TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 may participate in the process of the coexistence of asthma and OSA.

OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.

The Influence of Land Attachment on Land Abandonment from the Perspective of Generational Difference: Evidence from Sichuan Province, China.

The deepening of rural population aging and the lack of labor transfer cause the phenomenon of land abandonment to become more serious, which threatens regional and even national food security. Based on the survey data of 540 farmers in Sichuan Province, the theoretical analysis framework of land attachment, intergenerational difference and land abandonment was constructed, and Probit and Tobit models were constructed to empirically analyze the influence of land attachment and intergenerational difference on land abandonment. Research results show that: (1) 10.9% of the farmers abandoned their arable land, with an average area of 0.17 mu; the interviewed farmers are mainly of the middle-aged generation; the scores of the three dimensions of farmers' land attachment were all at the above average level. (2) Land dependence has no significant effect on land abandonment, while satisfaction and embeddedness have significant negative effects on land abandonment. (3) There are generational differences in the influence of land attachment on land abandonment. Among them, the land attachment of the middle-aged generation had no significant effect on land abandonment; the satisfaction and embeddedness of the older generation of farmers have negative effects on land abandonment; the satisfaction of the new-generation farmers has a significant negative effect on farmland abandonment. Based on this research, countermeasures and suggestions are put forward: (1) Pay attention to the emotional appeals of farmers and improve their well-being. (2) Cultivate new types of agricultural business entities and stimulate the potential of new human resources.

Clinicopathological features in two families with MARS-related Charcot-Marie-Tooth disease.

Mutations in MARS gene cause dominant Charcot-Marie-Tooth disease (CMT) 2U. The aim of this study is to investigate phenotypic heterogeneities and peripheral neuropathology of MARS-related CMT patients. We identified a heterozygous p. R199Q mutation and an already reported heterozygous p. P800T mutation of MARS gene in two unrelated families using targeted next-generation sequencing. The first pedigree comprised three patients over three generations and the second pedigree comprised two patients over two generations. In addition of an asymptomatic carrier in the second pedigree, all patients presented with childhood-onset length dependent sensorimotor neuropathy with pes cavus. Nerve conduction studies revealed slowing of motor nerve conduction velocities (MNCV) of the median nerve indicating intermediate neuropathy in the patient with the p. R199Q mutation, and normal MNCV with reduced compound muscle action potential indicating axonal neuropathy in the patient with the p. P800T mutation. Magnetic resonance imaging detected a pattern of nerve changes similar to those in demyelinating polyneuropathies in intermediate type (p. R199Q mutation) patients compared with normal in the axonal type (p. P800T mutation) patients. Additionally, sural nerve biopsy revealed loss of myelinated axons with onion bulb formation in both mutations. By electron microscopy, a marked decrease of myelinated and unmyelinated fiber, neurofilaments aggregate with degenerating mitochondria and microtubule loss in axons were frequently found. Denervated Schwann cell complexes and few collagen pockets indicated involvement of unmyelinated Schwann cells. Therefore, the investigated MARS mutations cause not only the known axonal type but also intermediate type neuropathy with involvement of both axons and Schwann cells. Those findings are useful for the differential diagnosis of CMT patients with unknown MARS variants.

Corneal densitometry after allogeneic small-incision intrastromal lenticule implantation for hyperopia correction.

PURPOSE: To evaluate corneal densitometry after allogeneic corneal small-incision intrastromal lenticule implantation (SILI) for hyperopia. METHODS: A retrospective study. Thirty-one hyperopic eyes of 24 patients who underwent SILI were enrolled in this study. Examinations took place preoperatively and 1 week, 1 month, 3 months, and 6 months postoperatively. Corneal densitometry (CD) from different concentric radial zones (0-2, 2-6, and 6-10 mm annulus) and layers (anterior, central, and posterior) were obtained using Scheimpflug imaging. The association between CD changes and the uncorrected distance visual acuity (UDVA), spherical equivalent (SE), central corneal thickness (CCT) and K value were examined. RESULTS: No serious intraoperative complications occurred during SILI. The mean total CD increased postoperatively compared to preoperatively (P < 0.01). However, no significant differences were found among the four subsequent follow-up time points (P > 0.05). At 6 months postoperatively, the CD values showed an increase of 2.71 ± 2.52, 2.23 ± 2.25, and 1.87 ± 2.46 at the 0-2, 2-6, and 6-10 mm annuli, respectively (all at P < 0.01). The anterior 120 µm displayed the highest densitometry before and after surgery (all at P < 0.01). No significant increase was found within the posterior 60 µm of the cornea (P > 0.05). No correlation was found between the CD and relevant parameters(all at P > 0.05). CONCLUSIONS: SILI resulted in an increase in CD within the surgically altered area, however such change has no significant correlation with visual outcomes.

