The relationship between postpartum negative life events and postpartum depression: a moderated mediation model of neuroticism and psychological flexibility.

BACKGROUND: Postpartum depression (PPD) is a major public health problem worldwide. Previous studies have shown that postpartum negative life events and neuroticism are both important risk factors for PPD. However, few studies have considered the role of protective factors in the influence of postpartum negative life events and neuroticism on PPD. Based on the diathesis-stress model and Acceptance and Commitment Therapy (ACT), a moderated mediating model was established to examine the mediating role of neuroticism between postpartum negative life events and PPD, as well as the moderating role of psychological flexibility in this mediating effect. METHODS: A sample of 776 parturients from three different Grade A hospitals in China were assessed using the Edinburgh Postpartum Depression Scale, the Postpartum Negative Life Events Scale, the Neuroticism Subscale of the Big Five Personality Scale, and the Acceptance and Action Questionnaire- II. RESULTS: PPD, postpartum negative life events, neuroticism, and experiential avoidance were significantly positively correlated with one another. Neuroticism partially mediated the relationship between postpartum negative life events and PPD. In this mediation model, the direct path and the second half of the mediation path were moderated by psychological flexibility. Specifically, the links between postpartum negative life events and PPD, as well as between neuroticism and PPD, were stronger when psychological flexibility was low, but weaker when psychological flexibility was high. CONCLUSIONS: The results show that psychological flexibility plays an important role in buffering the negative effects of postpartum negative life events and neuroticism on PPD. These findings provide implications for the prevention and intervention of PPD using an ACT approach.

Long Chain Non Coding RNA Targeting miR Signal Axis Regulates the Mechanism of Apoptosis and Invasion and Migration of Glioma U251 Cells.

The occurrence of glioma is gradually promoted by various factors, and it has gone through multiple stages of development, involving abnormal expression of multiple genes. One of the important reasons for the development of gliomas is the interaction of genetic factors and the environment. Non-coding transcripts can also form this high-level structure, and the formation of binding sites for interactions between lncRNA and proteins, DNA, and other RNA molecules may be related to their structural diversity. Due to the importance of glioma-related research and the potential effectiveness of lncRNA, this paper focuses on the mechanism of long-chain non-coding RNA targeting the Mir signal axis to regulate apoptosis, invasion and migration of glioma U251 cells. In this paper, human glioma cell line U251 was used as experimental material for simulation analysis. The results showed that after miR simulation, the pass rate of U251 stem cells through the filter was 17.3%, which was significantly less than 85.4% of group C; compared with 77.6% of the negative control group, the cell penetration rate of the miR inhibitor group was significantly improved. 92.5%. The miR expression level can affect the invasion ability of U251 stem cells, and can negatively regulate the expression of fzd4 to inhibit the invasion and metastasis of glioma U251 cells.

Temperature-dependent kinetics of the atmospheric reaction between CH2OO and acetone.

Criegee intermediates are important oxidants produced in the ozonolysis of alkenes in the atmosphere. Quantitative kinetics of the reactions of Criegee intermediates are required for atmospheric modeling. However, the experimental studies do not cover the full relevant range of temperature and pressure. Here we report the quantitative kinetics of CH2OO + CH3C(O)CH3 by using our recently developed dual strategy that combines coupled cluster theory with high excitation levels for conventional transition state theory and well validated levels of density functional theory for direct dynamics calculations using canonical variational transition theory including tunneling. We find that the W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ electronic structure method can be used to obtain quantitative kinetics of the CH2OO + CH3C(O)CH3 reaction. Whereas previous investigations considered a one-step mechanistic pathway, we find that the CH2OO + CH3C(O)CH3 reaction occurs in a stepwise manner. This has implications for the modeling of Criegee-intermediate reactions with other ketones and with aldehydes. In the kinetics calculations, we show that recrossing effects of the conventional transition state are negligible for determining the rate constant of CH2OO + CH3C(O)CH3. The present findings reveal that the rate ratio between CH2OO + CH3C(O)CH3 and OH + CH3C(O)CH3 has a significant negative dependence on temperature such that the CH2OO + CH3C(O)CH3 reaction can contribute as a significant sink for atmospheric CH3C(O)CH3 at low temperature. The present findings should have broad implications in understanding the reactions of Criegee intermediates with carbonyl compounds and ketones in the atmosphere.

