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The rate performance, power density, and energy efficiency of electrochemical devices are often limited by ionic conductivities in electrolyte and electrode materials. Framework Prussian blue analogs and dense niobium oxides have been identified as high-rate electrodes for sodium- and lithium-ion batteries, respectively, yet the origin of the extremely high solid-state Na + /Li + transport is not fully understood. Of critical importance is the fact that their ultra-low activation energy and anomalous pre-exponent factor cannot be satisfactorily rationalized from conventional theory of solid-state diffusion in the crystal lattice. Here, assisted by density-functional-theory calculations, we argued that the true origin is a unique surface-like diffusion mechanism of the intercalation ions. In a surface-like migration event, a mobile ion moves along the channel wall via a low coordination number and low migration barrier experiencing minimal steric hindrance. It is similar to surface diffusion in the conventional picture and contrasts with lattice diffusion from one interstitial/vacancy site to another one with high coordination number, crowded saddle-point geometry and high migration barrier. We found that the shifting from solid-state lattice diffusion to surface-like diffusion is determined by the size difference between the mobile ion and the diffusion channel, and a lowest migration energy barrier can be reached by mediating the channel size. The analogy to gas diffusion in molecular sieves shall be discussed. Additionally, the effects of defects and crystal water in Prussian blue analogs were also discussed for better understanding their rate performances in experimental scenarios., (© 2024 Wiley-VCH GmbH.)

Objective: This study aimed to identify candidate loci and genes related to sleep disturbances in depressed individuals and clarify the co-occurrence of sleep disturbances and depression from the genetic perspective., Methods: The study subjects (including 58,256 self-reported depressed individuals and 6,576 participants with PHQ-9 score ≥ 10, respectively) were collected from the UK Biobank, which were determined based on the Patient Health Questionnaire (PHQ-9) and self-reported depression status, respectively. Sleep related traits included chronotype, insomnia, snoring and daytime dozing. Genome-wide association studies (GWASs) of sleep related traits in depressed individuals were conducted by PLINK 2.0 adjusting age, sex, Townsend deprivation index and 10 principal components as covariates. The CAUSALdb database was used to explore the mental traits associated with the candidate genes identified by the GWAS., Results: GWAS detected 15 loci significantly associated with chronotype in the subjects with self-reported depression, such as rs12736689 at RNASEL (P = 1.00 × 10 - 09 ), rs509476 at RGS16 (P = 1.58 × 10 - 09 ) and rs1006751 at RFX4 (P = 1.54 × 10 - 08 ). 9 candidate loci were identified in the subjects with PHQ-9 ≥ 10, of which 2 loci were associated with insomnia such as rs115379847 at EVC2 (P = 3.50 × 10 - 08 ), and 7 loci were associated with daytime dozing, such as rs140876133 at SMYD3 (P = 3.88 × 10 - 08 ) and rs139156969 at ROBO2 (P = 3.58 × 10 - 08 ). Multiple identified genes, such as RNASEL, RGS16, RFX4 and ROBO2 were reported to be associated with chronotype, depression or cognition in previous studies., Conclusion: Our study identified several candidate genes related to sleep disturbances in depressed individuals, which provided new clues for understanding the biological mechanism underlying the co-occurrence of depression and sleep disorders., (© 2024. The Author(s).)

Background: Rare variants are believed to play a substantial role in the genetic architecture of mental disorders, particularly in coding regions. However, limited evidence supports the impact of rare variants on anxiety., Methods: Using whole-exome sequencing data from 200,643 participants in the UK Biobank, we investigated the contribution of rare variants to anxiety. Firstly, we computed genetic risk score (GRS) of anxiety utilizing genotype data and summary data from a genome-wide association study (GWAS) on anxiety disorder. Subsequently, we identified individuals within the lowest 50% GRS, a subgroup more likely to carry pathogenic rare variants. Within this subgroup, we classified individuals with the highest 10% 7-item Generalized Anxiety Disorder scale (GAD-7) score as cases (N = 1869), and those with the lowest 10% GAD-7 score were designated as controls (N = 1869). Finally, we conducted gene-based burden tests and single-variant association analyses to assess the relationship between rare variants and anxiety., Results: Totally, 47,800 variants with MAF ≤0.01 were annotated as non-benign coding variants, consisting of 42,698 nonsynonymous SNVs, 489 nonframeshift substitution, 236 frameshift substitution, 617 stop-gain and 40 stop-loss variants. After variation aggregation, 5066 genes were included in gene-based association analysis. Totally, 11 candidate genes were detected in burden test, such as RNF123 (P Bonferroni adjusted  = 3.40 × 10 -6 ), MOAP1(P Bonferroni adjusted  = 4.35 × 10 -4 ), CCDC110 (P Bonferroni adjusted  = 5.83 × 10 -4 ). Single-variant test detected 9 rare variants, such as rs35726701(RNF123)(P Bonferroni adjusted  = 3.16 × 10 -10 ) and rs16942615(CAMTA2) (P Bonferroni adjusted  = 4.04 × 10 -4 ). Notably, RNF123, CCDC110, DNAH2, and CSKMT gene were identified in both tests., Conclusions: Our study identified novel candidate genes for anxiety in protein-coding regions, revealing the contribution of rare variants to anxiety., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aqueous zinc-ion batteries are promising due to inherent safety, low cost, low toxicity, and high volumetric capacity. However, issues of dendrites and side reactions between zinc metal anode and the electrolyte need to be solved for extended storage and cycle life. Here, we proposed that an electrolyte additive with an intermediate chelation strength of zinc ion-strong enough to exclude water molecules from the zinc metal-electrolyte interface and not too strong to cause a significant energy barrier for zinc ion dissociation-can benefit the electrochemical stability by suppressing hydrogen evolution reaction, overpotential growth, and dendrite formation. Penta-sodium diethylene-triaminepentaacetic acid salt was selected for such a purpose. It has a suitable chelating ability in aqueous solutions to adjust solvation sheath and can be readily polarized under electrical loading conditions to further improve the passivation. Zn||Zn symmetric cells can be stably operated over 3500 h at 1 mA cm -2 . Zn||NH 4 V 4 O 10 full cells with the additive show great cycling stability with 84.6% capacity retention after 500 cycles at 1 A g -1 . Since the additive not only reduces H 2 evolution and corrosion but also modifies Zn 2+ diffusion and deposition, highlyreversible Zn electrodes can be achieved as verified by the experimental results. Our work offers a practical approach to the logical design of reliable electrolytes for high-performance aqueous batteries., (© 2024. The Author(s).)

Objectives: To assess whether there is a bidirectional causal relationship between the composition of gut microbiota and rheumatoid arthritis (RA), and to identify specific pathogenic bacterial taxa via the Mendelian randomisation (MR) analysis., Methods: We acquired single nucleotide polymorphisms (SNPs) associated with the composition of gut microbiota (n=18,340) and with RA (n=331,313) from publicly available genome-wide association studies (GWAS). The genome-wide threshold was 1 × 10-5 in the forward MR analysis and was 5 × 10-8 in the reverse MR analysis. Inverse variance weighted (IVW) was the main method to analyse causality, and MR results were verified by several sensitivity analyses including weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO)., Results: The IVW method suggested that eight taxa were positively correlated with RA, including: MollicutesRF9 (pIVW <0.01), Alphaproteobacteria (pIVW <0.01), Betaproteobacteria (p IVW =0.04), Bacteroidaceae (pIVW <0.01), Adlercreutzia (pIVW <0.01), Bacteroides (pIVW <0.01), Butyricimonas (p IVW =0.03) and Holdemanella (pIVW =0.03). Six bacterial taxa were negatively correlated with RA, including Desulfovibrionales (pIVW = 0.01), Methanobacteriales (pIVW <0.01), Methanobacteria (PIVW <0.01), Desulfovibrionaceae (pIVW <0.01), Methanobacteriaceae (pIVW <0.01) and Butyrivibrio (pIVW =0.02). Heterogeneity (p>0.05) and pleiotropy (p>0.05) analysis confirmed the robustness of the MR results., Conclusions: We identified some specific bacterial taxa that were causally associated with the risk of RA, providing new insights into prevention and diagnosis of RA.

