Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation.

To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice. The same increase in CG methylation was also observed in male vessels incubated with a physiological concentration of 17ß-estradiol (17ß-E2) for 48 hours. All vessels that displayed increases in CG methylation were concomitantly associated with decreases in their Ephx2 mRNA and protein, suggesting a methylation-induced gene silencing. Transient transfection assays indicate that the activity of Ephx2 promoter-coding luciferase was significantly attenuated in HEK293T cells treated with 17ß-E2, which was prevented by additional treatment with an estrogen receptor antagonist (ICI). ChIP analysis indicates significantly reduced binding activities of transcription factors (including SP1, AP-1, and NF-κB with their binding elements located in the Ephx2 promoter) in vessels of female mice and human cells treated with 17ß-E2, responses that were prevented by ICI and Decitabine (DNA methyltransferase inhibitor), respectively. In conclusion, estrogen/estrogen receptor-dependent methylation of the promoter of Ephx2 gene silences sEH expression, which is involved in specific transcription factor-directed regulatory pathways.

Biennial Upsurge and Molecular Epidemiology of Enterovirus D68 Infection in New York, USA, 2014 to 2018.

Enterovirus D68 (EV-D68) infection has been associated with outbreaks of severe respiratory illness and increased cases of nonpolio acute flaccid myelitis. The patterns of EV-D68 circulation and molecular epidemiology are not fully understood. In this study, nasopharyngeal (NP) specimens collected from patients in the Lower Hudson Valley, New York, from 2014 to 2018 were examined for rhinovirus/enterovirus (RhV/EV) by the FilmArray respiratory panel. Selected RhV/EV-positive NP specimens were analyzed using two EV-D68-specific real-time RT-PCR assays, Sanger sequencing and metatranscriptomic next-generation sequencing. A total of 2,398 NP specimens were examined. EV-D68 was detected in 348 patients with NP specimens collected in 2014 (n = 94), 2015 (n = 0), 2016 (n = 160), 2017 (n = 5), and 2018 (n = 89), demonstrating a biennial upsurge of EV-D68 infection in the study area. Ninety-one complete or nearly complete EV-D68 genome sequences were obtained. Genomic analysis of these EV-D68 strains revealed dynamics and evolution of circulating EV-D68 strains since 2014. The dominant EV-D68 strains causing the 2014 outbreak belonged to subclade B1, with a few belonging to subclade B2. New EV-D68 subclade B3 strains emerged in 2016 and continued in circulation in 2018. Clade D strains that are rarely detected in the United States also arose and spread in 2018. The establishment of distinct viral strains and their variable circulation patterns provide essential information for future surveillance, diagnosis, vaccine development, and prediction of EV-D68-associated disease prevalence and potential outbreaks.

Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome.

The extended-spectrum-ß-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different plasmids. In contrast, CN1 had one copy of blaKPC-2 and three copies of blaCTX-M-15 integrated in the chromosome, for which the blaCTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the blaKPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-blaKPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of blaCTX-M and blaKPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance.

Role of CgHOG1 in Stress Responses and Glycerol Overproduction of Candida glycerinogenes.

Candida glycerinogenes, the glycerol producer with excellent multi-stress tolerances, is considered to be a potential biotechnological host used in the production of glycerol and its derivatives under extreme fermentation conditions. In this study, to evaluate the multiple roles of mitogen-activated protein kinase CgHOG1, we constructed a gene disruption system in the diploid C. glycerinogenes to obtain CgHOG1 null mutant. Pseudohyphae generation of the CgHOG1 mutant under non-inducing condition indicated a repressor role in morphological transitions. Disruption of CgHOG1 resulted in increased sensitivities to osmotic, acetic acid, and oxidative stress but not involved in thermotolerance. In the CgHOG1 mutant, NaCl shock failed to stimulate the accumulation of intracellular glycerol and was fatal. In addition, the CgHOG1 mutant displayed a significant prolonged growth lag phase in YPD medium with no decrease in glycerol production, whereas the mutant cannot grow under hyperosmotic condition with no detectable glycerol in broth. These results suggested that CgHOG1 plays important roles in morphogenesis and multi-stress tolerance. The growth and glycerol overproduction under osmotic stress are heavily dependent on CgHOG1 kinase.

