Interactive effects of chronic ocean acidification and warming on the growth, survival, and physiological responses of adults of the temperate sea urchin Strongylocentrotusintermedius.

To investigate the interactive effects of chronic ocean acidification and warming (OAW) on the growth, survival, and physiological responses of sea urchins, adults of the temperate sea urchin Strongylocentrotus intermedius were incubated separately/jointly in acidic (ΔpHNBS = -0.5 units) and thermal (ΔT = +3.0 °C) seawater for 120 days under lab-controlled conditions based on the projected ocean pH and temperature for 2100 put forward by the Intergovernmental Panel on Climate Change (IPCC). Survival rate (SR), average food consumption rate (FCR), gut index (GuI), specific growth rate (SGR), digestive capability, energy production, and antioxidant capability were subsequently determined. The results showed that 1) the SR, FCR, GuI and SGR decreased sharply under OAW conditions. Significant interactive effects of OAW on SR and SGR were observed at 120 days post-incubation (dpi), and on FCR this occurred at 90 dpi. 2) OAW altered the activities of both digestive and antioxidant enzymes. There were significant interaction effects of OAW on the activities of amylase, trehalase, and superoxide dismutase. 3) The relative gene expression levels and activities of key enzymes involved in glycometabolism pathways (i.e., glycolysis and the tricarboxylic acid cycle) were significantly affected by OAW, resulting in an alteration of the total ATP content in the sea urchins. Interaction effects of OAW were observed in both relative gene expression and the activity of enzymes involved in glycolysis (hexokinase), the transformation of glycolysis end-products (lactate dehydrogenase), the tricarboxylic acid cycle (citrate synthetase), and ATP production (Na+/K+-ATPase). The data from this study will enrich our knowledge concerning the combined effects of global climate change on the survival, growth, and physiological responses of echinoderms.

The intention of college students to use electronic cigarettes: A study based on the theory of innovation diffusion.

INTRODUCTION: The purpose of this study is to examine the use of electronic cigarettes (e-cigarettes) among college students in Hangzhou, and to analyze the influencing factors of their intention to use e-cigarettes. METHODS: Using a stratified cluster sampling method, 775 students from two universities in Hangzhou were selected for an on-site questionnaire survey from March to April 2022. Adjusted logistic regression analysis was conducted on the influencing factors of use intention, based on innovation diffusion theory. RESULTS: Within our sample of college students, 16.5% of students had tried e-cigarettes; 6.32% had used e-cigarettes in the past month, and 8.0% had the intention to use e-cigarettes. There were significant differences in willingness to use e-cigarettes among different genders, economic status, smoking status of close friends around them, and their own use of tobacco and alcohol (p<0.05). The logistic regression model showed that the observability of e-cigarettes (AOR=1.28; p<0.05), personal factors (AOR=1.39; p<0.05), and social systems (AOR=1.63; p<0.05), were all influencing factors of intention to use e-cigarettes. CONCLUSIONS: College students in Hangzhou have a high intention to use e-cigarettes, and the impacts of the product itself, individual characteristics and the living environment are crucial. It is necessary to strengthen the promotion of tobacco knowledge at the social and family levels to reduce the occurrence of vaping.

Insulin resistance-related features are associated with cognitive decline: a cross-sectional study in adult patients with type 1 diabetes.

BACKGROUND: To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D). METHODS: A total of 117 adult patients with T1D were recruited in this cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis. RESULTS: A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance. CONCLUSIONS: We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function. TRIAL REGISTRATION: ClinicalTrials.gov NCT03610984.

Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor ß.

BACKGROUND: Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma. OBJECTIVE: This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma. METHODS: In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRß-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRß-siRNA and detected cell proliferation and migration. The expression of GRß and key components of MKP-1 and Erk1/2 were detected by western blotting. RESULTS: In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRß expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair. CONCLUSIONS: Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRß expression and activating the MAPK pathway.

Photoinduced Biomimetic Room-Temperature C-O Bond Cleavage over Mn Doped CdS.

Selective C-O bond cleavage is an efficient way for the biomass valorization to value-added chemicals, but is challenged to be operated at room temperature via conventional thermal catalysis. Herein, inspired from the DNA biosynthesis which involves a radical-mediated spin-center shift (SCS) C-O bond cleavage process, we report a biomimetic room-temperature C-O bond cleavage of vicinal diol (HOCHCH-OH). We construct a Mn doped CdS (Mn/CdS) as a photocatalyst to mimic the biologic SCS process. The Mn site plays pivotal role: (1) accelerates the photo-induced carrier separation, promoting the hole-mediated C-H bond cleavage to generate carbon-centered radicals, and (2) serves as the binding site for -OH groups, making it to be an easier leaving group. Mn/CdS achieves 0.28 mmol gcat -1 h-1 of hydroxyacetone (HA) from glycerol dehydration at room temperature under visible light irradiation, which is 3.5-fold that over pristine CdS and 40-fold that over bulk MnS/CdS. This study provides a new biomimetic room-temperature C-O bond cleavage process, which is promising for the biomass valorization.