Applying Information Gain to Explore Factors Affecting Small-Incision Lenticule Extraction: A Multicenter Retrospective Study.

Purpose: This retrospective study aimed to identify the key factors influencing postoperative refraction after small-incision lenticule extraction (SMILE) using information gain. Methods: This study comprised 2,350 eyes of 1,200 patients who underwent SMILE using a Visumax 500-kHz femtosecond laser (Carl Zeiss Meditec AG) in three ophthalmic centers: Tianjin Eye Hospital (center A), Jinan Mingshui Eye Hospital (center B), and Qingdao Eye Hospital (center C). Anterior segment features, including corneal curvature and central corneal thickness (CCT), were obtained from Pentacam HR (Oculus, Wetzlar, Germany). Information gain was calculated to analyze the importance of features affecting postoperative refraction. Results: Preoperative and postoperative mean spherical equivalent (SE) refraction were -5.00 (-6.13, -3.88) D and 0.00 (-0.25, 0.13) D, respectively. None of the patients lost more than two lines of corrected distance visual acuity. The safety index was 1.32 ± 0.24, 1.03 ± 0.08, and 1.13 ± 0.16 in centers A, B, and C, respectively. The efficacy index was 1.31 ± 0.25, 1.02 ± 0.08, and 1.13 ± 0.17 in centers A, B, and C, respectively. At least 95% of the eyes were within ±1.00 D of the attempted correction. Postoperative refraction was related to preoperative spherical diopter refraction (r = 0.369, p < 0.001), preoperative SE (r = 0.364, p < 0.001), maximum lenticule thickness (r = -0.311, p < 0.001), preoperative uncorrected distance visual acuity (r = 0.164, p < 0.001), residual stromal thickness (r = 0.139, p < 0.001), preoperative mean anterior corneal curvature (r = -0.127, p < 0.001), preoperative flattest anterior corneal curvature (r = -0.122, p < 0.001), nomogram (r = -0.100, p < 0.001) and preoperative CCT (r = -0.058, p = 0.005). Conclusions: SMILE was considered a safe and effective procedure for correcting myopia. Based on information gain, postoperative refraction was influenced by preoperative mean anterior corneal curvature, CCT, refraction, and residual stromal thickness.

Community Disaster Resilience and Risk Perception in Earthquake-Stricken Areas of China.

OBJECTIVE: The purpose of this study is to further deepen our understanding of the relationship between community resilience and disaster risk perception of residents, so as to provide beneficial enlightenment for the construction of community resilience disaster prevention system and disaster risk management. METHODS: This study surveyed 327 rural households in four counties of Sichuan Province, China, that were affected by the Wenchuan and Lushan earthquakes. Community disaster resilience was divided into five dimensions: connection and caring, resources, transformative potential, disaster management, and information and communication. Residents' disaster risk perception was divided into three dimensions: possibility, threat, and worry. This study analyzed the characteristics of community disaster resilience and residents' disaster risk perceptions. Ordinary least squares (OLS) methods were used to explore the correlations between these factors. RESULTS: The results show that (1) Residents' overall disaster risk perception was at a moderate level, and the community's overall disaster resilience were above the moderate level. (2) Community connection and caring has a positive significant correlation with the possibility perception of disaster occurrence; transformative potential has a negative significant correlation with the possibility perception of disaster occurrence; the overall community disaster resilience has negative significant correlations with the possibility and the overall residents' perception of disaster risk occurrence. CONCLUSIONS: The implication for the local government is that the government should appropriately increase its contact with external institutions/organizations, especially some Non-Governmental Organization, to strengthen the resilience and disaster prevention capacity of the community. Establish and improve information and communication networks to ensure the timely and effective transmission of effective disaster information, and strengthen the supervision of the dissemination of false information to reduce the losses caused by false information to residents. Attention should be paid to psychological counseling for people in disaster-hit areas to reduce the psychological trauma of the disaster.