METTL7B contributes to the malignant progression of glioblastoma by inhibiting EGR1 expression.

Glioblastoma (GBM), a predominant central nervous system (CNS) malignancy, is correlated with high mortality and severe morbidity. Mammalian methyltransferase-like 7B (METTL7B) as a methyltransferase has been identified to participate in cancer progression. However, its function in GBM is elusive. Accordingly, we aimed to explore the effect of METTL7B on GBM. The expression of METTL7B and EGR2 in GBM patients and GBM cells were detected by qPCR, western blots and immunohistochemical staining. Cell viability was assessed by CCK-8 assays. Cell proliferation was determined by EdU, colony formation, and tumor sphere formation assays. METTL7B shRNA was injected into the Balb/c nude mice. The size and weight of isolated tumor was measured. And the expression levels of Ki67, METTL7B and EGR1 were examined by immunohistochemical staining. METTL7B was significantly elevated, while EGR1 was downregulated in clinical GBM tissues. METTL7B upregulation was associated with the low overall survival of GBM patients. Moreover, METTL7B depletion remarkably attenuated GBM cell proliferation. Mechanistically, METTL7B overexpression inhibited EGR1 expression in GBM cells. EGR1 knockdown rescued the inhibitory effect of METTL7B depletion on GBM cell proliferation. Meanwhile, METTL7B depletion arrested more GBM cells at the G0/G1, but fewer cells at the S phase, which EGR1 knockdown reversed these effects. Furthermore, tumorigenicity analysis revealed that METTL7B promotes tumor growth of GBM cells in vivo. METTL7B contributes to the malignant progression of GBM by inhibiting EGR1 expression. METTL7B and EGR1 may be utilized as the treatment targets for GBM therapy.

Culturable Endophytes Diversity Isolated from Paeonia ostii and the Genetic Basis for Their Bioactivity.

Paeonia ostii is known for its excellent medicinal values as Chinese traditional plant. To date, the diversity of culturable endophytes associated with P. ostii is in its initial phase of exploration. In this study, 56 endophytic bacteria and 51 endophytic fungi were isolated from P. ostii roots in China. Subsequent characterization of 56 bacterial strains by 16S rDNA gene sequence analysis revealed that nine families and 13 different genera were represented. All the fungal strains were classed into six families and 12 genera based on ITS gene sequence. The biosynthetic potential of all the endophytes was further investigated by the detection of putative polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes. The PCR screens were successful in targeting thirteen bacterial PKS, five bacterial NRPS, ten fungal PKS and nine fungal NRPS gene fragments. Bioinformatic analysis of these detected endophyte gene fragments facilitated inference of the potential bioactivity of endophyte bioactive products, suggesting that the isolated endophytes are capable of producing a plethora of secondary metabolites. These results suggest that endophytes isolated from P. ostii had abundant population diversity and biosynthetic potential, which further proved that endophytes are valuable reservoirs of novel bioactive compounds.Paeonia ostii is known for its excellent medicinal values as Chinese traditional plant. To date, the diversity of culturable endophytes associated with P. ostii is in its initial phase of exploration. In this study, 56 endophytic bacteria and 51 endophytic fungi were isolated from P. ostii roots in China. Subsequent characterization of 56 bacterial strains by 16S rDNA gene sequence analysis revealed that nine families and 13 different genera were represented. All the fungal strains were classed into six families and 12 genera based on ITS gene sequence. The biosynthetic potential of all the endophytes was further investigated by the detection of putative polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes. The PCR screens were successful in targeting thirteen bacterial PKS, five bacterial NRPS, ten fungal PKS and nine fungal NRPS gene fragments. Bioinformatic analysis of these detected endophyte gene fragments facilitated inference of the potential bioactivity of endophyte bioactive products, suggesting that the isolated endophytes are capable of producing a plethora of secondary metabolites. These results suggest that endophytes isolated from P. ostii had abundant population diversity and biosynthetic potential, which further proved that endophytes are valuable reservoirs of novel bioactive compounds.

Role of Micronutrients on Dyeing Wastewater Treatment in Activated Sludge Process.

