Urinary eicosanoid levels in early life and risk of atopic disease in childhood.

BACKGROUND: Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease. METHODS: This study quantified the levels of 21 eicosanoids in urine from children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) (age 1 year, n = 450) and VDAART (Vitamin D Antenatal Asthma Reduction Trial) (age 3 years, n = 575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of type-2 inflammation, applying false discovery rate of 5% (FDR5%) multiple testing correction. RESULTS: In both cohorts, analyses adjusted for environmental determinants showed that higher TXA2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P < FDR5%) and type-2 inflammation (P < .05). In VDAART, lower PGE2 and PGI2 eicosanoids and higher isoprostanes were also associated with increased risk of atopic dermatitis (P < FDR5%). For wheeze/asthma, analyses in COPSAC2010 showed that lower isoprostanes and PGF2 eicosanoids and higher PGD2 eicosanoids at age 1 year associated with an increased risk at age 1-10 years (P < .05), whereas analyses in VDAART showed that lower PGE2 and higher TXA2 eicosanoids at age 3 years associated with an increased risk at 6 years (P < FDR5%). CONCLUSIONS: This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases.

Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors.

BACKGROUND: While dysregulated sphingolipid metabolism has been associated with risk of childhood asthma, the specific sphingolipid classes and/or mechanisms driving this relationship remain unclear. We aimed to understand the multifaceted role between sphingolipids and other established asthma risk factors that complicate this relationship. METHODS: We performed targeted LC-MS/MS-based quantification of 77 sphingolipids in plasma from 997 children aged 6 years from two independent cohorts (VDAART and COPSAC2010 ). We examined associations of circulatory sphingolipids with childhood asthma, lung function, and three asthma risk factors: functional SNPs in ORMDL3, low vitamin D levels, and reduced gut microbial maturity. Given racial differences between these cohorts, association analyses were performed separately and then meta-analyzed together. RESULTS: We observed elevations in circulatory sphingolipids with asthma phenotypes and risk factors; however, there were differential associations of sphingolipid classes with clinical outcomes and/or risk factors. While elevations from metabolites involved in ceramide recycling and catabolic pathways were associated with asthma and worse lung function [meta p-value range: 1.863E-04 to 2.24E-3], increased ceramide levels were associated with asthma risk factors [meta p-value range: 7.75E-5 to .013], but not asthma. Further investigation identified that some ceramides acted as mediators while some interacted with risk factors in the associations with asthma outcomes. CONCLUSION: This study demonstrates the differential role that sphingolipid subclasses may play in asthma and its risk factors. While overall elevations in sphingolipids appeared to be deleterious overall; elevations in ceramides were uniquely associated with increases in asthma risk factors only; while elevations in asthma phenotypes were associated with recycling sphingolipids. Modification of asthma risk factors may play an important role in regulating sphingolipid homeostasis via ceramides to affect asthma. Further function work may validate the observed associations.

Sleep quality mediates the effect of medical social support on depression symptoms in patients with HIV/AIDS.

OBJECTIVES: The purpose of our study is to further understanding of the depression symptoms of HIV/AIDS patients in Guilin, Guangxi via exploring whether there is a mediating effect of sleep quality on medical-social support and depression symptoms and therefore provide a theoretical basis for application of medical-social support to alleviate depression symptoms of HIV/AIDS patients. METHODS: A convenience sampling method was used to select 200 HIV/AIDS patients for the study. Depression symptoms, sleep quality, and medical-social support of the study participants were investigated using The Center for Epidemiological Studies Depression Scale (CES-D), The Pittsburg Sleep Quality Index (PSQI), and The Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Predictors of depression symptoms were explored by multiple linear regression, and Pearson correlation was used to analyze the relationship between sleep quality, medical-social support, and depression symptoms. Mediating effect analysis was performed by nonparametric Bootstrap test. RESULTS: In this study, the incidence of depression symptoms was 54.4%. Multiple linear regression analysis showed that leanness (ß = 0.161, P = 0.008), obesity (ß = 0.186, P = 0.002), sleep quality score > 7 (ß = 0.331, P < 0.001), and medical-social support score > 56 (ß = -0.247, P < 0.001) could influence depression symptoms of HIV and Pearson's correlation analysis demonstrated that there was a two-way correlation between sleep quality, medical social support and depression symptoms (P < 0.05). In addition, Bootstrap tests showed that medical-social support might affect depression symptoms not only directly but also indirectly through the mediating effect of sleep quality with the direct and mediating effects accounting for 77.25% and 22.75% of the total effect, respectively. CONCLUSION: The prevalence of depression symptoms is high among HIV/AIDS patients in Guilin City. The depressive symptoms of PLWHs(people living with HIV) are related to their sleep quality and medical-social support, and sleep quality partially mediates the relationship between medical-social support and depression symptoms. Therefore, interventions to improve sleep quality and medical-social support have the potential to allay the depression symptoms of HIV/AIDS patients.

