Publications by authors named "Heming Wang"

93 Publications

Associations of sleep duration and sleep-wake rhythm with lung parenchymal abnormalities on computed tomography: The MESA study.

J Sleep Res 2021 Sep 9:e13475. Epub 2021 Sep 9.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Impairment of the circadian rhythm promotes lung inflammation and fibrosis in pre-clinical models. We aimed to examine whether short and/or long sleep duration and other markers of sleep-wake patterns are associated with a greater burden of lung parenchymal abnormalities on computed tomography among adults. We cross-sectionally examined associations of sleep duration captured by actigraphy with interstitial lung abnormalities (n = 1111) and high attenuation areas (n = 1416) on computed tomography scan in the Multi-Ethnic Study of Atherosclerosis at Exam 5 (2010-2013). We adjusted for potential confounders in logistic and linear regression models for interstitial lung abnormalities and high attenuation area, respectively. High attenuation area models were also adjusted for study site, lung volume imaged, radiation dose and stratified by body mass index. Secondary exposures were self-reported sleep duration, sleep fragmentation index, sleep midpoint and chronotype. The mean age of those with longer sleep duration (≥ 8 hr) was 70 years and the prevalence of interstitial lung abnormalities was 14%. Increasing actigraphy-based sleep duration among participants with ≥ 8 hr of sleep was associated with a higher adjusted odds of interstitial lung abnormalities (odds ratio of 2.66 per 1-hr increment, 95% confidence interval 1.42-4.99). Longer sleep duration and higher sleep fragmentation index were associated with greater high attenuation area on computed tomography among participants with a body mass index < 25 kg m (p-value for interaction < 0.02). Self-reported sleep duration, later sleep midpoint and evening chronotype were not associated with outcomes. Actigraphy-based longer sleep duration and sleep fragmentation were associated with a greater burden of lung abnormalities on computed tomography scan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jsr.13475DOI Listing
September 2021

Towards Robust Speech Super-resolution.

IEEE/ACM Trans Audio Speech Lang Process 2021 25;29:2058-2066. Epub 2021 Jan 25.

Department of Computer Science and Engineering and the Center for Cognitive and Brain Sciences, The Ohio State University, Columbus, OH 43210 USA.

Speech super-resolution (SR) aims to increase the sampling rate of a given speech signal by generating high-frequency components. This paper proposes a convolutional neural network (CNN) based SR model that takes advantage of information from both time and frequency domains. Specifically, the proposed CNN is a time-domain model that takes the raw waveform of low-resolution speech as the input, and outputs an estimate of the corresponding high-resolution waveform. During the training stage, we employ a cross-domain loss to optimize the network. We compare our model with several deep neural network (DNN) based SR models, and experiments show that our model outperforms existing models. Furthermore, the robustness of DNN-based models is investigated, in particular regarding microphone channels and downsampling schemes, which have a major impact on the performance of DNN-based SR models. By training with proper datasets and preprocessing, we improve the generalization capability for untrained microphone channels and unknown downsampling schemes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/taslp.2021.3054302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386817PMC
January 2021

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

Genome Med 2021 Aug 26;13(1):136. Epub 2021 Aug 26.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.

Background: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.

Methods: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap.

Results: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways.

Conclusions: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-021-00917-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394596PMC
August 2021

Genetic analysis of dietary intake identifies new loci and functional links with metabolic traits.

Nat Hum Behav 2021 Aug 23. Epub 2021 Aug 23.

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and protein in 282,271 participants of European ancestry from the UK Biobank (n = 191,157) and Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 91,114), and identify 26 distinct genome-wide significant loci. Dietary intake signals map exclusively to specific brain regions and are enriched for genes expressed in specialized subtypes of GABAergic, dopaminergic and glutamatergic neurons. We identified two main clusters of genetic variants for overall variation in dietary intake that were differently associated with obesity and coronary artery disease. These results enhance the biological understanding of interindividual differences in dietary intake by highlighting neural mechanisms, supporting functional follow-up experiments and possibly providing new avenues for the prevention and treatment of prevalent complex metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41562-021-01182-wDOI Listing
August 2021

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells.