Recurrent TERT promoter mutations in urothelial carcinoma and potential clinical applications.

Increased telomerase activity is associated with almost all types of advanced human cancers with unknown molecular mechanism(s). Two recurrent point mutations in the promoter region of telomerase reverse transcriptase (TERT)--the key subunit of telomerase--have recently been identified in melanoma as well as a small sample of bladder cancer cell lines. However, the incidence and clinical-pathological significance of these mutations in urothelial carcinoma have not been well established yet. We collected 86 specimens of urothelial carcinoma including upper and lower urinary tract: high grade and low grade, invasive and noninvasive, and primary and metastatic. We also included some matched benign urothelium and common benign bladder lesions: cystitis, nephrogenic adenoma, and inverted papilloma. In addition, we collected urine samples for urothelial carcinoma workup; blood samples from patients underwent cystectomy with extensive lymphovascular invasion. All specimens were subject to polymerase chain reaction amplification and bidirectional Sanger sequencing for the TERT promoter mutations: C228T and C250T. We found that 64 (74%) of 86 carcinoma samples harbored 1 of the 2 TERT promoter mutations (C228T, n = 54; C250T, n = 10); the incidences were roughly equal regardless of site of origin, histologic grade, and invasive status. All matched benign and benign lesion samples showed wild-type sequence. These TERT promoter mutations are the most common genetic alterations in urothelial carcinoma and are not associated with tumor locations, grade, or invasiveness. Importantly, the feasibility of detecting these mutations in urine samples may provide a novel method to detect urothelial carcinoma in urine.

Evaluation of a Real-Time Reverse Transcription-PCR Assay for Detection of Enterovirus D68 in Clinical Samples from an Outbreak in New York State in 2014.

An outbreak of severe respiratory illness associated with enterovirus D68 (EV-D68) infection was reported in mid-August 2014 in the United States. In this study, we evaluated the diagnostic utility of an EV-D68-specific real-time reverse transcription-PCR (rRT-PCR) that was recently developed by the Centers for Disease Control and Prevention in clinical samples. Nasopharyngeal (NP) swab specimens from patients in a recent outbreak of respiratory illness in the lower Hudson Valley, New York State, were collected and examined for the presence of human rhinovirus or enterovirus using the FilmArray Respiratory Panel (RP) assay. Samples positive by RP were assessed using EV-D68 rRT-PCR, and the data were compared to results from sequencing analysis of partial VP1 and 5' untranslated region (5'-UTR) sequences of the EV genome. A total of 285 RP-positive NP specimens (260 from the 2014 outbreak and 25 from 2013) were analyzed by rRT-PCR; EV-D68 was detected in 74 of 285 (26.0%) specimens examined. Data for comparisons between rRT-PCR and sequencing analysis were obtained from 194 NP specimens. EV-D68 detection was confirmed by sequencing analysis in 71 of 74 positive and in 1 of 120 randomly selected negative specimens by rRT-PCR. The EV-D68 rRT-PCR showed diagnostic sensitivity and specificity of 98.6% and 97.5%, respectively. Our data suggest that the EV-D68 rRT-PCR is a reliable assay for detection of EV-D68 in clinical samples and has a potential to be used as a tool for rapid diagnosis and outbreak investigation of EV-D68-associated infections in clinical and public health laboratories.

Integrative expression vectors for overexpression of xylitol dehydrogenase (XYL2) in Osmotolerant yeast, Candida glycerinogenes WL2002-5.