Environmental and genetic associations with aberrant early-life gut microbial maturation in childhood asthma.

BACKGROUND: Environmental, genetic, and microbial factors are independently associated with childhood asthma. OBJECTIVE: We sought to determine the roles of environmental exposures and 17q12-21 locus genotype in the maturation of the early-life microbiome in childhood asthma. METHODS: We analyzed fecal 16s rRNA sequencing at age 3 to 6 months and age 1 year to characterize microbial maturation of offspring of participants in the Vitamin D Antenatal Reduction Trial. We determined associations of microbial maturation and environmental exposures in the mediation of asthma risk at age 3 years. We examined 17q12-21 genotype and microbial maturation associations with asthma risk in Vitamin D Antenatal Reduction Trial and the replication cohort Copenhagen Prospective Studies on Childhood Asthma 2010. RESULTS: Accelerated fecal microbial maturation at age 3 to 6 months and delayed maturation at age 1 year were associated with asthma (P < .001). Fecal Bacteroides was reduced at age 3 to 6 months in association with subsequent asthma (P = .006) and among subjects with lower microbial maturation at age 1 year (q = 0.009). Sixty-one percent of the association between breast-feeding and asthma was mediated by microbial maturation at age 3 to 6 months. Microbial maturation and 17q12-21 genotypes exhibited independent, additive effects on childhood asthma risk. CONCLUSIONS: The intestinal microbiome and its maturation mediates associations between environmental exposures including breast-feeding and asthma. The intestinal microbiome and 17q12-21 genotype appear to exert additive and independent effects on childhood asthma risk.

Maternal vitamin D-related metabolome and offspring risk of asthma outcomes.

BACKGROUND: Gestational vitamin D deficiency is implicated in development of respiratory diseases in offspring, but the mechanism underlying this relationship is unknown. OBJECTIVE: We sought to study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling. METHODS: Untargeted blood metabolic profiles were acquired using liquid chromatography-mass spectrometry at 1 week postpartum from 672 women in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort and at pregnancy weeks 32 to 38 from 779 women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) mother-child cohort. In COPSAC2010, we employed multivariate models and pathway enrichment analysis to identify metabolites and pathways associated with gestational vitamin D blood levels and investigated their relationship with development of asthma phenotypes in early childhood. The findings were validated in VDAART and in cellular models. RESULTS: In COPSAC2010, higher vitamin D blood levels at 1 week postpartum were associated with distinct maternal metabolome perturbations with significant enrichment of the sphingomyelin pathway (P < .01). This vitamin D-related maternal metabolic profile at 1 week postpartum containing 46 metabolites was associated with decreased risk of recurrent wheeze (hazard ratio [HR] = 0.92 [95% CI 0.86-0.98], P = .01) and wheeze exacerbations (HR = 0.90 [95% CI 0.84-0.97], P = .01) at ages 0 to 3 years. The same metabolic profile was similarly associated with decreased risk of asthma/wheeze at ages 0 to 3 in VDAART (odds ratio = 0.92 [95% CI 0.85-0.99], P = .04). Human bronchial epithelial cells treated with high-dose vitamin D3 showed an increased cytoplasmic sphingolipid level (P < .01). CONCLUSIONS: This exploratory metabolomics study in 2 independent birth cohorts demonstrates that the beneficial effect of higher gestational vitamin D exposure on offspring respiratory health is characterized by specific maternal metabolic alterations during pregnancy, which involves the sphingomyelin pathway.

