T cell cholesterol transport is a metabolic checkpoint that links intestinal immune responses to dietary lipid absorption.

The intrinsic pathways that control membrane organization in immune cells and the impact of such pathways on cellular function are not well defined. Here we report that the non-vesicular cholesterol transporter Aster-A links plasma membrane (PM) cholesterol availability in T cells to immune signaling and systemic metabolism. Aster-A is recruited to the PM during T-cell receptor (TCR) activation, where it facilitates the removal of newly generated "accessible" membrane cholesterol. Loss of Aster-A leads to excess PM cholesterol accumulation, resulting in enhanced TCR nano-clustering and signaling, and Th17 cytokine production. Finally, we show that the mucosal Th17 response is restrained by PM cholesterol remodeling. Ablation of Aster-A in T cells leads to enhanced IL-22 production, reduced intestinal fatty acid absorption, and resistance to diet-induced obesity. These findings delineate a multi-tiered regulatory scheme linking immune cell lipid flux to nutrient absorption and systemic physiology.

Can motor decline be a modifiable marker of clinical progression in subjective cognitive decline? A national prospective cohort study.

OBJECTIVES: Subjective cognitive decline represents a critical stage for preventing mild cognitive impairment and dementia, but the links between clinical progression in the subjective cognitive decline stage and various motor functions remain inconclusive. This cohort study aimed to elucidate the independent and joint associations between the clinical progression of subjective cognitive decline and motor functions. METHODS: We enrolled 4880 community-dwelling elderly participants from a national cohort and used Cox proportional hazard regression model and restricted cubic spline models to explore the longitudinal associations between motor functions (gait, strength, balance, and endurance) and the clinical progression of subjective cognitive decline. RESULTS: During 5-years follow-up, 1239 participants experienced clinical progression. After adjusting for demographics, vascular burden, body components, and polypharmacy, gait speed [hazard ratios (HRs)= 0.96, 95% confidence interval (CI) 0.94-0.99], chair stand test (HRs=1.02, 95%CI 1.01-1.03), and endurance limitation in jogging 1 kilometer (HRs=1.18, 95%CI 1.04-1.34) were significantly associated with clinical progression. Among all participants, individuals characterized by poor upper- and lower-body strength, as well as those with slow pace and reduced endurance, faced the highest risk of cognitive impairment. CONCLUSIONS: This study emphasizes the potential of gait speed, muscle strength, and endurance as non-cognitive indicators of clinical progression in subjective cognitive decline. Understanding their combined effectiveness may reveal primary physiological mechanisms contributing to the dual decline of motor and cognition.

Aster-B-dependent estradiol synthesis protects female mice from diet-induced obesity.

Aster proteins mediate the nonvesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). However, the importance of nonvesicular sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss of Aster-B leads to diet-induced obesity in female but not in male mice, and that this sex difference is abolished by ovariectomy. We further demonstrate that Aster-B deficiency impairs nonvesicular cholesterol transport from the PM to the ER in ovaries in vivo, leading to hypogonadism and reduced estradiol synthesis. Female Aster-B-deficient mice exhibit reduced locomotor activity and energy expenditure, consistent with established effects of estrogens on systemic metabolism. Administration of exogenous estradiol ameliorates the diet-induced obesity phenotype of Aster-B-deficient female mice. These findings highlight the key role of Aster-B-dependent nonvesicular cholesterol transport in regulating estradiol production and protecting females from obesity.

Oral frailty: A concept analysis.

AIM: To clarify the concept of oral frailty to provide a clear and standardized conceptual basis for further research in older people. DESIGN: Rodgers and Knafl's evolutionary concept analysis approach. METHODS: The narrative analysis detailedly extracted and synthesized the attributes of oral frailty, as well as its antecedents, consequences and related terms under the guidance of Rodgers' evolutionary method. DATA SOURCES: Multiple databases including Pubmed, CINAHL and Cochrane were searched using selected search terms 'oral frail*', 'oral health' and 'aged' respectively. Articles written between 2013 and 2023 were included, and grey literature was excluded. RESULTS: A total of 32 articles were included for further analysis and synthesis. The attributes of oral frailty were hypofunction, predisposing in nature, non-specific and multidimensional. Antecedents of prefrailty were classified into four categories, namely, sociodemographic characteristics, comorbidity, physical function and psychosocial factors. Consequences of oral frailty include three themes: increased risk of adverse outcomes, poor nutritional status and possibility of social withdrawal. Related terms that had shared attributes with oral frailty were oral health, functional dentition, oral hypofunction and deterioration of oral function. CONCLUSIONS: Oral frailty is an age-related phenomenon reflected in decreased oral function. The findings of this concept analysis are conducive to understanding and clarifying the oral frailty, which can help clinicians or other healthcare providers to consider how to distinguish oral frailty in older adults and further promote the development of this field. IMPACT: Oral frailty is increasingly recognized as an age-related phenomenon reflected in decreased oral function. As it is newly proposed, no consensus has been reached regarding the theoretical and operational concept of it. Through clarifying the concept, this paper will guide future healthcare research on oral frailty regarding the influencing factors, mechanisms and interventions, thus raising the awareness with regard to oral health among older adults. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: In the context of older adults, oral frailty is a concept that requires further research to guide future theoretical development, and the influencing factors, mechanisms and interventions need to be further studied. Raise awareness with regard to oral health among older people and more attention will be paid to the early identification and intervention of oral frailty, so as to further improve the quality of life of older adults.

