Coexisting Magnetism, Ferroelectric, and Ferrovalley Multiferroic in Stacking-Dependent Two-Dimensional Materials.

Two-dimensional (2D) multiferroic materials have widespread application prospects in facilitating the integration and miniaturization of nanodevices. However, the magnetic, ferroelectric, and ferrovalley properties in one 2D material are rarely coupled. Here, we propose a mechanism for manipulating magnetism, ferroelectric, and valley polarization by interlayer sliding in a 2D bilayer material. Monolayer GdI2 is a ferromagnetic semiconductor with a valley polarization of up to 155.5 meV. More interestingly, the magnetism and valley polarization of bilayer GdI2 can be strongly coupled by sliding ferroelectricity, making these tunable and reversible. In addition, we uncover the microscopic mechanism of the magnetic phase transition by a spin Hamiltonian and electron hopping between layers. Our findings offer a new direction for investigating 2D multiferroic devices with implications for next-generation electronic, valleytronic, and spintronic devices.

Impacts of litter microbial community on litter decomposition in the absence of soil microorganisms.

What is the effect of phyllosphere microorganisms on litter decomposition in the absence of colonization by soil microorganisms? Here, we simulated the litter standing decomposition stage in the field to study the differences in the composition and structure of the phyllosphere microbial community after the mixed decomposition of Populus × canadensis and Pinus sylvestris var. mongolica litter. After 15 months of mixed decomposition, we discovered that litters that were not in contact with soil had an antagonistic effect (the actual decomposition rate was 18.18%, which is lower than the expected decomposition rate) and the difference between the litters themselves resulted in a negative response to litter decomposition. In addition, there was no significant difference in bacterial and fungal community diversity after litter decomposition. The litter bacterial community was negatively responsive to litter properties and positively responsive to the fungal community. Importantly, we found that bacterial communities had a greater impact on litter decomposition than fungi. This study has enriched our understanding of the decomposition of litter itself and provided a theoretical basis for further exploring the "additive and non-additive effects" of litter decomposition and the mechanism of microbial drive. IMPORTANCE: The study of litter decomposition mechanism plays an important role in the material circulation of the global ecosystem. However, previous studies have often looked at contact with soil as the starting point for decomposition. But actually, standing litter is very common in forest ecosystems. Therefore, we used field simulation experiments to simulate the decomposition of litters without contact with soil for 15 months, to explore the combined and non-added benefits of the decomposition of mixed litters, and to study the influence of microbial community composition on the decomposition rate while comparing the differences of microbial communities.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Topological alterations in white matter anatomical networks in cervical dystonia.

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Interleukin 4 improved adipose-derived stem cells engraftment via interacting with fibro/adipogenic progenitors in dystrophic mice.

Adipose-derived stem cells (ADSC) therapy shows promise as an effective treatment for dystrophinopathy. Fibro-/adipogenic progenitors (FAPs) play an essential role in the myogenesis of muscle satellite cells and contribute to muscle fibrosis and adipocyte infiltration. The interleukin 4 (IL-4) pathway acts as a switch that regulates the functions of FAPs. The interaction between FAPs and engrafted cells remains unclear. In this study, we used a co-culture system to investigate possible crosstalk between the FAPs of dystrophic mice and ADSC overexpressing IL4 (IL4-ADSC) and control ADSC. Systemic transplantation of IL4-ADSC and control ADSC in dystrophic mice was conducted for 16 weeks, after which motor function and molecular improvements were evaluated. Overexpression of IL4 in ADSC significantly promoted myogenesis in vitro, increasing the expression of Pax7, Myogenin, and MyHC. Co-culture indicated that although myoblasts derived from control ADSC promoted adipogenic and fibrogenic differentiation of FAPs, FAPs did not significantly affect myogenesis of ADSC-derived myoblasts. However, overexpression of IL4 in ADSC inhibited their myotube-dependent promotion of FAPs differentiation on the one hand and promoted FAPs to enhance myogenesis on the other. Dystrophic mice administered with IL4-ADSC-derived myoblasts displayed significantly better motor ability, more engrafted cells showing dystrophin expression, and less muscle fibrosis, intramuscular adipocytes, and macrophage infiltration than mice administered control-ADSC-derived myoblasts. In conclusion, IL4 activation enhanced the therapeutic potential of ADSC transplantation in dystrophic mice, possibly by improving the myogenesis of IL4-ADSC and altering the crosstalk between engrafted stem cells and resident FAPs.

Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice.

Obesity increases the severity of airway hyperresponsiveness (AHR) in individuals with asthma, but the mechanism is not well elucidated. G-protein coupled receptor 40 (GPR40) has been found to induce airway smooth muscle contraction after activated by long-chain fatty acids (LC-FFAs), suggesting a close correlation between GPR40 and AHR in obese. In this study, C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization, the regulatory effects of GPR40 on AHR, inflammatory cells infiltration, and the expression of Th1/Th2 cytokines were evaluated by using a small-molecule antagonist of GPR40, DC260126. We found that the free fatty acids (FFAs) level and GPR40 expression were greatly elevated in the pulmonary tissues of obese asthmatic mice. DC260126 greatly reduced methacholine-induced AHR, ameliorated pulmonary pathological changes and decreased inflammatory cell infiltration in the airways in obese asthma. In addition, DC260126 could down-regulate the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and pro-inflammatory cytokines (IL-1ß, TNF-α), but elevated Th1 cytokine (IFN-γ) expression. In vitro, DC260126 could remarkedly reduce oleic acid (OA)-induced cell proliferation and migration in HASM cells. Mechanistically, the effects that DC260126 alleviated obese asthma was correlated with the down-regulation of GTP-RhoA and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1). Herein, we proved that targeting of GPR40 with its antagonist helped to mitigate multiple parameters of obese asthma effectively.

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

Houpo paiqi mixture promotes intestinal motility in constipated rats by modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

AIMS: Constipation is a common functional gastrointestinal disorder, which needs more effective treatment approaches. Houpo Paiqi Mixture (HPPQM) is a type of Chinese patent medicine developed from a classical formula that has been widely applied to the treatment of intestinal motility disorder. Here we aim to assess the effectiveness of HPPQM in the treatment of constipation in rat models and its potential mechanism. METHODS AND RESULTS: UPLC-MS/MS was performed to investigate the chemical component of HPPQM. Rats were randomly divided into normal control, constipation model (CM), HPPQM (low, middle and high dose) and mosapride groups. Loperamide 8 mg/kg was given orally to induce CM. The small intestine motility, colonic contraction, rectum propulsion, and histological feature of the colon were significantly improved in HPPQM group, compared with CM group (P < 0.05). Results of 16S rRNA sequencing revealed that HPPQM treatment strikingly restructured intestinal microbiota in constipated rats by increasing the relative abundances of Bacteroides and Akkermansia and decreasing the relative abundances of Prevotella and Lactobacillus. The levels of GPR43, 5-HT, 5-HT4R, cAMP, PKA were decreased while SERT was increased in constipated rats (P < 0.05), which could be restored to normal levels by treatment with HPPQM (P < 0.05). Differences in amplitude between experimental CLSMs (with HPPQM added) and control CLSMs were discovered, starting at the concentration of 40 nL/mL (P < 0.05). It was found that GLPG0974 and GR113808 could significantly reduce this reactivity (P < 0.05). CONCLUSIONS: HPPQM manifested a curative effect in constipated rats by promoting intestinal motility. The underlying mechanisms might be related to modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

Identification and Functional Prediction of CircRNAs in Leaves of F1 Hybrid Poplars with Different Growth Potential and Their Parents.

