An in vitro study of the impact of IL-17A and IL-22 on ciliogenesis in nasal polyps epithelium via the Hippo-YAP pathway.

BACKGROUND: Cilia loss and impaired motile ciliary functions are among the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). IL17A and IL22 are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL17A and IL22 on ciliated cells and investigate the potential involvement of Hippo-YAP signaling in their influence on ciliogenesis. METHODS: We assessed both the mRNA and protein expression levels of IL17A and IL22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL17A and IL22, we established a primary human nasal epithelial cell model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface culture. Additionally, we employed the inhibitor verteporfin to investigate whether IL17A and IL22 exert their effects on ciliated cells via the Hippo-YAP pathway. RESULTS: The mRNA and protein levels of IL17A and IL22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL17A and IL22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL17A and IL22 were found to reduce the number of ciliated cells. IL17A, but not IL22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL17A only. YAP inhibitors, such as verteporfin, markedly reversed the effects of IL17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. CONCLUSIONS: Both IL17A and IL22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.

Shape recovery from fusion of polarization binocular vision and shading.

The shape from polarization can recover the fine texture of the target surface. However, the gradient field for shape recovery by polarization is ambiguous, which is caused by the multi-value of the azimuth angle. In response to the problem, a method of correcting the ambiguity by the fusion of polarization binocular vision and shading information is proposed in this paper. An iterative optimization algorithm is designed to estimate the direction of the light source, which provides the basis for the shading method to calculate the depth map. Additionally. the low-frequency depth map generated by binocular matching is used to correct the polarization gradient field. The polarization gradient field of the holes and small zenith angle regions in the binocular are corrected by the improved shading method. In the experiment, four different material target objects were used for shape recovery and compared with other methods. The results of the fusion method proposed are better in terms of fine texture. At the camera working distance of  700 mm, the resolving power performs well and demonstrates that changes in the depth of at least 0.1 mm can be distinguished from that recovery result.

Which Is the Best Biologic for Nasal Polyps: Dupilumab, Omalizumab, or Mepolizumab? A Network Meta-Analysis.

INTRODUCTION: Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP. METHODS: We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included. RESULTS: Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746. CONCLUSION: This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.

The hippo pathway effector Yes-associated protein promotes epithelial proliferation and remodeling in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and development. However, its possible role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. We aim to investigate it on nasal epithelial proliferation and remodeling in CRSwNP. METHODS: The expressions of hippo pathway components as well as Ki-67 and E-cadherin in the sinonasal mucosa and nasal epithelial cells were analyzed in 14 controls, 14 eosinophilic CRSwNP, and 14 noneosinophilic CRSwNP. Nasal epithelial cells from 6 controls, 6 eosinophilic CRSwNP, and 6 noneosinophilic CRSwNP were cultured and treated with lipopolysaccharide (LPS), Poly(I:C), or a selective YAP inhibitor verteporfin (VP). RESULTS: The hippo pathway components MST1, LATS1/2, YAP, and TEAD1 were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells, along with upregulation of Ki-67 and downregulation of E-cadherin. The mRNA levels of YAP positively correlated with the Ki-67 mRNA levels, and negatively associated with the E-cadherin mRNA levels in polyp tissues and epithelial cells from nasal polyps (NPECs). LPS and Poly(I:C) upregulated the YAP expression in nasal epithelial cells accompanied by increased TEAD1 and Ki-67 expression. Conversely, YAP inhibition by VP decreased TEAD1 and Ki-67 expression in NPECs. CONCLUSIONS: Hippo pathway components are abnormally upregulated in NPECs, and its effector YAP promotes nasal epithelial cells proliferation and remodeling in CRSwNP. It provides a rationale to explore inhibition of YAP as a novel therapeutic strategy for reducing the epithelial proliferation and remodeling in CRSwNP.

BpTCP19 targets BpWRKY53 to negatively regulate jasmonic acid- and dark-induced leaf senescence in Betula platyphylla.