Front Immunol 2021 29;12:726909. Epub 2021 Jul 29.

Medical School of Chinese PLA, Beijing, China.

Mesenchymal stem cells (MSCs) have been widely used in preclinical and clinical trials for various diseases and have shown great potential in the treatment of sepsis and coronavirus disease (COVID-19). Inflammatory factors play vital roles in the pathogenesis of diseases. The interaction between inflammatory factors is extremely complex. Once the dynamics of inflammatory factors are unbalanced, inflammatory responses and cytokine storm syndrome develop, leading to disease exacerbation and even death. Stem cells have become ideal candidates for the treatment of such diseases due to their immunosuppressive and anti-inflammatory properties. However, the mechanisms by which stem cells affect inflammation and immune regulation are still unclear. This article discusses the therapeutic mechanism and potential value of MSCs in the treatment of sepsis and the novel COVID-19, outlines how MSCs mediate innate and acquired immunity at both the cellular and molecular levels, and described the anti-inflammatory mechanisms and related molecular pathways. Finally, we review the safety and efficacy of stem cell therapy in these two diseases at the preclinical and clinical levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.726909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358430PMC
August 2021

Presence and transmission of mitochondrial heteroplasmic mutations in human populations of European and African ancestry.

Mitochondrion 2021 Jul 21;60:33-42. Epub 2021 Jul 21.

Framingham Heart Study, Framingham, MA 01702, USA; Population Sciences Branch, NHLBI/NIH, Bethesda, MD 20892, USA.

We investigated the concordance of mitochondrial DNA heteroplasmic mutations (heteroplasmies) in 6745 maternal pairs of European (EA, n = 4718 pairs) and African (AA, n = 2027 pairs) Americans in whole blood. Mother-offspring pairs displayed the highest concordance rate, followed by sibling-sibling and more distantly-related maternal pairs. The allele fractions of concordant heteroplasmies exhibited high correlation (R = 0.8) between paired individuals. Discordant heteroplasmies were more likely to be in coding regions, be nonsynonymous or nonsynonymous-deleterious (p < 0.001). The number of deleterious heteroplasmies was significantly correlated with advancing age (20-44, 45-64, and ≥65 years, p-trend = 0.01). One standard deviation increase in heteroplasmic burden (i.e., the number of heteroplasmies carried by an individual) was associated with 0.17 to 0.26 (p < 1e - 23) standard deviation decrease in mtDNA copy number, independent of age. White blood cell count and differential count jointly explained 0.5% to 1.3% (p ≤ 0.001) variance in heteroplasmic burden. A genome-wide association and meta-analysis identified a region at 11p11.12 (top signal rs779031139, p = 2.0e - 18, minor allele frequency = 0.38) associated with the heteroplasmic burden. However, the 11p11.12 region is adjacent to a nuclear mitochondrial DNA (NUMT) corresponding to a 542 bp area of the D-loop. This region was no longer significant after excluding heteroplasmies within the 542 bp from the heteroplasmic burden. The discovery that blood mtDNA heteroplasmies were both inherited and somatic origins and that an increase in heteroplasmic burden was strongly associated with a decrease in average number of mtDNA copy number in blood are important findings to be considered in association studies of mtDNA with disease traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mito.2021.07.004DOI Listing
July 2021

Analysis of Long Noncoding RNAs in Aila-Induced Non-Small Cell Lung Cancer Inhibition.

Front Oncol 2021 21;11:652567. Epub 2021 Jun 21.

College of Clinical Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China.

