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1.
Epigenetics Chromatin ; 13(1): 51, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228774

RESUMO

BACKGROUND: Epigenome-wide association studies (EWAS) have been widely applied to identify methylation CpG sites associated with human disease. To date, the Infinium MethylationEPIC array (EPIC) is commonly used for high-throughput DNA methylation profiling. However, the EPIC array covers only 30% of the human methylome. Methylation Capture bisulfite sequencing (MC-seq) captures target regions of methylome and has advantages of extensive coverage in the methylome at an affordable price. METHODS: Epigenome-wide DNA methylation in four peripheral blood mononuclear cell samples was profiled by using SureSelectXT Methyl-Seq for MC-seq and EPIC platforms separately. CpG site-based reproducibility of MC-seq was assessed with DNA sample inputs ranging in quantity of high (> 1000 ng), medium (300-1000 ng), and low (150 ng-300 ng). To compare the performance of MC-seq and the EPIC arrays, we conducted a Pearson correlation and methylation value difference at each CpG site that was detected by both MC-seq and EPIC. We compared the percentage and counts in each CpG island and gene annotation between MC-seq and the EPIC array. RESULTS: After quality control, an average of 3,708,550 CpG sites per sample were detected by MC-seq with DNA quantity > 1000 ng. Reproducibility of DNA methylation in MC-seq-detected CpG sites was high among samples with high, medium, and low DNA inputs (r > 0.96). The EPIC array captured an average of 846,464 CpG sites per sample. Compared with the EPIC array, MC-seq detected more CpGs in coding regions and CpG islands. Among the 472,540 CpG sites captured by both platforms, methylation of a majority of CpG sites was highly correlated in the same sample (r: 0.98-0.99). However, methylation for a small proportion of CpGs (N = 235) differed significantly between the two platforms, with differences in beta values of greater than 0.5. CONCLUSIONS: Our results show that MC-seq is an efficient and reliable platform for methylome profiling with a broader coverage of the methylome than the array-based platform. Although methylation measurements in majority of CpGs are highly correlated, a number of CpG sites show large discrepancy between the two platforms, which warrants further investigation and needs cautious interpretation.

2.
Schizophr Bull ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33135075

RESUMO

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.

3.
Protein Cell ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165830

RESUMO

In the original publication the author's name 'Dimitri Lavillete' is published incorrectly. The correct author name should be spelt as 'Dimitri Lavillette' is provided in this correction.

4.
Mol Ecol Resour ; 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33188724

RESUMO

The common pheasant Phasianus colchicus, belonging to the order Galliformes and family Phasianidae, is the most widespread pheasant. Despite a long history of captivity, the domestication of this bird is preliminary. Recently, the demand for accelerating its transformation to poultry for meat and egg production has been increasing. In this study, we assembled high quality, chromosome scale genome of the common pheasant by using PacBio long reads, next-generation short reads, and Hi-C technology. The primary assembly has contig N50 size of 1.33 Mb and scaffold N50 size of 59.46 Mb, with a total size of 0.99 Gb, resolving most macrochromosomes into single scaffolds. A total of 23,058 genes and 10.71 Mb interspersed repeats were identified, constituting 30.31% and 10.71% of the common pheasant genome, respectively. Our phylogenetic analysis reveals that common pheasant shared common ancestors with turkey about 24.7-34.5 million years ago. Rapidly evolved gene families, as well as branch-specific positively selected genes, indicate that calcium-related genes are potentially related to the adaptive and evolutionary change of the common pheasant. Interestingly, we found that the common pheasant has a unique major histocompatibility complex B locus (MHC-B) structure: three major inversions occurred in the sequence compared with the chicken MHC-B. Furthermore, we detect signals of selection in five breeds of domestic common pheasant, several of which are production-oriented selection.

