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Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-β/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.

The rate of global climate change is projected to outpace the ability of many natural populations and species to adapt. Assisted migration (AM), which is defined as the managed movement of climate‐adapted individuals within or outside the species ranges, is a conservation option to improve species' adaptive capacity and facilitate persistence. Although conservation biologists have long been using genetic tools to increase or maintain diversity of natural populations, genomic techniques could add extra benefit in AM that include selectively neutral and adaptive regions of the genome. In this review, we first propose a framework along with detailed procedures to aid collaboration among scientists, agencies, and local and regional managers during the decision‐making process of genomics‐guided AM. We then summarize the genomic approaches for applying AM, followed by a literature search of existing incorporation of genomics in AM across taxa. Our literature search initially identified 729 publications, but after filtering returned only 50 empirical studies that were either directly applied or considered genomics in AM related to climate change across taxa of plants, terrestrial animals, and aquatic animals; 42 studies were in plants. This demonstrated limited application of genomic methods in AM in organisms other than plants, so we provide further case studies as two examples to demonstrate the negative impact of climate change on non‐model species and how genomics could be applied in AM. With the rapidly developing sequencing technology and accumulating genomic data, we expect to see more successful applications of genomics in AM, and more broadly, in the conservation of biodiversity.

Switching of airway smooth muscle (ASM) cell phenotype from differentiated-contractile to dedifferentiated-proliferative/synthetic state often occurs in asthmatic subjects with airway dysfunction. Evidence has been provided that chloroquine (an agonist of bitter taste receptors) presented benefits to ASM cell function implicated in asthma. However, the underlying mechanism is unclear. House dust mite (HDM)-sensitized mice were administered with chloroquine or dexamethasone before challenge. BALF and lung tissue were obtained for cell counting, histological analysis or ELISA. Primary cultured ASM cells were stimulated with transforming growth factor (TGF)-β1 or H 2 O 2 . Cells and supernatant were collected for the detection of ASM phenotype, ROS level, and proinflammatory cytokine production. In HDM-sensitized mice, chloroquine attenuated airway hyperresponsiveness (AHR), inflammation and remodeling with an inhibition of immunoglobulin E, IL-4/-13, and TGF-β1 in BALF. ASM cell proliferation (PCNA), hypertrophy (α-SMA), and parasecretion (MMP-9 and MMP-13) were strongly suppressed by chloroquine, hinting the rebalance of the heterogeneous ASM populations in asthmatic airway. Our data in vitro indicated that chloroquine markedly restrained maladaptive alteration in ASM phenotype in concert with a remission of ROS. Using H 2 O 2 and PI3K inhibitor (LY294002), we found that the inhibition of oxidative stress level and ROS-AKT signal by chloroquine may serve as a potential mechanism that dedicates to the restoration of the phenotypic imbalance in ASM cells. Overall, the present findings suggested that chloroquine improves asthmatic airway function by controlling ASM cell phenotype shift, sketching a novel profile of chloroquine as a new therapeutic candidate for airway remodeling.

Ample evidence has recognized the importance of teacher support for children’s mental health. However, less is known about the factors that may play a role in the association between teacher support and children’s mental health. In the present study, we examined the mediating role of self-concept and the moderating role of area (i.e., rural vs. urban area) in the relationship between teacher support and children’s mental health (i.e., depression and anxiety). We used a sample of Chinese elementary students who enrolled in grades 3 to 6 (N = 525, aged 8–13, 44.54% girls). Results showed that children who perceived more teacher support tended to report better mental health. Moreover, the relationship between perceived teacher support and mental health was mediated by each domain of self-concept. Lastly, the association between teacher support and mental health was moderated by area, with a stronger effect found for urban children compared with rural children. These findings highlight the importance of considering both individual and contextual factors in the association between teacher support and children’s mental health. Practical strategies are proposed for school teachers, professionals, and policymakers to foster children’s psychological well-being.

Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed. In the present study, increased levels of plasma proline and PYCR1 were observed in asthmatic patients. Similarly, proline and PYCR1 in lung tissues were higher in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout (KO) decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTOR1 and WNT3a/β-catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogeneous proline partially relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.

This study examined the levels of soluble CD146 (sCD146) in plasma samples from patients with chronic obstructive pulmonary disease (COPD) and assessed the relationship between sCD146 and the severity of COPD. A total of 97 COPD patients were recruited from 20 medical centers in Jiangsu, China, including 13 stable subjects and 84 exacerbated subjects. The plasma sCD146 level in exacerbated subjects (28.77 ± 10.80 ng/mL) was significantly lower than that in stable subjects (38.84 ± 15.00 ng/mL). In the high sCD146 group, the proportion of subjects with modified Medical Research Council (mMRC) scores of 0–1 was higher, the proportion of subjects with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 was lower, and the proportion of subjects with ≥1 hospitalizations in the past year was lower. The plasma sCD146 level was negatively correlated with the COPD Assessment Test (CAT) score (r = −0.2664, p = 0.0087). Logistic regression analysis showed that sCD146 was an independent risk factor for acute exacerbation of COPD (AECOPD). Receiver operating characteristic (ROC) analysis suggested that sCD146 combined with sex, age, pulmonary function, and acute exacerbations in the past year had clinical value for the accurate identification of AECOPD, with an area under the ROC curve (AUC) of 0.908 (95% CI: 0.810–1.000, p < 0.001). In addition, there was a significant negative correlation between plasma sCD146 and S100A9 (r = −0.3939, p < 0.001).