Background: Mental disorders are largely socially determined, yet the combined impact of multidimensional social factors on the two most common mental disorders, depression and anxiety, remains unclear., Methods: We constructed a polysocial risk score (PsRS), a multidimensional social risk indicator including components from three domains: socioeconomic status, neighborhood and living environment and psychosocial factors. Supported by the UK Biobank cohort, we randomly divided 110 332 participants into the discovery cohort (60%; n = 66 200) and the replication cohort (40%; n = 44 134). We tested the associations between 13 single social factors with Patient Health Questionnaire (PHQ) score, Generalized Anxiety Disorder Scale (GAD) score and self-reported depression and anxiety. The significant social factors were used to calculate PsRS for each mental disorder by considering weights from the multivariable linear model. Generalized linear models were applied to explore the association between PsRS and depression and anxiety. Genome-wide environmental interaction study (GWEIS) was further performed to test the effect of interactions between PsRS and SNPs on the risk of mental phenotypes., Results: In the discovery cohort, PsRS was positively associated with PHQ score (β = 0.37; 95% CI = 0.35-0.38), GAD score (β = 0.27; 95% CI = 0.25-0.28), risk of self-reported depression (OR = 1.29; 95% CI = 1.28-1.31) and anxiety (OR = 1.19; 95% CI = 1.19-1.23). Similar results were observed in the replication cohort. Emotional stress, lack of social support and low household income were significantly associated with the development of depression and anxiety. GWEIS identified multiple candidate loci for PHQ score, such as rs149137169 (ST18) (P discovery  = 1.08 × 10 -8 , P replication  = 3.25 × 10 -6 ) and rs3759812 (MYO9A) (P discovery  = 3.87 × 10 -9 , P replication  = 6.21 × 10 -5 ). Additionally, seven loci were detected for GAD score, such as rs114006170 (TMPRSS11D) (P discovery  = 1.14 × 10 -9 , P replication  = 7.36 × 10 -5 ) and rs77927903 (PIP4K2A) (P discovery  = 2.40 × 10 -9 , P replication  = 0.002)., Conclusions: Our findings reveal the positive effects of multidimensional social factors on the risk of depression and anxiety. It is important to address key social disadvantage in mental health promotion and treatment., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

The aberrant aging hypothesis of schizophrenia (SCZ) and autism spectrum disorder (ASD) has been proposed, and the DNA methylation (DNAm) clock, which is a cumulative evaluation of DNAm levels at age-related CpGs, could serve as a biological aging indicator. This study evaluated epigenetic brain aging of ASD and SCZ using Horvath's epigenetic clock, based on two public genome-wide DNA methylation datasets of post-mortem brain samples (N ASD  = 222; N SCZ  = 142). Total subjects were further divided into subgroups by gender and age. The epigenetic age acceleration (AgeAccel) for each sample was calculated as the residual value resulting from the regression model and compared between groups. Results showed DNAm age has a strong correlation with chronological age in both datasets across multiple brain regions (P < 0.05). When divided into equally sized age groups, the AgeAccel of the cerebellum (CB) region from people over 45 years of age was greater compared to the control sample (AgeAccel of ASD vs control: 5.069 vs -6.249; P < 0.001). And a decelerated epigenetic aging process was observed in the CB region of individuals with SCZ aged 50-70 years (AgeAccel of SCZ vs control: -3.171 vs 2.418; P < 0.05). However, our results showed no significant difference in AgeAccel between ASD and control groups, and between SCZ and control groups in the total and gender-specific groups (P > 0.05). This study's results revealed some evidence for aberrant epigenetic CB brain aging in old-aged patients with ASD and SCZ, indicating a different pattern of CB aging in older adults with these two diseases. However, further studies of larger ASD and SCZ cohorts are necessary to make definitive conclusions on this observation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although studies have shown that wearing masks can affect the skin microbiome, more detailed and comprehensive research on wearing masks needs to be further explored., Objective: This study aimed to characterize the influence of mask wearing on the diversity and structural characteristics of the facial skin microbial community of medical staff during the COVID-19 pandemic by means of metagenomic sequencing (mNGS)., Methods: A total of 40 samples were taken by swabbing the cheek in the 2 × 2 cm 2 area before and after wearing the masks. DNA was extracted for metagenomic sequencing., Results: A statistically significant decrease was found in the α diversity between BN and AN groups and between B2 h and A2 h groups. BN and AN mean groups before and after 8 h of wearing the medical protective mask (N95), including 10 volunteers, respectively. B2 h and A2 h mean groups before and after 8 h of wearing masks, including 10 volunteers changing mask every 2 h, respectively. The β diversity was found to be statistically reduced between BS and AS groups ( p  = 0.025), BN and AN groups ( p  = 0.009), and B2 h and A2 h group ( p  = 0.042). The fungal beta diversity was significantly decreased in every group before and after wearing masks. The main bacteria on the face before and after wearing masks were Cutibacterium (68.02 and 71.73%). Among the fungi, Malassezia predominated the facial skin surface before and after wearing masks (35.81 and 39.63%, respectively)., Conclusion: Wearing different types of masks and changing masks according to different frequency will have different effects on the facial skin's microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Jiang, Zhang, Liu, Kong, Hou, Qi, Sun and Jiang.)

Background: Smoking and alcohol consumption were associated with the development of depression and anxiety. 3'UTR APA quantitative trait loci (3'aQTLs) have been associated with multiple health states and conditions. Our aim is to evaluate the interactive effects of 3'aQTLs-alcohol consumption/tobacco smoking on the risk of anxiety and depression., Methods: The 3'aQTL data of 13 brain regions were extracted from the large-scale 3'aQTL atlas. The phenotype data (frequency of cigarette smoking and alcohol drinking, anxiety score, self-reported anxiety, depression score and self-reported depression) of 90,399-103,011 adults aged 40-69 years living in the UK and contributing to the UK Biobank during 2006-2010, were obtained from the UK Biobank cohort. The frequency of cigarette smoking and alcohol drinking of each subject were defined by the amount of smoking and alcohol drinking of self-reported, respectively. The continuous alcohol consumption/smoking terms were further categorized in tertiles. 3'aQTL-by-environmental interaction analysis was then performed to evaluate the associations of gene-smoking/alcohol consumption interactions with anxiety and depression using generalized linear model (GLM) of PLINK 2.0 with an additive mode of inheritance. Furthermore, GLM was also used to explore the relationship between alcohol consumption/smoking with hazard of anxiety/depression stratified by allele for the significant genotyped SNPs that modified the alcohol consumption/smoking-anxiety/depression association., Results: The interaction analysis identified several candidate 3'aQTLs-alcohol consumption interactions, such as rs7602638 located in PPP3R1 (β = 0.08, P = 6.50 × 10 -6 ) for anxiety score; rs10925518 located in RYR2 (OR = 0.95, P = 3.06 × 10 -5 ) for self-reported depression. Interestingly, we also observed that the interactions between TMOD1 (β = 0.18, P = 3.30 × 10 -8 for anxiety score; β = 0.17, P = 1.42 × 10 -6 for depression score), ZNF407 (β = 0.17, P = 2.11 × 10 -6 for anxiety score; β = 0.15, P = 4.26 × 10 -5 for depression score) and alcohol consumption was not only associated with anxiety, but related to depression. Besides, we found that relationship between alcohol consumption and hazard of anxiety/depression was significantly different for different SNPs genotypes, such as rs34505550 in TMOD1 (AA: OR = 1.03, P = 1.79 × 10 -6 ; AG: OR = 1.00, P = 0.94; GG: OR = 1.00, P = 0.21) for self-reported anxiety., Limitations: The identified 3'aQTLs-alcohol consumption/smoking interactions were associated with depression and anxiety, and its potential biological mechanisms need to be further revealed., Conclusions: Our study identified important interactions between candidate 3'aQTL and alcohol consumption/smoking on depression and anxiety, and found that the 3'aQTL may modify the associations between consumption/smoking with depression and anxiety. These findings may help to further explore the pathogenesis of depression and anxiety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The study aimed to evaluate the relationship between serum sodium and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage., Methods: This is a retrospective investigation of critically ill non-traumatic patients with subarachnoid hemorrhage (SAH) utilizing the MIMIC-IV database. We collected the serum sodium levels at admission and determined the all-cause death rates for the ICU and hospital. We employed a multivariate Cox proportional hazard regression model and Kaplan-Meier survival curve analysis to ascertain the relationship between serum sodium and all-cause mortality. In order to evaluate the consistency of correlations, interaction and subgroup analyses were also conducted., Results: A total of 864 patients with non-traumatic SAH were included in this study. All-cause mortality in the ICU and hospital was 32.6% (282/864) and 19.2% (166/864), respectively. Sodium levels at ICU admission showed a statistically significant J-shaped non-linear relationship with ICU and hospital mortality (non-linear P -value < 0.05, total P -value < 0.001) with an inflection point of ~141 mmol/L, suggesting that mortality was higher than normal serum sodium levels in hypernatremic patients. Multivariate analysis after adjusting for potential confounders showed that high serum sodium levels (≥145 mmol/L) were associated with an increased risk of all-cause mortality in the ICU and hospital compared with normal serum sodium levels (135-145 mmol/L), [hazard ratio (HR) = 1.47, 95% CI: 1.07-2.01, P = 0.017] and (HR = 2.26, 95% CI:1.54-3.32, P < 0.001). Similarly, Kaplan-Meier (K-M) survival curves showed lower survival in patients with high serum sodium levels. Stratified analysis further showed that the association between higher serum sodium levels and hospital all-cause mortality was stronger in patients aged < 60 years with a hospital stay of <7 days., Conclusion: High serum sodium levels upon ICU admission are related to higher ICU and hospital all-cause mortality in patients with non-traumatic SAH. A new reference is offered for control strategies to correct serum sodium levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Li, Zhang, Wang, Wang, Zhang and Zhang.)