Epidemiology and genetic diversity of norovirus GII genogroups among children in Hubei, China, 2017-2019.

Norovirus (NoV) is an important cause of viral acute gastroenteritis (AGE). To gain insights into the epidemiological characteristics and genetic diversity of NoV among children in Hubei, 1216 stool samples from children (≤ 5 years) obtained under AGE surveillance from January 2017 to December 2019 were analyzed. The results showed that NoV was responsible for 14.64% of AGE cases, with the highest detection rate in children aged 7-12 months (19.76%). Statistically significant differences were found between male and female infection rates (χ2 â€‹= â€‹8.108, P â€‹= â€‹0.004). Genetic analysis of RdRp and VP1 sequences showed that NoV GII genotypes were GII.4 Sydney [P31] (34.35%), GII.3 [P12] (25.95%), GII.2 [P16] (22.90%), GII.4 Sydney [P16] (12.98%), GII.17 [P17] (2.29%), GII.6 [P7] and GII.3 [P16] (each at 0.76%). GII.17 [P17] variants were divided into the Kawasaki323-like lineage and the Kawasaki308-like lineage. A unique recombination event was detected between strains of GII.4 Sydney 2012 and GII.4 Sydney 2016. Significantly, all GII.P16 sequences associated with GII.4/GII.2 obtained in Hubei were correlated with novel GII.2 [P16] variants that re-emerged in Germany in 2016. Antigenic site analysis of complete VP1 sequences from all GII.4 variants from Hubei identified notable variable residues of antibody epitopes. Genotyping under continuous AGE surveillance and observation of the antigenic sites of VP1 are important monitoring strategies for emerging NoV strains.

Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population.

OBJECTIVE: Gastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population. METHODS: A total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package "cluster profile". RESULTS: The TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35-0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06-2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19-0.94, p = 0.034). CONCLUSION: Our results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.

Cognitive function and neuroimaging characteristics in patients with childhood-onset type 1 diabetes mellitus.

AIMS: In this study, we used neuropsychological tests and neuroimaging to examine the cognitive functions and neuroimaging characteristics to explore the brain mechanism of cognitive deficits in patients with childhood-onset type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: A total of 30 patients with childhood-onset T1DM and 28 healthy controls (HC) participated in the study. Neuropsychological tests were used to assess intelligence quotient, memory, and executive function. Voxel-based morphometry-diffeomorphic anatomical registration through exponential lie algebra analysis and amplitude of low-frequent fluctuation (ALFF) were performed to evaluate the brain grey matter volume and neural spontaneous activity for each participant. RESULTS: Compared with HC, patients with childhood-onset T1DM showed a significant decline in verbal memory (p = 0.001) and visual memory (p = 0.002). Patients with T1DM had smaller grey matter volumes at the midbrain, thalamus, and cerebellar culmen. They demonstrated an increased ALFF value in the left precentral gyrus, left postcentral gyrus, left insula, and left supramarginal gyrus and a decreased ALFF value in the basal ganglia (putamen nucleus), right insula, right superior temporal gyrus, and cerebellar posterior lobe than the healthy control group. In the T1DM group, the ALFF value in the right insula was positively related to the verbal memory scores (r = 0.423, p = 0.025). CONCLUSIONS: Childhood-onset T1DM was associated with cognitive deficits and changes in brain structure and function. These findings suggest that the brain structural and functional alterations in these regions may be the neuropathology of cognitive deficits in patients with T1DM.

Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation.

