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Tobacco smoke exposure is a major environmental risk factor that facilitates the development and progression of asthma. Our previous study showed that CpG oligodeoxynucleotide (CpG-ODN) inhibits thymic stromal lymphopoietin (TSLP)-dendritic cells (DCs) to reduce Th2/Th17-related inflammatory response in smoke-related asthma. However, the mechanism underlying CpG-ODN -downregulated TSLP remains unclear. A combined house dust mite (HDM)/cigarette smoke extract (CSE) model was used to assess the effects of CpG-ODN on airway inflammation, Th2/Th17 immune response, and amount of IL-33/ST2 and TSLP in mice with smoke-related asthma induced by adoptive transfer of bone-marrow-derived dendritic cells (BMDCs) and in the cultured human bronchial epithelium (HBE) cells administered anti-ST2, HDM, and/or CSE. In vivo, compared to the HDM alone model, the combined HDM/CSE model had aggravated inflammatory responses, while CpG-ODN attenuated airway inflammation, airway collagen deposition, and goblet cell hyperplasia and reduced the levels of IL-33/ST2, TSLP, and Th2/Th17-cytokines in the combined model. In vitro, IL-33/ST2 pathway activation promoted TSLP production in HBE cells, which could be inhibited by CpG-ODN. CpG-ODN administration alleviated Th2/Th17 inflammatory response, decreased the infiltration of inflammatory cells into the airway, and improved the remodeling of smoke-related asthma. The underlying mechanism may be that CpG-ODN inhibits the TSLP-DCs pathway by downregulating the IL-33/ST2 axis. [ABSTRACT FROM AUTHOR]

Disrupted brain structures and several life environmental factors have been shown to influence depression and anxiety, but their interactions with anxiety and depression remain elusive. Genome‐wide association study datasets of 15 brain structure longitudinal changes (N = 15,640) were obtained from the published study. Genotype and phenotype‐related data of depression, anxiety, and life environmental factors (including smoking, alcohol drinking, coffee intake, maternal smoking, physical activity, vitamin D, insomnia, sleep duration, and family satisfaction) were collected from UK Biobank. We calculated the polygenic risk scores (PRS) of 15 brain structure changes and then conducted linear regression analyses to explore the interactions of brain structure changes and life environmental factors on depression and anxiety using 15 brain structure change‐related PRS, life environmental factors and interactions of them as instrumental variables, and depression score or anxiety score as outcomes. Sex stratification in all analyses was performed to reveal sex‐specific differences in the interactions. We found 14 shared interactions related to both depression and anxiety in total sample, such as alcohol drinking × cerebellum white matter 3 (WM; beta = −.003, p =.018 for depression; beta = −003, p =.008 for anxiety) and maternal smoking × nucleus accumbens 2 (beta =.088, p =.002 for depression; beta =.070, p =.008 for anxiety). We also observed sex‐specific differences in the interactions, for instance, alcohol drinking × cerebellum WM 3 was negatively associated with depression and anxiety in males (beta = −.004, p =.020 for depression; beta = −.005, p =.002 for anxiety). Our study results reveal the important interactions between brain structure changes and several life environmental factors on depression and anxiety, which may help to explore the pathogenesis of depression and anxiety. [ABSTRACT FROM AUTHOR]