Circular RNAs (CircRNAs) regulate plant growth and development; however, their role in poplar heterosis is unclear. We identified 3722 circRNAs in poplar leaves, most of which were intergenic (57.2%) and exonic (40.2%). The expression of circRNAs in F1 hybrids with high growth potential was higher than that in those with low growth potential. Non-additive expression of circRNAs and single-parent expression of circRNAs (SPE-circRNAs) might regulate poplar heterosis through microRNA sponging and protein translation, respectively. DECs among F1 hybrids with different growth potentials might regulate the growth potential of poplar via microRNA sponging. Correlation analysis between circRNA expression and its parent gene expression showed that SPE-M circRNA (circRNAs expressed by male parent only) might regulate poplar heterosis by inhibiting parent gene expression, while other circRNAs might regulate poplar heterosis by enhancing parent gene expression. Weighted correlation network analysis of gene/circRNA expression showed that circRNAs mainly regulate poplar heterosis via carbohydrate metabolism, amino acid metabolism, energy metabolism, and material transport. In addition, we identified seven circRNAs that positively or negatively regulate poplar heterosis. Thus, non-additively expressed circRNAs and SPE circRNAs are involved in regulating poplar heterosis, and DECs among F1 hybrids with different growth potentials were involved in regulating poplar growth potential.

Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm.

BACKGROUND AND PURPOSE: Accumulating evidence indicates that dynamic amplitude of low-frequency fluctuations (dALFF) or dynamic functional connectivity (dFC) can provide complementary information, distinct from static amplitude of low-frequency fluctuations (sALFF) or static functional connectivity (sFC), in detecting brain functional abnormalities in brain diseases. We aimed to examine whether dALFF and dFC can offer valuable information for the detection of functional brain abnormalities in patients with blepharospasm. METHODS: We collected resting-state functional magnetic resonance imaging data from 46 patients each of blepharospasm, hemifacial spasm (HFS), and healthy controls (HCs). We examined intergroup differences in sALFF and dALFF to investigate abnormal regional brain activity in patients with blepharospasm. Based on the dALFF results, we conducted seed-based sFC and dFC analyses to identify static and dynamic connectivity changes in brain networks centered on areas showing abnormal temporal variability of local brain activity in patients with blepharospasm. RESULTS: Compared with HCs, patients with blepharospasm displayed different brain functional change patterns characterized by increased sALFF in the left primary motor cortex (PMC) but increased dALFF variance in the right PMC. However, differences were not found between patients with HFS and HCs. Additionally, patients with blepharospasm exhibited decreased dFC strength, but no change in sFC, between right PMC and ipsilateral cerebellum compared with HCs; these findings were replicated when patients with blepharospasm were compared to those with HFS. CONCLUSIONS: Our findings highlight that dALFF and dFC are complementary to sALFF and sFC and can provide valuable information for detecting brain functional abnormalities in blepharospasm. Blepharospasm may be a network disorder involving the cortico-ponto-cerebello-thalamo-cortical circuit.

Morphological, physiological, and transcriptional responses to low nitrogen stress in Populus deltoides Marsh. clones with contrasting nitrogen use efficiency.

BACKGROUND: Nitrogen (N) is one of the main factors limiting the wood yield in poplar cultivation. Understanding the molecular mechanism of N utilization could play a guiding role in improving the nitrogen use efficiency (NUE) of poplar. RESULTS: In this study, three N-efficient genotypes (A1-A3) and three N-inefficient genotypes (C1-C3) of Populus deltoides were cultured under low N stress (5 µM NH4NO3) and normal N supply (750 µM NH4NO3). The dry matter mass, leaf morphology, and chlorophyll content of both genotypes decreased under N starvation. The low nitrogen adaptation coefficients of the leaves and stems biomass of group A were significantly higher than those of group C (p < 0.05). Interestingly, N starvation induced fine root growth in group A, but not in group C. Next, a detailed time-course analysis of enzyme activities and gene expression in leaves identified 2062 specifically differentially expressed genes (DEGs) in group A and 1118 in group C. Moreover, the sensitivity to N starvation of group A was weak, and DEGs related to hormone signal transduction and stimulus response played an important role in the low N response this group. Weighted gene co-expression network analysis identified genes related to membranes, catalytic activity, enzymatic activity, and response to stresses that might be critical for poplar's adaption to N starvation and these genes participated in the negative regulation of various biological processes. Finally, ten influential hub genes and twelve transcription factors were identified in the response to N starvation. Among them, four hub genes were related to programmed cell death and the defense response, and PodelWRKY18, with high connectivity, was involved in plant signal transduction. The expression of hub genes increased gradually with the extension of low N stress time, and the expression changes in group A were more obvious than those in group C. CONCLUSIONS: Under N starvation, group A showed stronger adaptability and better NUE than group C in terms of morphology and physiology. The discovery of hub genes and transcription factors might provide new information for the analysis of the molecular mechanism of NUE and its improvement in poplar.