Spatial-temporal pattern and spatial convergence of carbon emission intensity of rural energy consumption in China.

Based on the panel data of 30 provinces (municipalities and autonomous regions) in China from 2005 to 2019, this paper uses Gini coefficient decomposition and kernel density estimation to investigate the regional differences and dynamic evolution trend of rural energy carbon emission intensity in China. Then, the convergence model is used to analyze the convergence characteristics and influencing factors of carbon emission intensity. The study found the following: (1) During the observation period, the carbon emissions of coal energy and oil energy were much higher than those of gas energy. The carbon emissions of rural energy consumption experienced three stages of development, and the carbon emission intensity showed a downward trend as a whole. The spatial distribution pattern of total carbon emissions present an "adder" distribution, and the spatial agglomeration phenomenon gradually strengthens with the passage of time. (2) The Gini coefficient of China's rural energy consumption carbon emission intensity shows a trend of "Inverted N-shaped." The Gini coefficient of carbon emission intensity in the eastern and northeastern regions shows an increasing trend, while the Gini coefficient of carbon emission intensity in the western and central regions shows a downward trend. The super variable density is the main source of carbon emission intensity difference. The peak value of the main peak of the nuclear density curve of the carbon emission intensity increased significantly, the bimodal form evolved into a single peak form, and the density center moved to the left. (3) The carbon emission intensity of rural energy consumption in the whole, central, and western regions of China has the characteristic of σ convergence, while the carbon emission intensity in the eastern and northeastern regions does not have the characteristic of σ convergence. There is a significant spatial positive correlation in the carbon emission intensity, there is also a significant ß convergence characteristic, the speed of conditional ß convergence is significantly higher than that of absolute ß convergence, and the spatial interaction will further improve the convergence speed. Industrial structure, industrial agglomeration, and energy efficiency will increase the convergence speed. In terms of sub-regions, the conditional convergence rate of carbon emission intensity in the four regions shows a decreasing trend in the northeast, central, eastern, and western regions.

RNA m6A methylation modulates airway inflammation in allergic asthma via PTX3-dependent macrophage homeostasis.

N6-methyladenosine (m6A), the most prevalent mRNA modification, has an important function in diverse biological processes. However, the involvement of m6A in allergic asthma and macrophage homeostasis remains largely unknown. Here we show that m6A methyltransferases METTL3 is expressed at a low level in monocyte-derived macrophages from childhood allergic asthma patients. Conditional knockout of Mettl3 in myeloid cells enhances Th2 cell response and aggravates allergic airway inflammation by facilitating M2 macrophage activation. Loss and gain functional studies confirm that METTL3 suppresses M2 macrophage activation partly through PI3K/AKT and JAK/STAT6 signaling. Mechanistically, m6A-sequencing shows that loss of METTL3 impairs the m6A-YTHDF3-dependent degradation of PTX3 mRNA, while higher PTX3 expression positively correlates with asthma severity through promoting M2 macrophage activation. Furthermore, the METTL3/YTHDF3-m6A/PTX3 interactions contribute to autophagy maturation in macrophages by modulating STX17 expression. Collectively, this study highlights the function of m6A in regulating macrophage homeostasis and identifies potential targets in controlling allergic asthma.

Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.

Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.

Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis.