Background: Previous genetic studies of anxiety and depression were mostly based on independent phenotypes. This study aims to investigate the shared and specific genetic structure between anxiety and depression., Method: To identify the underlying factors of Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and their combined scale (joint scale), we employed exploratory factor analysis (EFA) using the eigenvalue of parallel analysis. Subsequently, we conducted a genome-wide association study (GWAS) for these factors. In addition, we utilized LD Score Regression (LDSC) to determine the genetic correlations between the identified factors and four common mental disorders, three sleep phenotypes, and other traits that have been previously linked to anxiety and depression., Results: The EFA uncovered two factors for the GAD-7 scale, namely nervousness and disturbance, two factors for the PHQ-9 scale, namely negative affect and sleep/appetite disturbance, and four factors for the joint scale, specifically nervousness, anhedonia, sleep/appetite disturbance, and fidget. We identified two genome-wide significant genomic loci, with overlap across GAD-7 factor 1 and joint scale factor 1: rs148579586 (P GAD-7  = 1.365 × 10 -09 , P Joint scale  = 1.434 × 10 -09 ) and rs201074060 (P GAD-7  = 3.672 × 10 -09 , P Joint scale  = 3.824 × 10 -09 ). Genetic correlations in factors ranged from 0.722 to 1.000 (all p < 1.786 × 10 -03 ) with 27 of 28 correlations being significantly smaller than one. The genetic correlations with external phenotypes showed small variation across the eight factors., Conclusion: Unidimensional structures can provide more precise scores, which can aid in identifying the shared and specific genetic associations between anxiety and depression. This is a crucial step in characterizing the genetic structure of these conditions and their co-occurrence., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Garnet oxides such as Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) are promising solid electrolyte materials for all-solid-state lithium-metal batteries because of high ionic conductivity, low electronic leakage, and wide electrochemical stability window. While LLZTO has been frequently discussed to be stable against lithium metal anode, it is challenging to achieve and maintain good solid-on-solid wetting at the metal/ceramic interface in both processing and extended electrochemical cycling. Here we address the challenge by a powder-form magnesium nitride additive, which reacts with the lithium metal anode to produce well-dispersed lithium nitride. The in situ formed lithium nitride promotes reactive wetting at the Li/LLZTO interface, which lowers interfacial resistance, increases critical current density (CCD), and improves cycling stability of the electrochemical cells. The additive recipe has been diversified to titanium nitride, zirconium nitride, tantalum nitride, and niobium nitride, thus supporting the general concept of reactive dispersion-plus-wetting. Such a design can be extended to other solid-state devices for better functioning and extended cycle life., (© 2023 Wiley-VCH GmbH.)

The aim of this study was to investigate the possible interaction of mitochondrial dysfunction and inflammatory cytokines in the risk of anxiety and depression. We utilized the UK Biobank for the sample of this study. A mitochondria-wide association(MiWAS) and interaction analysis was performed to investigate the interaction effects of mitochondrial DNA (mtDNA)×C-reactive protein (CRP) on the risks of self-reported anxiety (N = 72,476), general anxiety disorder (GAD-7) scores (N = 80,853), self-reported depression (N = 80,778), Patient Health Questionnaire (PHQ-9) scores (N = 80,520) in total samples, females and males, respectively, adjusting for sex, age, Townsend deprivation index (TDI), education score, alcohol intake, smoking and 10 principal components. In all, 25 mtSNPs and 10 mtSNPs showed significant level of association with self-reported anxiety and GAD-7 score respectively. A total of seven significant mtDNA × CRP interactions were found for anxiety, such as m.3915G>A(MT-ND1) for self-reported anxiety in total subjects (P = 6.59 × 10 -3 ), m.4561T>C(MT-ND2) (P = 3.04 × 10 -3 ) for GAD-7 score in total subjects. For depression, MiWAS identified 17 significant mtSNPs for self-reported depression and 14 significant mtSNPs for PHQ-9 scores. 17 significant mtDNA associations (2 for self-reported depression and 15 for PHQ-9 score) was identified, such as m.14869G>A(MT-CYB; P = 2.22 × 10 -3 ) associated with self-reported depression and m.4561T>C (MT-ND2; P value = 3.02 × 10 -8 ) associated with PHQ-9 score in all subjects. In addition, 5 common mtDNA shared with anxiety and depression were found in MiWAS, and 4 common mtDNA variants were detected to interact with CRP for anxiety and depression, such as m.9899T>C(MT-CO3). Our study suggests the important interaction effects of mitochondrial function and CRP on the risks of anxiety and depression., (© 2023. The Author(s).)

Objectives: Alcohol dependence accounts for a large proportion of the global burden of disease and disability. This study aims to investigate the candidate genes and chemicals associated with alcohol dependence., Methods: Using data from published alcohol dependence genome-wide association studies, we first conducted a proteome-wide association study of alcohol dependence by integrating alcohol dependence genome-wide association studies with 2 human brain reference proteomes of dorsolateral prefrontal cortex from the Religious Order Study and Rush Memory and Aging Project and the Banner Sun Health Research Institute. Then, based on the identified genes in proteome-wide association study, we conducted functional enrichment analysis and chemical-related functional enrichment analysis to detect the related Gene Ontology terms and chemicals., Results: Proteome-wide association study identified several potential candidate genes for alcohol dependence, such as GOT2 ( P = 7.59 × 10 -6 ) and C3orf33 ( P = 5.00 × 10 -3 ). Furthermore, functional enrichment analysis identified multiple candidate Gene Ontology terms associated with alcohol dependence, such as glyoxylate metabolic process (adjusted P = 2.99 × 10 -6 ) and oxoglutarate metabolic process (adjusted P = 9.95 × 10 -6 ). Chemical-related functional enrichment analysis detected several alcohol dependence-related candidate chemicals, such as pitavastatin ( P = 2.00 × 10 -4 ), cannabinoids ( P = 4.00 × 10 -4 ), 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid ( P = 4.00 × 10 -4 ), and gabapentin ( P = 2.00 × 10 -3 )., Conclusions: Our study reports multiple candidate genes and chemicals associated with alcohol dependence, providing novel clues for understanding the biological mechanism of alcohol dependence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

There is a strong link between irritable bowel syndrome and brain volumes, yet, to date, research examining the mediators of this association has been little. Based on the phenotypic data of 15 248 participants from the UK Biobank, a two-stage mediation analysis was performed to assess the association among brain volumes, anxiety, and irritable bowel syndrome. In the first stage, we identified the candidate mediating role of anxiety for irritable bowel syndrome associated with brain volumes using regression models. Then, we quantified the magnitude of the mediation effects by evaluating the average causal-mediated effect and proportion of mediation through performing mediation analyses in the R package in the second stage. In the first stage, we identified the partly mediating role of anxiety in the association between irritable bowel syndrome and the volume of thalamus ( P left = 1.16 × 10 -4 , P right = 2.41 × 10 -4 ), and grey matter ( P left = 3.22 × 10 -2 , P right = 1.18 × 10 -2 ) in the VIIIa cerebellum. In the second stage, we observed that the proportion of the total effect of irritable bowel syndrome on volume of thalamus mediated by anxiety was 14.3% for the left region ( β Average causal-mediated effect = -0.008, P Average causal-mediated effect = 0.004) and 14.6% for the right region ( β Average causal-mediated effect = -0.007, P Average causal-mediated effect = 0.006). Anxiety mediated 30.8% for the left region ( β Average causal-mediated effect = -0.013, P Average causal-mediated effect = 0.002) and 21.6% for the right region ( β Average causal-mediated effect = -0.010, P Average causal-mediated effect x= 0.018) of the total effect of irritable bowel syndrome on the volume of grey matter in the VIIIa cerebellum. Our study revealed the indirect mediating role of anxiety in the association between irritable bowel syndrome and brain volumes, promoting our understanding of the functional mechanisms of irritable bowel syndrome and its related psychosocial factors., Competing Interests: The authors declare that the publication of this paper has no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Single nucleotide mutations are highly related to the occurrence and development of cancer. The development of simple single nucleotide mutation detection methods with high sensitivity and specificity has great clinical significance for the prevention, diagnosis, treatment and prognosis evaluation of cancer. In recent years, CRISPR/Cas12a has been developed as a highly sensitive, simple and fast tool for nucleic acid detection. However, the specificity and universality of current detection methods based on it are still insufficient, so their clinical applications are limited. Herein, we developed a simple and rapid single nucleotide mutation detection method based on CRISPR/Cas12a system. This method not only solves the problem of PAM sequence restriction of CRISPR/Cas12a, but also significantly improves the specificity of CRISPR/Cas12a for single nucleotide mutation and greatly improves the sensitivity. We detected three clinically significant mutations, PTEN R130Q, BRAF V600E, and TP53 R248W, with a detection limit of 0.1%. Finally, we further verified the clinical practicability of this method. We selected TP53 R248W mutation site for testing. The accuracy of testing results for 10 clinical samples was as high as 100%. In conclusion, the detection method of specific PCR combined with CRISPR/Cas12a is simple, rapid, universal and highly sensitive. We believe that this method has promising application prospects in clinical diagnosis of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein, micron-sized silver particles were prepared using the chemical reduction method by employing a Y-type microjet reactor, silver nitrate as the precursor, ascorbic acid as the reducing agent, and gelatin as the dispersion at room temperature (23 °C ± 2°C). Using a microjet reactor, the two reaction solutions collide and combine outside the reactor, thereby avoiding microchannel obstruction issues and facilitating a quicker and more convenient synthesis process. This study examined the effect of the jet flow rate and dispersion addition on the morphology and size of silver powder particles. Based on the results of this study, spherical and dendritic silver particles with a rough surface can be prepared by adjusting the flow rate of the reaction solution and gelatin concentration. The microjet flow rate of 75 mL/min and the injected gelatin amount of 1% of the silver nitrate mass produced spherical ultrafine silver particles with a size of 4.84 μm and a tap density of 5.22 g/cm 3 .

