Heterogeneous changes in mobility in response to the SARS-CoV-2 Omicron BA.2 outbreak in Shanghai.

The coronavirus disease 2019 (COVID-19) pandemic and the measures taken by authorities to control its spread have altered human behavior and mobility patterns in an unprecedented way. However, it remains unclear whether the population response to a COVID-19 outbreak varies within a city or among demographic groups. Here, we utilized passively recorded cellular signaling data at a spatial resolution of 1 km × 1 km for over 5 million users and epidemiological surveillance data collected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 outbreak from February to June 2022 in Shanghai, China, to investigate the heterogeneous response of different segments of the population at the within-city level and examine its relationship with the actual risk of infection. Changes in behavior were spatially heterogenous within the city and population groups and associated with both the infection incidence and adopted interventions. We also found that males and individuals aged 30 to 59 y old traveled more frequently, traveled longer distances, and their communities were more connected; the same groups were also associated with the highest SARS-CoV-2 incidence. Our results highlight the heterogeneous behavioral change of the Shanghai population to the SARS-CoV-2 Omicron BA.2 outbreak and the effect of heterogenous behavior on the spread of COVID-19, both spatially and demographically. These findings could be instrumental for the design of targeted interventions for the control and mitigation of future outbreaks of COVID-19, and, more broadly, of respiratory pathogens.

The photomorphogenic repressors BBX28 and BBX29 integrate light and brassinosteroid signaling to inhibit seedling development in Arabidopsis.

B-box containing proteins (BBXs) integrate light and various hormonal signals to regulate plant growth and development. Here, we demonstrate that the photomorphogenic repressors BBX28 and BBX29 positively regulate brassinosteroid (BR) signaling in Arabidopsis thaliana seedlings. Treatment with the BR brassinolide stabilized BBX28 and BBX29, which partially depended on BR INSENSITIVE1 (BRI1) and BIN2. bbx28 bbx29 seedlings exhibited larger cotyledon aperture than the wild-type when treated with brassinazole in the dark, which partially suppressed the closed cotyledons of brassinazole resistant 1-1D (bzr1-1D). Consistently, overexpressing BBX28 and BBX29 partially rescued the short hypocotyls of bri1-5 and bin2-1 in both the dark and light, while the loss-of-function of BBX28 and BBX29 partially suppressed the long hypocotyls of bzr1-1D in the light. BBX28 and BBX29 physically interacted with BR-ENHANCED EXPRESSION1 (BEE1), BEE2, and BEE3 and enhanced their binding to and activation of their target genes. Moreover, BBX28 and BBX29 as well as BEE1, BEE2, and BEE3 increased BZR1 accumulation to promote the BR signaling pathway. Therefore, both BBX28 and BBX29 interact with BEE1, BEE2, and BEE3 to orchestrate light and BR signaling by facilitating the transcriptional activity of BEE target genes. Our study provides insights into the pivotal roles of BBX28 and BBX29 as signal integrators in ensuring normal seedling development.

Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors. METHODS: We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM. RESULTS: We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis. CONCLUSIONS: Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

Rapid Synthesis of 3-Methyleneisoindolin-1-ones via Metal-Free Tandem Reactions of Ester-Functionalized Aziridines.

We have disclosed a novel metal-free tandem cyclization reaction for the synthesis of 3-methyleneisoindolin-1-ones starting from ester-functionalized aziridines. This strategy can be effectively promoted by DBU and carboxylic acids. Mechanistically, it involves sequential ring opening of aziridines with carboxylic acids, lactamization, and elimination of carboxylic acids.

Differential Circular RNA Expression Profiles in Induced Sputum of Patients with Asthma.