Self-care challenges of patients with heart failure from the perspectives of patients and caregivers: A qualitative study.

OBJECTIVE: self-care is critically important for the long-term management of heart failure (HF) patients, with caregivers playing an important role in promoting self-care. However, adherence to self-care is typically low among HF patients worldwide. METHODS: In-depth qualitative interviews were conducted with individuals diagnosed with HF. To structure the interview guide and underpin the analysis, two established behavioral science frameworks, the Behavior Change Wheel (BCW) and the Theoretical Domains Framework (TDF), were used in this study. RESULTS: A total of 32 participants were included (n = 16 patients, n = 16 caregivers), with themes involving: barriers included: "Self-care with Limited Capability," "Insufficient External Support," "Lack of Motivation for Self-Care." Facilitators included: "Striving to Adapt to Disease Demands," "Adequate External Support," "Positive Health Behaviors and Experiences." CONCLUSIONS: Providing positive support to heart failure patients and their caregivers, along with cultivating intrinsic motivation for behavioral change, can enhance self-care ability.

Establishment of a prognostic model toward lung squamous cell carcinoma based on m7G-related genes in the cancer genome atlas.

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated genes (ADH1C, NTS, and ERLIN2). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome P-450, and metabolism of cytochrome P-450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.NEW & NOTEWORTHY Based on the differential expression of 7-methylguanosine (m7G) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our m7G-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that m7G modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between m7G modification-related genes, immunity, and drug sensitivity in LUSC.

Ultrasensitive Self-Driven Terahertz Photodetectors Based on Low-Energy Type-II Dirac Fermions and Related Van der Waals Heterojunctions.

The exotic electronic properties of topological semimetals (TSs) have opened new pathways for innovative photonic and optoelectronic devices, especially in the highly pursuit terahertz (THz) band. However, in most cases Dirac fermions lay far above or below the Fermi level, thus hindering their successful exploitation for the low-energy photonics. Here, low-energy type-II Dirac fermions in kitkaite (NiTeSe) for ultrasensitive THz detection through metal-topological semimetal-metal heterostructures are exploited. Furthermore, a heterostructure combining two Dirac materials, namely, graphene and NiTeSe, is implemented for a novel photodetector exhibiting a responsivity as high as 1.22 A W-1 , with a response time of 0.6 µs, a noise-equivalent power of 18 pW Hz-0.5 , with outstanding stability in the ambient conditions. This work brings to fruition of Dirac fermiology in THz technology, enabling self-powered, low-power, room-temperature, and ultrafast THz detection.

Deep learning for precise axial localization of trapped microspheres in reflective optical systems.

High-precision axial localization measurement is an important part of micro-nanometer optical measurement, but there have been issues such as low calibration efficiency, poor accuracy, and cumbersome measurement, especially in reflected light illumination systems, where the lack of clarity of imaging details leads to the low accuracy of commonly used methods. Herein, we develop a trained residual neural network coupled with a convenient data acquisition strategy to address this challenge. Our method improves the axial localization precision of microspheres in both reflective illumination systems and transmission illumination systems. Using this new localization method, the reference position of the trapped microsphere can be extracted from the identification results, namely the "positioning point" among the experimental groups. This point relies on the unique signal characteristics of each sample measurement, eliminates systematic repeatability errors when performing identification across samples, and improves the localization precision of different samples. This method has been verified on both transmission and reflected illumination optical tweezers platforms. We will bring greater convenience to measurements in solution environments and will provide higher-order guarantees for force spectroscopy measurements in scenarios such as microsphere-based super-resolution microscopy and the surface mechanical properties of adherent flexible materials and cells.

Phenotypically driven subgroups of ASD display distinct metabolomic profiles.

