The unique environment of the lungs is protected by complex immune interactions. Human lung tissue-resident memory T cells (TRM) have been shown to position at the pathogen entry points and play an essential role in fighting against viral and bacterial pathogens at the frontline through direct mechanisms and also by orchestrating the adaptive immune system through crosstalk. Recent evidence suggests that TRM cells also play a vital part in slowing down carcinogenesis and preventing the spread of solid tumors. Less beneficially, lung TRM cells can promote pathologic inflammation, causing chronic airway inflammatory changes such as asthma and fibrosis. TRM cells from infiltrating recipient T cells may also mediate allograft immunopathology, hence lung damage in patients after lung transplantations. Several therapeutic strategies targeting TRM cells have been developed. This review will summarize recent advances in understanding the establishment and maintenance of TRM cells in the lung, describe their roles in different lung diseases, and discuss how the TRM cells may guide future immunotherapies targeting infectious diseases, cancers and pathologic immune responses.

Background: The best way to administer steroids for sudden sensorineural hearing loss (SSHL) is still unclear. The present study was aimed at estimating the efficacy of steroids by intratympanic, systemic, and combined therapy (CT) routes. Methods: A systematic literature search was performed from 1950 to October 2019 for randomized controlled trials comparing the use of intratympanic, systemic, and combined steroid therapy for SSHL. The outcomes of recovery rate and pure tone average (PTA) improvement were assessed by random-effects and fixed-effects meta-analysis. Results: A total of 20 articles identified from 7 countries were eligible for analysis. Although no significant difference in recovery rate was observed between intratympanic steroid therapy (IST) and systemic steroid therapy (SST), IST did demonstrate better hearing improvement, as evidenced by a higher PTA than SST. Compared with SST, CT comprising IST and SST had significant recovery rate improvement. Patients treated with CT had a significantly higher PTA than those treated with SST. Through subgroup analysis based on the equivalent dose of prednisone, it was shown that CT led to a significantly higher PTA than SST only in the high-dose CT versus high-dose SST groups and moderate-dose CT versus high-dose SST groups. Conclusion: Moderate and high dose of CT could accelerate hearing improvement in SSHL.

In the therapist-centered rehabilitation program, the experienced therapists can observe emotional changes of stroke patients and make corresponding decisions on their intervention strategies. Likewise, robotic-assisted stroke rehabilitation systems will be more appreciated if they can also perceive emotional states of the stroke patients and enhance their engagements by exploring emotion-based dynamic difficulty adjustments. Nevertheless, few research have addressed this issue. A two-phase pilot study with anxiety as the target emotion state was conducted in this article. In phase I, the motor performances and the physiological responses to the stroke subject's anxiety with high, medium, and low intensities were statistically analyzed, and anxiety models with three intensities were offline developed using support vector machinebased classifiers. In phase II, anxiety-based closed-loop robot-aided training task adaptation and its impacts on patientrobot interaction engagements were explored. As a comparison, a performance-based robotic behavior adaptation was also implemented. Experimental results with 12 recruited stroke patients conducted on the Barrett WAM TM manipulator verified that the rehabilitation robot can implicitly recognize the anxiety intensities of the stroke survivors and the anxietybased real-time robotic behavior adaptation shows more engagements in the human-robot interactions.

BackgroundMetastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.MethodsThirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.ResultArecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.ConclusionWe found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.