INTRODUCTION: circRNA played a role in a variety of diseases. This paper aimed to explore the differentially expressed circRNA in induced sputum cells of asthma patients, so as to provide new potential biomarkers and new ideas for the study of asthma. METHODS: All subjects were from the First Affiliated Hospital of Sun Yat-sen University. Differentially expressed circRNAs of asthma patients were screened by high-throughput sequencing. qRT-PCR was used to verify the expression of differential circRNAs. The association between circRNA and asthma was explored by analyzing the correlation between circRNA and clinical data and some cytokines of asthma patients. The possible ceRNA network was analyzed and predicted by online software, and the expression of each molecule in the network was preliminary verified by qRT-PCR in induced sputum cells and 16HBE cell. RESULTS: We screened a total of 49 circRNAs differentially expressed in asthma patients (including 12 circRNAs with elevated expression and 37 circRNAs with decreased expression), among which has_circSORT1 and has_circSERPINB1 were significantly elevated. Correlation analysis showed that has_circSORT1 was correlated with FeNO, EOS%, IL-17A, IFN-γ, and PC20, and has_circSERPINB1 was correlated with IL-6, IL-17A, IFN-γ, FEV1%, and FVC%. The possible existence of has_circSORT1/has-miR-185-3p/ZNFX1, a ceRNA regulatory network, in induced sputum cells of asthma patients was hypothesized by online software prediction and qRT-PCR in sputum cells and 16HBE. CONCLUSION: Differentially expressed circRNAs existed in induced sputum cells of asthma patients, among which has_circSORT1 and has_circSERPINB1 were significantly upregulated and may be involved in the process of asthma disease, which could be expected to be a potential biomarker for asthma diagnosis. In addition, a ceRNA regulatory network, has_circSORT1/has-miR-185-3p/ZNFX1, may exist in asthma.

TCN1 Expression Is Increased in Asthma.

INTRODUCTION: Asthma is a chronic disease that affects populations worldwide. The purpose of this study was to investigate the expression of TCN1 in sputum and its correlation with inflammation and lung function in asthma. METHODS: We recruited 141 subjects, detected TCN1 mRNA level by quantitative reverse transcription polymerase chain reaction, detected TCN1 protein expression by Western blot, detected TCN1 protein level by enzyme-linked immunosorbent assay, and analyzed the correlation between TCN1 and fraction of exhaled nitric oxide (FeNO), IgE, EOS%, lung functions, and some Th2 cytokines. The diagnostic value of TCN1 was evaluated by receiver operating characteristics curve. The expression of TCN1 was further confirmed by human bronchial epithelial cell in vitro. RESULTS: Compared with the health group, the expression of TCN1 in induced sputum cells increased in asthma group and was correlated with FeNO, IgE, and EOS%. TCN1 level was also elevated in the induced sputum supernatant of asthma patients. The protein level of TCN1 in induced sputum supernatant was correlated with FeNO, IgE and PC-20, forced expiratory volume in the first second (FEV1)%pred, FEV1/FVC, and some cytokines (IL-4, IL-5, IL-10, IL-13, MUC5AC). TCN1 was also differentially expressed in patients with different severity of asthma. Four weeks after ICS treatment, the expression of TCN1 in induced sputum supernatant increased. In vitro, the protein level of TCN1 in human bronchial epithelial cells' supernatant increased after stimulated with IL-4 and IL-13. CONCLUSION: The expression of TCN1 was increased in asthma patients' sputum, and was positively correlated with some inflammatory markers, negatively correlated with lung function. TCN1 may be used as a potential biomarker for the diagnosis and treatment of asthma.

Increased expression of IL1-RL1 is associated with type 2 and type 1 immune pathways in asthma.

BACKGROUND: Asthma is a common chronic airway disease in the world. The purpose of this study was to explore the expression of IL1-RL1 in sputum and its correlation with Th1 and Th2 cytokines in asthma. METHODS: We recruited 132 subjects, detected IL1-RL1 protein level in sputum supernatant by ELISA, and analyzed the correlation between the expression level of IL1-RL1 and fraction of exhaled nitric oxide (FeNO), IgE, peripheral blood eosinophil count (EOS#), and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8). The diagnostic value of IL1-RL1 was evaluated by ROC curve. The expression of IL1-RL1 was further confirmed by BEAS-2B cell in vitro. RESULTS: Compared with the healthy control group, the expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma increased. The AUC of ROC curve of IL1-RL1 in sputum supernatant and serum were 0.6840 (p = 0.0034), and 0.7009 (p = 0.0233), respectively. IL1-RL1 was positively correlated with FeNO, IgE, EOS#, Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8) in induced sputum supernatant. Four weeks after inhaled glucocorticoids (ICS) treatment, the expression of IL1-RL1 in sputum supernatant and serum was increased. In vitro, the expression of IL1-RL1 in BEAS-2B was increased after stimulated by IL-4 or IL-13 for 24 h. CONCLUSION: The expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma was increased, and was positively correlated with some inflammatory markers in patients with asthma. IL1-RL1 may be used as a potential biomarker for the diagnosis and treatment of asthma.