Adequate individual supplements of Zn, Co and Mo increased chemical oxygen demand (COD) removal and specific oxygen uptake rates during activated sludge treatment of dyeing wastewater, while overdoses of micronutrients can decrease metabolic rates. The effects of combing Zn, Co, and Mo at different doses were investigated using response surface methodology, with a second order polynomial equation: Y = 78.19+ 0.17X1 + 37.33 X2 + 20.20X3 - 5.58X1X2 - 63.05 X2X3, where Y means COD removal rate (%), X1 means Co concentration, X2 means Zn concentration, X3 means Mo concentration. The maximum COD removal efficiency of 89.41% was achieved with doses of 0.02 mg/L Co, 0.24 mg/L Zn and 0.45 mg/L Mo. Both the combinations of Zn-Co and Zn-Mo acted antagonistically for COD removal efficiency, and the combination of Co-Mo was negligible to COD removal efficiency. Doses of micronutrients, particularly Zn, Co and Mo, were beneficial for microbial shift towards Planctomyces and Bacteroidetes.

[miR-200b suppresses glioma cell invasion by targeting PROM1].

OBJECTIVE: To explore whether miR-200b suppresses tumor cell invasion by targeting PROM1, thus to reveal the molecular mechanism that miR-200b functions as a tumor suppressor in glioma. METHODS: PROM1 3'UTR-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-200b on luciferase activity. Human glioblastoma U87 cells were transfected with miR-200b mimics, and next qRT-PCR and Western blotting were performed to detect the expressions of PROM1 mRNA and protein. The effect of PROM1 down-regulation on invasion was observed after PROM1 siRNA were transfected into U87 cells. RESULTS: The miR-200b bound to the 3'-untranslated region (UTR) of PROM1 and inhibited the luciferase activity. Its luciferase activity was down-regulated by 57.0% (P < 0.01). PROM1 protein and mRNA expressions were significantly down-regulated when miR-200b was overexpressed in the U87 cells (P < 0.05). siRNA-mediated down-regulation of PROM1 suppressed the potential of cell invasion. The invasion ability of SKOV3 cells after transfection with siRNA-PROM1 was significantly lower than that in the negative control cells (P < 0.05). CONCLUSION: miR-200b may suppress cell invasion by targeting PROM1 in glioma.

MicroRNA218 inhibits glioma migration and invasion via inhibiting glioma-associated oncogene homolog 1 expression at N terminus.

Glioma is characterized by high invasion, migration and proliferation abilities. However, the molecular mechanism that triggers the development and recurrence of this tumor is also elusive. This study aims to investigate the biological function and molecular mechanism of microRNA218 in glioma. Human glioma samples were obtained and employed to investigate the correlation between microRNA218 and glioma pathological grading. Glioma cell viability was detected by the cell-counting kit-8 (CCK-8) cell counting assay. Transwell assay and wound-healing assay were employed to examine the migration and invasion of the glioma cells. The mRNA transcription and protein expression of glioma-associated oncogene homolog 1 (GLI1) were analyzed by quantitative RT-PCR and Western blot analysis, respectively. Southwestern blot assay was utilized to explore the possible interaction site of GLI1 and microRNA218. The results indicated that microRNA218 is significantly down-regulated in glioma samples and negatively correlated with the pathological grading. The cell viability was significantly decreased, and migration and invasion were significantly inhibited in microRNA218 treated cells, compared with un-treated cells. GLI1 was discovered acting as a functional downstream target of microRNA218, by which microRNA218 inhibited glioma cell migration and invasion. Southwestern blot result showed that microRNA218 targeted directly the N terminus of GLI1 molecular, and repressed the GLI1 expression in U87MG cells. In conclusion, microRNA218 could reduce the invasion and migration, and inhibit proliferation of glioma cells by suppressing the expression of GLI1 protein at the interacting with the N terminus.

The effect of childhood sexual abuse on depressive symptoms in female college students: a serial mediation model.