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality among all carcinomas. However, it is difficult to diagnose in the early stage, and current therapeutic efficacy is not ideal. Although numerous studies have revealed that Ailanthone (Aila), a natural product, can inhibit multiple cancers by reducing cell proliferation and invasion and inducing apoptosis, the mechanism by which Aila represses NSCLC progression in a time-dependent manner remains unclear. In this study, we observed that most long noncoding RNAs (lncRNAs) were either notably up- or downregulated in NSCLC cells after treatment with Aila. Moreover, alterations in lncRNA expression induced by Aila were crucial for the initiation and metastasis of NSCLC. Furthermore, in our research, expression of was significantly downregulated in NSCLC cells after treatment with Aila and regulated expression levels of . In conclusion, our findings demonstrate that Aila is a potent natural suppressor of NSCLC by modulating expression of and .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.652567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255921PMC
June 2021

Alkaline thermal pretreatment of waste activated sludge for enhanced hydrogen production in microbial electrolysis cells.

J Environ Manage 2021 Sep 12;294:113000. Epub 2021 Jun 12.

State Key Laboratory of Heavy Oil Processing, Beijing Key Lab of Oil & Gas Pollution Control, China University of Petroleum, Beijing, 102249, China; College of Chemical Engineering and Environment, China University of Petroleum, Beijing, 102249, China. Electronic address:

Resource utilization of waste activated sludge (WAS) has become a mainstream development direction. Alkaline thermal pretreatment (TPT) was found to greatly promote the bioaccessibility and biodegradability of the sludge. The organic matter including soluble chemical oxygen demand (SCOD), soluble carbohydrate, soluble protein and volatile fatty acids (VFAs) after low temperature (90 °C) pretreatment was 4.8%-65.9% higher than that after high temperature (180 °C) pretreatment. These increasements could be contributed by the alkaline treatment condition and the longer treatment time. The alkaline condition reduced the resistance of cell wall to the temperature. The pretreatment time at 90 °C was two times of that at 180 °C, allowing more organic matter to be released. But the total energy consumption of low temperature pretreatment (2580.7 kJ/L) was 30.5% lower than that of high temperature pretreatment (3711.8 kJ/L). The sludge fermentation liquid (SFL) was then employed as the substrate in microbial electrolysis cells (MECs), and the utilization efficiency of acetic acid was the highest (74.9%-83.2%). The hydrogen yield using low temperature pretreated sludge was 0.44 m/(m·d), which was higher than that of using high temperature pretreated sludge (0.31 m/(m·d)). These results suggested that alkaline TPT at 90 °C was an effective way to hydrolyze sludge and further enhance hydrogen production in MECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2021.113000DOI Listing
September 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Single-mode characteristic of a supermode microcavity Raman laser.

Proc Natl Acad Sci U S A 2021 Jun;118(22)

State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, 100871 Beijing, China;

Microlasers in near-degenerate supermodes lay the cornerstone for studies of non-Hermitian physics, novel light sources, and advanced sensors. Recent experiments of the stimulated scattering in supermode microcavities reported beating phenomena, interpreted as dual-mode lasing, which, however, contradicts their single-mode nature due to the clamped pump field. Here, we investigate the supermode Raman laser in a whispering-gallery microcavity and demonstrate experimentally its single-mode lasing behavior with a side-mode suppression ratio (SMSR) up to 37 dB, despite the emergence of near-degenerate supermodes by the backscattering between counterpropagating waves. Moreover, the beating signal is recognized as the transient interference during the switching process between the two supermode lasers. Self-injection is exploited to manipulate the lasing supermodes, where the SMSR is further improved by 15 dB and the laser linewidth is below 100 Hz.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2101605118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179179PMC
June 2021

Removal of refractory organics in wastewater by coagulation/flocculation with green chlorine-free coagulants.

Sci Total Environ 2021 Sep 8;787:147654. Epub 2021 May 8.