BACKGROUND: The Brg1 (Brahma-related gene 1) is an important chromatin remodeling factor protein. The Brg1 protein can promote the transcriptional activation or inhibit target genes through regulating ATP hydrolysis which rearranges the nucleosomes position and the histone DNA interaction. In this study, we explored the role of Brg1 in house dust mite (HDM) stimulated airway inflammation. METHODS: The wild-type C57BL/6 mice (wild-type, WT) and alveolar epithelial cells specifically knockout Brg1 mice (Brg1fl/fl) were selected as the experimental subjects. HDM was used to stimulate human bronchial epithelial cells (16HBE) to construct an model of airway inflammation in vitro. The asthma group was established with HDM, and the control group was treated with normal saline. Wright's staining for the detection of differential counts of inflammatory cells in bronchoalveolar lavage fluid (BALF). Invasive lung function was used to assess the airway compliance. Hematoxylin and eosin (HE) staining and periodic acid-schiff (PAS) staining were used to detect mucus secretion. Immunohistochemistry was used to measure mucin glycoprotein 5AC (MUC5AC) protein expression in airway epithelium. Western blotting was used to detect the MUC5AC and JAK1/2-STAT6 proteins in mouse lung tissues and 16HBE cells. Co-immunoprecipitation (Co-IP) and Chromatin Immunoprecipitation (CHIP) were used to detect whether Brg1 could regulate the JAK1/2-STAT6 signaling pathway. RESULTS: The airway inflammation, pulmonary ventilation resistance, airway mucus secretion, MUC5AC and IL-13 in BALF and MUC5AC protein expression in lung tissue of Brg1 knockout mice stimulated by HDM were lower than those of wild-type mice. The expression of MUC5AC protein in HDM stimulated Brg1 knockdown 16HBE cells was significantly lower than that in the control group. In vivo and in vitro, it was found that the activation of JAK1/2-STAT6 signal pathway in mouse lung tissue or 16HBE cells was inhibited after knockdown of Brg1 gene. The Co-IP and CHIP results showed that Brg1 could bind to the JAK1/2 promoter region and regulate the expression of JAK1/2 gene. CONCLUSION: The Brg1 may promote the secretion of airway mucus stimulated by HDM through regulating the JAK1/2-STAT6 pathway. Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation.

Sleep quality and subjective well-being in healthcare students: examining the role of anxiety and depression.

Objective: Sleep issues, negative emotions, and health conditions are commonly co-occurring, whereas their associations among healthcare students have yet to be elucidated. This study aimed to examine whether anxiety and depression mediate the relationship between sleep quality and subjective well-being in healthcare students. Methods: A cross-sectional survey was conducted among Chinese healthcare students (N = 348). A battery of paper-and-pencil questionnaires-the Sleep Quality Questionnaire (SQQ), World Health Organization-Five Well-Being Index (WHO-5), and Patient Health Questionnaire-4 (PHQ-4) were applied. Descriptive analysis with means (standard deviations) and counts (proportions), Spearman correlation analysis between the SQQ, WHO-5, and PHQ-4, and mediation analysis via structural equation models were performed. Results: Correlation analysis revealed statistically significant associations between sleep quality, anxiety and depression, and well-being among healthcare students. Mediation analysis identified that poor sleep quality produced relatively low levels of self-reported well-being, which were entirely attributable to anxiety and depression. Conclusion: Sleep quality was associated with subjective well-being, and this interrelationship was fully mediated by anxiety and depression. Interventions aimed at promoting sleep quality of healthcare students may contribute to promoting their well-being by reducing anxiety and depression.

Potassium Salt Coordination Induced Ion Migration Inhibition and Defect Passivation for High-Efficiency Perovskite Solar Cells.

The disordered distribution of trap states and ion migration limit the commercial application of perovskite solar cells (PSCs). Herein, we apply an oxamic acid potassium salt (OAPS) as a bifunctional additive of perovskite film. The Lewis base group C=O of OAPS can interact with the uncoordinated Pb2+ caused by the I site substitution by Pb and the dangling bonds of the perovskite, which is beneficial to reduce the nonradiative recombination loss. In addition, the countercation K+ of OAPS is confirmed to occupy the perovskite lattice interstitial sites and result in lattice expansion, inhibiting the formation of iodide Frenkel defects and I- ion migration. As a result, the synergistic effect achieves enhanced power conversion efficiency (PCE) from 19.98 to 23.02%, with a fill factor reaching up to 81.90% and suppressed current-voltage hysteresis. The device also presents improved stability, maintaining 93% of the initial PCE after 2000 h of storage.

Modeling lung diseases using reversibly immortalized mouse pulmonary alveolar type 2 cells (imPAC2).