Objective: Childhood sexual abuse (CSA) can have a negative impact on women's psychological, emotional and social functioning. The purpose of this study was to explore the relationship between CSA and depressive symptoms in female college students, as well as the mediating roles of negative core schema and experiential avoidance. Methods: 515 female college students responded to the Sexual Abuse subscale of the Childhood Trauma Questionnaire, the Depression subscale of the Depression Anxiety Stress Scale, the Brief Core Schema Scales, and the Acceptance and Action Questionnaire - II. The structural equation modeling was used for the mediation analysis. Results: There was a significant positive correlation between CSA and depressive symptoms in female college students. The theoretical model was well fitted, χ2/df = 3.422, RMSEA = 0.069, CFI = 0.929, TLI = 0.919. The negative core schema played a mediating role between CSA and depressive symptoms. Experiential avoidance played a mediating role between CSA and depressive symptoms. The negative core schema and experiential avoidance played a serial mediating role between CSA and depressive symptoms. Conclusion: These results deepen our understanding of the relationship between CSA and depressive symptoms in female college students, and provide theoretical guidance for the prevention of depression in female college students. Attention should be paid to female college students who have experienced CSA, to eliminate the adverse influence of negative core schema on these students. Meanwhile, we should teach female college students to accept themselves as they are, and thereby reduce their use of experiential avoidance strategies.

Spatio-temporal characteristics and driving mechanism of land degradation sensitivity in Northwest China.

Northwest China has been experiencing severe land degradation for a long time due to various natural and social elements. Evaluating and analyzing the process of occurrence and driving mechanism of land degradation sensitivity in this area is crucial for enhancing the local ecological environment. In this study, 18 social and environmental elements were used to construct a land degradation sensitivity index (LDSI) evaluation system in the area from vegetation, climate, management, soil, and geomorphology five factors. The spatio-temporal characteristics of LDSI in Northwest China from 2000 to 2020 were evaluated on the basis of analyzing the developmental changes of each factor. Correlation analysis and multiscale geographical weighting regression (MGWR) were used to reveal the driving mechanism of land degradation sensitivity. The results indicated a high level of land degradation sensitivity in Northwest China, with >66 % of the area (190.96 × 104 km2) in the critical sensitive class from 2000 to 2020. But the land degradation sensitivity decreased in 18.52 % of the area (53.58 × 104 km2) from 2000 to 2020, the overall trend was weakening. The spatial distribution mainly showed stronger sensitivity in the northwest and weaker sensitivity in the southeast. By exploring the driving mechanism of land degradation sensitivity, it was found that vegetation and climate showed a strong correlation, with a correlation coefficient >0.8. Drought resistance played a strong role in the dynamic process of land degradation. The basic dynamic elements showed some spatial variability in land degradation in different regions. This study is of significance for land degradation prevention and sustainable development in Northwest China.

Genomics and proteomics to determine novel molecular subtypes and predict the response to immunotherapy and the effect of bevacizumab in glioblastoma.

Glioblastoma (GBM) is a highly aggressive, infiltrative malignancy that cannot be completely cured by current treatment modalities, and therefore requires more precise molecular subtype signatures to predict treatment response for personalized precision therapy. Expression subtypes of GBM samples from the Cancer Genome Atlas (TCGA) were identified using BayesNM and compared with existing molecular subtypes of GBM. Biological features of the subtypes were determined by single-sample gene set enrichment analysis. Genomic and proteomic data from GBM samples were combined and Genomic Identification of Significant Targets in Cancer analysis was used to screen genes with recurrent somatic copy-number alterations phenomenon. The immune environment among subtypes was compared by assessing the expression of immune molecules and the infiltration of immune cells. Molecular subtypes adapted to immunotherapy were identified based on Tumor Immune Dysfunction and Exclusion (TIDE) score. Finally, least absolute shrinkage and selection operator (LASSO) logistic regression was performed on the expression profiles of S2, S3 and S4 in TCGA-GBM and RPPA to determine the respective corresponding best predictive model. Four novel molecular subtypes were classified. Specifically, S1 exhibited a low proliferative profile; S2 exhibited the profile of high proliferation, IDH1 mutation, TP53 mutation and deletion; S3 was characterized by high immune scores, innate immunity and adaptive immune infiltration scores, with the lowest TIDE score and was most likely to benefit from immunotherapy; S4 was characterized by high proliferation, EGFR amplification, and high protein abundance, and was the most suitable subtype for bevacizumab. LASSO analysis constructed the best prediction model composed of 13 genes in S2 with an accuracy of 96.7%, and the prediction model consisting of 17 genes in S3 with an accuracy of 86.7%, and screened 14 genes as components of the best prediction model in S4 with an accuracy of 93%. To conclude, our study classified reproducible and robust molecular subtypes of GBM, and these findings might contribute to the identification of patients responding to immunotherapy, thereby improving GBM prognosis.