Increased SERPINB10 Expression in Induced Sputum Was Associated with Airway Type 2 Inflammation in Asthma.

BACKGROUND: Asthma is a common chronic airway inflammation in the world. The aim of this study was to investigate the expression of SERPINB10 in induced sputum and its correlation with airway type 2 inflammation in asthma. METHODS: We recruited 90 subjects and detected SERPINB10 levels in induced sputum by ELISA and analyzed the correlation between SERPINB10 expression levels and FeNO, eosinophils in peripheral blood, lung function, and Th2 cytokines (IL-4, IL-5, and IL-13). RESULTS: The levels of SERPINB10 in induced sputum in asthmatic patients were higher than healthy controls. SERPINB10 levels in induced sputum were positively correlated with FeNO (r = 0.4620, p < 0.0001) and eosinophils in peripheral blood (r = 0.2500, p = 0.0218) and negatively correlated with FEV1 (%predicted) (r = -0.4161, p < 0.0001) and FEV1/FVC% (r = -0.4383, p < 0.0001). SERPINB10 levels were correlated with Th2 cytokines IL-4 (r = 0.6274, p < 0.0001), IL-5 (r = 0.5166, p < 0.0001), and IL-13 (r = 0.5212, p = 0.0003) in asthma. CONCLUSIONS: SERPINB10 levels in induced sputum of asthmatic patients were significantly increased and correlated with asthmatic airway type 2 inflammation. Induced sputum SERPINB10 may be a signature protein for type 2 high asthma and may be a potential target for airway eosinophilic inflammation in asthma.

Correlation between Increased Monocyte Chemotactic Protein 1 Level and Lung Function in Patients with Asthma.

BACKGROUND: The altered expression of monocyte chemotactic protein 1 (MCP1) in bronchoalveolar fluid was observed in patients and animal models of allergic asthma. However, the correlation between induced sputum MCP1 level and asthma clinical features remains poorly understood. OBJECTIVE: This study aims to explore the relationship of MCP1 protein expression in induced sputum with Th2 inflammation and asthma clinical features. METHODS: MCP1 protein expression in induced sputum and serum was detected by ELISA in patients with asthma, and its correlation with Th2 inflammation and lung function was analyzed. The effect of inhaled corticosteroids (ICSs) on MCP1 expression was also evaluated. RESULTS: The MCP1 level in induced sputum (p = 0.0006) and serum (p = 0.0035) was markedly increased and negatively correlated with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)% (r = -0.3674, p = 0.0001) and PC-20 (r = -0.5746, p < 0.0001) in patients with asthma. The area under the curve (AUC) of MCP1 level receiver operating characteristic curve in induced sputum and serum was 0.7134 (p = 0.0007) and 0.7589 (p = 0.0042), respectively. The patients with asthma were grouped into four according to their induced sputum MCP1 level and Th2 signature categories (Th2Hi MCP1Hi, Th2Hi MCP1Low, Th2Low MCP1Hi, and Th2Low MCP1Low). The Th2Low MCP1Hi subgroup had the lowest FEV1/FVC% and histamine concentration required to cause a 20% decline in FEV1. After 4 weeks of ICS treatment, the MCP1 levels in induced sputum and serum were significantly reduced. CONCLUSIONS: The MCP1 level in induced sputum and serum increased in patients with asthma but decreased after ICS treatment. The Th2Low MCP1Hi subgroup had the worst lung function and highest airway hyperresponsiveness. The combination of MCP1 level in induced sputum and Th2 inflammation defines a new phenotype that can be used to predict lung function and treatment response in patients with asthma.

Elevated CEACAM5 Levels in Patients with Asthma.

