IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

Effect of health rights accessibility on the urban integration of minority rural migrants in China: a cross-sectional study.

BACKGROUND: Accessing health rights is an integral component of people's aspirations for a better life. Existing discussions and evaluations regarding the accessibility of health rights for minority rural migrants are insufficient. In comparison to objective health conditions, inequalities in health rights lead to chronic and long-term depletion of human capital among minority rural migrants. This study aimed to assess the overall impact, heterogeneity effects, and mechanisms of health rights accessibility on the urban integration of minority rural migrants. METHODS: Based on the 2017 China Migrants Dynamic Survey Data (CMDS), this study employs OLS models, 2SLS models, conditional mixed process (CMP) methods, and omitted variable tests to estimate the impact of health rights accessibility on the urban integration of minority rural migrants. Additionally, from the perspectives of migration scope and illness experience, this study explored the heterogeneity in the relationship between health rights accessibility and urban integration. Finally, using the Karlson-Holm-Breen (KHB) model, this study dissects the mechanisms through which health rights accessibility influences the urban integration of minority rural migrants. RESULTS: Health rights accessibility significantly enhances the urban integration of minority rural migrants. Moreover, compared to minority rural migrants who move across provinces and who have no history of illness, those who migrate within the same province and who have experienced illness are more sensitive to the positive impact of health rights accessibility. However, the enhancing effect of health rights accessibility does not significantly differ between the new and old generations of minority rural migrants. Furthermore, health rights accessibility can indirectly improve the urban integration of minority rural migrants by elevating health levels, improving health habits, and reinforcing health behaviors. Among these, the indirect effects mediated by health habits are more pronounced. CONCLUSION: The research conclusions underscore the issue of health accessibility and urban integration among minority rural migrants, providing a reexamination and clarification of the policy effects of health rights in promoting the urban integration of minority rural migrants. Relevant policy design should commence with improving the health rights of minority rural migrants, enhancing their health integration capabilities, and effectively boosting their ability to integrate into urban life.

How does choice of residential community affect the social integration of rural migrants: insights from China.

The construction of public space is a new and important way to integrate rural migrants into urban society. Existing studies mainly discussed the factors affecting the social integration of rural migrants from the micro-individual and macro-system levels. Still, they seldom analyzed the differences between rural migrants' residential communities and the roles these differences play in their social integration, especially from the perspective of residential space. Based on the data of the 2014 China Migrants Dynamic Monitoring Survey, this paper systematically examines the impact of residential community selection on the social integration of rural migrants and its possible effects using OLS, 2SLS, CMP, omitted variable test method, and KHB mediating effect model. It is found that the choice of residential community has a significant positive impact on the social integration of rural migrants, and the social integration of rural migrants living in formal communities has increased by 2.44%-3.20%. To overcome the potential endogeneity problems and selection bias of the empirical model, the study further adopted an instrumental variable estimation approach, combined with the omitted variable method for robustness check; the results still revealed the positive effect of living in formal communities on the social integration of rural migrants. The heterogeneous results showed that living in formal communities has a greater effect on the social integration of women and older-generation rural migrants. The farther the migration range and the longer the residence time of rural migrants, the greater the effect of living in the formal community on their social integration. Further mechanism testing revealed that living in formal communities not only directly enhances the social integration of rural migrants but also indirectly improves their social integration through public resource allocation, human capital accumulation, social status screening, and social network expansion. The indirect effect of capital accumulation is even greater. Therefore, to accelerate the full integration of rural migrants into urban society and achieve real urbanization and citizenship, the study proposes that the government should scientifically plan the layout of rural migrants' living space and the construction of supporting facilities.

P2X7 receptor of olfactory bulb microglia plays a pathogenic role in stress-related depression in mice with allergic rhinitis.

The aim of this study was to explore the role and mechanism of the olfactory bulb (OB) microglial P2X7 receptor (P2X7R) in allergic rhinitis (AR)-related depression, with the objective of identifying a potential clinical target. An AR mouse model was induced using ovalbumin (OVA), while chronic stress was employed to induce depression. The study used P2X7R-specific antagonists and OB microglia-specific P2X7R knockdown mice as crucial tools. The results showed that mice in the OVA + stress group exhibited more pronounced depressive-like phenotypes. Furthermore, there was an observed increase in microglial activation in the OB, followed by a rise in the level of inflammation. The pharmacological inhibition of P2X7R significantly mitigated the depression-like phenotype and the OB inflammatory response in OVA + stress mice. Notably, the specific knockdown of microglial P2X7R in the OB resulted in a similar effect, possibly linked to the regulation of IL-1ß via the "ATP-P2X7R-Caspase 1" axis. These findings collectively demonstrate that microglial P2X7R in the OB acts as a direct effector molecule in AR-related depression, and its inhibition may offer a novel strategy for clinical prevention and treatment.