The increasing incident of age-related cognitive impairment worldwide and the lack of pharmaceutical treatments emphasizes the value of non-pharmaceutical therapy. Emerging evidence suggested photobiomodulation (PBM) is a popular intervention to brain disorder; however, it remains unclear the efficacy of PBM for patients with age-related cognitive impairment. The purpose of this systematic review is to compare the different parameters used in PBM, analyze the beneficial effects of PBM as a potential therapy for age-related cognitive impairment. Five electronic database, PubMed, Web of Science, Cochrane Library, CINAHL, and PsycINFO, were systematically searched from inception to November 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eleven RCTs evaluating PBM interventions were included. The systematic review and meta-analysis has been registered in PROSPERO(CRD42022374562). Results showed that PBM had a significant moderated effect on global cognition function (SMD=0.51, 95% CI [0.162, 0.864], p=0.004). We found that multiple wavelength PBM (SMD=0.648, 95% CI [0.220, 1.075], p=0.003) had significant effects while single wavelength PBM was non-significant (SMD=0.385, 95% CI [-0.168, 0.987], p=0.172). Laser effect (SMD=0.682, 95% CI [0.37, 0,994], p<0.001) was larger than LED effect (SMD=0.582, 95% CI [0.269, 0.895], p<0.001). PBM in clinical setting (SMD=0.468, 95% CI [0.050, 0.887], p=0.028) had significant effect, but there was no significant effect of home-used PBM (SMD=0.616, 95% CI [-0.121, 1.354], p=0.101). The pool effect of multi-modality PBM (SMD=0.720, 95% CI [0.027, 1.414], p=0.040) was significantly higher in the studies of transcranial irradiation (SMD=0.616, 95% CI [-0.121, 1.354], p=0.010). Cumulative irradiation time was a moderator between the PBM and cognitive function improvement. Photobiomodulation have the potential to improve cognitive function in aging adults. Cumulative irradiation duration, light source, device type, penetration modality, and intervention site can affect the effectiveness of PBM intervention.

Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier.

Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn2+ concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.

Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia.

Full spectrum flow cytometry brings a breakthrough for minimal residual disease (MRD) detection in acute myeloid leukemia (AML). We aimed to explore the role of a new panel in MRD detection. We established a 24-color full-spectrum flow cytometry panel. A tube of 24-color antibodies included CD45, CD117, CD34, HLA-DR, CD15, CD64, CD14, CD11c, CD11b, CD13, CD33, CD371, CD7, CD56, CD19, CD4, CD2, CD123, CD200, CD38, CD96, CD71, CD36, and CD9. We discovered that when a tube meets 26 parameters (24 colors), these markers were not only limited to the observation of MRD in AML, but also could be used for fine clustering of bone marrow cells. Mast cells, basophils, myeloid dendritic cells, and plasmacoid dendritic cells were more clearly observed. In addition, immune checkpoint CD96 had the higher expression in CD117+ myeloid naive cells and CD56dimNK cells, while had the lower expression in CD56briNK cells in AML-MRD samples than in normal bone marrow samples. CD200 expression was remarkably enhanced in CD117+ myeloid naive cells, CD4+ T cells, T cells, activated T cells, CD56dimNK cells, and CD56briNK cells in AML-MRD samples. Our results can be used as important basis for auxiliary diagnosis, prognosis judgment, treatment guidance, and immune regulation in AML.

Remnant cholesterol, but not other cholesterol parameters, is associated with gestational diabetes mellitus in pregnant women: a prospective cohort study.

OBJECTIVE: No evidence has been found of a relationship between remnant cholesterol (RC) and the likelihood of gestational diabetes mellitus (GDM) in pregnant women. The aim of our study was to investigate the link between serum RC at 12-14 weeks of gestation and the risk of GDM. METHODS: This was a secondary analysis with data from a prospective cohort study in Korea. A total of 590 single pregnant women attending two hospitals in Korea, up to 14 weeks gestation, from November 2014 to July 2016 were included in the study. The formula used to calculate RC in detail was RC (mg/dL) = TC (mg/dL)-HDL-c (mg/dL)-LDL-c (mg/dL). Logistic regression models were employed to examine the relationship between RC and GDM and explore the association between other lipoprotein cholesterol parameters and the risk of GDM. Furthermore, receiver operating characteristic (ROC) analysis was performed to assess the ability of RC to identify GDM. Additionally, sensitivity and subgroup analyses were conducted. RESULTS: The mean age of participants was 32.06 ± 3.80 years. The median of RC was 34.66 mg/dL. 37 pregnant women (6.27%) were eventually diagnosed with GDM. Multivariate adjusted logistic regression analysis showed that RC was positively associated with the risk of GDM (OR = 1.458, 95% CI 1.221, 1.741). There was no significant association between other lipoprotein cholesterols (including TC, LDL-c, HDL-c) and the risk of GDM. The area under the ROC curve for RC as a predictor of GDM was 0.8038 (95% CI 0.7338-0.8738), and the optimal RC cut-off was 24.30 mg/dL. Our findings were demonstrated to be robust by performing a series of sensitivity analyses. CONCLUSION: Serum RC levels at 12-14 weeks of gestation are positively associated with GDM risk in pregnant women. RC in early pregnancy is an early warning indicator of GDM in pregnant women, especially those with normal HDL-c, LDL-c, and TC that are easily overlooked. There is a high risk of developing GDM in pregnant women whose RC is more than 24.30 mg/dL. This study may help optimize GDM prevention in pregnant women and facilitate communication between physicians, pregnant patients, and their families.