BACKGROUND: A healthy alveolar epithelium is critical to the gas exchange function of the lungs. As the major cell type of alveolar epithelium, alveolar type 2 (AT2) cells play a critical role in maintaining pulmonary homeostasis by serving as alveolar progenitors during lung injury, inflammation, and repair. Dysregulation of AT2 cells may lead to the development of acute and chronic lung diseases and cancer. The lack of clinically relevant AT2 cell models hampers our ability to understand pulmonary diseases. Here, we sought to establish reversibly immortalized mouse pulmonary alveolar type 2 cells (imPAC2) and investigate their potential in forming alveolar organoids to model pulmonary diseases. METHODS: Primary mouse pulmonary alveolar cells (mPACs) were isolated and immortalized with a retroviral expression of SV40 Large T antigen (LTA). Cell proliferation and survival was assessed by crystal violet staining and WST-1 assays. Marker gene expression was assessed by qPCR, Western blotting, and/or immunostaining. Alveolar organoids were generated by using matrigel. Ad-TGF-ß1 was used to transiently express TGF-ß1. Stable silencing ß-catenin or overexpression of mutant KRAS and TP53 was accomplished by using retroviral vectors. Subcutaneous cell implantations were carried out in athymic nude mice. The retrieved tissue masses were subjected to H & E histologic evaluation. RESULTS: We immortalized primary mPACs with SV40 LTA to yield the imPACs that were non-tumorigenic and maintained long-term proliferative activity that was reversible by FLP-mediated removal of SV40 LTA. The EpCAM+ AT2-enriched subpopulation (i.e., imPAC2) was sorted out from the imPACs, and was shown to express AT2 markers and form alveolar organoids. Functionally, silencing ß-catenin decreased the expression of AT2 markers in imPAC2 cells, while TGF-ß1 induced fibrosis-like response by regulating the expression of epithelial-mesenchymal transition markers in the imPAC2 cells. Lastly, concurrent expression of oncogenic KRAS and mutant TP53 rendered the imPAC2 cells a tumor-like phenotype and activated lung cancer-associated pathways. Collectively, our results suggest that the imPAC2 cells may faithfully represent AT2 populations that can be further explored to model pulmonary diseases.

Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Type II Cell Proliferation and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia.

Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

Hypoxic preconditioning improves the survival and pro-angiogenic capacity of transplanted human umbilical cord mesenchymal stem cells via HIF-1α signaling in a rat model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic respiratory disease that predominates in the neonatal period. Currently, efficacious and effective specific treatments are lacking. Mesenchymal stem cells (MSCs) transplantation has emerged as a promising option for treating BPD. However, the lower cell survival rate limits its therapeutic efficacy. Hypoxic preconditioning is a direct and effective strategy for promoting MSCs survival, proliferation, and paracrine secretion in the recipient after transplantation, which is greatly important to tissue engineering. We investigated whether hypoxia-pretreated MSCs (HPMSCs) confer superior benefit in an experimental BPD rat model. Neonatal Sprague-Dawley rats were exposed to 80-85% O2 for 14 days. Before tracheal transplantation, the MSCs were pretreated for 48 h with deferoxamine, a chemical hypoxia-mimicking agent. In vitro, the HPMSCs reduced the apoptosis rare, caspase-3 expression, and reactive oxygen species (ROS) generation and promoted proliferation, hypoxia inducible factor-1α (HIF-1α) expression, VEGF secretion, and human umbilical vein endothelial cell tube formation (p < 0.05). In vivo, the HPMSCs restored alveolar structure and lung function, ameliorated pulmonary hypertension, increased vessel density in the BPD rat model (p < 0.05). This work demonstrates for the first time that HPMSCs could have a markedly improved therapeutic effect in BPD, presenting a new potential strategy for the clinical implementation of stem cell biotechnology.

Drastic decline in sera neutralization against SARS-CoV-2 Omicron variant in Wuhan COVID-19 convalescents.

Global concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.529). So far, the infection features and immune escape ability of the Omicron variant have not been extensively studied. Here, we produced the Omicron pseudovirus and compared its entry, membrane fusion, and immune escape efficiency with the original strain and the dominating Delta variant. We found the Omicron variant showed slightly higher infectivity than the Delta variant and a similar ability to compete with the Delta variant in using Angiotensin-converting enzyme 2 (ACE2) in a BHK21-ACE2 cell line. However, the Omicron showed a significantly reduced fusogenicity than the original strain and the Delta variant in both BHK21-ACE2 and Vero-E6 cells. The neutralization assay testing the Wuhan convalescents' sera one-year post-infection showed a more dramatic reduction (10.15 fold) of neutralization against the Omicron variant than the Delta variant (1.79 fold) compared with the original strain with D614G. Notably, immune-boosting through three vaccine shots significantly improved the convalescents' immunity against the Omicron variants. Our results reveal a reduced fusogenicity and a striking immune escape ability of the Omicron variant, highlighting the importance of booster shots against the challenge of the SARS-CoV-2 antigenic drift.

Enhanced Activation Energy Released by Coordination of Bifunctional Lewis Base d-Tryptophan for Highly Efficient and Stable Perovskite Solar Cells.