Genetic Variant of PP2A Subunit Gene Confers an Increased Risk of Primary Liver Cancer in Chinese.

BACKGROUND: Protein phosphatase 2A (PP2A, a serine/threonine phosphatase) is frequently inactivated in many types of cancer, including primary liver cancer (PLC). Genetic variations in PP2A subunits have been reported to be associated with the risk of many types of cancer but rarely in PLC. This study aims to assess the association between functional polymorphisms of PP2A subunit genes and the risk of PLC in Chinese. METHODS: In a case-control study with a total of 541 PLC patients and 547 controls in Guangxi province of Southern China, we genotyped six putatively functional polymorphisms (rs10421191G>A, rs11453459del>insG, rs1560092T>G, rs7840855C>T, rs1255722G>A and rs10151527A>C) of three PP2A subunit genes (PPP2R1A, PPP2R2A and PPP2R5E) using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform. RESULTS: The rs11453459insG variant genotypes (ins/ins+del/ins) of PPP2R1A were found to be significantly associated with an increased risk of PLC compared with the del/del genotype (adjusted OR = 1.290, 95% CI = 1.009-1.650), and the number of insert G allele worked in a dose-dependent manner (P trend= 0.007). The stratified analysis showed that the effects of rs11453459insG variant genotypes were more evident in the subgroup who drink pond-ditch water (adjusted OR = 3.051, 95% CI = 1.264-7.364) than those never drink (P = 0.041). The carriers of rs11453459 del/ins genotype had a significantly lower level of PPP2R1A mRNA expression in liver cancer tissues than those of the del/del genotype (P = 0.021). Furthermore, we used microcystin-LR, a carcinogen presents in the pond-ditch water, to treat human peripheral blood mononuclear cells and found that the cells from carriers of rs11453459insG variant genotypes induced more DNA oxidative damages than those from the del/del genotype carriers (P < 0.001). CONCLUSION: These findings suggest that the PPP2R1A rs11453459del>insG polymorphism is associated with an increased risk of PLC, especially for persons with a history of drinking pond-ditch water. This insertion/deletion polymorphism may be a susceptible biomarker for PLC in Chinese.

Mn2+ Directly Activates cGAS and Structural Analysis Suggests Mn2+ Induces a Noncanonical Catalytic Synthesis of 2'3'-cGAMP.

DNA binding allosterically activates the cytosolic DNA sensor cGAS (cyclic GMP-AMP [cGAMP] synthase) to synthesize 2'3'-cGAMP, using Mg2+ as the metal cofactor that catalyzes two nucleotidyl-transferring reactions. We previously found that Mn2+ potentiates cGAS activation, but the underlying mechanism remains unclear. Here, we report that Mn2+ directly activates cGAS. Structural analysis reveals that Mn2+-activated cGAS undergoes globally similar conformational changes to DNA-activated cGAS but forms a unique η1 helix to widen the catalytic pocket, allowing substrate entry and cGAMP synthesis. Strikingly, in Mn2+-activated cGAS, the linear intermediates pppGpG and pGpA take an inverted orientation in the active pocket, suggesting a noncanonical but accelerated cGAMP cyclization without substrate flip-over. Moreover, unlike the octahedral coordination around Mg2+, the two catalytic Mn2+ are coordinated by triphosphate moiety of the inverted substrate, independent of the catalytic triad residues. Our findings thus uncover Mn2+ as a cGAS activator that initiates noncanonical 2'3'-cGAMP synthesis.

Disaster Risk Perception, Sense of Pace, Evacuation Willingness, and Relocation Willingness of Rural Households in Earthquake-Stricken Areas: Evidence from Sichuan Province, China.