A serial mediation model reveals the association between parental over-protection and academic entitlement among nursing students.

The study aims to explore the influence of parental over-protection on academic entitlement of nursing students, and examine the mediating roles of external locus of control and psychological entitlement. The study sampled two medical universities in Guizhou and Yunnan provinces, China. Participants were nursing students in grades one to four (N = 1003; mean age = 19.51 years; 81.95% female). Using a structural equation model, we examined the mediating effect of external locus of control and psychological entitlement on parental over-protection and academic entitlement. The results show that there was a significant correlation between all variables, and external locus of control and psychological entitlement played a serial mediating role between parental over-protection and academic entitlement. Our findings suggest that academic entitlement of nursing students can be reduced by adjusting parental rearing behaviors, reducing students' psychological entitlement, and teaching them how to form a healthier attribution style.

MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma.

MicroRNAs can coordinately repress multiple target genes and interfere with the biological functions of the cell, such as proliferation and apoptosis. In the present study, we report that miR-200b was downregulated in malignant glioma cell lines and specimens. Overexpression of miR-200b suppressed the proliferation and colony formation of glioma cells. An oncogene encoding cAMP responsive element-binding protein 1 (CREB1), which has been shown to be an important transcription factor involved in the proliferation, survival, and metastasis of tumor cells, was here confirmed as a direct target gene of miR-200b. CREB1 was also found to be present at a high level in human glioma tissues. This was inversely correlated with miR-200b expression. Ectopic expression of CREB1 attenuated the growth suppressive phenotypes of glioma cells caused by miR-200b. These results indicate that miR-200b targets the CREB1 gene and suppresses glioma cell growth, suggesting that miR-200b shows tumor-suppressive activity in human malignant glioma.

Syringic Acid Suppressed Proliferation, Invasion, and Migration via Inhibition of Matrix Metalloproteinases Expression on Glioblastoma Cells by Promoting Apoptosis.

BACKGROUND: Human brain tumor glioblastoma (GBM) is the most hostile malignancy, currently lacking a successful cure and good prognosis. OBJECTIVE: To examine the anticancer effects of syringic acid (SA) on human cancer GBM cells. METHODOLOGY: The different doses of SA were added to GBM cells to study its effect on viability, invasion, relocation, apoptosis, and mRNA and protein levels. Hence, we explored the antiproliferative, anti-invasive, and apoptotic activity of SA on GBM human U-251 cells. RESULTS: MTT assay and live/dead assay revealed the anti-proliferative activity of SA on U-251 glioma cells. Apoptotic activity of SA was shown by DAPI staining, caspase-3, Bax, and Bcl-2 mRNA expressions. The cell cycle regulation was also confirmed by reducing the mRNA expression of cyclinD1, CDK4, and CDK6. Treatment of SA with U-251 cells suppressed MMPs expressions and enhanced TIMPs protein levels. CONCLUSION: Our findings put forward that SA could prevent GBM cells' invasion and relocation. SA is an ideal neuroprotective agent for controlling brain malignancy.

Family functioning and suicidal ideation in college students: a moderated mediation model of depression and acceptance.

Objective: To explore the mediating role of depression in the relationship between family functioning and suicidal ideation (SI) in college students, and to explore whether acceptance (It is one of the core components of psychological flexibility) plays a moderating role in this mediating model. Methods: In a cross-sectional study, questionnaires were distributed to college students during November and December 2022. The sample of Chinese college students (n = 592, 43.07% male, 56.93% female, mean age 19.40 years, SD = 1.24 years) completed the Family Adaptability and Cohesion Evaluation Scale (FACES III), the Center for Epidemiological Depression Scale (CES-D), the Positive and Negative Suicide Ideation Inventory (PANSI), and the Acceptance and Action Questionnaire-Second Edition (AAQ II). SPSS 25.0 for Windows and PROCESS 2.15 macros were used for data analysis. Results: There was a significant negative correlation between family functioning and SI, and depression played a mediating role in this relationship. Acceptance moderated the indirect effects of depression and SI in college students. In college students with a lower acceptance level (i.e., higher experiential avoidance level), depression had more influence on SI, while the influence of depression on SI was less in college students with a higher acceptance level (i.e., lower experiential avoidance level). Family functioning indirectly influenced SI through the moderation of acceptance. Conclusion: Mental health educators in colleges and universities should pay more attention to identifying and relieving depression in college students, thereby dealing with suicide risk more effectively. At the same time, college students should be discouraged from excessive use of experiential avoidance strategies, and instead taught to master effective emotional regulation strategies such as mindfulness, distress tolerance, and radical acceptance skills to improve their acceptance level and alleviate the influence of depression on SI.