Topological Alterations in White Matter Structural Networks in Blepharospasm.

BACKGROUND: Accumulating evidence indicates regional structural changes in the white matter (WM) of brains in patients with blepharospasm (BSP); however, whether large-scale WM structural networks undergo widespread reorganization in these patients remains unclear. OBJECTIVE: We investigated topology changes and global and local features of large-scale WM structural networks in BSP patients compared with hemifacial spasm (HFS) patients or healthy controls (HCs). METHODS: This cross-sectional study applied graph theoretical analysis to assess deterministic diffusion tensor tractography findings in 41 BSP patients, 41 HFS patients, and 41 HCs. WM structural connectivity in 246 cortical and subcortical regions was assessed, and topological parameters of the resulting graphs were calculated. Networks were compared among BSP, HFS, and HCs groups. RESULTS: Compared to HCs, both BSP and HFS patients showed alterations in network integration and segregation characterized by increased global efficiency and modularity and reduced shortest path length. Moreover, increased nodal efficiency in multiple cortical and subcortical regions was found in BSP and HFS patients compared with HCs. However, these differences were not found between BSP and HFS patients. Whereas all participants showed highly similar hub distribution patterns, BSP patients had additional hub regions not present in either HFS patients or HCs, which were located in the primary head and face motor cortex and basal ganglia. CONCLUSIONS: Our findings suggest that the large-scale WM structural network undergoes an extensive reorganization in BSP, probably due to both dystonia-specific abnormalities and facial hyperkinetic movements. © 2021 International Parkinson and Movement Disorder Society.

Prepregnancy BMI, gestational weight gain and risk of childhood atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Maternal weight before and during pregnancy influences the health of offspring. Several observational studies have investigated a link between the risk of childhood atopic dermatitis (AD) and prepregnancy maternal body mass index (BMI) and gestational weight gain (GWG), but the conclusions of these studies were inconsistent. The aim of this review was to evaluate the association between the risk of childhood AD and prepregnancy maternal BMI and GWG. METHODS: The PubMed, Embase, Cochrane, Web of Science, and Scopus databases were searched from inception to February 2, 2021. Observational studies investigating the association between the risk of childhood AD and prepregnancy maternal BMI and GWG were included. Fixed- or random-effects models with inverse variance weights were used to calculate pooled risk estimates. Subgroup analysis and sensitivity analysis were used to explore the sources of heterogeneity. RESULTS: Thirteen studies with a total of 114 485 participants were included. Ten studies reported prepregnancy maternal BMI, and five reported GWG. Maternal underweight was associated with a higher risk of childhood AD (odds ratio [OR] = 1.06; 95% confidence interval [CI], 1.02-1.10). Continuous BMI was not related to childhood AD (OR = 1.00; 95% CI, 0.98-1.02). In comparison with normal GWG, moderate/very high GWG increased the risk of childhood AD (OR = 1.05; 95% CI, 1.02-1.08; OR = 1.13; 95% CI, 1.07-1.19, respectively), while low GWG decreased the risk (OR = 0.92; 95% CI, 0.89-0.96). Excessive GWG relative to recommendations was associated with a higher risk of childhood AD (OR = 1.05; 95% CI, 1.01-1.10), while a lower risk of childhood AD was associated with inadequate GWG relative to recommendations (OR = 0.87, 95% CI: 0.83-0.91). CONCLUSIONS: Maternal underweight, high GWG, and excessive GWG relative to recommendations are associated with an elevated risk of childhood AD, while low GWG and inadequate GWG relative to recommendations decreased the risk. Weight management before and during pregnancy is encouraged for primary prevention of childhood AD.

Risk factors for readmission of children hospitalized with acute asthma attacks in South China.