Based on survey data from 327 rural households in the areas affected by the Wenchuan Earthquake and Lushan Earthquake in Sichuan Province, this study systematically analyzed disaster risk perception, sense of place, evacuation willingness, and relocation willingness among residents in these earthquake-stricken areas. Further, this study constructed an ordinal logistic regression analysis to probe the correlations between residents' disaster risk perception or sense of place and evacuation willingness and relocation willingness, respectively. The results showed that (1) faced with the threat of earthquake disasters, residents have a strong willingness to evacuate and relocate. Specifically, 93% and 78% of the residents in the Wenchuan Earthquake and Lushan Earthquake areas were willing to evacuate and relocate, respectively, whereas 4% and 17% of the residents were unwilling to evacuate and relocate, respectively. (2) Place dependence and the severity of disaster occurrence were significantly positively correlated with residents' evacuation willingness, while the interaction term between place dependence and the severity of disaster occurrence was negatively related to residents' evacuation willingness. Specifically, when everything else remains constant, every one-unit increase in place dependence and severity corresponds to increases in the odds of willingness to evacuate by factors of 0.042 and 0.051, respectively; every one-unit increase in place dependence × severity corresponds to a decrease in the odds of willingness to evacuation by a factor of 0.004. (3) Place identity was significantly negatively correlated with residents' relocation willingness, while place dependence and severity of disaster occurrence were positively related to residents' relocation willingness. The interaction term between place dependence and the severity of disaster occurrence as well as the interaction term between place identity and severity of disaster occurrence were significantly negatively correlated with residents' relocation willingness. Specifically, every one-unit increase in place identity corresponds to a decrease in the odds of willingness to relocate by a factor of 0.034, while every one-unit increase in place dependence and severity corresponds to increases in the odds of willingness to relocate by factors of 0.041 and 0.028, respectively, and every one-unit increase in place dependence × severity and place identity × severity corresponds to decreases in the odds of willingness to relocate by factors of 0.003 and 0.003, respectively.

Financial Preparation, Disaster Experience, and Disaster Risk Perception of Rural Households in Earthquake-Stricken Areas: Evidence From the Wenchuan and Lushan Earthquakes in China's Sichuan Province.

Sichuan is a province in Southwest China that is famous worldwide for its earthquakes. However, few quantitative studies in China have probed the correlations between rural households' financial preparation, disaster experience, and disaster-risk perception. Using survey data of 327 rural households from four areas stricken by the Wenchuan Earthquake and Lushan Earthquake in Sichuan, the ordinary least square (OLS) method was used to quantitatively explore the correlations between these three factors. The results show that rural households' total family cash income, asset diversity, and whether rural households can borrow money from relatives and friends whenever there is a catastrophe such as an earthquake are significantly negatively correlated with the probability of disaster occurrence. Asset diversity and whether rural households can borrow money from banks whenever there is a catastrophe such as an earthquake are significantly positively related to the severity of disaster occurrence. The severity of residents' disaster experience is not significantly correlated with the probability of disaster occurrence, but is significantly positively related to the severity of the disaster. The research results can provide useful enlightenment for the improvement of financial preparedness and disaster risk management for rural households in earthquake-stricken areas.

Down-regulation of GCLC is involved in microcystin-LR-induced malignant transformation of human liver cells.

Microcystin-LR (MCLR) is a potent hepatotoxin which could lead to the development of hepatocellular carcinoma. However, the mechanisms of its carcinogenic action remain obscure. The catalytic subunit of glutamylcysteine ligase (GCLC) primarily regulates de novo synthesis of glutathione and is central to the antioxidant capacity of the cell, but emerging data suggest that the GCLC expression is associated with cancer development. The purpose of this study was to investigate the role and molecular mechanisms of GCLC in MCLR-induced malignant transformation of a human liver cell line WRL68. During MCLR-induced cell transformation, the expression of GCLC and activity of glutamate-cysteine ligase (GCL) decreased continuously, accompanied with consistent low levels of glutathione (GSH) but high levels of oxidative DNA damages. Furthermore, MCLR markedly inhibited protein phosphatase 2 A (PP2 A), and increased the level of GCLC phosphorylation. In contrast, overexpression of GCLC significantly enhanced the levels of GSH, inhibited oxidative DNA damages, and suppressed MCLR-induced cell invasion and migration, as well as tumor growth in nude mice. GCLC overexpression partially attenuated MCLR-induced PP2 A inhibition. Together, the current results suggest that down-regulation of GCLC is involved in MCLR-induced malignant transformation of human liver cells by inducing oxidative stress.