INTRODUCTION: Asthma is a common chronic respiratory disease. This study aimed to explore the expression level of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in induced sputum supernatant, induced sputum cells, and serum of asthma patients. METHODS: The protein levels of CEACAM5 in induced sputum supernatant and serum were detected by enzyme-linked immunosorbent assay. The expression of CEACAM5 in induced sputum cells was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We analyzed the correlations between CEACAM5 expression and the clinical characteristics (FeNO and IgE) of asthma. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CEACAM5 in asthma. The expression level of CEACAM5 in 16HBE and BEAS-2B cells was detected by qRT-PCR. RESULTS: The expression of CEACAM5 in induced sputum supernatant, induced sputum cells, and serum of asthma patients was significantly upregulated. Asthma patients with high CEACAM5 expression in induced sputum supernatant had higher levels of FeNO, IgE, and IL-13. The expression levels of CEACAM5 in induced sputum supernatant and induced sputum cells were positively correlated with FeNO and IgE. The ROC curve showed that CEACAM5 had a good diagnostic value in asthma. CEACAM5 expression was upregulated in BEAS-2B and 16HBE cells after IL-4 or IL-13 stimulation for 48 h. CONCLUSION: The expression levels of CEACAM5 in induced sputum supernatant, induced sputum cells, and serum of asthma patients were significantly increased. CEACAM5 may be involved in eosinophilic inflammation of asthma and may be used as a diagnostic biomarker and therapeutic target of asthma.

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma.

INTRODUCTION: CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported. OBJECTIVE: We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications. METHODS: The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored. RESULTS: The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function. CONCLUSIONS: Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.

Exploration of induced sputum BIRC3 levels and clinical implications in asthma.

BACKGROUND: Baculoviral IAP repeat-containing 3 (BIRC3) which encodes a member of the IAP family of proteins upregulated in the asthma expression profile dataset. However, there was few research on studying the clinical implication of BIRC3 in asthma. OBJECTIVE: To validate BIRC3 expression and its clinical implications in induced sputum of asthma. METHODS: Based on the GSE76262 (118 asthma cases and 21 healthy controls) dataset, differentially expressed genes were screened using R software. Subsequently, BIRC3 mRNA and protein were clinically verified in induced sputum samples through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Besides, the correlations between BIRC3 expression and asthmatic eosinophilic/allergic inflammation indicators (FeNO, IgE, and EOS%), pulmonary function (FEV1, FEV1% pred, FVC% pred, and FEV1/FVC), and inflammatory cytokines (IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP) were analyzed. Finally, BIRC3 mRNA was detected in human primary bronchial epithelial cells stimulated by cytokines (IL-4 or IL-13). RESULTS: BIRC3 was screened as a candidate gene in the GSE76262, which was highly expressed in asthma. Highly expressed BIRC3 was positively correlated with eosinophilic and allergic indicators, including FeNO, blood eosinophil, and serum IgE. Moreover, BIRC3 protein was positively associated with inflammation cytokines, like IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP, while negatively correlated with FEV1, FEV1%pred, FVC% pred, and FEV1/FVC. Furthermore, the expression of BIRC3 could be induced in primary bronchial epithelial cells treated by cytokines IL-4 or IL-13. CONCLUSIONS: BIRC3 significantly increased in induced sputum of asthma and positively correlated with airway eosinophilic and peripheral blood allergic inflammation, type 2 cytokines, and airway obstruction. Increased BIRC3 might be involved in the pathogenesis of asthma by affecting the eosinophilic and allergic inflammation.

Defective STING expression potentiates IL-13 signaling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. OBJECTIVE: Our aim was to explore the expression, regulation, and function of STING in CRSwNP. METHODS: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro. RESULTS: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. CONCLUSIONS: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.

The IL-37-Mex3B-Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: The role of IL-37, an immunosuppressive cytokine, in patients with inflammatory diseases is unclear. OBJECTIVE: We sought to explore the expression and pathogenic function of IL-37 in patients with chronic rhinosinusitis (CRS). METHODS: Expression levels of IL-37, IL-18 receptor α, IL-1 receptor 8, Mex3 RNA binding family member B (Mex3B), and thymic stromal lymphopoietin (TSLP) in nasal samples were studied by using quantitative RT-PCR, immunohistochemistry, Western blotting, and ELISA. Human nasal epithelial cells (HNECs) and the BEAS-2B cell line were stimulated with various cytokines and Toll-like receptor (TLR) agonists. In some experiments BEAS-2B cells were transfected with Mex3B small interfering RNA or overexpressing lentiviruses. Genes regulated by IL-37b in HNECs were studied by using RNA sequencing analysis. IL-37b function was confirmed in mice in vivo. RESULTS: Compared with control subjects, although mRNA and protein expression of IL-37 were upregulated in diseased tissues, especially in nasal epithelial cells, in patients with CRS without nasal polyps or in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), IL-37 levels in nasal secretions were reduced in patients with eosinophilic CRSwNP. Type 2 cytokines inhibited IL-37 secretion from HNECs. HNECs expressed IL-37 receptors, IL-18 receptor α, and IL-1 receptor 8. IL-37b downregulated the expression of Mex3B, a TLR3 coreceptor, in HNECs. IL-37b suppressed polyinosinic-polycytidylic acid-induced TSLP production in HNECs in vitro and in murine nasal epithelial cells in vivo. Knocking down or overexpressing Mex3B in BEAS-2B cells abolished the inhibitory effect of IL-37b. Secreted IL-37 levels negatively correlated with Mex3B and TSLP levels and eosinophil numbers in patients with eosinophilic CRSwNP. CONCLUSIONS: The suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with CRSwNP.