Autism Spectrum Disorder (ASD) is a heterogeneous condition that includes a broad range of characteristics and associated comorbidities; however, the biology underlying the variability in phenotypes is not well understood. As ASD impacts approximately 1 in 100 children globally, there is an urgent need to better understand the biological mechanisms that contribute to features of ASD. In this study, we leveraged rich phenotypic and diagnostic information related to ASD in 2001 individuals aged 4 to 17 years from the Simons Simplex Collection to derive phenotypically driven subgroups and investigate their respective metabolomes. We performed hierarchical clustering on 40 phenotypes spanning four ASD clinical domains, resulting in three subgroups with distinct phenotype patterns. Using global plasma metabolomic profiling generated by ultrahigh-performance liquid chromatography mass spectrometry, we characterized the metabolome of individuals in each subgroup to interrogate underlying biology related to the subgroups. Subgroup 1 included children with the least maladaptive behavioral traits (N = 862); global decreases in lipid metabolites and concomitant increases in amino acid and nucleotide pathways were observed for children in this subgroup. Subgroup 2 included children with the highest degree of challenges across all phenotype domains (N = 631), and their metabolome profiles demonstrated aberrant metabolism of membrane lipids and increases in lipid oxidation products. Subgroup 3 included children with maladaptive behaviors and co-occurring conditions that showed the highest IQ scores (N = 508); these individuals had increases in sphingolipid metabolites and fatty acid byproducts. Overall, these findings indicated distinct metabolic patterns within ASD subgroups, which may reflect the biological mechanisms giving rise to specific patterns of ASD characteristics. Our results may have important clinical applications relevant to personalized medicine approaches towards managing ASD symptoms.

Mechanistic Insights into the Folding Mechanism of Region V in Ice-Binding Protein Secreted by Marinomonas primoryensis Revealed by Single-Molecule Force Spectroscopy.

The Gram-negative bacteria Marinomonas primoryensis secrete an ice-binding protein (MpIBP), which is a vital bacterial adhesin facilitating the adaptation and survival of the bacteria in the harsh Antarctic environment. The C-terminal region of MpIBP, known as region V (RV), is the first domain to be exported into the Ca2+-rich extracellular environment and acts as a folding nucleus for the entire adhesin. However, the mechanisms underlying the secretion and folding of RV remain poorly understood. Here, we used optical tweezers (OT) to investigate the secretion and folding mechanisms of RV at the single-molecule level. In the absence of Ca2+, apo-RV remains unstructured, while Ca2+-bound RV folds into a mechanically stable structure. The folding of RV could occur via the formation of an intermediate state. Even though this folding intermediate is "hidden" during the folding process of wild type RV in vitro, it likely forms in vivo and plays an important role in facilitating protein secretion. Additionally, our results revealed that the N-terminal part of the RV can significantly stabilize its C-terminal structure. Our study paves the way for further investigations into the structure and functions of MpIBP that help bacteria survive in challenging environments.

Arthrobacter zhaoxinii sp. nov. and Arthrobacter jinronghuae sp. nov., isolated from Marmota himalayana.

Four yellow-coloured strains (zg-Y815T/zg-Y108 and zg-Y859T/zg-Y826) were isolated from the intestinal contents of Marmota himalayana and assigned to the 'Arthrobacter citreus group'. The four strains grew optimally on brain heart infusion agar with 5 % defibrinated sheep blood plate at 30 °C, pH 7.0 and with 0.5 % NaCl (w/v). Comparative analysis of their 16S rRNA genes indicated that the two strain pairs belong to the genus Arthrobacter, showing the highest similarity to Arthrobacter yangruifuii 785T (99.52 %), which was further confirmed by the 16S rRNA gene and genome-based phylogenetic analysis. The comparative genomic analysis [digital DNA-DNA hybridization, (dDDH) and average nucleotide identity (ANI)] proved that the four strains are two different species (zg-Y815T/zg-Y108, 71.7 %/96.8 %; zg-Y859T/zg-Y826, 87.3 %/98.5 %) and differ from other known species within the genus Arthrobacter (zg-Y815T, 19.6-32.3 %/77.2-88.0 %; zg-Y859T, 19.5-29.3 %/77.4-86.3 %). Strain pairs zg-Y815T/zg-Y108 and zg-Y859T/zg-Y826 had the same major cellular fatty acids (iso-C16 : 0 and anteiso-C15 : 0), with MK-8(H2) as their dominant respiratory quinone (70.6 and 61.7 %, respectively). The leading polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylinositol. The detected amino acids and cell-wall sugars of the two new species were identical (amino acids: alanine, glutamic acid, and lysine; sugars: rhamnose, galactose, mannose, glucose, and ribose). According to the phylogenetic, phenotypic, and chemotaxonomic analyses, we concluded that the four new strains represented two different novel species in the genus Arthrobacter, for which the names Arthrobacter zhaoxinii sp. nov. (zg-Y815T= GDMCC 1.3494T = JCM 35821T) and Arthrobacter jinronghuae sp. nov. (zg-Y859T = GDMCC 1.3493T = JCM 35822T) are proposed.