Lipid Droplets from Plants and Microalgae: Characteristics, Extractions, and Applications.

Plant and algal LDs are gaining popularity as a promising non-chemical technology for the production of lipids and oils. In general, these organelles are composed of a neutral lipid core surrounded by a phospholipid monolayer and various surface-associated proteins. Many studies have shown that LDs are involved in numerous biological processes such as lipid trafficking and signaling, membrane remodeling, and intercellular organelle communications. To fully exploit the potential of LDs for scientific research and commercial applications, it is important to develop suitable extraction processes that preserve their properties and functions. However, research on LD extraction strategies is limited. This review first describes recent progress in understanding the characteristics of LDs, and then systematically introduces LD extraction strategies. Finally, the potential functions and applications of LDs in various fields are discussed. Overall, this review provides valuable insights into the properties and functions of LDs, as well as potential approaches for their extraction and utilization. It is hoped that these findings will inspire further research and innovation in the field of LD-based technology.

Clinical value of glucocorticoids for severe community-acquired pneumonia: A systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: Severe community-acquired pneumonia (sCAP) is characterized by severe symptoms and a poor prognosis, especially with the recent global impact of novel coronavirus in recent years. The use of glucocorticoids in sCAP is currently a subject of debate. To evaluate the clinical efficacy and safety of glucocorticoids and provide guidance for their rational use in clinical practice, we conducted this study. METHODS: We searched PubMed, Web of Science, and China National Knowledge Infrastructure using the following search terms: "pneumonia", "pneumonias", "Pulmonary Inflammation", "Pulmonary Inflammations", "Lung Inflammation", and "Lung Inflammations". The primary outcomes included mortality and the length of hospital stay. The secondary outcomes included the duration of mechanical ventilation, duration of vasoactive drug use, gastrointestinal bleeding, and multiple infections. The Cochrane Collaboration was used to assess the risk of bias of the included studies. Stata/MP14 was used for meta-analysis. RESULTS: These studies contained information on 1252 patients who received glucocorticoids and 1280 patients who did not. Meta-analysis showed that there was no difference in terms of mortality [risk ratio (RR) = 0.93, 95% confidence interval (CI): 0.81-1.07, P  > .05], gastrointestinal bleeding (RR = 1.38, 95% CI: 0.83-2.30, P  <  .05), multiple infections (RR = 1.17, 95% CI: 0.90-1.53, P  > .05) and length of hospital stay (mean difference [MD] = -0.87, 95% CI: -2.35 to 0.61, P  > .05) between the hormonal and nonhormonal groups. However, there was a significant difference in the duration of mechanical ventilation (MD = -1.54; 95% CI, -1.89 to -1.12, P  <  .05) and the duration of use of vasoactive drugs (MD = -14.09, 95% CI: -15.72 to -12.46, P < .05). CONCLUSION: Glucocorticoids reduced the duration of mechanical ventilation duration and vasoactive drug use in sCAP patients without increasing the risk of adverse events including hyperglycemia and multiple infections. However, there was no significant difference in mortality or length of hospital stay in sCAP patients between glucocorticoid and non-glucocorticoid groups. Glucocorticoids could be recommended for patients with sCAP with respiratory failure or hemodynamic instability.

Simvastatin Reduces NETosis to Attenuate Severe Asthma by Inhibiting PAD4 Expression.