We aim to explore the combined effects of the smoking and breastfeeding on offspring mental health outcomes. We used data from UK biobank (N = 342,846) to evaluate joint effect of breastfeeding and maternal smoke during pregnancy (MSDP) on seven adult offspring mental health outcomes (self-reported depression, depression score, self-reported anxiety, anxiety score, neuroticism score, self-harm, suicide). We stratified individuals to MSDP group and non-MSDP group as well as breastfeeding group and non-breastfeeding group. Multiple linear regression and logistic regressions analysis were performed between independent variables (MSDP or breastfeeding) and dependent variables separately (seven mental health outcomes) in each stratum. Effect estimates were expressed as β values and OR values. Sex, age, 10 principle components of population structure, smoking, alcohol use, and Townsend deprivation index were examined as covariates. At MSDP grouping level, coefficients (odds ratio [OR]) for association of breastfed as a baby with self-reported anxiety (category variable) were 0.87 (95%CI, (0.82-0.93), P = 1.74 × 10 -5 ) in the MSDP group and 0.83 (95%CI, (0.79-0.87), P = 2.76 × 10 -17 ) in the non-MSDP group. At breastfeeding grouping level, OR for association of MSDP and self-reported anxiety were 1.15 (95%CI, (1.10-1.20), P = 5.36 × 10 -11 ) in breastfeeding group and 1.12(95%CI, (1.06-1.20), P = 2.02 × 10 -4 ) in non-breastfeeding group. At MSDP grouping level, negatively associations were found for breastfeeding and anxiety score (continuable variable) in MSDP group (-0.04 SD change per SD change in MSDP, 95% CI, (- 0.06, - 0.02), P = 2.42 × 10 -3 ) and non-MSDP group (-0.06 SD change per SD change in MSDP, 95%CI, (- 0.07, - 0.04), P = 1.70 × 10 -11 ). At breastfeeding grouping level, positive association was found for MSDP and anxiety score in the breastfeeding group (0.07 SD change per SD change in MSDP, 95%CI, (0.06-0.09), P = 1.49 × 10 -20 ) and non-breastfeeding group (0.07 SD change per SD change in MSDP, 95%CI, (0.05-0.09), P = 7.19 × 10 -8 ). Compared with non-MSDP group, the protective effect (reflected by coefficients) of breastfeeding on anxiety in the MSDP decreased. Our preliminary study found MSDP may lower the protective effect of breastfeeding on the adult offspring anxiety, depression and neuroticism, providing useful recommendations for health care service via quitting smoking during pregnancy and encouraging prolonged breastfeeding., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Psychiatric disorders have great health hazards and the exact pathogeny remains elusive now. We aim to explore the potential interaction effects of mitochondrial function and human behavior on the risks of anxiety and depression., Methods: The genome-wide association study (GWAS) data of mitochondrial function (N = 383,476-982,072) were obtained from published studies. Individual level genotype and phenotype data of anxiety, depression and behavioral factors (including drinking, smoking and physical activity) were all from the UK Biobank (N = 84,805-85,164). We first calculated the polygenic risk scores (PRS) of mitochondrial function as the instrumental variables, and then constructed linear regression analyses to systematically explore the potential interaction effects of mitochondrial function and human behavior on anxiety and depression., Results: In total samples, we observed mitochondrial heteroplasmy (MtHz) vs. Drinking (P GAD-7  = 6.49 × 10 -3 ; P PHQ-9  = 1.89 × 10 -3 ) was positively associated with both anxiety and depression. In males, MtHz vs. Drinking (P Male  = 3.46 × 10 -5 ) was positively correlated with depression. In females, blood mitochondrial DNA copy number (mtDNA-CN) vs. Drinking (P Female  = 8.63 × 10 -3 ) was negatively related to anxiety. Furthermore, we identified additional 6 suggestive interaction effects (P < 0.05) for anxiety and depression., Limitations: Considering all subjects were from UK Biobank, it should be careful to extrapolate our findings to other populations with different genetic background., Conclusions: Our results suggest the significant impacts of mitochondrial function and human behavior interactions on the development of anxiety and depression, providing new clues for clarifying the pathogenesis of anxiety and depression., Competing Interests: Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective To explore how alveolar macrophages from chronic obstructive pulmonary disease (COPD)-model rats affect proliferation and secretion of 16HBE human bronchial epithelial cells and investigate the associated mechanism. Methods Alveolar macrophages were extracted from COPD rats induced by cigarette smoke exposure and LPS instillation through bronchoalveolar lavage, then co-cultured with 16HBE cells in vitro. Exosomes were extracted from alveolar macrophages of rats with exosome isolation kit. The differentially expressed miRNA in exosomes derived from macrophages of rats in COPD group and control group was detected by PCR. miR-380 was overexpressed with miR-380 mimic while the expression of cystic fibrosis transmembrane transduction regulator (CFTR) was knocked down with siRNA in 16HBE cells. The proliferation of 16HBE cells was detected with CCK-8 assay. The migration ability of 16HBE cells was evaluated with Transwell TM migration assay. The levels of mucins (MUC5AC, MUC5B, MUC2) and CFTR expressed by 16HBE cells were detected with Western blot analysis. The expression of TNF-α and IL-6 in the supernatant of 16HBE cells was detected with ELISA. Results The alveolar macrophages from COPD rats enhanced the proliferation and migration of 16HBE cells. The production of mucins and TNF-α as well as IL-6 in 16HBE cells were increased by COPD macrophages. The expression of miR-380 was significantly elevated in exosomes derived from COPD alveolar macrophages. Both overexpression of miR-380 and inhibition of CFTR decreased the expression of CFTR, resulting in the significantly enhanced proliferation and migration of 16HBE cells as well as increased expression of MUC5AC, MUC5B, MUC2 and TNF-α, IL-6. Conclusion The alveolar macrophages from COPD rats can enhance the proliferation and mucin expression as well as inflammatory cytokine secretion of 16HBE cells. This process may be involved with abnormal expression of miR-380 in exosomes of COPD alveolar macrophages and down-regulation of CFTR in bronchial epithelial cells.