Yeasts are excellent hosts for the production of recombinant proteins. Candida glycerinogenes WL2002-5, an osmotolerant yeast with extremely high glycerol productivity, provides an attractive eukaryotic expression platform. The integrative vectors PURGAP-gfp and PURGPD-gfp harbouring phleomycin-resistance coding sequence and GFP coding sequence with PCgGAP, PCgGPD promoter, respectively, were constructed. The recombinant plasmid PURPpGAP-gfp with the promoter PPpGAP based on the sequence of Pichia pastoris GAPDH gene and the plasmid PURScGAP-gfp with the promoter PScGAP from Saccharomyces cerevisiae were constructed. After transformation, the copy number of gfp gene, which determined using fluorescent quantitative real-time polymerase chain reaction (FQ-RTPCR) in genome of C. glycerinogenes is 1. Expressions of gfp at different levels were conducted using different promoters by osmotic stress containing NaCl or glucose for the recombinant strains. In this study, C. glycerinogenes WL2002-5, expressing xylitol dehydrogenase (XYL2) gene from Pichia stipitis, has the ability to produce glycerol from xylose entered into pentose phosphate pathway. Two recombinant strains of PURGAPX, PURGPDX with XYL2 overexpression were constructed to ferment a mixture of glucose and xylose simultaneously in batch fermentation. Compared to C. glycerinogenes WL2002-5 strain, glycerol production from xylose in strains PURGAPX, PURGPDX were increased by 95.9 and 121.1 %, respectively.

Heterogeneity of TERT promoter mutations status in squamous cell carcinomas of different anatomical sites.

Squamous cell carcinoma (SCC) can arise from different anatomical sites including the skin, head and neck, lung, esophagus, genital area, and so on. Despite the same histopathologic features and immunohistochemistry profile, the SCCs of different body sites can show tremendous differences in their presenting symptoms, risk factor associations, natural history, prognosis, and response to treatment. This may reflect the fact that SCCs are heterogenous and likely have unique molecular characteristics at different anatomical sites. Recurrent somatic mutations in the TERT promoter region were first reported in human melanomas. Subsequently, other tumors including cutaneous SCC were found to demonstrate high frequencies of the same mutations. However, the incidences of TERT promoter mutation in noncutaneous SCCs have not been systemically studied. We investigated the TERT promoter mutation status among SCCs from different sites. We collected 84 cases of SCC from the skin (27), head and neck (12), lung (25), and cervix (10), as well as 10 cases of urothelial carcinoma with squamous differentiation (UC-SqD). We found that the frequencies of TERT promoter mutation among SCC of different sits are quite heterogenous: ~70% in skin SCC and UC-SqD, 16.67% in head and neck SCC, and 0% in lung and cervix SCC. These results may support the hypothesis of different carcinogenesis mechanisms of SCC in different sites. It also indicates that TERT promoter mutation could be a biomarker for distinguishing skin SCC or UC-SqD vs pulmonary SCC.

Identification of a novel clone, ST736, among Enterococcus faecium clinical isolates and its association with daptomycin nonsusceptibility.

Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycin-nonsusceptible enterococcal clinical isolates. In this study, we assessed the population genetics of daptomycin-nonsusceptible Enterococcus faecium (DNSE) clinical isolates by multilocus sequence typing (MLST) and whole-genome sequencing analysis. Forty-two nonduplicate DNSE isolates and 43 randomly selected daptomycin-susceptible E. faecium isolates were included in the analysis. All E. faecium isolates were recovered from patients at a tertiary care medical center in suburban New York City from May 2009 through December 2013. The daptomycin MICs of the DNSE isolates ranged from 6 to >256 µg/ml. Three major clones of E. faecium (ST18, ST412, and ST736) were identified among these clinical isolates by MLST and whole-genome sequence-based analysis. A newly recognized clone, ST736, was seen in 32 of 42 (76.2%) DNSE isolates and in only 14 of 43 (32.6%) daptomycin-susceptible E. faecium isolates (P < 0.0001). This report provides evidence of the association between E. faecium clone ST736 and daptomycin nonsusceptibility. The identification and potential spread of this novel E. faecium clone and its association with daptomycin nonsusceptibility constitute a challenge for patient management and infection control at our medical center.

Identification of a novel HOG1 homologue from an industrial glycerol producer Candida glycerinogenes.