State Key Laboratory of Heavy Oil Processing, Beijing Key Lab of Oil & Gas Pollution Control, China University of Petroleum, Beijing 102249, China; College of Chemical Engineering and Environment, China University of Petroleum, Beijing 102249, China. Electronic address:

Coagulation/flocculation is considered an economical and practical technology to remove refractory organic matter from wastewater. Coagulants containing chlorine may release chloride ions into water, thereby resulting in corrosion. A green chlorine-free coagulant of polyaluminum ferric silicate (PSAF) was synthesized to treat non-oily (e.g., humus wastewater) and oily refractory wastewaters (e.g., lubricating oil wastewater). Results showed that the highest removal efficiency of humus substances in non-oily wastewater achieved 96.0% at pH 7.0 using PSAF alone. When treating oily wastewater, the dosage and addition sequence of PAMALAM significantly affected the coagulation performance. The removal efficiencies of turbidity, chemical oxygen demand, and total nitrogen were increased by 0.3, 1.8, and 5.9 folds, respectively, with the optimal adding sequence of PSAF +0.08% PAMALAM. More fulvic acid-like substances can be removed during this process. The analysis of zeta potential and floc properties revealed that charge neutralization, sweep, and adsorption/entrapment mechanisms existed during the single PSAF coagulation process, and PAMALAM mainly improved the adsorption, bridging, and sweep function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.147654DOI Listing
September 2021

Baicalein Induces Apoptosis of Pancreatic Cancer Cells by Regulating the Expression of miR-139-3p and miR-196b-5p.

Front Oncol 2021 30;11:653061. Epub 2021 Apr 30.

Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.

Pancreatic cancer is a common malignant tumor with a high incidence and mortality rate. The prognosis of patients with pancreatic cancer is considerably poor due to the lack of effective treatment in clinically. Despite numerous studies have revealed that baicalein, a natural product, is responsible for suppressing multiple cancer cells proliferation, motility and invasion. The mechanism by which baicalein restraining pancreatic cancer progression remains unclear. In this study, we firstly verified that baicalein plays a critical role in inhibiting pancreatic tumorigenesis and . Then we analyzed the alteration of microRNAs (miRNAs) expression levels in Panc-1 cells incubated with DMSO, 50 and 100 μM baicalein by High-Throughput sequencing. Intriguingly, we observed that 20 and 39 miRNAs were accordingly up- and down-regulated through comparing Panc-1 cells exposed to 100 μM baicalein with the control group. Quantitative PCR analysis confirmed that miR-139-3p was the most up-regulated miRNA after baicalein treatment, while miR-196b-5p was the most down-regulated miRNA. Further studies showed that miR-139-3p induced, miR-196b-5p inhibited the apoptosis of Panc-1 cells targeting NOB1 and ING5 respectively. In conclusion, we demonstrated that baicalein is a potent inhibitor against pancreatic cancer by modulating the expression of miR-139-3p or miR-196b-5p.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.653061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120266PMC
April 2021

Cutting the fat: advances and challenges in sleep apnoea genetics.

Eur Respir J 2021 05 6;57(5). Epub 2021 May 6.

Division of Sleep and Circadian Disorders, Dept of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.04644-2020DOI Listing
May 2021

Fucoidan Inhibits the Progression of Hepatocellular Carcinoma Causing lncRNA LINC00261 Overexpression.

Front Oncol 2021 13;11:653902. Epub 2021 Apr 13.

Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.

Hepatocellular carcinoma (HCC) as a main type of primary liver cancers has become one of the most deadly tumors because of its high morbidity and poor prognosis. Fucoidan is a family of natural, heparin-like sulfated polysaccharides extracted from brown algae. It is not only a widely used dietary supplement, but also participates in many biological activities, such as anti-oxidation, anti-inflammation and anti-tumor. However, the mechanism of fucoidan induced inhibition of HCC is elusive. In our study, we demonstrated that fucoidan contributes to inhibiting cell proliferation and , restraining cell motility and invasion and inducing cell cycle arrest and apoptosis. According to High-Throughput sequencing of long-non-coding RNA (lncRNA) in MHCC-97H cells treated with 0.5 mg/mL fucoidan, we found that 56 and 49 lncRNAs were correspondingly up- and down-regulated. LINC00261, which was related to the progression of tumor, was highly expressed in fucoidan treated MHCC-97H cells. Moreover, knocking down LINC00261 promoted cell proliferation by promoting the expression level of miR-522-3p, which further decreased the expression level of downstream SFRP2. Taken together, our results verified that fucoidan effectively inhibits the progression of HCC causing lncRNA LINC00261 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.653902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078595PMC
April 2021