Background: Previous studies have suggested a potential association between sleep and telomere length (TL), but its genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between TL and insomnia., Methods: The genome-wide association study (GWAS) datasets of TL and insomnia-related traits were used, including insomnia, snoring, daytime dozing and napping. Based on the polygenic risk scores (PRS) of TL, linear regression and linkage disequilibrium score (LDSC) regression were used to preliminarily explore the association between TL and insomnia parameters in the UK Biobank cohort. Then, we investigated the causal association between TL and insomnia by mendelian randomization (MR) analysis and colocalization analysis., Results: In the UK Biobank cohort, the association between TL and insomnia was observed in the female samples (t = 2.968, P = 3.00 × 10 -3 ). LDSC detected a genetic correlation between short TL and insomnia (Rg = -9.27 × 10 -2 , P = 8.00 × 10 -4 ). We found no evidence supporting significant causal association between insomnia and TL in IVW method (b = -5.95 × 10 -3 , P = 0.57), with horizontal pleiotropy and heterogeneity tests indicating the validity of our MR study. Finally, rs12638862 was classified as colocalized by COLOC (PP4 = 0.99), and TERC may be involved in regulating the association between insomnia and TL., Conclusions: Our study found no evidence for causal association between insomnia and TL in individuals of European ancestry. We detected a candidate gene associated with both insomnia and TL, providing novel clues for understanding the roles of this association., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Comparing with the general population, the pain in depression patients has more complex biological mechanism. We aim to explore the etiological mechanism of pain in depression patients from the perspective of genetics., Methods: Utilizing the UK Biobank samples with self-reported depression status or PHQ score ≥10, we conducted genome-wide association studies (GWAS) of seven pain traits (N = 1,133-58,349). Additionally, we used FUSION pipeline to perform proteome-wide association study (PWAS) and transcriptome-wide association study (TWAS) by integrating GWAS summary data with two different proteome reference weights (ROS/MAP and Banner) and Rnaseq gene expression reference weights, respectively., Results: GWAS identified 3 significant genes associated with different pain traits in depression patients, including TRIOBP (P GWAS  = 4.48 × 10 -8 ) for stomach or abdominal pain, SLC9A9(P GWAS  = 2.77 × 10 -8 ) for multisite chronic pain (MCP) and ADGRF1 (P GWAS  = 1.51 × 10 -8 ) for neck or shoulder pain. In addition, PWAS and TWAS analysis also identified multiple candidate genes associated with different pain traits in depression patients, such as TPRG1L (P PWAS-Banner  = 3.38 × 10 -2 ) and SIRPA (P PWAS-Banner  = 3.65 × 10 -2 ) for MCP, etc. Notably, when comparing the results of PWAS and TWAS analysis, we found overlapping candidate genes in these pain traits, such as GSTM3 (P PWAS - Banner  = 3.38 × 10 -2 , P TWAS  = 6.92 × 10 -3 ) in the stomach or abdominal pain phenotype, ATG7 (P PWAS - Rosmap  = 3.15 × 10 -2 , P TWAS  = 2.98 × 10 -2 ) in the MCP, etc. CONCLUSIONS: We identified multiple novel candidate genes for pain traits in depression patients from different perspectives of genetics, which provided novel clues for understanding the genetic mechanisms underlying the pain in depression patients., Competing Interests: Declaration of competing interest All authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The role of neurological proteins in the development of bipolar disorder (BD) and schizophrenia (SCZ) remains elusive now. The current study aims to explore the potential genetic correlations of plasma neurological proteins with BD and SCZ., Methods: By using the latest genome-wide association study (GWAS) summary data of BD and SCZ (including 41,917 BD cases, 11,260 SCZ cases, and 396,091 controls) derived from the Psychiatric GWAS Consortium website (PGC) and a recently released GWAS of neurological proteins (including 750 individuals), we performed a linkage disequilibrium score regression (LDSC) analysis to detect the potential genetic correlations between the two common psychiatric disorders and each of the 92 neurological proteins. Two-sample Mendelian randomisation (MR) analysis was then applied to assess the bidirectional causal relationship between the neurological proteins identified by LDSC, BD and SCZ., Results: LDSC analysis identified one neurological protein, NEP , which shows suggestive genetic correlation signals for both BD (coefficient = -0.165, p value = 0.035) and SCZ (coefficient = -0.235, p value = 0.020). However, those association did not remain significant after strict Bonferroni correction. Two sample MR analysis found that there was an association between genetically predicted level of NEP protein, BD (odd ratio [OR] = 0.87, p value = 1.61 × 10 -6 ) and SCZ (OR = 0.90, p value = 4.04 × 10 -6 ). However, in the opposite direction, there is no genetically predicted association between BD, SCZ, and NEP protein level., Conclusion: This study provided novel clues for understanding the genetic effects of neurological proteins on BD and SCZ.

Deformations or remodeling of the lamina cribrosa (LC) induced by elevated intraocular pressure (IOP) are associated with optic nerve injury. The quantitative analysis of the morphology changes of the LC will provide the basis for the study of the pathogenesis of glaucoma. After the chronic high-IOP rat model was induced by cauterizing episcleral veins with 5-Fluorouracil subconjunctival injection, the optic nerve head (ONH) cross sections were immunohistochemically stained at 2 w, 4 w, 8 w, and 12 w. Then the sections were imaged by a confocal microscope, and six morphological parameters of the ONH were calculated after the images were processed using Matlab. The results showed that the morphology of the ONH changed with the duration of chronic high IOP. The glial LC pore area fraction, the ratio of glial LC pore area to the glial LC tissue area, first decreased at 2 w and 4 w and then increased to the same level as the control group at 8 w and continued to increase until 12 w. The number and density of nuclei increased significantly at 8 w in the glial LC region. The results might mean the fraction of glial LC beam increased and astrocytes proliferated at the early stage of high IOP. Combined with the images of the ONH, the results showed the glial LC was damaged with the duration of chronic elevated IOP.

Background: Growing evidence supports that alterations in the gut microbiota play an essential role in the etiology of anxiety, depression, and other psychiatric disorders. However, the potential effect of oral microbiota on mental health has received little attention., Methods: Using the latest genome-wide association study (GWAS) summary data of the oral microbiome, polygenic risk scores (PRSs) of 285 salivary microbiomes and 309 tongue dorsum microbiomes were conducted. Logistic and linear regression models were applied to evaluate the relationship between salivary-tongue dorsum microbiome interactions with anxiety and depression. Two-sample Mendelian randomization (MR) was utilized to compute the causal effects between the oral microbiome, anxiety, and depression., Results: We observed significant salivary-tongue dorsum microbiome interactions related to anxiety and depression traits. Significantly, one common interaction was observed to be associated with both anxiety score and depression score, Centipeda periodontii SGB 224 × Granulicatella uSGB 3289 (P depressionscore = 1.41 × 10 -8 , P anxietyscore = 5.10 × 10 -8 ). Furthermore, we detected causal effects between the oral microbiome and anxiety and depression. Importantly, we identified one salivary microbiome associated with both anxiety and depression in both the UKB database and the Finngen public database, Eggerthia (P IVW - majordepression - UKB = 2.99 × 10 -6 , P IVW - Self - reportedanxiety/panicattacks - UKB = 3.06 × 10 -59 , P IVW - depression - Finngen = 3.16 × 10 , - 16 P IVW - anxiety - Finngen = 1.14 × 10 -115 )., Conclusion: This study systematically explored the relationship between the oral microbiome and anxiety and depression, which could help improve our understanding of disease pathogenesis and propose new diagnostic targets and early intervention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chen, Wen, Jia, Cheng, Liu, Zhang, Pan, Zhang, Zhang, Yang, Meng, Yao and Zhang.)

Objectives: To explore the roles of rare and high-impact variants in sleep duration., Design: Based on the recently released UK Biobank 200k exome dataset, an exome-wide association study was conducted to detect rare variants (minor allele frequency <0.01) contributing to sleep duration. Variant annotations were performed by the software tool ANNOVAR. Gene-based burden tests of sleep duration were conducted by the SKAT R-package. After quality control, 137,047 subjects were included in this study. CAUSALdb database was used to explore the related mental traits of identified genes., Results: We detected 730,572 variants with MAF < 1%, including 3873 frameshift variants, 3977 nonframeshift variants, 449,632 nonsynonymous variants, 1293 startloss variants, 10,254 stopgain variants, 413 stoploss variants, 261,130 synonymous variants, and 3102 variants are annotated as unknown. The burden test of exonic variants detected two exome-wide significant associations for sleep duration including TMIE at 3p21.31 (P Bonferroni adjusted  = 0.015) and ZIC2 at 13q32.3 (P Bonferroni adjusted  = 0.047). There are only nonsynonymous contained in TMIE; as for ZIC2, we detected 2 annotations of variants: nonsynonymous (P Bonferroni adjusted =2.04 × 10 -4 ) and nonframeshift (P Bonferroni adjusted =0.85). TMIE and ZIC2 were reported to be associated with several mental traits, such as chronotype, depression, and brain natriuretic peptide in published study., Conclusion: This study reported 2 novel candidate genes for a sleep duration, supporting the roles of rare genetic variants in the regulation of sleep duration., Competing Interests: Declaration of Conflicts of Interest All authors declared that they have no conflicts of interest to this work., (Copyright © 2022 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