Aster-dependent non-vesicular transport facilitates dietary cholesterol uptake.

Intestinal cholesterol absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1), the target of the drug ezetimibe (EZ), assists in the initial step of dietary cholesterol uptake. However, how cholesterol moves downstream of NPC1L1 is unknown. Here we show that Aster-B and Aster-C are critical for non-vesicular cholesterol movement in enterocytes, bridging NPC1L1 at the plasma membrane (PM) and ACAT2 in the endoplasmic reticulum (ER). Loss of NPC1L1 diminishes accessible PM cholesterol in enterocytes and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate cholesterol at the PM and display evidence of ER cholesterol depletion, including decreased cholesterol ester stores and activation of the SREBP-2 transcriptional pathway. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, we show that the Aster pathway can be targeted with a small molecule inhibitor to manipulate dietary cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption. One-Sentence Summary: Identification of a targetable pathway for regulation of dietary cholesterol absorption.

Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity.

Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.

Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung Inflammation following PM2.5 and Indeno[1,2,3-cd]pyrene Exposure.

BACKGROUND: Ambient particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) is suggested to act as an adjuvant for allergen-mediated sensitization and recent evidence suggests the importance of T follicular helper (Tfh) cells in allergic diseases. However, the impact of PM2.5 exposure and its absorbed polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains unknown. OBJECTIVES: We aimed to explore the impact of environmental PM2.5 and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. METHODS: PM2.5- or IP-mediated remodeling of cellular composition in lung lymph nodes (LNs) was determined by mass cytometry in a house dust mite (HDM)-induced mouse allergic lung inflammation model. The differentiation and function of Tfh cells in vitro were analyzed by flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, immunoprecipitation, and western blot analyses. RESULTS: Mice exposed to PM2.5 during the HDM sensitization period demonstrated immune cell population shifts in lung LNs as compared with those sensitized with HDM alone, with a greater number of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) response and pulmonary inflammation. Similarly enhanced phenotypes were also found in mice exposed to IP and sensitized with HDM. Further, IP administration was found to induce interleukin-21 (Il21) and Il4 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 cells. DISCUSSION: These findings suggest that the PM2.5 (IP)-AhR-c-Maf axis in Tfh2 cells was important in allergen sensitization and lung inflammation, thus adding a new dimension in the understanding of Tfh2 cell differentiation and function and providing a basis for establishing the environment-disease causal relationship. https://doi.org/10.1289/EHP11580.

30-color full spectrum flow cytometry panel for deep immunophenotyping of T cell subsets in murine tumor tissue.

This 30-color full spectrum flow cytometry panel was developed and optimized for in-depth analysis T cells immunophenotype in tumor microenvironment and peripheral lymphoid organs. The panel presented here first identify the main cell subsets including myeloid cells, B cells, NKT cells, γδ T cells, CD4+ T cells and CD8+ T cells. For CD4+ T cells or CD8+ T cells, the panel includes markers for further characterization by including a selection of activation status(CD44, CD62L, CD69, Ki67, CD127, KLRG1 and CXCR3), costimulatory/co-inhibitory molecules (ICOS, OX-40, PD-1, LAG3, TIM-3, CTLA-4 and TIGIT), pro-inflammatory/anti-inflammatory cytokines (IFN-γ, TNF-α and IL-10) and cytotoxic molecules (Perforin, Granzymes B and CD107a). The panel has been tested on the tumor infiltrating T cells and corresponding spleen T cells in B16-F10 murine melanoma models.

Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis.