Kcnh2 deletion is associated with rat embryonic development defects via destruction of KCNH2­integrin ß1 complex.

The Kv11.1 potassium channel encoded by the Kcnh2 gene is crucial in conducting the rapid delayed rectifier K+ current in cardiomyocytes. Homozygous mutation in Kcnh2 is embryonically lethal in humans and mice. However, the molecular signaling pathway of intrauterine fetal loss is unclear. The present study generated a Kcnh2 knockout rat based on edited rat embryonic stem cells (rESCs). Kcnh2 knockout was embryonic lethal on day 11.5 of development due to a heart configuration defect. Experiments with human embryonic heart single cells (6.5­7 weeks post­conception) suggested that potassium voltage­gated channel subfamily H member 2 (KCNH2) plays a crucial role in the development of compact cardiomyocytes. By contrast, apoptosis was found to be triggered in the homozygous embryos, which could be attributed to the failure of KCNH2 to form a complex with integrin ß1 that was essential for preventing the process of apoptosis via inhibition of forkhead box O3A. Destruction of the KCNH2/integrin ß1 complex reduced the phosphorylation level of AKT and deactivated the glycogen synthase kinase 3 ß (GSK­3ß)/ß­catenin pathway, which caused early developmental abnormalities in rats. The present work reveals a basic mechanism by which KCNH2 maintains intact embryonic heart development.

Risk Factors for Acute Rhinosinusitis in Childhood Asthma.

INTRODUCTION: Specific pathogen infections associated with acute rhinosinusitis (ARS) in infants are risk factors for allergic asthma in adolescents. However, the risk factors for ARS onset remain largely unknown in asthmatic children. In this study, we aim to investigate the risk factors for ARS in childhood asthma. METHODS: This study retrospectively compared and analyzed the clinical characteristics of asthmatic children with (n = 194) or without ARS (n = 799). Univariate regression analyses were performed to identify ARS-associated risk factors in asthmatic children, and subsequent multivariate backward stepwise logistic regression analyses were performed to identify independent risk factors. RESULTS: The onset age, values of blood eosinophils (EOS) (%), and total IgE were significantly lower in patients with ARS than in those without ARS. Moreover, the proportions of patients allergic to Dermatophagoides pteronyssinus (d1) and Dermatophagoides farinae (d2) were significantly smaller in children with ARS (all p values <0.05). Univariate analyses showed that an older onset age, a higher body mass index, a higher value of blood EOS (%) were protective factors, while a higher value of blood lymphocytes (%) and a higher degree of sensitization to d1 and d2 were risk factors for ARS. Further backward stepwise multivariate logistic regression analyses confirmed that a younger onset age and allergic sensitization to d1 were independent risk factors for ARS in childhood asthma. CONCLUSION: Younger onset age and allergic sensitization to d1 are risk factors for the onset of ARS in childhood asthma, so allergen intervention should be performed as early as possible in asthmatic children.

Brain response in asthma: the role of "lung-brain" axis mediated by neuroimmune crosstalk.

In addition to typical respiratory symptoms, patients with asthma are frequently accompanied by cognitive decline, mood disorders (anxiety and depression), sleep disorders, olfactory disorders, and other brain response manifestations, all of which worsen asthma symptoms, form a vicious cycle, and exacerbate the burden on families and society. Therefore, studying the mechanism of neurological symptoms in patients with asthma is necessary to identify the appropriate preventative and therapeutic measures. In order to provide a comprehensive reference for related research, we compiled the pertinent literature, systematically summarized the latest research progress of asthma and its brain response, and attempted to reveal the possible "lung-brain" crosstalk mechanism and treatment methods at the onset of asthma, which will promote more related research to provide asthmatic patients with neurological symptoms new hope.

P2X7 receptor of microglia in olfactory bulb mediates the pathogenesis of olfactory dysfunction in a mouse model of allergic rhinitis.

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.

IL-1ß and Allergy: Focusing on Its Role in Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic upper airway immune-inflammation response mediated by immunoglobulin E (IgE) to allergens and can seriously affect the quality of life and work efficiency. Previous studies have shown that interleukin-1ß (IL-1ß) acts as a key cytokine to participate in and promote the occurrence and development of allergic diseases. It has been proposed that IL-1ß may be a potential biomarker of AR. However, its definitive role and potential mechanism in AR have not been fully elucidated, and the clinical sample collection and detection methods were inconsistent among different studies, which have limited the use of IL-1ß as a clinical diagnosis and treatment marker for AR. This article systematically summarizes the research advances in the roles of IL-1ß in allergic diseases, focusing on the changes of IL-1ß in AR and the possible interventions. In addition, based on the findings by our team, we provided new insights into the use of IL-1ß in AR diagnosis and treatment, in an attempt to further promote the clinical application of IL-1ß in AR and other allergic diseases.