Psychiatric disorders and neuroticism are closely associated with central nervous system, whose proper functioning depends on efficient protein renewal. This study aims to systematically analyze the association between anxiety / depression / neuroticism and each of the 439 proteins. 47,536 pQTLs of 439 proteins in brain, plasma and cerebrospinal fluid (CSF) were collected from recent genome-wide association study. Polygenic risk scores (PRS) of the 439 proteins were then calculated using the UK Biobank cohort, including 120,729 subjects of neuroticism, 255,354 subjects of anxiety and 316,513 subjects of depression. Pearson correlation analyses were performed to evaluate the correlation between each protein and each of the mental traits by using calculated PRSs as the instrumental variables of protein. In general population, six correlations were identified in plasma and CSF such as plasma protease C1 inhibitor (C1-INH) with neuroticism score (r = − 0.011, P = 2.56 × 10− 9) in plasma, C1-INH with neuroticism score (r = -0.010, P = 3.09 × 10− 8) in CSF, and ERBB1 with self-reported depression (r = − 0.012, P = 4.65 × 10− 5) in CSF. C1-INH and ERBB1 may induce neuroticism and depression by affecting brain function and synaptic development. Gender subgroup analyses found that BST1 was correlated with neuroticism score in male CSF (r = − 0.011, P = 1.80 × 10− 5), while CNTN2 was correlated with depression score in female brain (r = − 0.013, P = 6.43 × 10− 4). BST1 and CNTN2 may be involved in nervous system metabolism and brain health. Six common candidate proteins were associated with all three traits (P < 0.05) and were confirmed in relevant proteomic studies, such as C1-INH in plasma, CNTN2 and MSP in the brain. Our results provide novel clues for revealing the roles of proteins in the development of anxiety, depression and neuroticism. [ABSTRACT FROM AUTHOR]

Background: T-2 toxin is thought to induce the growth plate and articular cartilage damage of Kashin-Beck disease (KBD), an endemic osteochondropathy in China. This study aims to explore the potential underlying mechanism of such toxic effects by integrating DNA methylation and gene expression profiles. Methods: In this study, C28/I2 chondrocytes were treated with T-2 toxin (5 ng/mL) for 24 h and 72 h. Global DNA methylation level of chondrocyte was tested by Enzyme-Linked Immuno Sorbent Assay. Genome-wide DNA methylation and expression profiles were detected using Illumina Infinium HumanMethylation850 BeadChip and RNA-seq technique, respectively. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified mainly for two stages including 24 h group versus Control group and 72 h group versus 24 h group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by Metascape. DMGs and DEGs were further validated by Sequenom MassARRAY system and quantitative real-time polymerase chain reaction. Results: The global DNA methylation levels of chondrocytes exposed to T-2 toxin were significantly increased (P < 0.05). For 24 h group versus Control group (24 VS C), 189 DEGs and 590 DMGs were identified, and 4 of them were overlapping. For 72 h group versus 24 h group (72 VS 24), 1671 DEGs and 637 DMGs were identified, and 45 of them were overlapping. The enrichment analysis results of DMGs and DEGs both showed that MAPK was the one of the mainly involved signaling pathways in the regulation of chondrocytes after T-2 toxin exposure (DEGs: P24VSc = 1.62 × 10− 7; P72VS24 = 1.20 × 10− 7; DMGs: P24VSc = 0.0056; P72VS24 = 3.80 × 10− 5). Conclusions: The findings depicted a landscape of genomic methylation and transcriptome changes of chondrocytes after T-2 toxin exposure and suggested that dysfunction of MAPK pathway may play important roles in the chondrocytes damage induced by T-2 toxin, which could provide new clues for understanding the potential biological mechanism of KBD cartilage damage induced by T-2 toxin. [ABSTRACT FROM AUTHOR]

Background Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene–environment interactions. Methods We developed a novel polygenic and gene–environment interaction risk score (PGIRS) integrating the major genetic effect and gene–environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N  = 42 886) and cardiac function (N  = 1791) in the subjects with or without exposing to smoking and alcohol drinking. Results We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (β  = −0.037, FDR = 1.00 × 10−8), contrasting with no significant association with PRS (β  = −0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (β  = 0.088, FDR = 0.010), whereas no such association was found with PRS (β  = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (β  = −0.042, FDR = 6.30 × 10−9), but not with PRS (β  = −0.003, FDR = 0.857). Conclusions Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene–environment interactions in PRS-based studies. [ABSTRACT FROM AUTHOR]