Objective: Patients with severe asthma respond poorly to corticosteroids, and their care accounts for more than 60% of the total costs attributed to asthma. Neutrophils form neutrophil extracellular traps (NETs), which play a crucial role in severe asthma. Statins have shown anti-inflammatory effects by reducing NETosis. In this study, we investigate if simvastatin can attenuate severe asthma by reducing NETosis and the underlying mechanism. Methods: Mice were concomitantly sensitized with ovalbumin (OVA), house dust mite (HDM), and lipopolysaccharide (LPS) during sensitization to establish a mouse model of severe asthma with neutrophil predominant inflammation (OVA+LPS mice) and treated with or without simvastatin. In inflammatory response, proportions of Th2, Th17, and Treg cells in lung tissue were detected by flow cytometry, and the levels of cytokines, dsDNA, and MPO-DNA in bronchoalveolar lavage fluid (BALF) were analyzed by ELISA. Citrullinated histone H3 (CitH3) and peptidyl arginine deiminase 4 (PAD4) in lung tissue were determined by Western blot and immunofluorescence imaging. PAD4 mRNA was determined by quantitative PCR (qPCR). HL-60 cells were differentiated into neutrophil-like cells by 1.25% DMSO. The neutrophil-like cells were treated with or without LPS, and simvastatin was then stimulated with PMA. CitH3 and PAD4 expressions were determined. Results: Sensitization with OVA, HDM, and LPS resulted in neutrophilic inflammation and the formation of NETs in the lungs. Simvastatin treatment reduced the inflammation score, cytokine levels, total cells, and neutrophil counts in the BALF and reduced proportions of Th2 and Th17 but increased Treg cells in lungs of OVA+LPS mice. Simvastatin-treated OVA+LPS mice show reduced NET formation in BALF and lung tissue compared to control mice. Adoptive transfer of neutrophils was sufficient to restore NETosis and neutrophilic inflammation in simvastatin-treated OVA+LPS mice. Simvastatin reduced PAD4 mRNA and protein expression in lung tissues and neutrophils isolated from lungs of OVA+LPS mice and consequent NET formation. In vitro, simvastatin reduced LPS-induced PAD4 upregulation and NETosis in HL-60-differentiated neutrophil-like cells. Furthermore, PAD4-overexpressed lentiviral transduction was sufficient to restore PAD4 protein expression and NETosis in simvastatin-treated HL-60-differentiated neutrophil-like cells. Conclusions: Simvastatin reduces Th17-mediated neutrophilic inflammation and airway hyperreactivity by reducing PAD4 expression and inhibiting NETosis in a mouse model of severe asthma. Severe asthmatic patients with high levels of circulating NETs or sputum NETs may show improved responses to statin treatment.

Family functioning and adolescent depression: A moderated mediation model of self-esteem and peer relationships.

In consideration of family system theory, the vulnerability model of depression, and the stress buffering model of social support, the current study examined the effect of family functioning on adolescent depression, the mediating effect of self-esteem, and the moderating effect of peer relationships. A sample of Chinese adolescents (n = 562, 47.15% male, 52.85% female, mean age 14.33 years, SD = 1.81 years) completed questionnaires regarding family functioning, depression, self-esteem, and peer relationships. The results showed that: (1) family functioning had a significant negative predictive effect on adolescent depression; (2) self-esteem plays a mediating role between family functioning and adolescent depression; and (3) peer relationships have a moderating effect on the relationship between self-esteem and adolescent depression, supporting the moderated mediation model. These results reveal the influence mechanism of family functioning on adolescent depression and have implications for adolescent depression intervention.

Estimation formula of finished bridge pre-camber in continuous rigid-frame bridges.

Continuous rigid-frame bridges are widely used, but the large deflection in the mid-span during operation has always been their disease. This problem is generally solved by setting the finished bridge pre-camber. There are many calculation methods for pre-camber, and the effects are different. In this paper, based on a large number of design parameters of continuous rigid-frame bridges obtained from the investigation, 18 finite element analysis models of different span combinations were established, and 30 sets of valid data were obtained under the action of multi-factor. The results show that the shrinkage and creep of concrete is the most important factor for the mid-span deflection of continuous rigid frame bridges, and the deflection amount has an obvious functional relationship with the span. The effect of prestress loss on mid-span deflection is second, and stiffness reduction has little effect on mid-span long-term deflection. In this paper, the least-squares method is used to perform polynomial fitting, and the fitting formula for the mid-span finished bridge pre-camber is finally obtained. The applicability of the calculation formula is proved by comparing it with the specification solution, the empirical solution, and the measured value.