Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation.

Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

BACKGROUND: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. OBJECTIVE: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP. METHODS: Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils. RESULTS: Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+ MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation. CONCLUSIONS: MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

Personality Traits and Tinnitus Distress: Results Based on Patients with Tinnitus in China.

Background: Due to the socio-cultural differences between China and other countries, which may affect the development of an individual's personality and behavior, it is necessary to explore the relationship between personality traits and tinnitus distress in the context of China's socio-cultural background. Methods: The Tinnitus Handicap Inventory and the Eysenck Personality Questionnaire Short Scale Chinese version were used to explore the influence of personality traits on tinnitus distress in Chinese patients with tinnitus. Results: The results were not entirely consistent with previous studies from other countries. First, extroversion was significantly higher in patients with bothersome tinnitus, both in acute and chronic conditions. Second, the personality traits that affected the patients with bothersome tinnitus were different in different conditions. Finally, the tridimensional personality structure, high psychoticism / normal extroversion / normal neuroticism, was significantly higher in people with bothersome tinnitus. Furthermore, the difference became more obvious with a prolonged disease course. Conclusions: This study suggested that the relationship between personality traits and tinnitus distress in Chinese patients with tinnitus was not the same as in other countries. "High psychoticism / normal extroversion / normal neuroticism" may be a risk factor for chronic bothersome tinnitus in China.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

Social Support and Tinnitus Distress: The Importance of Developing Positive Psychological Qualities in Patients with Chronic Tinnitus.

INTRODUCTION: The role of social support in the relief of tinnitus distress and related mechanisms remains unclear. This study aimed to confirm a hypothesis that the influence of social support on tinnitus distress is mediated by resilience and self-esteem. METHODS: The Social Support Rating Scale, Connor-Davidson Resilience Scale, Positive Version of Rosenberg Self-Esteem Scale, and Tinnitus Handicap Inventory were used to assess 296 patients who experience chronic subjective tinnitus. The collected data were subjected to correlational analysis, mediating effect testing, and structural equation model analysis using R 3.3.1 with the mediate and lavaan packages. RESULTS: The result showed that social support had significant positive correlations with resilience and self-esteem, while resilience and self-esteem had significant negative correlations with tinnitus distress. Furthermore, social support indirectly affected tinnitus distress through the full mediating effects of resilience and self-esteem and could indirectly affect resilience through the partial mediating effects of self-esteem. CONCLUSION: These results suggested that the key to social support for alleviating tinnitus distress lies in the development of patients' resilience and self-esteem. Promoting the development of positive psychological quality of tinnitus patients and improving their perception of social support may become the new approaches of clinical management of tinnitus.

Analysis of Studies in Tinnitus-Related Gene Research.

OBJECTIVE: Summarize and analyze the current research results of tinnitus-related genes, explore the potential links between the results of each study, and provide reference for subsequent studies. METHODS: Collect and sort out the research literature related to tinnitus genes included in PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform before December 31, 2019. Then the relevant contents of the literature were sorted out and summarized. RESULTS: Fifty-one articles were finally selected for analysis: 31 articles (60.8%) were classified as researches on animal models of tinnitus, and 20 (39.2%) as researches on tinnitus patients. Existing studies have shown that genes related to oxidative stress, inflammatory response, nerve excitation/inhibition, and nerve growth are differentially expressed in tinnitus patients or animal models, and have presented the potential links between genes or proteins in the occurrence and development of tinnitus. CONCLUSION: The research on tinnitus-related genes is still in the exploratory stage, and further high-quality research evidence is needed.

Etiology of newborn hearing impairment in Guangdong province: 10-year experience with screening, diagnosis, and follow-up.

BACKGROUND: Hearing impairment is one of the most common birth defects in children. Universal newborn hearing screenings have been performed for 19 years in Guangdong province, China. A screening/diagnosis/intervention system has gradually been put in place. Over the past 10 years, a relatively complete data management system had been established. In the present study, an etiological analysis of newborn cases that failed the initial and follow-up screenings was performed. METHODS: The nature and degree of hearing impairment in newborns were confirmed by a set of procedures performed at the time of initial hearing screening, rescreening and final hearing diagnosis. Then, multiple examinations were performed to explore the associated etiology. RESULTS: Over a period of 10 years, 720 children were diagnosed with newborn hearing loss. Among these children, 445 (61.81%) children had a clearly identified cause, which included genetic factor(s) (30.56%), secretory otitis media (13.30%), maternal rubella virus infection during pregnancy (5.83%), inner ear malformations (4.86%), maternal human cytomegalovirus infection during pregnancy (2.92%), malformation of the middle ear ossicular chain (2.50%) and auditory neuropathy (1.81%). In addition, 275 cases of sensorineural hearing loss of unknown etiology accounted for 38.19% of the children surveyed. CONCLUSIONS: Long-term follow-up is needed to detect delayed hearing impairment and auditory development in children. The need for long-term follow-up should be taken into account when designing an intervention strategy. Furthermore, the use of the deafness gene chip should further elucidate the etiology of neonatal hearing impairment.

Localized Light-Au-Hyperthermia Treatment for Precise, Rapid, and Drug-Free Blood Clot Lysis.

Thrombus diseases, induced by blood stasis or vascular embolization normally, frequently occur with high disability and mortalities worldwide. At present, drug thrombolysis, a primary clinical therapy for blood clot lysis, could increase the lethal risk for hemorrhage when thrombolysis agents are overused in the whole body. Therefore, a novel and advanced therapy for blood clot lysis, based on remote physical signals, is helpful for assisting clinical therapy. Here, we used the localized light-Au-hyperthermia (LAH) treatment, induced by gold nanorods (Au NRs) irradiated with near-infrared light (808 nm), for precise, rapid, and drug-free blood clot lysis. The LAH technology was first introduced in the murine hematoma model and the murine myocardial infarction model for blood clot lysis. Compared with traditional therapy, LAH was assured to shorten the time of detumescence in the murine hematoma model owing to their precise and localized hyperthermia. Meanwhile, we also discovered that LAH was a benefit to vascular recanalization in the murine myocardial infarction model. In addition, the Au NRs used in LAH present ideal biocompatibility in the murine model, which endows it to be suitable for blood clot lysis in vivo.

Silver nanowire net knitted anisotropic aerogel as an ultralight and sensitive physiological activity monitor.

Inherent highly ordered anisotropic aerogels were prepared through a facile celery-carbonization process. The subsequent modification of silver nanowire knitted nets endowed the prepared carbonaceous aerogel with several valuable properties, including broad-spectrum antibacterial activity, near-infrared responsive heating, lightweight cushioning and anisotropic pressure-sensitive conductivity. With the aid of 3D printing technology, this versatile material could be applied as an ultralight monitor to realize the visualized detection of different physiological activities, such as ankle movements and cardiac arrhythmias.