Analysis of the association between dietary patterns and nonalcoholic fatty liver disease in a county in Guangxi.

BACKGROUND: This study aims to investigate the relationship between different dietary patterns and non-alcoholic fatty liver disease (NAFLD). METHODS: Residents over 30 years old in the ecological longevity cohort in Gongcheng Yao Autonomous County, Guangxi Province were the research objects selected from 2018 to 2019. Physical examination, baseline population survey, and food frequency questionnaire (FFQ) survey were conducted. Dietary patterns were analyzed by factor analysis. Influencing factors of NAFLD were analyzed by multiple logistic regression. RESULTS: NAFLD was diagnosed in 241 of 2664 participants based on ultrasonography, and the detection rate was 9.0%. Factor analysis yielded a total of three dietary patterns, namely, traditional Chinese, Western, and cereal-potato dietary patterns. Results of multivariate logistic regression analysis showed that after adjusting for confounding factors, participants in the highest quartile of the Western dietary pattern exhibited a higher prevalence of NAFLD (OR = 2.799; 95% CI: 1.620-4.837; p < 0.05) than participants in the lowest quartile. Participants in the highest quartile of the cereal-potato pattern exhibited a decreased risk of NAFLD compared with those in the lowest quartile (OR = 0.581; 95% CI: 0.371-0.910, p < 0.05). The traditional Chinese patterns did not show any association with the risk of NAFLD. CONCLUSIONS: The Western dietary pattern increases the risk of NAFLD, whereas the cereal-potato dietary pattern reduces the risk of NAFLD. It is important for the prevention and control of NAFLD to adhere to the cereal-potato dietary.

Experience of using a virtual reality rehabilitation management platform for breast cancer patients: a qualitative study.

PURPOSES: Postoperative rehabilitation of upper limb function is crucial for breast cancer. Therefore, we developed a rehabilitation management platform using virtual reality to improve rehabilitation compliance and effect. The purpose of this research was to understand the user usability experience of breast cancer patients about the postoperative rehabilitation management of upper limb function using virtual reality. METHODS: A qualitative descriptive research was designed. We used a maximum difference purpose sampling method. According to the inclusion and exclusion criteria, a 3-armor hospital in Changchun was selected for the recruitment. A one-on-one semi-structured interviews were conducted with patients after breast cancer operation. The Colaizzi seven-step analysis method was used to classify data under summarized themes. RESULTS: Twenty patients participated in this semi-structured interview. User experience could be summarized into four themes as follows: 1) experience and feeling after using the virtual reality rehabilitation management platform; 2) factors influencing the use of the virtual reality rehabilitation management platform; 3) willingness to recommend the virtual reality rehabilitation management platform to peers; and 4) suggestions to improve the virtual reality rehabilitation management platform. CONCLUSIONS: Breast cancer patients who used the rehabilitation management platform had a good experience, and their recognition and satisfaction were high. The use of the platform is influenced by many factors, and most patients are willing to recommend this platform to their peers. Future studies should be conducted according to patients' feedback and suggestions on how to further optimize and improve the platform.