Observational studies have shown that alterations in gut microbiota composition are associated with low back pain. However, it remains unclear whether the association is causal. To reveal the causal association between gut microbiota and low back pain, a two‐sample bidirectional Mendelian randomization (MR) analysis is performed. The inverse variance weighted regression (IVW) is performed as the principal MR analysis. MR‐Egger and Weighted Median is further conducted as complementary analysis to validate the robustness of the results. Finally, a reverse MR analysis is performed to evaluate the possibility of reverse causation. The inverse variance weighted (IVW) method suggests that Peptostreptococcaceae (odds ratio [OR] 1.056, 95% confidence interval [CI] [1.015–1.098], PIVW = 0.010), and Lactobacillaceae (OR 1.070, 95% CI [1.026–1.115], PIVW = 0.003) are positively associated with back pain. The Ruminococcaceae (OR 0.923, 95% CI [0.849–0.997], PIVW = 0.033), Butyricicoccus (OR 0.920, 95% CI [0.868 ‐ 0.972], PIVW = 0.002), and Lachnospiraceae (OR 0.948, 95% CI [0.903–0.994], PIVW = 0.022) are negatively associated with back pain. In this study, underlying causal relationships are identified among gut microbiota and low back pain. Notably, further research is needed on the biological mechanisms by which gut microbiota influences low back pain. [ABSTRACT FROM AUTHOR]

Grain size control is an important aspect to manipulate the microstructure and high temperature stability of ceramic fibers. In the present work, phase competition mechanism was proposed to regulate the grain size of ZrO2/CaZrO3 composite fibers. Calcium precursor with different molar ratio of Ca/Zr was introduced to the zirconia system not only for phase stabilization of ZrO2 but also for phase competition between solid‐solution CaxZr1‐xO2‐x and new phase CaZrO3. Effects of Ca/Zr molar ratio on the thermal pyrolysis, crystallization, solid reaction of precursor fibers were fully explored. The change of grain size of fibers with various Ca/Zr molar ratio was characterized and discussed. Furthermore, the near‐infrared reflectivity and high‐temperature stability of fibrous membranes were also presented. The results indicated that ZrO2/CaZrO3 fibrous membrane has promising applications in high‐temperature for the excellent thermal stability and high near infrared (NIR) reflectivity. [ABSTRACT FROM AUTHOR]

Zirconate fibrous membranes show promising applications in high thermal insulating areas for the high melting point, low thermal conductivity and good phase stability. To satisfy the high-temperature mechanical demands, the microstructure of zirconate fibers needs further modification to accommodate high-temperature stability. In consideration of the slow ion diffusion rate and enhanced stability of solid solution, Ca x Sr 1- x ZrO 3 fibrous membranes were electrospun with molar ratio of Ca/Sr varied from 0.9 to 0.5 for the present work. The effects of strontium precursor on the pyrolysis process, phase formation and microstructure evolution were fully characterized. Modified microstructures with smaller grain size and narrow particle size distribution were achieved. Furthermore, the NIR reflectivity, thermal conductivity, and high-temperature stability were also presented. The special expansion character of fibrous membrane at high temperature would make it promising candidate to compensate the shrinkage of other oxide fibrous membrane. [ABSTRACT FROM AUTHOR]

The Ce3+-, Ho3+-, and Sm3+- single and co-doped oxyfluoride silicate glasses for light emitting diodes are studied. These glasses were prepared by melt quenching method and their optical and structural properties were investigated by absorption spectra, photoluminescence spectra, Commission International de I'Eclairage chromaticity coordinates, X-ray diffraction, and Fourier transform infrared spectra. It is found that the introduction of Al2O3 in glass composition can improve the emissions of Ho3+ and Sm3+. While the presence of B2O3 has the adverse effect and can suppress the emissions of Ho3+ and Sm3+. With substituting Na2O for CaO in the glass compositions, CaF2 crystals can be formed during the melt quenching process. We find the formation of CaF2 crystals can change the emission behavior of Ho3+ and Sm3+ ions. White light emissions can be achieved in the glasses and the luminescence colors can be tuned by varying the concentrations of the doped rare-earth ions and the composition of glass matrix. The Ce3+-, Ho3+-, and Sm3+-doped oxyfluoride silicate glasses presented here demonstrate promising applications in the fields of light emitting diodes. [ABSTRACT FROM AUTHOR]