OBJECTIVE: Asthma seriously endangers the health of children. Re-hospitalization for childhood asthma consumes a large amount of medical and health resources. The present study aimed to assess the rates and risk factors for hospital readmission of children with acute asthma attacks in south China. METHODS: We retrospectively enrolled 1702 acute asthma patients aged < 18 years from 1/1/2007 to 12/31/2015. Patients who were readmitted within one year after index hospital discharge were divided into a readmission group. Index hospitalization data were acquired from clinical records. Chi-square tests and multivariate logistic regression analyses were used to evaluate the risk factors. RESULTS: There were 90 (5.29%) readmitted patients from 1702 acute asthma patients. Considering the large sample differences between readmitted and single-admitted patients, 123 single-admitted patients (1.5-fold as many as the readmitted group) were randomly selected. Further univariate Chi-square tests and multivariate logistic regression analyses showed that the predictors of readmission included eczema history (odds ratio (OR) 3.122, p = 0.003) and mycoplasma pneumoniae (MP) antibody immunoglobulin M(IgM) (OR 2.386, p = 0.037). CONCLUSIONS: Among the children admitted to a hospital in south China with acute asthma attacks, 5.29% were readmitted within the following year. Patients with history of eczema and positive MP antibody IgM had significantly increased the chances of one-year readmission, underlining the importance of targeted long-term postdischarge follow-up of these children.

Elevated Th17 cell frequencies and Th17/Treg ratio are associated with airway hyperresponsiveness in asthmatic children.

Introduction: The elevation of T helper (Th)17 cell frequencies and the imbalance of Th17/regulatory T (Treg) cells occur in asthma pathogenesis. Airway hyperresponsiveness (AHR) is a cardinal feature of asthma, and Th17 responses can promote AHR. We hypothesized that changes in Th17 cells and the Th17/Treg ratio correlate with AHR in asthmatic children.Methods: Twenty asthmatic children and twenty healthy children were included in the study. The peak expiratory flow (PEF) % pred, forced expiratory volume in 1 s (FEV1) % pred and the FEV1/forced vital capacity (FVC) ratio were measured in all subjects. Methacholine challenge test (MCT) was performed in asthmatic children. Flow cytometric analysis was used to determine the proportions of Th17 and Treg cells in peripheral blood mononuclear cells. ELISA was used to assess serum levels of interleukin (IL)-17A and IL-10.Results: Th17 cell frequencies (2.272 ± 0.207% in asthmatics, 1.193 ± 0.131% in controls, P < 0.01) and Th17/Treg ratios (0.371 ± 0.0387 in asthmatics, 0.183 ± 0.020 in controls, P < 0.01) were significantly increased in asthmatic children compared to controls. In asthmatic children, the MCT grade had positive correlations with the Th17 cell frequencies [r = 0.718, P < 0.01], serum IL-17A level [r = 0.753, P < 0.01] and Th17/Treg ratio [r = 0.721, P < 0.01], while the log10PD20-FEV1 value was negatively correlated with the Th17 cell frequencies [r = -0.654, P < 0.01], serum IL-17A level [r = -0.652, P < 0.01] and Th17/Treg ratio [r = -0.625, P < 0.01].Conclusion: Th17 cell, IL-17A and Th17/Treg ratio were positively correlated with AHR in asthmatic children. It may be helpful to monitor Th17 cells and the Th17/Treg ratio as indicators of AHR in clinical practice.

Piper nigrum extract attenuates food allergy by decreasing Th2 cell response and regulating the Th17/Treg balance.

Piper nigrum is extensively utilized because of its antioxidation, antiallergic, antitumor, antiinflammatory, antidiarrhea, and gastrointestinal protection. We attempted to indicate whether the Piper nigrum extract (PNE) could alleviate ovalbumin (OVA)-induced food allergy, and to explore its potential mechanism. An OVA-induced food allergy mouse model was established, and different concentrations of PNE were administrated. Symptoms of food allergy, levels of immunoglobulin E (IgE), mucosal mast cell protease-1 (mMCP-1), and intestine pathological changes were assessed. Additionally, the expressions of T helper (Th) 2, Th17 and regulatory T (Treg)-associated cytokines and the proportion of Th17 and Treg cells in CD4+ T cells were measured. We found PNE attenuated symptoms of food allergy and decreased the levels of IgE and mMCP-1. In PNE group, the infiltration degree of inflammatory cells was ameliorated and the villi of small intestine were more complete. Moreover, the expressions of Th2 and Th17 cell-associated cytokines were down-regulated by PNE pretreatment, while the levels of Treg cell-associated cytokines were up-regulated. PNE decreased the number of Th17 cells, while increased the Tregs cells. PNE treatment dose-dependently improved the Th17/Treg balance. PNE plays a protective role in OVA-induced food allergy through inhibiting Th2 cell response and regulating the Th17/Treg balance.