TCP (TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1) is a plant-specific transcription factor that has garnered significant attention due to its wide-ranging involvement in the regulation of plant growth or developmental processes. However, the molecular mechanisms through which TCP genes orchestrate leaf senescence have not been extensively elucidated. BpTCP19, a member of the PCF subfamily in Betula platyphylla, and has high homology to AtTCP19. BpTCP19 displayed pronounced downregulation in response to methyl jasmonate (MeJA) and dark treatment. Overexpressing BpTCP19 in Betula platyphylla led to a delay in leaf senescence, resulting in prolonged leaf greenness under both MeJA and dark conditions. Transcriptome analysis revealed that overexpression of BpTCP19 induced alterations in the expression levels of genes linked to cell proliferation, hormone signaling transduction, and leaf senescence, including the early responsive factor BpWRKY53. Furthermore, through Yeast one-hybrid assays and GUS analysis, BpTCP19 was shown to bind to the promoter region of BpWRKY53, suppressing its expression and thereby retarding leaf senescence. This study elucidates the physiological and molecular functions of BpTCP19 as a central transcriptional regulatory module in leaf senescence and provides a potential target gene for delaying leaf senescence by mitigating sensitivity to external aging signals such as Jasmonic acid (JA) and darkness.

Novel insights into central compartment atopic disease - a literature review.

INTRODUCTION: Central compartment atopic disease (CCAD) is a newly recognized variant subtype of chronic rhinosinusitis (CRS). Although CCAD has been reported to be correlated with allergy, there is still a considerable gap in our knowledge regarding CCAD. AREAS COVERED: We have conducted a thorough analysis of the literature on CCAD. This review provides current understanding and therapeutic strategies of CCAD. In this article, we will review the clinical presentations and parameters, allergy-related etiology, endotypes, and recommended management of CCAD. EXPERT OPINION: CCAD is considered as an aeroallergen-driven type 2/eosinophilic inflammatory pattern. Although CCAD can be diagnosed by endoscopy and radiology, as well as allergen test, pathogenesis and management strategies leave much to be desired, and further studies are needed.

Bi2Fe4O9@ZnIn2S4 S-scheme laminated heterojunction photocatalyst towards optimized photocatalytic performance.

Reasonable design of heterojunction photocatalysts can effectively promote charge separation, thus improving their photocatalytic performance. Herein, a Bi2Fe4O9@ZnIn2S4 S-scheme laminated heterojunction photocatalyst with 2D/2D interface interaction is prepared via a hydrothermal-annealing-hydrothermal method. The photocatalytic hydrogen production rate of Bi2Fe4O9@ZnIn2S4 is up to 3964.26 µmol h-1 g-1, which is 12.1 times higher than that of pristine ZnIn2S4. In addition, its photocatalytic tetracycline degradation efficiency (99.9%) is also optimized. The enhanced photocatalytic performance can be attributed to the formation of S-scheme laminated heterojunctions that facilitate charge separation as well as strong 2D/2D laminated interface interactions favoring charge transfer. By combining in situ irradiation X-ray photoelectron spectroscopy with other characterization methods, the photoexcited charge transfer mechanism of S-scheme heterojunctions has been proved. Photoelectric chemical tests demonstrate the effectiveness of the S-scheme laminated heterojunction in improving the charge separation. This strategy provides a novel perspective for designing other high-efficient S-scheme laminated heterojunction photocatalysts.

Mental Health Evaluation Based on Visual Analysis Technology.

In order to solve the problems existing in the current mental health assessment system and how to better help individuals analyze their mental health, propose a mental health assessment method based on visual analysis technology; through the study of mental health assessment methods, use the SCL-90 symptom self-rating scale as the mental health assessment scale of this article. Combined with the conceptual design proposed in this article, realize a mental health assessment based on visual analysis technology. The system conducts visual analysis of personal current data and historical data and helps users understand their current mental health. Evaluate the system through user surveys and system quality, and the feasibility and practicability of this method are verified.

A Study on Satisfaction and Influencing Factors of Educational Practice of Preschool Education Majors in Higher Vocational Colleges.

In September 2020, the Ministry of Education and other nine departments issued the notice of "Action Plan for Improving the Quality of Vocational Education (2020-2023)" which emphasizes strong practical teaching. The state pays more and more attention to the quality of practical practice in higher vocational colleges. From the perspective of student satisfaction, this study explores the satisfaction of preschool education students on educational practice and related influencing factors, so as to carry out better educational practice and improve the quality of students' educational practice in colleges and universities. This study uses the questionnaire method, according to the existing literature and theory to build the results of self-compiled "higher vocational college students majoring in preschool education practice satisfaction and influencing factors questionnaire." A total of 463 students majoring in preschool education in higher vocational colleges were investigated. The following research results are obtained. 1. The overall satisfaction of students majoring in preschool education in higher vocational colleges to educational practice is above the average. In descending order of satisfaction question scores, other factors influencing student's satisfaction are the tutors in the educational practice park, the educational practice base, the content of educational practice, the management of educational practice, the tutors in the school of educational practice, and the time of educational practice. 2. For constructing the influencing factor model of educational practice satisfaction, it is found that the influencing factors of educational practice satisfaction are university management rational factors, support factors from the educational base, and students' own factors.