Background: Longevity is one of the most complex phenotypes, and its genetic basis remains unclear. This study aimed to explore the genetic correlation and potential causal association between gut microbiota and longevity. Results: Linkage disequilibrium score (LDSC) regression analysis and a bi-directional two-sample Mendelian Randomization (MR) analysis were performed to analyze gut microbiota and longevity-related traits. LDSC analysis detected four candidate genetic correlations, including Veillonella (genetic correlation = 0.5578, P = 4.67 × 10− 2) and Roseburia (genetic correlation = 0.4491, P = 2.67 × 10− 2) for longevity, Collinsella (genetic correlation = 0.3144, P = 4.07 × 10− 2) for parental lifespan and Sporobacter (genetic correlation = 0.2092, P = 3.53 × 10− 2) for healthspan. Further MR analysis observed suggestive causation between Collinsella and parental longevity (father's age at death) (weighted median: b = 1.79 × 10− 3, P = 3.52 × 10− 2). Reverse MR analysis also detected several causal effects of longevity-related traits on gut microbiota, such as longevity and Sporobacter (IVW: b = 7.02 × 10− 1, P = 4.21 × 10− 25). Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Conclusion: Our study found evidence that gut microbiota is causally associated with longevity, or vice versa, providing novel clues for understanding the roles of gut microbiota in aging development. [ABSTRACT FROM AUTHOR]

Although previous genome-wide association studies (GWASs) on post-traumatic stress disorder (PTSD) have identified multiple risk loci, how these loci confer risk of PTSD remains unclear. Through the FUSION pipeline, we integrated two human brain proteome reference datasets (ROS/MAP and Banner) with the PTSD GWAS dataset, respectively, to conduct a proteome-wide association study (PWAS) analysis. Then two transcriptome reference weights (Rnaseq and Splicing) were applied to a transcriptome-wide association study (TWAS) analysis. Finally, the PWAS and TWAS results were investigated through brain imaging analysis. In the PWAS analysis, 8 and 13 candidate genes were identified in the ROS/MAP and Banner reference weight groups, respectively. Examples included ADK (pPWAS-ROS/MAP = 3.00 × 10−5) and C3orf18 (pPWAS-Banner = 7.07 × 10−31). Moreover, the TWAS also detected multiple candidate genes associated with PTSD in two different reference weight groups, including RIMS2 (pTWAS-Splicing = 3.84 × 10−2), CHMP1A (pTWAS-Rnaseq = 5.09 × 10−4), and SIRT5 (pTWAS-Splicing = 4.81 × 10−3). Further comparison of the PWAS and TWAS results in different populations detected the overlapping genes: MADD (pPWAS-Banner = 4.90 × 10−2, pTWAS-Splicing = 1.23 × 10−2) in the total population and GLO1(pPWAS-Banner = 4.89 × 10−3, pTWAS-Rnaseq = 1.41 × 10−3) in females. Brain imaging analysis revealed several different brain imaging phenotypes associated with MADD and GLO1 genes. Our study identified multiple candidate genes associated with PTSD in the proteome and transcriptome levels, which may provide new clues to the pathogenesis of PTSD. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets. Results: TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus Bifidobacterium in transverse colon (PPERM.ANL = 1.68 × 10–3) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (PPERM.ANL = 5.69 × 10–3). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for Streptococcus (PIP = 0.685) in sigmoid colon, ANO7 for Erysipelotrichaceae (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10–4), KEGG_RENIN_ANGIOTENSIN_SYSTEM for Anaerostipes (FDR P = 3.16 × 10–2). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of Proteobacteria was related to atherosclerosis, and FUT2 for Bifidobacterium was associated with Crohn's disease. Conclusions: Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases. [ABSTRACT FROM AUTHOR]

Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (β = − 0.009, P = 2.2 × 10–3), G_Akkermansia (β = − 0.008, P = 7.60 × 10–3), F_Acidaminococcaceae (β = 0.008, P = 1.22 × 10–2), G_Holdemanella (β = − 0.007, P = 1.39 × 10–2) and O_Lactobacillales (β = 0.006, P = 1.79× 10–2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (β = 0.010, P = 4.00× 10–4), O_Selenomonadales (β = − 0.010, P = 1.20 × 10–3), O_Clostridiales (β = 0.009, P = 2.70 × 10–3) and G_Holdemanella (β = − 0.008, P = 4.20 × 10–3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) exposure increases corticosteroid insensitive asthma related to increased Th17 phenotype, and new treatment strategies are needed for CS-associated asthma. Histone deacetylase 2 (HDAC2), found in the airway epithelium, is critical for ameliorating glucocorticoids insensitivity. We recently demonstrated the anti-inflammatory effects of CpG oligodeoxynucleotides (CpG-ODNs) on CS-exposure asthma. However, the effects of CpG-ODNs on HDAC2 expression and enzymatic activity remain unclear. This study aimed to assess whether CpG-ODNs protect against excessive Th17 immune responses in CS-induced asthma through HDAC2-dependent mechanisms and compared their effects with those of corticosteroids. Methods: The effects of CpG-ODNs alone and in combination with budesonide (BUD) on airway inflammation and Th2/Th17-related airway immune responses were determined using an in vivo model of CS-induced asthma and in cultured bronchial epithelial (HBE) cells administered ovalbumin (OVA) and/or cigarette smoke extract (CSE). HDAC2 and retinoid-related orphan nuclear receptor γt (RORγt) expression were also assessed in mouse lung specimens and HBE cells. Results: CpG-ODNs and BUD synergistically attenuated CS exposure asthmatic responses in vivo by modulating the influx of eosinophils and neutrophils, airway remodeling, Th2/Th17 associated cytokine and chemokine production, and airway hyperresponsiveness and blocking RORγt-mediated Th17 inflammation through induced HDAC2 expression/activity. In vitro, CpG-ODNs synergized with BUD to inhibit Th17 cytokine production in OVA- and CSE-challenged HBE cells while suppressing RORγt and increasing epithelial HDAC2 expression/activity. Conclusions: CpG-ODNs reversed CS-induced HDAC2 downregulation and enhanced the sensitivity of CS-exposed asthmatic mice and CSE-induced HBE cells to glucocorticoid treatment. This effect may be associated with HDAC2 restoration via RORγt/IL-17 pathway regulation, suggesting that CpG-ODNs are potential corticosteroid-sparing agents for use in CS-induced asthma with Th17-biased immune conditions. [ABSTRACT FROM AUTHOR]

A novel hybrid porous carbon has been synthesized by a facile method blending chitosan with gelatin in acetic acid solution. Gelatin changes the morphology of the chitosan-derived carbon materials and produces abundant micro- and mesopores with the help of KHCO3. More importantly, gelatin brings heteroatoms and pseudo-capacitance into hybrids to improve the capacitive performance as the nitrogen source. A unique tangerine pith-like morphology comes into being on the chitosan-derived hybrid porous carbon, and there are lots of interconnected micropores forming with high specific surface area of 927.17 m2 g−1. This particular morphology, high nitrogen content and specific surface area ensure the as-obtained carbon electrode wonderful capacitive performance with specific capacitance of 331 F g−1 in 6 mol L−1 KOH electrolyte at 1 A g−1, high retention of 73% and excellent capacity stability of 90% after 10000 cycles at 10 A g−1. Additionally, the chitosan-derived hybrid porous carbon shows remarkable energy density of 34 W h kg−1 with the power density of 900 W kg−1, superior to majority of the commercial devices. The simple and efficient strategy and the excellent electrochemical performance are of great significance to the large-scale application of biomass-based supercapacitors. [ABSTRACT FROM AUTHOR]

Ferrimagnetic nano‐crystal glass‐ceramics and glass fibers were prepared based on the ferrosilicate glass system of SiO2–Fe2O3–B2O3–Al2O3 using large amount of pyrite slag (PS) and small quantities of pure chemicals. Two different fabrication methods were employed, eg, annealing and fiber‐drawing method, without performing any nucleation and crystallization heat treatments. The influence of PS content on the magnetite spontaneous crystallization is investigated by the X‐ray diffraction, FTIR, SEM, and TEM. The X‐ray diffraction patterns show the presence of nanometric magnetite crystals in glass matrix. The ferrimagnetic glass fibers with a diameter of about 20 μm were one‐step drawn. The magnetic hysteresis loops of the glass‐ceramic and glass fiber samples were analyzed using a vibrating sample magnetometer (VSM). Electromagnetic parameters of samples were also examined. [ABSTRACT FROM AUTHOR]