Candida glycerinogenes, a glycerol production industrial strain with hyperosmo-adaptation can grow well in 15 % (w/v) NaCl or 55 % (w/v) glucose. To understand the osmo-adaptation mechanism in C. glycerinogenes, the mitogen-activated protein kinase HOG1 gene (CgHOG1), which plays an essential role in the yeast hyperosmotic response, was isolated by degenerate PCR and SEFA-Formed Adaptor PCR. The CgHOG1 gene was then transformed in Saccharomyces cerevisiae hog1Δ null mutant, which restored the recombination S. cerevisiae to the wild-type phenotype with osmo-adaptation. To further clarify the function of CgHOG1, the phosphorylation of CgHOG1 and transcription of the glycerol-3-phosphate dehydrogenase gene (GPD1) of the CgHOG1-harbouring S. cerevisiae mutant was detected, and found to be similar to that of wild-type S. cerevisiae. In addition, the recombination S. cerevisiae with CgHOG1 gene significantly accumulated intracellular glycerol when stressed with NaCl.

CTX-M ß-lactamase-producing Klebsiella pneumoniae in suburban New York City, New York, USA.

CTX-M extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae isolates are infrequently reported in the United States. In this study, we analyzed nonduplicate ESBL-producing K. pneumoniae and Escherichia coli clinical isolates collected during 2005-2012 at a tertiary care medical center in suburban New York City, USA, for the presence of blaCTX-M, blaSHV, blaTEM, and blaKPC genes. Despite a high prevalence of blaCTX-M genes in ESBL-producing E. coli since 2005, blaCTX-M genes were not detected in K. pneumoniae until 2009. The prevalence of CTX-M-producing K. pneumoniae increased significantly over time from 1.7% during 2005-2009 to 26.4% during 2010-2012 (p<0.0001). CTX-M-15 was the dominant CTX-M genotype. Pulsed-field gel electrophoresis and multilocus sequence typing revealed high genetic heterogeneities in CTX-M-producing K. pneumoniae isolates. This study demonstrates the recent emergence and polyclonal spread of multidrug resistant CTX-M-producing K. pneumoniae isolates among patients in a hospital setting in the United States.

Cloning and characterization of a novel NAD(+) -dependent glyceraldehyde-3-phosphate dehydrogenase gene from Candida glycerinogenes and use of its promoter.

A 3950 bp genomic fragment from Candida glycerinogenes, WL2002-5, containing the CgGAP gene encoding a glyceraldehyde-3-phosphate dehydrogenase homologous to GAP genes in other yeasts using degenerate primers, was cloned and characterized with inverse PCR. Sequence analysis revealed a 1164 bp open reading frame encoding a putative peptide of 387 deduced amino acids, with a molecular mass of 36 kDa. The CgGAP protein consisted of an N-terminal NAD(+) -binding domain and a central catalytic domain. Six stress-response elements were found in the upstream region of the CgGAP gene. The influence of CgGAP on glycolysis was investigated. Functional analysis revealed that Saccharomyces cerevisiae transformed with CgGAP was restored to the wild-type phenotype when cultured in high-osmolarity medium, suggesting that it is a functional GAP protein. Promoter studies in S. cerevisiae using the green fluorescent protein (gfp) gene as a reporter showed that the GAP promoter (PCgGAP ) is constitutively expressed in S. cerevisiae cells grown on glucose.

Advances in the bioconversion mechanism of lovastatin to wuxistatin by Amycolatopsis sp. CGMCC 1149.

Wuxistatin, a novel statin and more potent than lovastatin, was converted from lovastatin by Amycolatopsis sp. (CGMCC 1149). Product I, an intermediate product, was found in the fermentation broth, and the structure analysis showed that product I had an additional hydroxyl group at the methyl group attached to C3 compared to lovastatin, which indicates that product I is one isomer of wuxistatin. Isotope tracing experiment proved that hydroxyl group of wuxistatin was provided by product I and the reaction from product I to wuxistatin was an intramolecular transfer. Hydroxylation reaction established in a cell-free system could be inhibited by CO and enhanced by ATP, Fe(2+), and ascorbic acid, which were consistent with the presumption that the hydroxylase was an induced cytochrome P450. Study on proteomics of Amycolatopsis sp. CGMCC 1149 suggested that three identified proteins, including integral membrane protein, Fe-S oxidoreductase, and GTP-binding protein YchF, were induced by lovastatin and required during hydroxylation reaction. In conclusion, bioconversion mechanism of wuxistatin by Amycolatopsis sp. CGMCC 1149 was proposed: lovastatin is firstly hydroxylated to product I by a hydroxylase, namely cytochrome P450, and then product I is rearranged to wuxistatin by isomerases.

budC knockout in Klebsiella pneumoniae for bioconversion from glycerol to 1,3-propanediol.