Metal-organic framework (MOF)-5/CuO@ZnIn2S4 core-shell Z-scheme tandem heterojunctions for improved charge separation and enhanced photocatalytic performance.

Interface engineering is regarded as an effective strategy for charge separation. Metal-organic framework (MOF)-5/CuO@ZnIn2S4 core-shell Z-scheme tandem heterojunctions with a three-dimensional floral spherical shape are prepared by a two-step solvothermal and oxidative method. The flower spherical core-shell structure enhances multiple reflections and refractions of light and thus improves light utilization efficiently. In addition, this core-shell structure can supply sufficient active sites for photocatalytic reactions. Meanwhile, the composition of Z-scheme tandem heterojunctions and the photothermal effect contributed to the spatial charge separation and accelerated the photocatalytic process. The photocatalytic hydrogen production rate of MOF-5/CuO@ZnIn2S4 (1938.3 µmol g-1 h-1) is 18 times higher than that of pristine MOF-5, and the photocatalytic degradation efficiency of 2,4-dichlorophenol and phenol can reach up to 98.7% and 97.3%, respectively. In addition, multiple cycle experiments demonstrate high stability, which is favorable for practical applications.

Predictive significance of Charcot-Leyden crystal structures for nasal polyp recurrence.

BACKGROUND: Charcot-Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. METHODS: A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow-up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. RESULTS: Thirty three (30.00%) patients developed recurrence during a 24-month postoperative follow-up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. CONCLUSIONS: The crystalline CLC structures in nasal tissues may serve as an easy-counting and promising biomarker to predict CRSwNP recurrence.

Chinese Central Compartment Atopic Disease: The Clinical Characteristics and Cellular Endotypes Based on Whole-Slide Imaging.

Purpose: Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI). Methods: A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0. Results: CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP. Conclusion: Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Olfactory Sensitivity Is Related to Erectile Function in Adult Males.

BACKGROUND: The olfactory system influences human social behavior, in particular the selection of a spouse. However, there is currently a lack of clinical research on the relationship between the olfactory system and erectile dysfunction (ED) in adult males. AIM: We explored the association between olfactory sensitivity and erectile function and its possible mechanisms. RESULTS: A total of 574 patients, adult males aged between 19 and 42 years, diagnosed with ED in the Department of Infertility and Sexual Medicine of the Third Affiliated Hospital of Sun Yat-sen University from 2015 to 2018 were analyzed retrospectively. Among them, 115 patients (20.03%) had rhinologic diseases (RDs). In addition, in 201 adult male patients who underwent nasal surgery in the ENT department from 2012 to 2016, including 29 (14.43%) with ED, nasal congestion, nasal discharge, and hyposmia were the most common complaints based on the numerical rating scale (NRS). Furthermore, a prospective study was performed in a total of 102 sequential outpatients (male adults) with RD only (n = 46), ED only (n = 42) and both RD and ED (n = 14) in 2019, together with 40 healthy (male adults) volunteers as controls. The results showed that ED patients with RD had severe nasal discomfort and decreased erectile function (P < 0.0001). The olfactory sensitivity of patients with ED was lower than that of the controls, and patients with both ED and RD had the worst olfactory sensitivity (P < 0.0001). Spearman correlation analyses showed that sense of smell was positively correlated with the International Index of Erectile Function-5 score (R = 0.507, P ≤ 0.0001) and the Erection Hardness Scale score (R = 0.341, P < 0.0001). Logistic regression analyses showed that having an olfactory disorder (OD), RD, age, and visual analog scale (VAS, over 5) score were risk factors for ED outcome, indicating that OD patients had a 16.479-fold increased risk for an ED outcome (P < 0.05). CONCLUSION: A significant correlation was detected between olfactory sensitivity and erectile function in adult males. In particularly, impairment of olfactory sensitivity is more common in patients with both ED and RD than in patients suffering from a single disease.