Aiming at the problem of the deformation of the roadway floor plate during the laneway during the retention period, the mechanical model of the roadway floor is established, and the deformation characteristics of the roadway floor and the change law of the bottom drum are studied and analyzed through theoretical calculation and calculus simulation, revealing the instability mechanism of the surrounding rock of the roadway under the stress disturbance environment, and when not affected by the adoption, the roadway forms a certain stress concentration area within the effective range of support. During mining, under the comprehensive action of the original peripheral stress field and the mining stress field, the cliffhanger is unstable under the comprehensive action of the original peripheral stress field and the mining stress field, and the extrusion and stretching effect of the unflapped part of the rock layer above the goaf section of the coal seam is set up along the air, resulting in violent deformation such as the bottom drum, and the rotational sinking of this part of the unflinted rock layer further aggravates the transfer of the overburden load to the surrounding rock of the lane, so that the surrounding rock along the empty lane is subjected to a large additional stress, and the mining stress field plays a leading role, and the mining stress “far field” is the compound stress field, of which the tensile stress is the leading destructive factor. The deformation of the surrounding rock is mainly based on the bottom, and the horizontal stress on the bottom plate along the empty lane is mainly generated by the horizontal strain that occurs after the lower rock layer of the filling body and the coal gang is subjected to the supporting pressure transmitted by the top plate. With the mining of the working surface, the roof of the goaf area is broken and collapsed to form the characteristics of “vertical three belts,” which is affected by the “large support” of the coal body of the working surface and the “small support” of the surrounding rock along the empty roadway, and the pressure relief of the cut roof can make the roof plate along the empty lane change from the “long arm beam” structure when the roof is not cut into the “short arm beam” structure, blocking the lateral stress of the goaf area to the roof plate of the alley and significantly reducing the degree of stress superposition of the roof plate of the alley. The technical means of blasting cutting roof active pressure relief and protective lane are used to block the transmission of lateral support pressure, the roof slate layer is precracked in advance, the sinking of the rock layer is accelerated, the disturbance time is reduced, the vertical stress of the rock layer and the rock layer above it along the empty roadway is reduced, the vertical stress concentration of the roadway is reduced, the stress concentration coefficient is reduced, the degree of damage of the surrounding rock after the top is weakened, the damage range is reduced, and the technical problem of large deformation prevention and control along the bottom drum of the empty alley can be solved. Constructing the mechanical structure model of the top plate of the cut top pressure relief and the uncut top pressure relief along the empty lane, the stress change characteristics of the active protective rock surrounding rock along the hollow top of the cut top pressure relief were calculated, and after the technical scheme of the blasting cut top active pressure relief and protection lane was adopted, the deformation along the empty roadway was significantly weakened, the stability of the surrounding rock of the roadway after the blasting of the cut roof was significantly improved, the maintenance state along the section of the empty roadway was good, and the cross-sectional convergence rate was reduced by 37.3% compared with the original section. Cutting the roof active pressure relief and protective lane can effectively improve the stability of the surrounding rock.

Background The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma. Methods House dust mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured. Results In response to the challenge of house dust mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and autophagy in the lung, leading to the attenuation of allergic asthma. Conclusion KIF2A suppressed mTORC1-mediated autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma.

Objective The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. Methods House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. Results In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. Conclusions These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation. Most research on the IL‐33/ST2 axis has been conducted in type 2 immunity‐mediated eosinophilic asthma, but less research has focused on neutrophilic asthma. In this study, we found that IL‐33/ST2 axis deficiency aggravated neutrophil‐dominant allergic airway inflammation induced by house‐dust mite and lipopolysaccharide coexposure, which may account for the more proinflammatory status of IL‐33/ST2 axis‐deficient macrophages and lung epithelial cells.

Understanding others’ thoughts and feelings is a social-cognitive capacity known as the theory of mind (ToM). Previous studies have attempted to explore children’s ToM from a specific domain (personal or moral) while lacking comprehensive evidence across domains. Based on the social domain theory, the present study is the first in our knowledge to explore the developmental characteristics of the ToM within different domains of left-behind preschoolers in rural China. This study used a mixed experimental design of 3 (age groups: 4-, 5-, 6-year-old) × 2 (left-behind status: left-behind, non-left-behind) × 3 (domain types: moral, conventional, personal) with 231 rural children aged 4–6 years, combined with a story–question approach to explore the developmental characteristics of their ToM in moral, conventional, and personal domains through tasks, such as rule awareness and false beliefs. The results showed significant main effects of age group, left-behind status, and domain type. Moreover, the interaction effect of age group and domain type was significant. The following conclusions were obtained: (1) The developmental level of the ToM in moral, conventional, and personal domains of rural preschoolers increased with age and the older preschoolers had a more accurate and comprehensive understanding of the ToM in each domain; (2) The experience of being left behind was detrimental to the development of preschoolers’ ToM in each domain; (3) There were differences in children’s development in the moral-, conventional-, and personal-related ToM tasks, with the personal domain ToM developing more slowly; (4) The younger preschoolers showed a clear differentiation between the domains of ToM, with a higher level of development in domains of morality and convention. As preschoolers get older, their performance in the domains becomes more comparable.