Perovskite defect passivation with molecule doping shows great potential in boosting the efficiency and stability of perovskite solar cells (PSCs). Herein, an efficient and low-cost bifunctional Lewis base additive d-tryptophan is introduced to control the crystallization and growth of perovskite grains and passivation defects. It is found that the additive doped in the solution precursors could retard crystal growth by increasing activation energy, resulting in improved crystallization of large grains with reduced grain boundaries, as well as inhibiting ion migration and PbI2 aggregation. As a result, the PSCs incorporated with d-tryptophan additives achieve an improved power conversion efficiency from 18.18 to 21.55%. Moreover, the d-tryptophan passivation agent improves the device stability, which retains 86.85% of its initial efficiency under ambient conditions at room temperature after 500 h. This work provides Lewis base small-molecule d-tryptophan for efficient defect passivation of the grain boundaries toward efficient and stable PSCs.

Sustained Attention Deficits in Adults With Juvenile-Onset Type 1 Diabetes Mellitus.

OBJECTIVE: This study aimed to investigate whether patients with juvenile-onset type 1 diabetes mellitus (T1DM) have poorer sustained attention than their counterparts with adult-onset T1DM, and whether there is a relationship between diabetes-related variables and sustained attention. METHODS: This study included 76 participants with juvenile-onset T1DM, 68 participants with adult-onset T1DM, and 85 healthy controls (HCs). All participants completed the Sustained Attention to Response Task, Beck Depression Inventory-II, and the Chinese version of the Wechsler Adult Intelligence Scale. RESULTS: The juvenile-onset group showed more omission errors (p = .007) than the adult-onset group and shorter reaction time (p = .005) than HCs, whereas the adult-onset group showed no significant differences compared with HCs. Hierarchical linear regression analysis revealed that the age of onset was associated with omission errors in T1DM participants (ß = -0.275, t = -2.002, p = .047). In the juvenile-onset group, the omission error rate were associated with the history of severe hypoglycemia (ß = 0.225, t = 1.996, p = .050), whereas reaction time was associated with the age of onset (ß = -0.251, t = -2.271, p = .026). Fasting blood glucose levels were significantly associated with reaction time in both the juvenile-onset and adult-onset groups (ß = -0.236, t = -2.117, p = .038, and ß = 0.259, t = 2.041, p = .046, respectively). CONCLUSIONS: Adults with juvenile-onset T1DM have sustained attention deficits in contrast to their adult-onset counterparts, suggesting that the disease adversely affects the developing brain. Both the history of severe hypoglycemia and fasting blood glucose levels are factors associated with sustained attention impairment. Early diagnosis and treatment in juvenile patients are required to prevent the detrimental effects of diabetes.

Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.

GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.

GITRL on dendritic cells aggravates house dust mite-induced airway inflammation and airway hyperresponsiveness by modulating CD4+ T cell differentiation.

BACKGROUND: Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. METHODS: In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. RESULTS: GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. CONCLUSIONS: This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Transformation of Microbial Negative Correlations into Positive Correlations by Saccharomyces cerevisiae Inoculation during Pomegranate Wine Fermentation.

The application of starter is a common practice to accelerate and steer the pomegranate wine fermentation process. However, the use of starter needs a better understanding of the effect of the interaction between the starter and native microorganisms during alcoholic fermentation. In this study, high-throughput sequencing combined with metabolite analysis was applied to analyze the effect of commercial Saccharomyces cerevisiae inoculation on the native fungal community interaction and metabolism during pomegranate wine fermentation. Results showed that there were diverse native fungi in pomegranate juice, including Hanseniaspora uvarum, Hanseniaspora valbyensis, S. cerevisiae, Pichia terricola, and Candida diversa Based on ecological network analysis, we found that S. cerevisiae inoculation transformed the negative correlations into positive correlations among the native fungal communities and decreased the Granger causalities between native yeasts and volatile organic compounds. This might lead to decreased contents of isobutanol, isoamylol, octanoic acid, decanoic acid, ethyl laurate, ethyl acetate, ethyl hexadecanoate, phenethyl acetate, and 2-phenylethanol during fermentation. This study combined correlation and causality analysis to gain a more integrated understanding of microbial interaction and the fermentation process. It provided a new strategy to predict certain behaviors between inoculated and selected microorganisms and those coming directly from the fruit.IMPORTANCE Microbial interactions play an important role in flavor metabolism during traditional food and beverage fermentation. However, we understand little about how selected starters influence interactions among native microorganisms. In this study, we found that S. cerevisiae inoculation changed the interactions and metabolisms of native fungal communities during pomegranate wine fermentation. This study not only suggests that starter inoculation should take into account the positive features of starters but also characterizes the microbial interactions established among the starters and the native communities. It may be helpful to select appropriate starter cultures for winemakers to design different styles of wine.