5.
Oncol Rep ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169799

RESUMO

Following the publication of the above article, an interested reader drew to the authors' attention that an error was made in the assembly of the data panels shown in Fig. 4A. The 'NC' and 'FoxO3a­KD' panels (specifically, the upper left margins of the three 'NC' data panels and the lower right margins of the three 'FoxO3a­KD' panels) contained overlapping data. The authors were able to consult their original data, and realized that errors had occurred inadvertently during the figure compilation process. The revised version of Fig. 4A, featuring the corrected data panels for the 'NC' experiments, is shown opposite. The authors have confirmed that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 37: 2391­2397, 2017; DOI: 10.3892/or.2017.5459].

6.
Artigo em Inglês | MEDLINE | ID: mdl-33226224

RESUMO

Bacterial infection has become an urgent health problem in the world. Especially, the evolving resistance of bacteria to antibiotics makes the issue more challenging, and thus new treatments to fight these infections are needed. Antibacterial photodynamic therapy (aPDT) is recognized as a novel and promising method to inactivate a wide range of bacteria with few possibilities to develop drug resistance. However, the photosensitizers (PSs) are not effective against Gram-negative bacteria in many cases. Herein, we use conjugated meso-tetra(4-carboxyphenyl)porphine (TCPP) and triaminoguanidinium chloride (TG) to construct self-assembled cationic TCPP-TG nanoparticles (NPs) for efficient bacterial inactivation under visible light illumination. The TCPP-TG NPs can rapidly adhere to both Gram-negative and Gram-positive bacteria and display promoted singlet oxygen (1O2) generation compared with TCPP under light irradiation. The high local positive charge density of TCPP-TG NPs facilitates the interaction between the NPs and bacteria. Consequently, the TCPP-TG NPs produce an elevated concentration of local 1O2 under light irradiation, resulting in an extraordinarily high antibacterial efficiency (99.9999% inactivation of the representative bacteria within 4 min). Furthermore, the TCPP-TG NPs show excellent water dispersity and stability during 4 months of storage. Therefore, the rationally designed TCPP-TG NPs are a promising antibacterial agent for effective aPDT.

7.
Bioresour Technol ; 320(Pt A): 124326, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33166881

RESUMO

In this study, the effect of Fe3+ on the start-up of Anammox process was investigated. Four EGSB reactors were operated with the addition of 0 (R1), 0.04 (R2), 0.08 (R3) and 0.14 (R4) mmol/L Fe3+, respectively. The results showed that Fe3+ remarkably improved the nitrogen loading rate (NLR) and operation efficiency of the reactor. After 180 days, the influent NH4+-N concentration in the four reactors was 201.4, 301.8, 343.2, 380.2 mg N/L, and the NLR was 589.3, 877.6, 993.0, 1105.8 mg N/(L·d), respectively. And the nitrogen removal rate (NRR) in R2, R3 and R4 was respectively 1.54, 1.73 and 1.94 times of that in R1. High throughput sequencing revealed that Fe3+ could promote the enrichment of Anammox bacteria Candidatus Brocadia. Moreover, the analysis by qPCR indicated that the abundance of Anammox 16S rRNA gene and the functional gene hzsB increased, which showed a positive correlation with the concentration of Fe3+.

8.
Nat Prod Bioprospect ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219498

RESUMO

Two new quinazoline derivatives versicomides E (1) and F (2), and 10 known compounds (3-12) were isolated from the moss endophytic fungus Aspergillus sp. Their structures were determined on the basis of extensive spectroscopic data analysis and ECD calculations. Among them, the compound 7 (6-hydroxy-3-methoxyviridicatin) was first reported as a natural product. Inhibition on LPS-induced NO production in RAW 264.7 murine macrophages found that compounds 5, 7 and 8 showed significant inhibitory effects on NO production, with IC50 values of 49.85, 22.14 and 46.02 µM respectively.

