminal hydrolase 2 (USP2) as well as upregulated E-cadherin (a cell adhesion mediator). miR-1915-3p's effects on chemosensitivity and EMT were mediated by its regulation of PFKFB3 and USP2. CONCLUSION: Exosomal delivery of miR-1915-3p can improve the chemotherapeutic efficacy of oxaliplatin in CRC cells by suppressing the EMT-promoting oncogenes PFKFB3 and USP2.

MNL-Network: A Multi-Scale Non-local Network for Epilepsy Detection From EEG Signals.

Epilepsy is a prevalent neurological disorder that threatens human health in the world. The most commonly used method to detect epilepsy is using the electroencephalogram (EEG). However, epilepsy detection from the EEG is time-consuming and error-prone work because of the varying levels of experience we find in physicians. To tackle this challenge, in this paper, we propose a multi-scale non-local (MNL) network to achieve automatic EEG signal detection. Our MNL-Network is based on 1D convolution neural network involving two specific layers to improve the classification performance. One layer is named the signal pooling layer which incorporates three different sizes of 1D max-pooling layers to learn the multi-scale features from the EEG signal. The other one is called a multi-scale non-local layer, which calculates the correlation of different multi-scale extracted features and outputs the correlative encoded features to further enhance the classification performance. To evaluate the effectiveness of our model, we conduct experiments on the Bonn dataset. The experimental results demonstrate that our MNL-Network could achieve competitive results in the EEG classification task.

Tape Casting of High-Performance Low-Temperature Solid Oxide Cells with Thin La0.8Sr0.2Ga0.8Mg0.2O3-δ Electrolytes and Impregnated Nano Anodes.

Low-temperature solid oxide cells (LT-SOCs), operating at 400 to 650 °C, have great potential for commercialization since they can provide lower cost and improved long-term durability. Low operating temperature can also enable high round-trip efficiency of SOCs as reversible energy storage devices. This paper describes Sr0.8La0.2TiO3-α (SLT) anode supported LT-SOC with thin La0.8Sr0.2Ga0.8Mg0.2O3-δ (LSGM) electrolyte made by tape casting, with screen printed La0.6Sr0.4Fe0.8Co0.2O3-δ (LSCF) cathode and impregnated Ni anode. Optimization of the anode functional layers is described; the best anodes had 68 vol % LSGM and 12.3 vol % Ni and yielded maximum power density of 1.6 Wcm-2 with a cell area specific resistance (ASR) of 0.21 Ωcm2 at 650 °C. Most of the cell ASR was associated with the cathode. Reversible electrolysis and fuel cell operation yielded similar characteristics with both 50% H2-50% H2O and syngas fuel. Life testing over 500 h showed that the cathode impedance stabilized after an initial break-in period; the ohmic and anode resistances, though relatively small, increased slightly with time.