Integration of Light and Brassinosteroid Signaling during Seedling Establishment.

Light and brassinosteroid (BR) are external stimuli and internal cue respectively, that both play critical roles in a wide range of developmental and physiological process. Seedlings grown in the light exhibit photomorphogenesis, while BR promotes seedling etiolation. Light and BR oppositely control the development switch from shotomorphogenesis in the dark to photomorphogenesis in the light. Recent progress report that substantial components have been identified as hubs to integrate light and BR signals. Photomorphogenic repressors including COP1, PIFs, and AGB1 have been reported to elevate BR response, while photomorphogenesis-promoting factors such as HY5, BZS1, and NF-YCs have been proven to repress BR signal. In addition, BR components also modulate light signal. Here, we review the current research on signaling network associated with light and brassinosteroids, with a focus on the integration of light and BR signals enabling plants to thrive in the changeable environment.

microRNA-218-5p plays a protective role in eosinophilic airway inflammation via targeting δ-catenin, a novel catenin in asthma.

BACKGROUND: microRNA (miR)-218-5p is involved in cigarette smoke-induced airway inflammation. In our earlier asthma epithelial miRNA profiling data, miR-218-5p was the top 2 down-regulated miRNA. We hypothesize that miR-218-5p plays a role in asthma airway inflammation. OBJECTIVE: To unveil the role of miR-218-5p and its target gene in asthma airway inflammation. METHODS: We measured miR-218-5p expression in bronchial brushings of asthma patients (n = 50) and healthy controls (n = 15), and analysed the correlations between miR-218-5p expression and airway eosinophilia. We examined whether CTNND2 was a target of miR-218-5p, and the expression of 12 catenin family members in bronchial brushings, in cultured human bronchial epithelial (HBE) cells and BEAS-2B cells. We explored the role of miR-218-5p-CTNND2 pathway using a murine model of allergic airway inflammation. RESULTS: Epithelial miR-218-5p expression was significantly decreased and negatively correlated with eosinophils in induced sputum and bronchial biopsies, and other type 2 biomarkers in asthma patients. We verified that CTNND2 (encoding δ-catenin) was a target of miR-218-5p. Remarkably, CTNND2 was the most significantly up-regulated catenin compared with the other 11 catenin family members in bronchial brushings of asthma patients, IL-13-stimulated HBE and BEAS-2B cells. Moreover, epithelial CTNND2 expression positively correlated with airway eosinophilia in asthma. Airway mmu-miR-218-5p expression was also decreased, and Ctnnd2 expression was increased in a murine model of allergic airway inflammation. Intriguingly, mmu-miR-218-5p overexpression suppressed airway hyperresponsiveness, eosinophilic airway inflammation and Ctnnd2 up-regulation in the mouse model. Finally, perturbation of miR-218-5p or CTNND2 expression significantly altered chemokine CCL26 expression in the cell cultures and the mouse model. CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial miR-218-5p plays a protective role in eosinophilic airway inflammation via targeting CTNND2, a novel catenin in asthma, and suppressing chemokine CCL26 expression.

Effects of interfacial adsorption configurations on dye-sensitized solar cell performance at the stoichiometric and defective TiO2 anatase (101) surfaces: a theoretical investigation.