Comprehensive analysis of the expression profile of circRNAs and their predicted protein-coding ability in the muscle of mdx mice.

Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disease that is characterized by progressive muscle wasting and by defects in the regenerative capacity and inflammatory infiltration of muscle. Many noncoding RNAs (ncRNAs) participate in the pathophysiological mechanisms of this disease. To explore the role of circular RNAs (circRNAs), a type of ncRNAs, in DMD, microarray analysis was performed to explore the expression patterns of circRNAs in the gastrocnemius muscles in mdx mice, a DMD animal model, and C57 mice. The microarray data were validated by qRT-PCR. Further, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the function of the differentially expressed circRNAs (DEcRNAs). A circRNA/microRNA (miRNA) interaction network was predicted by bioinformatics. We also predicted the protein-coding ability of the circRNAs based on their N6-methyladenosine motifs and open-reading frames. We identified 197 differentially expressed circRNAs between mdx mice and C57 mice. Of the 197 DEcRNAs, 6 circRNAs were randomly selected to validate the microarray data, and twenty-two circRNAs were randomly selected to construct a circRNA/miRNA interaction network. Bioinformatics analysis showed that the linear counterparts of the DEcRNAs were mainly associated with muscle structure, nervous system development, and the cAMP signaling pathway. A total of 189 circRNAs were predicted to have protein-coding potential, and there were 98 circRNAs that could potentially be translated into polypeptides with 150 or more amino acids. This work described the expression pattern of circRNAs in mdx mice and indicated that circRNAs may play pivotal roles in the pathophysiological mechanisms of DMD.

Contribution of excess inflammation to a possible rat model of eclamptic reversible posterior leukoencephalopathy syndrome induced by lipopolysaccharide and pentylenetetrazol: A preliminary study.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical-imaging syndrome as well as a critical maternal complication. The precise pathophysiological mechanism remains controversial, mostly due to the lack of a reliable experimental animal model. Because women with eclampsia almost always present with RPLS as a complication, we hypothesize that seizures induced by preeclampsia may lead to RPLS in rats. METHODS: Pregnant Sprague-Dawley rats received pentylenetetrazol (PTZ, 40 mg/kg, intraperitoneal injection) after lipopolysaccharide (LPS, 1 µg/kg, tail vein injection) to induce eclampsia-like seizures. An anatomical view and brain water content were used to ascertain the success of the model. Moreover, blood pressure, serum biochemical indicators, serum and cerebrospinal fluid (CSF) inflammatory factors, neuroinflammation markers (Iba-1 for microglia and GFAP for astrocytes by immunofluorescence) and blood brain barrier (BBB) injury markers (VE-cadherin and ZO-1 protein by Western blotting) were measured to determine the possible mechanism. RESULTS: The rat cerebral cortex was congested and oedematous, and water contents were significantly higher following LPS and PTZ treatments. Additionally, the BP, serum and CSF inflammatory factors and neuroinflammation markers were significantly elevated, while the expression levels of VE-cadherin and ZO-1 protein were significantly decreased by LPS and PTZ treatments. CONCLUSIONS: Excess inflammation may account for the phenotypes observed in this possible eclamptic RPLS rat model induced by LPS and PTZ, providing a better understanding of mechanism of RPLS. Specifically, excess inflammation leads to BBB dysfunction and subsequently results in fluid leakage that causes lesions and increases the entrance of inflammatory factors into the brain, thus increasing the neuronal excitability that triggers seizures.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.