2,3-Butanediol (2,3-BD) is a major by-product of 1,3-propanediol (1,3-PDO) fermentation by Klebsiella pneumoniae ZG25. It not only consumes large amounts of its carbon source and nicotinamide adenine dinucleotide to diminish synthesis of 1,3-PDO, but also serves as an obstacle to high-purity 1,3-PDO in downstream processes. To decrease the formation of 2,3-BD and make an intrinsic improvement in 1,3-PDO production, the budC gene in K. pneumoniae, coding 2,3-BD dehydrogenase, which is a key gene of the 2,3-BD pathway, was successfully knocked out using the Red recombination system described in this paper. The results of the mutant fed-batch fermentation showed that the 1,3-PDO concentration, productivity per cell dry weight, and conversion rate increased to 880 mmol L(-1) , 22.0 mmol L(-1) h(-1) , and 0.700 mol mol(-1) , respectively, increasing by 10%, 15%, and 11% compared with the parent strain. Meanwhile, 2,3-BD was still found in fermentation broth with the 2,3-BD metabolic pathway blocked, which implies that K. pneumoniae possesses a pathway of the 2,3-BD cycle as a replenishment pathway.

Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo.

Allergic asthma is associated with Th2-mediated inflammation. Several flavonoids were isolated from Glycyrrhiza uralensis, one of the herbs in the anti-asthma herbal medicine intervention. The aim of this investigation was to determine whether Glycyrrhiza uralensis flavonoids have inhibitory effects on memory Th2 responses in vitro and antigen-induced Th2 inflammation in vivo. The effects of three Glycyrrhiza uralensis flavonoids on effector memory Th2 cells, D10.G4.1 (D10 cells), were determined by measuring Th2 cytokine production. Isoliquiritigenin, 7, 4'-dihydroxyflavone (7, 4'-DHF) and liquiritigenin significantly suppressed IL-4 and IL-5 production in a dose-dependent manner, 7, 4'-DHF being most potent. It was also evaluated for effects on D10 cell proliferation, GATA-3 expression and IL-4 mRNA expression, which were suppressed, with no loss of cell viability. Chronic treatment with 7, 4'-DHF in a murine model of allergic asthma not only significantly reduced eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increased IFN-γ production in lung cell cultures in response to antigen stimulation.

[Cloning and characterization of an HOG1 MAPK homologous gene CgHOG1 from Candida glycerinogenes].

OBJECTIVE: This study was aimed to obtain a key gene of osmo-adaptation and glycerol synthesis regulation in Candida glycerinogenes, namely mitogen-activated protein kinase HOG1 gene (CgHOG1), and to verify its function of osmo-regulation. METHODS: The gene CgHOG1 was amplified by Degenerate PCR and Self-Formed Adaptor PCR from the C. glycerinogenes genome and the bioinformatic analysis of CgHOG1 gene was conducted. The CgHOG1 gene was transformed in Saccharomyces cerevisiae hog1delta null mutant and its salt tolerance characteristics was investigated. RESULTS: The gene CgHOG1 encoded a protein of 387 amino acids with an open reading frame of 1164 bp and the amino acid sequence showed 86% identity to Hog1 p of Ogataea parapolymorpha. Heterologous expression of CgHOG1 gene in S. cerevisiae W303 hog1 delta null mutant showed an increase in salt tolerance and glycerol production compared to S. cerevisiae W303 hog1 delta null mutant. CONCLUSION: The CgHOG1 obtained in this study is a novel HOG1 gene from C. glycerinogenes, which plays an essential role in the yeast hyperosmotic response and glycerol synthesis. We supplied a new gene for the osmo-adaptation mechanism in C. glycerinogenes and molecular modification of the salt-tolerant and drought-resistant crops.

Frequency of Positive Polymerase Chain Reaction (PCR) Testing for Borrelia burgdorferi on Whole Blood Samples That Tested Positive for Babesia microti by PCR from an Endemic Area for Both Infections in New York State.