Interfacial adsorption configuration plays a crucial role in influencing the photovoltaic performance of dye-sensitized solar cells (DSSCs), and thus, theoretical investigations are needed to further understand the impacts of different absorption configurations on stoichiometric and defective TiO2(101) surfaces on the short-circuit photocurrent density (JSC) and open-circuit voltage (VOC) of DSSCs. Herein, calculations of isolated dyes and dye/TiO2 systems were performed on the donor-π bridge-acceptor (D-π-A) type porphyrin sensitizers bearing different donor moieties and an α-cyanoacrylic acid anchoring group (T1-3), using DFT and TD-DFT methods. And, for the first time, comparative analysis of interfacial electron transfer (IET) and density of states (DOS) were carried out on dye/TiO2 systems with stoichiometric and defective surfaces to provide further insight into the electronic factors influencing the efficiency of DSSCs, which can well explain the experimental variation trends of JSC and VOC values. It turned out that attachment via the carboxyl and cynao groups in a tridentate binding mode can result in more efficient IET rates and an upshifted conduction band in comparison with those of the bidentate attachment. More interestingly, we found that the adsorption configuration on defective surfaces containing an O2c vacancy induced more upshifted CBM and relatively fast IET, especially for the bonding mode through two O atoms of the carboxyl group.

Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation.

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.

Decreased epithelial and sputum miR-221-3p associates with airway eosinophilic inflammation and CXCL17 expression in asthma.

Airway eosinophilic inflammation is a key feature of type 2 high asthma. The role of epithelial microRNA (miR) in airway eosinophilic inflammation remains unclear. We examined the expression of miR-221-3p in bronchial brushings, induced sputum, and plasma from 77 symptomatic, recently diagnosed, steroid-naive subjects with asthma and 36 healthy controls by quantitative PCR and analyzed the correlation between miR-221-3p expression and airway eosinophilia. We found that epithelial, sputum, and plasma miR-221-3p expression was significantly decreased in subjects with asthma. Epithelial miR-221-3p correlated with eosinophil in induced sputum and bronchial biopsies, fraction of exhaled nitric oxide, blood eosinophil, epithelial gene signature of type 2 status, and methacholine provocative dosage required to cause a 20% decline in forced expiratory volume in the first second in subjects with asthma. Sputum miR-221-3p also correlated with airway eosinophilia and was partially restored after inhaled corticosteroid treatment. Inhibition of miR-221-3p expression suppressed chemokine (C-C motif) ligand (CCL) 24 (eotaxin-2), CCL26 (eotaxin-3), and periostin (POSTN) expression in BEAS-2B bronchial epithelial cells. We verified that chemokine (C-X-C motif) ligand (CXCL) 17, an anti-inflammatory chemokine, is a target of miR-221-3p, and epithelial CXCL17 expression significantly increased in asthma. CXCL17 inhibited CCL24, CCL26, and POSTN expression via the p38 MAPK pathway. Airway overexpression of miR-221-3p exacerbated airway eosinophilic inflammation, suppressed CXCL17 expression, and enhanced CCL24, CCL26, and POSTN expression in house dust mite-challenged mice. Taken together, epithelial and sputum miR-221-3p are novel biomarkers for airway eosinophilic inflammation in asthma. Decreased epithelial miR-221-3p may protect against airway eosinophilic inflammation by upregulating anti-inflammatory chemokine CXCL17.

Application-oriented computational studies on a series of D-π-A structured porphyrin sensitizers with different electron-donor groups.

A series of D-π-A zinc porphyrin sensitizers bearing a substituted iminodibenzyl group at the porphyrin meso position, which is expected to have different electron-donating abilities, were designed. Theoretical studies were performed to examine the photovoltaic properties of these molecules in dye-sensitized solar cells (DSSCs). In particular, the important concepts, the Fukui function and the extended condensed Fukui function, are employed to describe the electron-donating abilities accurately at the quantitative level. Tangui Le Bahers model was adopted to analyze charge transfer (CT) during electron transition. A correlation between the electron donating abilities of the derived iminodibenzyl group and CT was built to evaluate the cell performance based on sensitizers . The theoretical studies showed that porphyrins bearing an extremely strong electron-donating group (EDG) would fail in the generation of photocurrent in the closed circuit when applied in DSSCs due to the higher level of the HOMO energy than the redox potential of the redox couple (I(-)/I3(-)). The one with a weaker EDG () is expected to show better photovoltaic performance than porphyrin with an unsubstituted iminodibenzyl group. This study demonstrates a reliable method involving the employment of the Fukui function, the extended condensed Fukui function and the Tangui Le Bahers model for the evaluation of newly designed D-π-A type porphyrin sensitizers for use in DSSCs, and as guidance for future molecular design.