Brain response in allergic rhinitis: Profile and proposal.

In addition to typical nasal symptoms, patients with allergic rhinitis (AR) will further lead to symptoms related to brain function such as hyposmia, anxiety, depression, cognitive impairment, memory loss, etc., which seriously affect the quality of life of patients and bring a heavy burden to the patient's family and society. Some scholars have speculated that there may be potential "nose-brain communication" mechanism in AR that rely on neuro-immunity. This mechanism plays an important role in AR-associated brain response process. However, no study has directly demonstrated which neural circuits will change in the connection between the nose and brain during the onset of AR, and the mechanism which underlines this question is also lack. Focusing on the topic of "nose-brain communication", this paper systematically summarizes the latest research progress between AR and related brain responses and discusses the mechanism of AR-related neurological phenotypes. Hope new diagnostic and therapeutic targets to ameliorate the brain function-related symptoms and improve the quality of life of AR patients will be developed.

Laryngeal extra-skeletal Ewing sarcoma treated with DC-CTL immunotherapy: A case report and review of the literature.

Extra-skeletal Ewing sarcoma (EES) is a rare sarcoma composed primarily of small round cells, capable of metastasizing and relapsing. Few cases of EES originating from the larynx have been reported, and no publications regarding laryngeal EES treated with dendritic cells-cytotoxic T lymphocytes (DC-CTL) immunotherapy have been found. We described a 29-year-old woman with a mass found in the larynx. Diffuse small round cells with scanty cytoplasm shown by histology test and extremely positive staining of CD99 revealed by immunohistochemistry helped determine the diagnosis of laryngeal EES. The patient survived for seven years with no signs of recurrence or metastasis after six cycles of DC-CTL immunotherapy based on traditional treatments. This case indicates that DC-CTL immunotherapy could be considered a new option for treating EES.

Voting with Your Feet: The Impact of Urban Public Health Service Accessibility on the Permanent Migration Intentions of Rural Migrants in China.

The accessibility of urban public health services is not only relevant to the health status of rural migrants but also plays an increasingly important role in their migration decisions. Most existing studies have focused on the effects of the level of public health service provision and parity on rural migrants' migration behavior, ignoring the role of public health service accessibility. This paper systematically examines the overall impact, heterogeneous impact and mechanism of action of public health service accessibility on rural migrants' intentions to migrate permanently based on data from the 2017 China Mobile Population Dynamics Monitoring Survey using probit, IVprobit, eprobit, omitted variable test model and KHB mediating effect model. It was found that: (1) public health service accessibility significantly increased rural migrants' intentions to migrate permanently, and the results remained robust after using instrumental variables to mitigate endogeneity problems and omitted variable tests. (2) Heterogeneity analysis shows that public health service accessibility has a greater effect on enhancing the intentions to migrate permanently among females and rural migrants born in 1980 and later. (3) Further mechanism testing revealed that public health service accessibility could indirectly increase rural migrants' intentions to migrate permanently by improving health habits, health status, identity, and social integration, with identity playing a greater indirect effect. The findings of this paper not only provide empirical evidence for the existence of Tiebout's "voting with your feet" mechanism in China but also contribute to the scientific understanding of the role of equalization of public health services in the process of population migration.

Functionalization of clay surface for the removal of uranium from water.

A modification method of clay mineral surface was developed to improve its adsorption capacity of uranium. Uranium is a radionuclide with high toxicity and extremely long half-life, which can pollute the environment and endanger human health. This study proposes a new method of activation of clay mineral surface with phosphoric acid for rapid adsorption of uranium from aqueous solution. Compared with other modification methods, this method has the advantages of availability of raw materials, simple operation and good adsorption effects. It provides a cost-effective material to capture uranium ions from water. The essences of this new development are as following: • Activation and changes of clay minerals' surface functionalities with the treatment of phosphoric acid • Controlled modifications of the surface properties of the clay towards the enhancement of U adsorption capacity • Rapid removal of uranium from water.

Irisin restores high glucose-induced cell injury in vascular endothelial cells by activating Notch pathway via Notch receptor 1.

Diabetic foot ulcers (DFU) are a vascular complication of diabetes mellitus (DM). It has been confirmed that irisin is closely related to DM. However, the effect of irisin on DFU is obscure and needs further study. After human umbilical vein endothelial cell lines (HUVECs) were treated with different concentrations' irisin, normal glucose, high glucose (HG), HG plus irisin-high (H) or sh-Notch1, cell biological behaviors, LDH, and VEGFA were detected by cell function experiments. Apoptosis- and Notch pathway-related protein levels were evaluated by Western blot. Irisin has no cytotoxicity, and irisin-H elevated cell viability and inhibited apoptosis and LDH level in HG-induced HUVECs. Meanwhile, irisin-H restored HG-repressed migration and angiogenesis in HUVECs. Irisin-H inhibited apoptosis-related protein levels and promoted VEGFA and Notch pathway-related protein levels in HG-treated HUVECs. Additionally, sh-Notch1 reversed the protective effect of irisin-H in HG-treated HUVECs. Irisin restores HG-induced cell injury and angiogenesis in HUVECs by activating Notch pathway via Notch1.