Improved perioperative quality of life in endoscopic sinus surgery by application of enhanced recovery after surgery.

Background: Endoscopic sinus surgery (ESS) has been the definitive treatment for chronic rhinosinusitis (CRS), but the complications caused perioperatively may affect patients' quality of life (QoL). This study aims to evaluate the effects of enhanced recovery after surgery (ERAS) on improving perioperative QoL in ESS. Materials and methods: Seventy-four patients with chronic rhinosinusitis with nasal polyps (CRSwNP) met the criteria for inclusion. Participants undergoing ESS were randomly divided into an ERAS group and a control group, and QoL assessment was performed using the Chinese version of the 22-item Sinonasal Outcomes Test (SNOT-22). Measurements were administered at baseline, and on postoperative day 1 (POD1), POD3 and POD6. Complications such as nausea/emesis, hemorrhage, aspiration and dizziness were also recorded. Results: The preoperative global SNOT-22 scores (mean ± SD) were 39.89±4.86 in the ERAS group and 40.52±3.61 in the control group (t=0.643, P=0.522). On POD1, the global SNOT-22 scores increased significantly to 51.77±5.59 and 62.02±3.86 (t=9.218, P<0.01), and on POD3 they increased to 48.22±6.22 and 51.11±5.14, respectively (t=2.179, P<0.05). However, the scores recovered to 39.39±4.73 and 40.13±3.31 in the respective groups on POD6, which were lower than but not statistically significant different from the baseline (t=0.786, P=0.434). There were statistically significant improvements across all subdomains of SNOT-22 for patients in the two groups only in POD1 (all P<0.05). The ERAS group did not have an increased incidence of complications such as nausea/emesis (χ 2=0.223, P>0.05), hemorrhage, aspiration and dizziness compared to the control group. Conclusion: ERAS could improve perioperative QoL in patients with CRSwNP undergoing ESS, and SNOT-22 can be used for ERAS evaluation as a patients' outcome report.

Enhanced recovery after surgery protocols in functional endoscopic sinus surgery for patients with chronic rhinosinusitis with nasal polyps: a randomized clinical trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speed up recovery. This study aimed to assess the impact of ERAS protocols for functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: One hundred and two patients with CRSwNP undergoing FESS were randomly divided into the ERAS group and the control group. The outcomes of the Self-Rating Anxiety Scale (SAS), Visual Analogue Scale (VAS), Medical Outcomes Study Sleep Scale (MOS-SS) and Kolcaba Comfort Scale Questionnaire (GCQ) were determined in both groups. The serum levels of C-reactive protein (CRP) were compared preoperatively and 24 hours postoperatively. RESULTS: The ERAS group had a significantly better SAS scores than did the control group (28 [24, 35] vs. 43 [42, 47], Z = 5.968, P < 0.001). The rhinalgia and headache scores at 2, 24 and 48 hours postoperatively were lower in the ERAS group than that in the control group (all P < 0.001). The outcomes of the MOS-SS (43 [42, 39] vs. 28 [22, 35], Z = 7.071, P < 0.001) and GCQ (76 [68, 87] vs. 64 [50, 75], Z = 4.806, P < 0.001) were significantly different between the two groups. No significant difference was found in the preoperative CRP levels between the two groups (1.3 [0.6, 2.8] vs. 0.5 [0.5, 1.2], Z = 3.049, P > 0.05); However, the CRP level in 24 hours postoperatively was significantly lower in the ERAS group than that in the control group (2.5 [1.4, 3.9] vs. 6.6 [3.8, 9.0], Z = 5.027, P < 0.001). The incidence rates of complications, such as nausea/emesis (χ = 0.343, P > 0.05), hemorrhage, aspiration and tumble, were not increased in the ERAS group compared with those in the control group. The ERAS group had a significantly shorter length of hospital stay (5 [4, 5] days vs. 8 [8,9] days, Z = 8.939, P < 0.001) and hospitalization expenses ($ 2670 [2375, 2740] vs. $3129 [3116, 3456], Z = 8.514, P < 0.001). CONCLUSIONS: ERAS protocols might optimize FESS for patients with CRSwNP by reducing psychological and physical stress, shortening the length of hospital stay and lowering hospitalization expenses without increasing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800015791; http://www.chictr.org.cn/showproj.aspx?proj=26872.