In cell models, changes in the 'accessible' pool of plasma membrane (PM) cholesterol are linked with the regulation of endoplasmic reticulum sterol synthesis and metabolism by the Aster family of nonvesicular transporters; however, the relevance of such nonvesicular transport mechanisms for lipid homeostasis in vivo has not been defined. Here we reveal two physiological contexts that generate accessible PM cholesterol and engage the Aster pathway in the liver: fasting and reverse cholesterol transport. During fasting, adipose-tissue-derived fatty acids activate hepatocyte sphingomyelinase to liberate sequestered PM cholesterol. Aster-dependent cholesterol transport during fasting facilitates cholesteryl ester formation, cholesterol movement into bile and very low-density lipoprotein production. During reverse cholesterol transport, high-density lipoprotein delivers excess cholesterol to the hepatocyte PM through scavenger receptor class B member 1. Loss of hepatic Asters impairs cholesterol movement into feces, raises plasma cholesterol levels and causes cholesterol accumulation in peripheral tissues. These results reveal fundamental mechanisms by which Aster cholesterol flux contributes to hepatic and systemic lipid homeostasis.

Optical mapping of the evolution of water content during the swelling of hydrophilic polymers.

The water content of hydrophilic polymers is a fundamental property that regulates their performance. Herein, we report a new technique for optically imaging the water content of hydrophilic polymers both in static and dynamic evolution during swelling, based on mapping the interfacial refractive index of hydrophilic polymers with label-free total internal reflection microscopy.

Dyadic profiles of family resilience among patients with first-episode stroke: A longitudinal study of the first 6 months after stroke.

BACKGROUND: The importance of family resilience in the recovery of stroke patients has been demonstrated in numerous studies. However, little is known about post-stroke family resilience. AIMS: To investigate the family resilience of stroke patients from a patient-caregiver dyadic perspective during the first 6 months after stroke. METHODS: A total of 288 dyads of patients diagnosed with a first-episode stroke and their principal caregivers were recruited from neurology departments of 7 tertiary hospitals in Shanghai and Shangqiu, China. Family resilience and family function were assessed during hospitalisation and at 1, 3 and 6 months after stroke. K-means cluster analysis was used to identify different clusters of family resilience based on family resilience of patients and caregivers during hospitalisation. The STROBE guidelines for observational studies were followed. RESULTS: Three clusters of family resilience were identified with distinct trajectories: cluster of high resilience (HR), cluster of low resilience (LR) and cluster of discrepant resilience (DR). The level of family function was consistently highest in cluster HR and lowest in cluster with LR at four time points. Most (69.8%) families fell into the cluster with low resilience and low family function. Characteristics such as the Rankin scores and education level of patients, education level of caregivers, family monthly income and living district were different among the three clusters. CONCLUSIONS: We concluded that family resilience was linked to the family functioning of patients with a first-episode stroke, however, the levels of resilience in most families were low. Factors, including the education level, family income and stroke severity of patients were revealed to influence the family resilience and its development. RELEVANCE TO CLINICAL PRACTICE: A resilience-focused approach to family-related treatment is beneficial for families. Therefore, understanding family resilience among stroke survivors is needed to inform the development of interventions for enhancing the recovery of stroke families.

circS100A11 enhances M2a macrophage activation and lung inflammation in children with asthma.

BACKGROUND: Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined. METHODS: The differential expression profiles of circRNAs were analyzed by microarray. The effects and mechanisms by which circRNAs influence macrophage activation were detected by quantitative real-time PCR, RNA immunoprecipitation assay, and chromatin immunoprecipitation assay, among others. The roles of circRNA and its host gene in asthma were tested in a cockroach allergen extract (CRE)-induced murine asthma model. RESULTS: We identified 372 circRNAs that were differentially expressed in PBMCs of children with asthma as compared with healthy controls. A circRNA with unknown function, circS100A11, was dominantly expressed in monocytes and significantly upregulated in children with asthma. circS100A11 facilitated M2a macrophage activation by enhancing translation of its host gene, S100A11, and exacerbated lung inflammation in a CRE-induced murine asthma model with macrophage-specific overexpression of circS100A11. Mechanistically, circS100A11 promoted S100A11 translation by competitively binding to CAPRIN1 to decrease the suppression of CAPRIN1 upon S100A11 translation. Then, S100A11 liberated SP3 from nucleolin and promoted SP3 binding to the STAT6 promoter to enhance STAT6 expression and M2a macrophage activation. Macrophage-specific knockdown of S100A11 could alleviate lung inflammation in a CRE-induced murine asthma model in vivo. CONCLUSIONS: circS100A11 and S100A11 promote M2a macrophage activation and lung inflammation in asthma model and may serve as potential therapeutic and diagnostic targets in children with asthma.