ERG1 plays an essential role in rat cardiomyocyte fate decision by mediating AKT signaling.

ERG1, a potassium ion channel, is essential for cardiac action potential repolarization phase. However, the role of ERG1 for normal development of the heart is poorly understood. Using the rat embryonic stem cells (rESCs) model, we show that ERG1 is crucial in cardiomyocyte lineage commitment via interactions with Integrin ß1. In the mesoderm phase of rESCs, the interaction of ERG1 with Integrin ß1 can activate the AKT pathway by recruiting and phosphorylating PI3K p85 and focal adhesion kinase (FAK) to further phosphorylate AKT. Activation of AKT pathway promotes cardiomyocyte differentiation through two different mechanisms, (a) through phosphorylation of GSK3ß to upregulate the expression levels of ß-catenin and Gata4; (b) through promotion of nuclear translocation of nuclear factor-κB by phosphorylating IKKß to inhibit cell apoptosis, which occurs due to increased Bcl2 expression. Our study provides solid evidence for a novel role of ERG1 on differentiation of rESCs into cardiomyocytes.

Allergic Rhinitis and Depression: Profile and Proposal.

In addition to nasal symptoms, patients with allergic rhinitis (AR) often experience mental and psychological disorders such as depression. Depression not only makes the treatment of AR more difficult and expensive but also poses a serious impact on the patients' daily activities and quality of life, thus bringing additional burden to the families and the society. Here we systematically review the recent research advances in the correlation between AR and depression, analyze the possible causes and mechanisms of depression in AR, summarize the current diagnosis and treatment strategies, and provide our insights into the AR-related depression; in addition, we introduce briefly the basic research status on AR-related depression. We hope that this review article will provide evidence for future studies.

Luteolin Protects Pheochromocytoma (PC-12) Cells against Aß 25-35-Induced Cell Apoptosis through the ER/ERK/MAPK Signalling Pathway.

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aß 25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aß 25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aß 25-35-induced decrease in cell viability and inhibits Aß 25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERß and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aß 25-35-induced cell apoptosis via selectively acting on ERß. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD.

A simple method for the synthesis of biochar nanodots using hydrothermal reactor.

Biochar is a stable carbon rich by-product synthesized through pyrolysis of plant and animal based biomass, and nano-biochar material has gained increasing attention due to its unique properties for environmental applications. In the present study, a simple cost-effective method for the synthesis of biochar nanoparticles through hydrothermally using agricultural residuals and by-products was developed. Both soybean straw and cattle manure were selected as the feedstock to produce the bulk-biochar. The synthesis procedure involved the digestion of the bulk-biochar with concentrated nitric acid and sulfuric acid in a high pressure condition using a hydrothermal reactor. The suspension was isolated using vacuum filtration with 0.22-µm membrane followed by drying at 65 °C in an oven. Scanning electron microscopy results revealed that both of the biochars had a well-developed porous structure following pyrolysis. Both transmission electron microscopy and the dynamic light scattering results of the hydrothermally treated biochar indicated that the soybean straw and cattle manure biochar nanodots had an average of 5-nm and 4-nm in size, respectively. Overall two raw materials produced 8.5-10% biochar nanodots. The present method presents a simple, quick and cost-effective method for synthesis of biochar nanodots. The method provided a useful tool discovering the applicability biochar nanodots for environmental applications. • Nano-biochar formation from bulk-biochar using hydrothermal reactor • Evaluate nano-biochar's environmental fate and behavior in soil and water • Synthesize multifunctional adsorbent using nano-biochar as primary material.

Efficacy of prostaglandina E1 for the treatment of patients with thrombo-occlusive vasculitis: A protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to explore the efficacy and safety of prostaglandina E1 (PE1) for the treatment of patients with thrombo-occlusive vasculitis (TOV). METHODS: Electronic databases (Cochrane Library, PUBMED, EMBASE, Web of Science, Scopus, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be sought from onset to the March 1, 2020 without language and publication status restrictions. We will include any potential randomized controlled trials that examined the efficacy of PE1 for the treatment of patients with TOV. We will appraise study quality using Cochrane risk of bias tool, and will assess the evidence quality using Grading of Recommendations Assessment Development and Evaluation. We will use RevMan 5.3 Software for statistical analysis. RESULTS: A high-quality synthesis of present evidence of PE1 for the treatment of patients with TOV will be provided in this study. CONCLUSION: This study will provide evidence to judge whether PE1 is an effective intervention for TOV. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040081.