CPA-seq reveals small ncRNAs with methylated nucleosides and diverse termini.

Cell Discov 2021 Apr 19;7(1):25. Epub 2021 Apr 19.

School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

High-throughput sequencing reveals the complex landscape of small noncoding RNAs (sRNAs). However, it is limited by requiring 5'-monophosphate and 3'-hydroxyl in RNAs for adapter ligation and hindered by methylated nucleosides that interfere with reverse transcription. Here we develop Cap-Clip acid pyrophosphatase (Cap-Clip), T4 polynucleotide kinase (PNK) and AlkB/AlkB(D135S)-facilitated small ncRNA sequencing (CPA-seq) to detect and quantify sRNAs with terminus multiplicities and nucleoside methylations. CPA-seq identified a large number of previously undetected sRNAs. Comparison of sRNAs with or without AlkB/AlkB(D135S) treatment reveals nucleoside methylations on sRNAs. Using CPA-seq, we profiled the sRNA transcriptomes (sRNomes) of nine mouse tissues and reported the extensive tissue-specific differences of sRNAs. We also observed the transition of sRNomes during hepatic reprogramming. Knockdown of mesenchymal stem cell-enriched U1-5' snsRNA promoted hepatic reprogramming. CPA-seq is a powerful tool with high sensitivity and specificity for profiling sRNAs with methylated nucleosides and diverse termini.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41421-021-00265-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053708PMC
April 2021

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P = 2 × 10). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P < 10). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-021-01087-0DOI Listing
April 2021

Dispersive-wave induced noise limits in miniature soliton microwave sources.

Nat Commun 2021 Mar 4;12(1):1442. Epub 2021 Mar 4.

T. J. Watson Laboratory of Applied Physics, California Institute of Technology, Pasadena, CA, USA.

Compact, low-noise microwave sources are required throughout a wide range of application areas including frequency metrology, wireless-communications and airborne radar systems. And the photonic generation of microwaves using soliton microcombs offers a path towards integrated, low noise microwave signal sources. In these devices, a so called quiet-point of operation has been shown to reduce microwave frequency noise. Such operation decouples pump frequency noise from the soliton's motion by balancing the Raman self-frequency shift with dispersive-wave recoil. Here, we explore the limit of this noise suppression approach and reveal a fundamental noise mechanism associated with fluctuations of the dispersive wave frequency. At the same time, pump noise reduction by as much as 36 dB is demonstrated. This fundamental noise mechanism is expected to impact microwave noise (and pulse timing jitter) whenever solitons radiate into dispersive waves belonging to different spatial mode families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21658-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933157PMC
March 2021

A-to-I RNA Editing in Cancer: From Evaluating the Editing Level to Exploring the Editing Effects.

Front Oncol 2020 11;10:632187. Epub 2021 Feb 11.

Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China.

As an important regulatory mechanism at the posttranscriptional level in metazoans, adenosine deaminase acting on RNA (ADAR)-induced A-to-I RNA editing modification of double-stranded RNA has been widely detected and reported. Editing may lead to non-synonymous amino acid mutations, RNA secondary structure alterations, pre-mRNA processing changes, and microRNA-mRNA redirection, thereby affecting multiple cellular processes and functions. In recent years, researchers have successfully developed several bioinformatics software tools and pipelines to identify RNA editing sites. However, there are still no widely accepted editing site standards due to the variety of parallel optimization and RNA high-seq protocols and programs. It is also challenging to identify RNA editing by normal protocols in tumor samples due to the high DNA mutation rate. Numerous RNA editing sites have been reported to be located in non-coding regions and can affect the biosynthesis of ncRNAs, including miRNAs and circular RNAs. Predicting the function of RNA editing sites located in non-coding regions and ncRNAs is significantly difficult. In this review, we aim to provide a better understanding of bioinformatics strategies for human cancer A-to-I RNA editing identification and briefly discuss recent advances in related areas, such as the oncogenic and tumor suppressive effects of RNA editing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.632187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905090PMC
February 2021