Because both Babesia microti and Borrelia burgdorferi can be transmitted by the bite of a single coinfected Ixodes scapularis tick, an attempt was made to determine the frequency with which whole blood samples that tested positive for B. microti infection by polymerase chain reaction (PCR) would also test positive by PCR for B. burgdorferi infection. Over a 7-year period from 2013 to 2019, 119 different patients tested positive for B. microti infection by PCR on at least one blood sample. Among the 118 patients with a positive B. microti PCR blood sample that could also be tested by a qualitative PCR for B. burgdorferi, only one patient tested positive (0.85%, 95% CI 0.02 to 4.6%). Routine PCR testing of every B. microti PCR-positive blood specimen to detect B. burgdorferi coinfection appears to have a low yield, even in a highly endemic geographic area for both of these infections.

The construction of a new integrative vector with a new selective marker of copper resistance for glycerol producer Candida glycerinogenes.

Candida glycerinogenes WL2002-5 has been used for industrial-scale fermentation of glycerol and may be a promising genetic host due to its tolerance to high osmotic pressure and fast growth. It resists many kinds of drugs, such as G418/hygromycin/cycloheximide. In previous studies, only Zeocin was used as a drug-resistant marker. But Zeocin is so expensive that it largely limits the genetic and molecular study. Here, we constructed a eukaryotic integrative vector pGAPZU, based on pGAPZB, to gain a new selectable marker of copper resistance for this strain. The results showed that the CUP1 gene of Saccharomyces cerevisiae elevated copper resistance of C. glycerinogenes. The C. glycerinogenes transformed with recombinant vector pGUC, obtained from introducing CUP1 gene into plasmid pGAPZU, could resist 21 mM copper, while the minimum inhibitory concentration (MIC) of wild type was 18 mM in solid YEPD medium. With copper resistance as a selective marker, research cost was largely reduced from 114.0 $/L with Zeocin as selective marker to 0.1 $/L. The new expression vector pGUC and selective marker of copper resistance gene establish a good foundation for further study on this industrial strain.

Daytime naps and depression risk: A meta-analysis of observational studies.

Background: The relationship between daytime napping and depression remains debatable. Thus, a meta-analysis in this study was conducted to evaluate the relationship between daytime napping and depression. Methods: The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched up to February 2022, and the reference lists of the included studies were also retrieved. A random-effects model was used to estimate the combined effect size. Results: Nine studies with 649,111 participants were included in the final analysis. The pooled odds ratio (OR) was 1.15 (95% confidence interval: 1.01-1.31) with a significant heterogeneity (I 2 = 91.3%, P for heterogeneity <0.001), and the results demonstrated an increased risk of depressive symptoms among daytime nappers. Visual inspection of the funnel plot and Egger's and Begg's tests identified no obvious evidence of publication bias. Conclusion: This meta-analysis indicates that daytime naps are a predictor of depression. The effects of daytime napping on depression may vary depending on the characteristics of people, the pattern of naps, and the individual's sleep experience. The findings may have significant implications for future research on depression.

Screen time and depression risk: A meta-analysis of cohort studies.

Background: The impact of screen time on mental health, including depression, has attracted increasing attention from not only children and adolescents but also the elderly. Thus, we conducted a meta-analysis of cohort studies to evaluate the association between screen time and depression risk. Methods: The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for cohort studies up to May 2022, and the reference lists of the included studies were also retrieved. A random-effect model was used to estimate the combined effect size. Heterogeneity was assessed with the I 2 statistic. Potential publication bias was evaluated using a funnel plot and Begg's and Egger's tests. Results: The final analysis included 18 cohort studies with a combined total of 241,398 participants. The pooled risk ratio (RR) was 1.10 (95% confidence interval: 1.05-1.14), with significant heterogeneity (I 2 = 82.7%, P < 0.001). The results of subgroup analyses showed that the pooled RRs varied according to geographic locations, gender, age group, screen time in the control group, depression at the baseline, and whether the study was conducted during the COVID-19 pandemic. No obvious evidence of publication bias was found. Conclusion: This study indicates that screen time is a predictor of depressive symptoms. The effects of screen time on depression risk may vary based on the participant's age, gender, location, and screen time duration. The findings could have important implications for the prevention of depression.