We aim to explore the potential interaction effects of brain aging and gut microbiota on the risks of sleep, anxiety and depression disorders. The genome-wide association study (GWAS) datasets of brain aging (N = 21,407) and gut microbiota (N = 3,890) were obtained from published studies. Individual level genotype and phenotype data of psychiatric traits (including sleep, anxiety and depression) were all from the UK Biobank (N = 107,947-374,505). We first calculated the polygenic risk scores (PRS) of 62 brain aging modes and 114 gut microbiota taxa as the instrumental variables, and then constructed linear and logistic regression analyses to systematically explore the potential interaction effects of brain aging and gut microbiota on psychiatric disorders. We observed the interaction effects of brain aging and gut microbiota on sleep, anxiety and depression disorders, such as Putamen/caudate T2* vs. Rhodospirillales (β = -0.012, P = 8.4 × 10 -4 ) was negatively associated with chronotype, Fornix MD vs. Holdemanella (β = -0.007, P = 1.76 × 10 -2 ) was negatively related to general anxiety disorder (GAD) scores, and White matter lesions vs. Acidaminococcaceae (β = 0.019, P = 1.29 × 10 -3 ) was positively correlated with self-reported depression. Interestingly, Putamen volume vs. Intestinibacter was associated with all three psychiatric disorders, including chronotype (negative correlation), GAD scores (positive correlation) and self-reported depression (positive correlation). Our study results suggest the significant impacts of brain aging and gut microbiota on the development of sleep, anxiety and depression disorders, providing new clues for clarifying the pathogenesis of these disorders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 ( p PWAS-ROS/MAP = 3.00 × 10 -5 ) and C3orf18 ( p PWAS-Banner = 7.07 × 10 -31 ). Moreover, the TWAS also detected multiple candidate genes associated with PTSD in two different reference weight groups, including RIMS2 ( p TWAS-Splicing = 3.84 × 10 -2 ), CHMP1A ( p TWAS-Rnaseq = 5.09 × 10 -4 ), and SIRT5 ( p TWAS-Splicing = 4.81 × 10 -3 ). Further comparison of the PWAS and TWAS results in different populations detected the overlapping genes: MADD ( p PWAS-Banner = 4.90 × 10 -2 , p TWAS-Splicing = 1.23 × 10 -2 ) in the total population and GLO1 ( p PWAS-Banner = 4.89 × 10 -3 , p TWAS-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.

Multiple previous studies explored the associations between early life factors and the age at onset of the depression. However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Based on previous genome-wide association study (GWAS) data, we first calculated polygenic risk score (PRS) for depression. Regression analyses were conducted to assess the interacting effects of depression PRS and 5 early life factors, including felt hated by family member (N = 40,112), physically abused by family (N = 40,464), felt loved (N = 35633), and sexually molested (N = 41,595) in childhood and maternal smoking during pregnancy (N = 38,309), on the age at onset of the depression. Genome-wide environment interaction studies (GWEIS) were then performed to identify the genes interacting with early life factors for the age at onset of the depression. In regression analyses, we observed significant interacting effects of felt loved as a child and depression PRS on the age at onset of depression in total sample (β = 0.708, P = 5.03 × 10 -3 ) and males (β = 1.421, P = 7.64 × 10 -4 ). GWEIS identified a novel candidate loci interacting with felt loved as a child at GSAP (rs2068031, P = 4.24 × 10 -8 ) and detected several genes with suggestive significance association, such as CMYA5 (rs7343, P = 2.03 × 10 -6 ) and KIRREL3 (rs535603, P = 4.84 × 10 -6 ) in males. Our results indicate emotional care in childhood may affect the age at onset of depression, especially in males, and GSAP plays an important role in their interaction., (© 2022. The Author(s).)

Background: Despite cumulative evidence showing obesity is associated with changes in sleep quality and quantity, the study about the relationships between sleep and body composition is scarce, and whether the relationship is causal remains unknown. In this study, we examined whether there are causal associations between sleep and body composition., Methods: First, we estimated genetic correlations between sleep-related phenotypes and body composition using the linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis was then conducted to test 2-way causal relationships on phenotypes with significant genetic associations. Finally, Bayesian colocalization (COLOC) analysis was performed to calculate the posterior probability of causal variation and identify the common genes to verify the results of MR., Results: For the LDSC analysis, we observed some significant genetic correlations (rG), such as snoring and right leg fat mass (rG = 0.376, P = 7.21 × 10-80). For the MR analysis, we identified some significant causal relationships, such as snoring is the causal risk factor for whole-body fat-free mass (Pweighted median = 1.28 × 10-6, PMR-PRESSO = 1.35 × 10-7), dozing is the causal risk factor for right leg fat mass (Pweighted median = 9.22 × 10-4, PMR-PRESSO = 9.55 × 10-4), and right arm fat mass (Pweighted median = 1.11 × 10-40, PMR-PRESSO = 4.93 × 10-55) is the causal risk factor for snoring. For the COLOC analysis, we identified rs143384 mapping on GDF5 and 6 overlapped single nucleotide polymorphisms (eg, rs1421085, rs11642015) mapping on FTO., Conclusion: Our study identified the causal relationships between sleep-related phenotypes and body composition. These findings may give insights into the mechanism of sleep disturbances and provide novel therapeutic targets., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite thousands of common genetic loci of major depression disorders (MDD) have been identified by GWAS to date, a large proportion of genetic variation predisposing to MDD remains unaccounted for. By utilizing the newly released UK Biobank 200,643 exome dataset, we conducted an exome-wide association study to identify rare risk variants contributing to MDD. After quality control, 120,033 participants with MDD polygenic risk scores (PRS) values were included. The individuals with lower 30% quantile of the PRS value were filtered for case and control selecting. Then the cases were set as the individuals with upper 10% quantile of the PHQ depression score and lower 10% quantile were set as controls. Finally, 1612 cases and 1612 controls were included in this study. The variants were annotated by ANNOVRA software. After exclusions, 34,761 qualifying variants, including 148 frameshift variant, 335 non-frameshift variant, 33,758 nonsynonymous, 91 start-loss, 393 stop-gain, 36 stop-loss variants were imported into the SKAT R-package to perform single variants, gene-based burden and robust burden tests with minor allele frequency (MAF) < 0.01. Single variant association testing identified one variant, rs4057749 (P = 5.39 × 10 -9 ), within OR8B4 gene at an exome-wide significance level. The gene-based burden test of the exonic variants identified genome-wide significant associations in OR8B4 (P SKAT  = 6.23 × 10 -5 , P SKAT Robust  = 4.49 × 10 -5 ), TRAPPC11 (P SKAT  = 0.014, P SKAT Robust  = 0.015), SBK3 (P SKAT  = 0.020, P SKAT Robust  = 0.025) and TNRC6B (P SKAT  = 0.026, P SKAT Robust  = 0.036). We identified multiple novel rare risk variants contributing to MDD in the individuals with lower PRS of MDD. The findings can help to broaden the genetic insights of the MDD pathogenesis., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Acute myeloid leukemia (AML) is a common hematologic malignancy. To this day, diagnose of AML and its genetic mutation still rely on invasive and time-consuming methods. In this study, 222 plasma samples were collected to discuss the performance of surface-enhanced Raman spectroscopy (SERS) to discriminate AML subtype acute promyelocytic leukemia and acute monocytic leukemia based on plasma. The Ag nanoparticles-based SERS technique was used to explore the biochemical differences among different AML subtypes. With the help of powerful supervised and unsupervised algorithms, the performance using the whole spectra and band intensities was confirmed to identify different subtypes of AML. The results demonstrated the intensities of several bands and band-intensity ratios were significantly different between groups, thus related to the discrimination of several AML subtypes and control. Combining indexes of band-intensity ratios, the result of multi-indexes ROC has excellent performance in differentiating AML patient with healthy control. Our work demonstrated the great potential of SERS technique as a rapid and micro detection method in clinical laboratory field, it's a new and powerful tool for analyzing human blood plasma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The effects of gene-by-environment (G×E) interactions on complex diseases are significant, especially the superimposed effects of multiple environmental factors. However, research on the multi-environments-gene interactions of anxiety, depression, and self-harm is still limited. This study included white individuals (N = 66,041-74,482) from the UK Biobank. We fitted all environmental factors to a single environmental score (ES), and the estimated ES was used to calculate the multiplicative interaction effects between ES and genome-wide SNPs. Heritability was stratified by minor allele frequency (MAF) and linkage disequilibrium (LD). Our research found 10 loci with significant interaction effects, such as rs114830993 (PRICKLE2, P = 2.30 × 10 -8 ), rs151323364 (ASTN2, P = 2.71 × 10 -10 ) and rs536631793 (SYN3, P = 4.09 × 10 -8 ). In addition, we found that G×E heritability has a significant contribution to the depression of Patient Health Questionnaire-9 (PHQ-9) scores (h 2 G×E (female)  = 6.1%, h 2 G×E (male)  = 8.7%). Our research supported the important influence of multi-environments-gene interactions on anxiety, depression, and self-harm and provided clues for the prevention and etiological research of them., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Garnet-type Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) electrolyte is considered as a promising solid electrolyte because of its relatively high ionic conductivity and excellent electrochemical stability. The surface contamination layer and poor Li/LLZTO interface contact cause large interfacial resistance and quick Li dendrite growth. In this paper, a porous hard carbon layer is introduced by the carbonization of a mixed layer of phenolic resin and polyvinyl butyral on the LLZTO surface to improve Li/garnet interfacial wettability. The multi-level pore structure of the hard carbon interlayer provides capillary force and large specific surface area, which, together with the chemical activity of the carbon material with Li, promote the molten Li infiltration with garnet electrolyte. The Li/LLZTO interface delivers a low interfacial resistance of 4.7 Ω∙cm 2 at 40 °C and a higher critical current density, which can achieve stable Li + conduction for over 800 h under current densities of 0.1 and 0.2 mA∙cm -2 . The solid-state battery coupled with Li and LiFePO 4 exhibits excellent rate and cycling performance, demonstrating the application feasibility of the hard carbon interlayer for a solid state Li metal battery., (© 2021 Wiley-VCH GmbH.)