Genetic determinants of daytime napping and effects on cardiometabolic health.

Nat Commun 2021 02 10;12(1):900. Epub 2021 Feb 10.

Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20585-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876146PMC
February 2021

Dirac solitons in optical microresonators.

Light Sci Appl 2020 Dec 23;9(1):205. Epub 2020 Dec 23.

T. J. Watson Laboratory of Applied Physics, California Institute of Technology, Pasadena, CA, 91125, USA.

Mode-coupling-induced dispersion has been used to engineer microresonators for soliton generation at the edge of the visible band. Here, we show that the optical soliton formed in this way is analogous to optical Bragg solitons and, more generally, to the Dirac soliton in quantum field theory. This optical Dirac soliton is studied theoretically, and a closed-form solution is derived in the corresponding conservative system. Both analytical and numerical solutions show unusual properties, such as polarization twisting and asymmetrical optical spectra. The closed-form solution is also used to study the repetition rate shift in the soliton. An observation of the asymmetrical spectrum is analysed using theory. The properties of Dirac optical solitons in microresonators are important at a fundamental level and provide a road map for soliton microcomb generation in the visible band.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41377-020-00438-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758338PMC
December 2020

Dendrobium nobile Lindl. polysaccharides reduce cerebral ischemia/reperfusion injury in mice by increasing myeloid cell leukemia 1 via the downregulation of miR-134.

Neuroreport 2021 02;32(3):177-187

BDAcademic & Research Center, Beidou Life Science Corp. Ltd, Guangzhou, China.

Objective: The traditional Chinese medicine, Dendrobium nobile Lindl. polysaccharides (DNLP), reportedly has neuroprotective effects. However, its effects following ischemic stroke remain unclear. This study aimed to explore the role and mechanism of DNLP in experimental models of inflammation and apoptosis.

Methods: Inflammation and apoptosis were induced by in vivo ischemia/reperfusion and by in vitro oxygen glucose deprivation/reperfusion (OGD/R). In the in vivo model, immediately after the induction of cerebral ischemia, 50, 100, and 200 mg/kg DNLP were injected intraperitoneally. We subsequently detected indicators of neuronal damage.

Results: Treatment with Dendrobium nobile Lindl. polysaccharide significantly reduced cerebral ischemic injury. After in vivo and in vitro middle cerebral artery occlusion/reperfusion or OGD/R-induced hypoxia injury, miR-134 expression in neurons was significantly increased. Altering the expression of miR-134 induced changes in myeloid cell leukemia 1 (MCL-1), one of its target proteins. In addition, DNLP significantly downregulated the in vivo and in vitro expression of miR-134 after ischemic injury, and influenced inflammation and apoptotic proteins by altering the level of MCL-1 protein. DNLP also had a protective effect on neurons damaged by OGD/R, which could improve cell survival rates and inhibit lactate dehydrogenase release as well as apoptosis.

Conclusions: DNLP may protect the brain and neurons from hypoxic damage in mice with ischemic stroke by activating MCL-1 and downregulating miR-134, providing a new therapeutic target for ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0000000000001562DOI Listing
February 2021

Non-REM Apnea and Hypopnea Duration Varies across Population Groups and Physiologic Traits.

Am J Respir Crit Care Med 2021 05;203(9):1173-1182

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.

Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea-hypopnea index (AHI). Respiratory event duration is a heritable trait associated with mortality that may further characterize OSA. We evaluated how hypopnea and apnea durations in non-REM (NREM) sleep vary across demographic groups and quantified their associations with physiological traits (loop gain, arousal threshold, circulatory delay, and pharyngeal collapsibility). Data were analyzed from 1,546 participants from the Multi-Ethnic Study of Atherosclerosis with an AHI ≥5. Physiological traits were derived using a validated model fit to the polysomnographic airflow signal. Multiple linear regression models were used to evaluate associations of event duration with demographic and physiological factors. Participants had a mean age ± SD of 68.9 ± 9.2 years, mean NREM hypopnea duration of 21.73 ± 5.60, and mean NREM apnea duration of 23.87 ± 7.44 seconds. In adjusted analyses, shorter events were associated with younger age, female sex, higher body mass index ( < 0.01, all), and Black race ( < 0.05). Longer events were associated with Asian race ( < 0.01). Shorter event durations were associated with lower circulatory delay (2.53 ± 0.13 s,  < 0.01), lower arousal threshold (1.39 ± 0.15 s,  < 0.01), reduced collapsibility (-0.71 ± 0.16 s,  < 0.01), and higher loop gain (-0.27 ± 0.11 s,  < 0.05) per SD change. Adjustment for physiological traits attenuated age, sex, and obesity associations and eliminated racial differences in event duration. Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202005-1808OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314913PMC
May 2021

Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis.

Int J Epidemiol 2021 07;50(3):817-828

MRC Integrative Epidemiology Unit, at the University of Bristol, Bristol, UK.

Background: It is established that Alzheimer's disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD.

Methods: We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep traits (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness), and AD. Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters on AD risk.

Results: Overall, there was little evidence to support a causal effect of sleep traits on AD risk. There was some suggestive evidence that self-reported daytime napping was associated with lower AD risk [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.50-0.99). Some other sleep traits (accelerometer-measured 'eveningness' and sleep duration, and self-reported daytime sleepiness) had ORs of a similar magnitude to daytime napping, but were less precisely estimated.

Conclusions: Overall, we found very limited evidence to support a causal effect of sleep traits on AD risk. Our findings provide tentative evidence that daytime napping may reduce AD risk. Given that this is the first MR study of multiple self-report and objective sleep traits on AD risk, findings should be replicated using independent samples when such data become available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyaa183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271193PMC
July 2021

Greater than one billion Q factor for on-chip microresonators.

Opt Lett 2020 Sep;45(18):5129-5131

High optical quality (Q) factors are critically important in optical microcavities, where performance in applications spanning nonlinear optics to cavity quantum electrodynamics is determined. Here, a record Q factor of over 1.1 billion is demonstrated for on-chip optical resonators. Using silica whispering-gallery resonators on silicon, Q-factor data is measured over wavelengths spanning the C/L bands (100 nm) and for a range of resonator sizes and mode families. A record low sub-milliwatt parametric oscillation threshold is also measured in 9 GHz free-spectral-range devices. The results show the potential for thermal silica on silicon as a resonator material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.394940DOI Listing
September 2020

Quantifying China's iron in-use stock and its driving factors analysis.

J Environ Manage 2020 Nov 19;274:111220. Epub 2020 Aug 19.

State Environmental Protection Key Laboratory of Eco-Industry, Northeastern University, Shenyang, 110819, China.