Dual Requirement of CHD8 for Chromatin Landscape Establishment and Histone Methyltransferase Recruitment to Promote CNS Myelination and Repair.

Disruptive mutations in chromatin remodeler CHD8 cause autism spectrum disorders, exhibiting widespread white matter abnormalities; however, the underlying mechanisms remain elusive. We show that cell-type specific Chd8 deletion in oligodendrocyte progenitors, but not in neurons, results in myelination defects, revealing a cell-intrinsic dependence on CHD8 for oligodendrocyte lineage development, myelination and post-injury remyelination. CHD8 activates expression of BRG1-associated SWI/SNF complexes that in turn activate CHD7, thus initiating a successive chromatin remodeling cascade that orchestrates oligodendrocyte lineage progression. Genomic occupancy analyses reveal that CHD8 establishes an accessible chromatin landscape, and recruits MLL/KMT2 histone methyltransferase complexes distinctively around proximal promoters to promote oligodendrocyte differentiation. Inhibition of histone demethylase activity partially rescues myelination defects of CHD8-deficient mutants. Our data indicate that CHD8 exhibits a dual function through inducing a cascade of chromatin reprogramming and recruiting H3K4 histone methyltransferases to establish oligodendrocyte identity, suggesting potential strategies of therapeutic intervention for CHD8-associated white matter defects.

The change of nuclear LC3 distribution in acute myeloid leukemia cells.

Making sure the change of nuclear LC3 distribution in the autophagy of acute myeloid leukemia (AML) cell and finding out the regulation mechanism may lead to a breakthrough for killing AML cells. Western blots were performed to assess the expression of autophagy proteins. Changes in the LC3 distribution were monitored by immunofluorescence assays together with western blots, and the expression levels of Sirt1, DOR, Beclin1, HMGB1, and AMPK mRNA were detected via fluorescent quantitative PCR. The effects of Sirt1 and DOR on cell proliferation and survival were analyzed by MTT, flow cytometry, and western blotting assays. We found that treating AML cells with Ara-c or Sorafenib resulted in autophagy enhancement, and when autophagy was enhanced, nuclear LC3 moved into the cytoplasm. Notably, when autophagy was inhibited by blocking the nuclear LC3 shift, the cytotoxicity of drugs was enhanced. Our results also identified Sirt1 and DOR as regulatory molecules for the observed nuclear LC3 shift, and these molecules further affected the expression of Beclin1, HMGB1, and AMPK. Our results suggest the distribution of nuclear LC3 can be a novel way for further studying death of AML cells,and the regulatory molecules may be new targets for treating AML.

miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS.

A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice. Integrated transcriptome profiling and biotin-affinity miRNA pull-down approaches reveal stage-specific miR-219 targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune encephalomyelitis, principal animal models of multiple sclerosis. Together, our findings identify context-specific miRNA-regulated checkpoints that control myelinogenesis and a therapeutic role for miR-219 in CNS myelin repair.

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch.

Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here, we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Hdac3 ablation leads to a significant increase of astrocytes with a concomitant loss of oligodendrocytes. Lineage tracing indicates that the ectopic astrocytes originate from oligodendrocyte progenitors. Genome-wide occupancy analysis reveals that Hdac3 interacts with p300 to activate oligodendroglial lineage-specific genes, while suppressing astroglial differentiation genes including NFIA. Furthermore, we find that Hdac3 modulates the acetylation state of Stat3 and competes with Stat3 for p300 binding to antagonize astrogliogenesis. Thus, our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrocyte identity while inhibiting NFIA and Stat3-mediated astrogliogenesis, and thereby regulates phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision.

The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice.

It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio.

Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model.

The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation.

ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice.

A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development.

The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain (NICD). A Disintegrin and Metalloprotease 10 (ADAM10) might be a physiological rate-limiting S2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is critical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAM10 mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 (E14.5) to postnatal day 1 (P1). ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin (neural stem cell marker), Tuj1 (mature neuron marker), and S100ß (glia marker) showed that ADAM10 expression highly matched that of S100ß and partially matched that of Tuj1 at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.