Purpose: Most previous genetic studies of sleep behaviors were conducted individually, without comprehensive consideration of the complexity of various sleep behaviors. Our aim is to identify the genetic architecture and potential biomarker of the sleep health score, which more powerfully represents overall sleep traits., Patients and Methods: We conducted a genome-wide association study (GWAS) of sleep health score (overall assessment of sleep duration, snoring, insomnia, chronotype, and daytime dozing) using 336,463 participants from the UK Biobank. Proteome-wide association study (PWAS) and transcriptome-wide association study (TWAS) were then performed to identify candidate genes at the protein and mRNA level, respectively. We finally used linkage disequilibrium score regression (LDSC) to estimate the genetic correlations between sleep health score and other functionally relevance traits., Results: GWAS identified multiple variants near known candidate genes associated with sleep health score, such as MEIS1, FBXL13, MED20 and SMAD5. HDHD2 ( P PWAS = 0.0146) and GFAP ( P PWAS = 0.0236) were identified associated with sleep health score by PWAS. TWAS identified ORC4 ( P TWAS = 0.0212) and ZNF732 ( P TWAS = 0.0349) considering mRNA expression level. LDSC found significant genetic correlations of sleep health score with 3 sleep behaviors (including insomnia, snoring, dozing), 4 psychiatry disorders (major depressive disorder, attention deficit/hyperactivity disorder, schizophrenia, autism spectrum disorder), and 9 plasma protein (such as Stabilin-1, Stromelysin-2, Cytochrome c) (all LDSC P LDSC < 0.05)., Conclusion: Our results advance the comprehensive understanding of the aetiology and genetic architecture of the sleep health score, refine the understanding of the relationship of sleep health score with other traits and diseases, and may serve as potential targets for future mechanistic studies of sleep phenotype., Competing Interests: All authors declare that they have no competing interest., (© 2022 Yao et al.)

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 (P PERM.ANL  = 1.68 × 10 -3 ) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (P PERM.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&#95;NUCLEOSIDE&#95;DIPHOSPHATASE&#95;ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10 -4 ), KEGG&#95;RENIN&#95;ANGIOTENSIN&#95;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., (© 2021. The Author(s).)

Objective: This study was aimed to evaluate the associations of adult heel bone mineral density (BMD) with birth weight and growth parameters at the age of ten years., Methods: The analysis data (97178-178,494 subjects) was derived from the UK Biobank cohort. Birth weight, comparative body size and height size at the age of ten years were determined by self-report. The heel BMD was estimated by the Quantitative Ultrasound Index through the calcaneus. Linear regression analysis was applied to test the associations of adult heel BMD with birth weight and growth parameters at the age of ten years, respectively. Age, sex, body mass index and 10 principle components (PC) of population structure were used as covariates in the regression analysis of total samples. In sex-specific analysis, age, body mass index and 10 PC were used as covariates., Results: We observed significant associations of heel BMD with birth weight (b = -0.020, P = 1.974 × 10 -13 ), comparative body size (b = 0.020, P = 2.539 × 10 -6 ) and comparative height size (b = -0.020, P = 5.892 × 10 -11 ) at the age of ten years in total samples. In females, birth weight (b = -0.040, P = 2.870 × 10 -24 ) and comparative height size (b = -0.040, P = 2.034 × 10 -20 ) were statistically associated with adult heel BMD. In males, comparative body size appeared to be associated with adult heel BMD (b = 0.030, P = 1.590 × 10 -7 )., Conclusion: Our study results support the predictive effects of birth weight and growth parameters at the age of ten years on adult heel BMD. We also observed sex-specific association between adult heel BMD and growth parameters at the age of ten years., (Copyright © 2021. Published by Elsevier Inc.)

Previous studies have suggested that vitamin D (VD) was associated with psychiatric diseases, but efforts to elucidate the functional relevance of VD with depression and anxiety from genetic perspective have been limited. Based on the UK Biobank cohort, we first calculated polygenic risk score (PRS) for VD from genome-wide association study (GWAS) data of VD. Linear and logistic regression analysis were conducted to evaluate the associations of VD traits with depression and anxiety traits, respectively. Then, using individual genotype and phenotype data from the UK Biobank, genome-wide environment interaction studies (GWEIS) were performed to identify the potential effects of gene × VD interactions on the risks of depression and anxiety traits. In the UK Biobank cohort, we observed significant associations of blood VD level with depression and anxiety traits, as well as significant associations of VD PRS and depression and anxiety traits. GWEIS identified multiple candidate loci, such as rs114086183 ( p = 4.11 × 10 -8 , LRRTM4) for self-reported depression status and rs149760119 ( p = 3.88 × 10 -8 , GNB5) for self-reported anxiety status. Our study results suggested that VD was negatively associated with depression and anxiety. GWEIS identified multiple candidate genes interacting with VD, providing novel clues for understanding the biological mechanism potential associations between VD and psychiatric disorders.

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&#95;Ruminococcaceae (β = - 0.009, P = 2.2 × 10 -3 ), G&#95;Akkermansia (β = - 0.008, P = 7.60 × 10 -3 ), F&#95;Acidaminococcaceae (β = 0.008, P = 1.22 × 10 -2 ), G&#95;Holdemanella (β = - 0.007, P = 1.39 × 10 -2 ) and O&#95;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&#95;Bacteroidales (β = 0.010, P = 4.00×  10 -4 ), O&#95;Selenomonadales (β = - 0.010, P = 1.20 × 10 -3 ), O&#95;Clostridiales (β = 0.009, P = 2.70 × 10 -3 ) and G&#95;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., (© 2021. The Author(s).)

The use of the conventional pressure-composition-temperature (PCT) method to determine the thermodynamics of metal hydrides is a time-consuming process. This work presents an efficient method based on thermogravimetric analysis (TGA), to characterize the thermodynamic parameters. Through cycling catalyzed magnesium hydride in a TGA apparatus under a flowing gas with a constant hydrogen partial pressure, TGA curves can be used to determine absorption/desorption equilibrium temperatures. Based on the van't Hoff analysis, the reaction enthalpies and entropies can be derived from the equilibrium temperatures as a function of hydrogen pressure. Using the results of this work we calculated the hydrogenation and dehydrogenation enthalpies, which are 79.8 kJ per mol per H2 and 76.5 kJ per mol per H2, respectively. These values are in good agreement with those reported values using the PCT method. These results demonstrate that the TGA can be an efficient and effective method for measuring thermodynamic parameters of metal hydrides.

Background: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities., Methods: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations., Results: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, P =0.001), angina (OR=10.155, P =0.025) and hypertension (OR=3.142, P =0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample., Conclusion: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index - BODEx - and comorbidity parameters can identify patients at high risk of acute exacerbation., Competing Interests: The authors declare that they have no competing interests., (© 2021 Ge et al.)