China is experiencing unprecedented industrialization and urbanization which promotes the rapid growth of iron resource consumption and in-use stock. The material flow analysis (MFA) model and the average use life method were applied to analyze China's iron in-use stock (IIUS), and the IIUS reached 7.07 billion tons in 2016 in the reference scenario. Three driving factors of the intensity of IIUS were analyzed. Among them, the per capita IIUS was rising, and it was 5.11 t/cap in 2016 in the reference scenario. In addition, the per capita crude steel output has stabilized, which was 0.58 t/cap in 2016. The intensity of crude steel use was declining and showed the inverted U-shape. The decoupling indicator was applied to analyze the relationship between IIUS and economic growth. The decoupling of IIUS from economic growth was later than that of actual iron consumption, and the IIUS did not decoupling from economic growth in recent years. The actual iron consumption has continued to decoupling from economic growth since 2010, and the decoupling indicator peaked at 1.76 in 2015. The future per capita IIUS was predicted in different scenario and the relationship between future IIUS and GDP was analyzed. The per capita IIUS will reach saturation in 2030-2040, and the intensity of IIUS also conforms to the inverted U-shape.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2020.111220DOI Listing
November 2020

Detecting fitness epistasis in recently admixed populations with genome-wide data.

BMC Genomics 2020 Jul 11;21(1):476. Epub 2020 Jul 11.

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.

Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population.

Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment.

Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-020-06874-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353720PMC
July 2020

Integrated turnkey soliton microcombs.

Nature 2020 06 17;582(7812):365-369. Epub 2020 Jun 17.

ECE Department, University of California Santa Barbara, Santa Barbara, CA, USA.

Optical frequency combs have a wide range of applications in science and technology. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators. Such soliton microcombs have been applied to spectroscopy, the search for exoplanets, optical frequency synthesis, time keeping and other areas. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor SiN resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2358-xDOI Listing
June 2020

Low oxygen saturation during sleep reduces CD1D and RAB20 expressions that are reversed by CPAP therapy.

EBioMedicine 2020 Jun 5;56:102803. Epub 2020 Jun 5.

Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.

Background: Sleep Disordered Breathing (SDB) is associated with a wide range of pathophysiological changes due, in part, to hypoxemia during sleep. We sought to identify gene transcription associations with measures of SDB and hypoxemia during sleep, and study their response to treatment.

Methods: In two discovery cohorts, Framingham Offspring Study (FOS; N = 571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580), we studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. Associated genes were used for analysis of gene expression in the blood of 15 participants with moderate or severe obstructive sleep apnea (OSA) from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. These genes were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses.

Findings: Twenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated following CPAP treatment (HeartBEAT).

Interpretation: Low oxygen saturation during sleep is associated with alterations in gene expression and transcriptional programs that are partially reversed by CPAP treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276515PMC
June 2020

Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.

Circ Genom Precis Med 2020 08 8;13(4):e002772. Epub 2020 Jun 8.

Department of Epidemiology, School of Public Health (L.F.B., J.A.S., W.Z., S.L.R.K.), University of Michigan, Ann Arbor, MI.

Background: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.

Methods: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered.

Results: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (, , , , , , , and ) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (=6.65×10 for the interaction test) and replicated at nominal significance level (=0.013) in .

Conclusions: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCGEN.119.002772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442680PMC
August 2020

Chaos-assisted two-octave-spanning microcombs.

Nat Commun 2020 05 11;11(1):2336. Epub 2020 May 11.

State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-optoelectronics, School of Physics, Peking University, 100871, Beijing, China.

Since its invention, optical frequency comb has revolutionized a broad range of subjects from metrology to spectroscopy. The recent development of microresonator-based frequency combs (microcombs) provides a unique pathway to create frequency comb systems on a chip. Indeed, microcomb-based spectroscopy, ranging, optical synthesizer, telecommunications and astronomical calibrations have been reported recently. Critical to many of the integrated comb systems is the broad coverage of comb spectra. Here, microcombs of more than two-octave span (450 nm to 2,008 nm) is demonstrated through χ and χ nonlinearities in a deformed silica microcavity. The deformation lifts the circular symmetry and creates chaotic tunneling channels that enable broadband collection of intracavity emission with a single waveguide. Our demonstration introduces a new degree of freedom, cavity deformation, to the microcomb studies, and our microcomb spectral range is useful for applications in optical clock, astronomical calibration and biological imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15914-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214461PMC
May 2020
-->