Genome-Wide Analysis of the MADS-Box Gene Family in Hibiscus syriacus and Their Role in Floral Organ Development.

Hibiscus syriacus belongs to the Malvaceae family, and is a plant with medicinal, edible, and greening values. MADS-box transcription factor is a large family of regulatory factors involved in a variety of biological processes in plants. Here, we performed a genome-wide characterization of MADS-box proteins in H. syriacus and investigated gene structure, phylogenetics, cis-acting elements, three-dimensional structure, gene expression, and protein interaction to identify candidate MADS-box genes that mediate petal developmental regulation in H. syriacus. A total of 163 candidate MADS-box genes were found and classified into type I (Mα, Mß, and Mγ) and type II (MIKC and Mδ). Analysis of cis-acting elements in the promoter region showed that most elements were correlated to plant hormones. The analysis of nine HsMADS expressions of two different H. syriacus cultivars showed that they were differentially expressed between two type flowers. The analysis of protein interaction networks also indicated that MADS proteins played a crucial role in floral organ identification, inflorescence and fruit development, and flowering time. This research is the first to analyze the MADS-box family of H. syriacus and provides an important reference for further study of the biological functions of the MADS-box, especially in flower organ development.

Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.

Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Addressing the imaging limitations of a microsphere-assisted nanoscope.

In the past decade, microsphere-assisted nanoscopy has been developed rapidly to overcome the diffraction limit. However, due to the limited size and high surface curvature of microspheres, the magnified imaging still suffers from problems like limited view scope, imaging distortion, and low contrast. In this paper, we specialize in the imaging mechanism of microspheres and find irradiance as the key factor for microsphere imaging quality. Utilizing a modified optical tweezer system, we achieve precise manipulation of microspheres and further propose a high-quality large-field magnified imaging scheme. The results show that the imaging area of 5 µm microspheres can reach 16×12 µm2 with the minimum identifiable feature of 137 nm. This scheme provides a new solution for extending the measuring scope of microsphere-assisted nanoscope, and will certainly promote the application of this technology in practice.

Excessive sleep increased the risk of incidence of cognitive impairment among older Chinese adults: a cohort study based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

STUDY OBJECTIVES: Based on a cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aimed to evaluate the relationship between sleep duration and the incidence of cognitive impairment among older Chinese adults. METHODS: We conducted a prospective analysis based on 3692 participants from the CLHLS at baseline (in 2011), and as a 3-year follow-up (till 2014), 531 participants (14.4%) had cognitive impairment, which was defined as a Mini-Mental State Examination score <24. Sleep duration was classified into three groups: short (≤5 hours/day), normal (>5 but <10 hours), and long (≥10 hours/day). A logistic regression model was used to examine the association between baseline sleep duration and cognitive impairment after adjusting for sociodemographic data, living habits, and health conditions. RESULTS: Five hundred sixty-two participants (15.2%) were in the short-duration group, and 608 participants (16.5%) were in the long-duration group. After adjusting for multiple potential confounders, compared with normal sleep duration, long sleep duration was associated with the incidence of cognitive impairment (OR = 1.309, 95% CI: 1.019-1.683), especially among men (OR = 1.527, 95% CI: 1.041-2.240) and those having a primary and above education level (OR = 1.559, 95% CI: 1.029-2.361). No significant association was observed between short sleep duration and cognitive impairment (OR = 0.860, 95% CI: 0.646-1.145). CONCLUSIONS: Excessive sleep may increase the risk of cognitive impairment in older individuals. It may be a suggestive sign of early neurodegeneration and may be a useful clinical tool to identify those at a higher risk of progressing to cognitive impairment.

Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14.

Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)-fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3',5'-cyclic monophosphate-responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis. Exogenous overexpression of USP14 in the liver significantly increased hepatic glucose output. Consistent with this, liver-specific knockdown of USP14 abrogated the effects of ER stress on glucose metabolism, and also improved hyperglycemia and glucose intolerance in obese mice. In conclusion, our findings show a mechanism underlying ER stress-induced disruption of glucose homeostasis, and present USP14 as a potential therapeutic target against T2DM.