Purpose: The present study aimed to investigate the prevalence and associated factors of suboptimal daily peak inspiratory flow (PIF) and technical misuse of three commonly used dry powder inhalers (DPIs) in outpatients with stable chronic airway diseases., Patients and Methods: Included in this study were 85 outpatients with stable asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD Overlap (ACO) and had previously used any of Turbuhaler ® (TUR), Diskus ® (DIS), HandiHaler ® (HAN) between December 2018 and September 2019. The patient's daily PIF against the resistance of a specific DPI and operation technique was investigated by two pharmacists by using In-Check DIAL G16 and a checklist., Results: Of the 85 patients, the proportion of patients with a suboptimal daily PIF and technical misuse was 38.8% and 65.9%, respectively. In logistic regression, we observed that the factors that increase the risk for suboptimal daily PIF were age (OR=1.06) and combination with respiratory diseases (OR = 6.59). The factor that decreases the risk for misuse was the higher education level (OR =0.63)., Conclusion: Even if patients have received training at the time of initial prescription, the standardization of the use of DPIs by patients in our center was still unoptimistic. Age and combined with respiratory diseases were associated with suboptimal PIF. Higher education level decreased the incidence of technique misuse., Competing Interests: The authors have no conflicts of interest in this work., (© 2021 Ding et al.)

Background: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma., Methods: OVA sensitized asthma mouse model and house dust mite treated 16HBE cellular model were established and hydrogen/oxygen mixture was used to treat asthmatic mice and 16HBE cells. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-κB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and/or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array., Results: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H 2 in asthmatic mice. The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H 2 . ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H 2 . E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H 2 treatment. H 2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM + H 2 treated 16HBE cells were identified., Conclusions: These data demonstrated that H 2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammatory processes, and exacerbation of COPD represents a critical moment in the progression of COPD. Several biomarkers of inflammation have been proposed to have a predictive function in acute exacerbation. However, their use is still limited in routine clinical practice. The purpose of our study is to explore the prognostic efficacy of novel inflammatory hemogram indexes in the exacerbation among stable COPD patients. Method: A total of 275 stable COPD patients from the Shanghai COPD Investigation Comorbidity Program were analyzed in our study. Blood examinations, especially ratio indexes like platelet-lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio [systemic immune-inflammation index (SII)], and monocyte × neutrophil/lymphocyte ratio [systemic inflammation response index (SIRI)], lung function test, CT scans, and questionnaires were performed at baseline and routine follow-ups. Clinical characteristics and information of exacerbations were collected every 6 months. The relationship between hemogram indexes and diverse degrees of exacerbation was assessed by logistic regression. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the ability of hemogram indexes to predict exacerbation of COPD. Furthermore, the discrimination and accuracy of combined indexes were measured by ROC and calibration curve. Result: There was a significant positive correlation between PLR levels and total exacerbation of COPD patients in a stable stage in a year. Also, the predictive ability of PLR exceeded any other ratio indexes, with an AUC of 0.66. SII and SIRI ranked second only to PLR, with an AUC of 0.64. When combining PLR with other indexes (sex, COPD year, and St. George's Respiratory Questionnaire scores), they were considered as the most suitable panel of index to predict total exacerbation. Based on the result of the ROC curve and calibration curve, the combination shows optimal discrimination and accuracy to predict exacerbation events in COPD patients. Conclusion: The hemogram indexes PLR, SII, and SIRI were associated with COPD exacerbation. Moreover, the prediction capacity of exacerbation was significantly elevated after combining inflammatory hemogram index PLR with other indexes, which will make it a promisingly simple and effective marker to predict exacerbation in patients with stable COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Liu, Ge, Feng, Hang, Zhang, Jin, Bao, Zhou, Han, Li, Qian, Jie, Gu, Gao, Yu, Wang, Ji, Zhang and Zhu.)

Background: Skin commensal bacteria play important roles in skin homeostasis. Langerhans cells (LCs) are epidermis-resident dendritic cells that sense environmental stimuli and are critical in the induction of immune tolerance to allergen and bacterial skin flora. However, response of LCs to the metabolites of the skin microbiota is not clear., Objective: To explore the effects of the skin microbial metabolites on LCs activation., Methods: LCs derived from CD34+ hematopoietic stem cells in the cord blood were treated with a microbial metabolite of tryptophan, indole-3-aldehyde (IAId). Activation aryl hydrocarbon receptor (AhR) signaling, production of IL-10, and expression of receptor activator of NF-κB (RANK) / receptor activator of NF-κB ligand (RANKL) in LCs or keratinocytes were analyzed using quantitative PCR, western blotting and flow cytometry. LCs maturation induced by IAId and CD4 + T cell response induced by IAId-conditioned LCs were also investigated., Results: IAId induced the production of indoleamine 2,3-dioxygenase (IDO) and IL-10 in LCs through the activation of AhR. IAId promoted the expression of RANK and RANKL on LCs and keratinocytes in an AhR-dependent manner respectively, which might result in activation of NF-κB signaling and production of IL-10. Moreover, a mature phenotype of LCs was induced by IAId, and IAId-activated LCs inhibited CD4 + T cell proliferation and induced IL-10 secretion., Conclusions: Our study revealed a negatively regulatory function of a tryptophan metabolite on LCs through the activation of AhR, and the microbial metabolites could be utilized in future treatment for inflammatory skin diseases., (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

As an indispensable component, separator is close related to electrochemical performance and safety of lithium-ion batteries (LIBs). However, the current widely applied polyolefin microporous separator impedes the development of high power LIBs due to poorer electrolyte wettability and inferior thermal stability. Herein, heat-resistant polyphenylene sulfide (PPS) fibers and cellulose fibers (CFs) are adopted to fabricate a novel composite separator (CFs/PPS) via a facile papermaking process. The as-prepared CFs/PPS separator exhibits higher porosity, improved electrolyte uptake and superior wettability. These boost its ionic conductivity and decrease interfacial resistance between CFs/PPS separator and electrode, which further endow battery with good rate capability. Moreover, in comparison to commercial polypropylene separator, CFs/PPS separator gives superior thermal stability, satisfactory mechanical strength, broader electrochemical window and more stable cycle performance. Accordingly, CFs/PPS composite separator is very promising for application in high power LIBs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Anti-PLA2R antibody is only expressed in podocytes from patients with idiopathic membranous nephropathy (IMN). The detection of anti-PLA2R antibody in serum is therefore able to obtain essential information for rapid diagnosis and evaluation of the disease activity of IMN. In the present study, a polydopamine nanosphere-based fluorescent sensor was constructed for direct detection of anti-PLA2R antibodies in human serum. In this sensing system, the double-stranded DNA was phosphorylated under the action of anti-PLA2R antibody and the single-stranded DNA was cut by exonuclease. The single-stranded DNA was then adsorbed on polydopamine microspheres. The fluorescent groups labeled on the DNA were quenched, and the concentration of anti-PLA2R antibody was detected quantitatively by measuring the fluorescence signal changes before and after the reaction. The experimental results show that the method has a good linear detection range between 0.05 and 10 μg/mL for anti-PLA2R antibody and the detection limit is 0.02 μg/mL. Graphical abstract.

The aim of this study was to explore the predictive value of procalcitonin (PCT) in Gram-negative bloodstream infections (BSIs) in hematological patients with febrile neutropenia. A total of 1466 samples (396 blood culture (BC)-positive, 1052 BC-negative, and 18 contaminated specimens) were included, comprising 268 Gram-negative, 88 Gram-positive, 19 fungal, and 21 polymicrobial BSIs. Median PCT value (0.72 ng/mL; IQR: 0.23-3.87) was significantly higher in Gram-negative than Gram-positive (0.34 ng/mL; IQR: 0.14-2.23; p  < .01), or fungal (0.27 ng/mL; IQR: 0.13-0.40; p  < .01) BSIs. In mono-microbial BSIs, the best PCT cutoff distinguishing Gram-negative BSIs from all other fever causes was 0.56 ng/ml, with a specificity of 76.8%. PCT levels were significantly higher in BSIs from multidrug-resistant (MDR) Gram-negative strains than from non-MDR (p <  .01). This study confirms that elevated PCT may predict Gram-negative BSIs in hematological patients with febrile neutropenia, and demonstrates higher PCT levels in MDR Gram-negative BSIs in these patients.

Previous studies have shown independently that the skin and gut microbiota are closely associated with atopic dermatitis (AD); however, the microbiota across different habitats of AD patients as an integrated community has not been characterized. In the present study, we comparatively analyzed the structure and function of the microbial communities in the skin, oral cavity, and gut of 172 AD patients and 120 healthy controls through 16S ribosomal RNA gene amplicon sequencing. The skin and oral cavity, but not the gut, of AD patients demonstrated differential reduction in the microbial diversity, and these were distinctly correlated with disease severity. Different degrees of shifts in the community structure were found among different habitats, and the lineage distance between the skin and oral microbiota of AD patients was closer than that observed in the controls. The different habitats of AD patients exhibited site-specific alterations at the genus level, and many oral-specific microbes of AD showed opposing directions of enrichment in the skin and oral cavity. Most interestingly, an inverse association in the functional pathways was found between the skin and oral microbiota of AD patients. Additionally, the alterations of the microbiota in different body sites of AD patients were differentially affected by age., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)