9.
Neurosci Lett ; 740: 135441, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33184037

RESUMO

BACKGROUND: A recent study on early onset Parkinson's disease (PD) revealed that NUS1 is a risk gene for PD. Clinically, essential tremor (ET) is closely related to PD. In this study, we aimed to detect NUS1 variants and assess the effect of those variants on patients with ET. METHODS: The 5 coding regions and the exon-intron boundaries of NUS1 were directly sequenced in 395 patients with ET and an equal number of healthy controls, matched for age and sex. The function of variants was assessed by pathogenic predictive software programs. Genetic analysis of variants was used to evaluate susceptibility to ET. RESULTS: A total of 6 exonic variants were identified, including 3 synonymous and 3 missense variants. The non-synonymous variants were predicted to be tolerable. No variants had significant association with ET (none of the p-values were less than 0.05, using Fisher's exact test). CONCLUSION: Our study suggested that NUS1 variants may not contribute to the risk of ET.

11.
Langmuir ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206532

RESUMO

Electrocoalescence technology is an important method for the demulsification of crude oil emulsion, but its development is restricted by the short circuit caused by droplet chain formation. To reveal the formation mechanism of droplet chains, the electrocoalescence behaviors of two droplets and droplet clusters under pulsed direct current (DC) electric fields are experimentally studied. The two droplets usually successively undergo complete coalescence, partial coalescence, and noncoalescence as the electric field strength increases. The critical electric field strengths for complete coalescence under pulsed DC electric fields with different frequencies are obtained. The effects of the electric field waveform and frequency on the noncoalescence characteristics of two droplets and the stability of droplet chains are explored. The droplet chains under a high-frequency electric field are more stable and longer than those under a low-frequency electric field due to the reduction of the movement distance and the generation of daughter droplets from tip streaming. The reversal of the composition of electric forces due to charge transfer is the fundamental mechanism of noncoalescence of two droplets and chain formation in the emulsion under a pulsed DC electric field.

12.
Hum Brain Mapp ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210798

RESUMO

Dynamic functional connectivity (DFC) analysis can capture time-varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting-state functional magnetic resonance imaging and a sliding-window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k-means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4-group differences (SZ, BD, MDD, and HC groups; q < .05, false-discovery rate [FDR]-corrected) in DFC were nearly only in State 1. Post hoc analyses (q < .05, FDR-corrected) in State 1 showed that transdiagnostic dysconnectivity patterns among SZ, BD and MDD featured consistently decreased connectivity within most networks (the visual, somatomotor, salience and frontoparietal networks), which was most obvious in both range and extent for SZ. Our findings suggest that there is more common dysconnectivity across SZ, BD and MDD than we previously expected and that such dysconnectivity is state-dependent, which provides new insights into the pathophysiological mechanism of major psychiatric disorders.

13.
Microb Cell Fact ; 19(1): 202, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138821

RESUMO

BACKGROUND: In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called "Genetic pH Shooting (GPS)" to realize microbial self-regulation of pH. RESULTS: In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%. CONCLUSIONS: The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications.

14.
Cell Metab ; 32(5): 699-701, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33147482

RESUMO

Nutrient acquisition and metabolism are integral components of cell growth, proliferation, and differentiation programs. In a recent study in Nature, Bian et al. (2020) revealed that cancer cells outcompete T cells for methionine uptake, resulting in diminished SAM production, attenuated H3K79 dimethylation, decreased STAT5 expression, and impaired T cell immunity to cancer.

15.
Chemosphere ; : 128794, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33139049

RESUMO

This study aimed to investigate the effects and biological mechanism of external static magnetic fields (SMFs) on enhancing nitrogen removal at different influent ammonium nitrogen (NH4+) concentrations. Four sequential batch reactors (SBRs) with SMFs of 0, 15, 30, and 50 mT were operated continuously for 196 days, during which the influent NH4+-N concentration increased stepwise as 50, 100, 350, and 600 mg L-1. The results showed that 50 mT had optimum effects on enhancing nitrogen removal, especially at high NH4+-N concentrations (350 and 600 mg L-1). The biological mechanism by which SMF influences nitrogen removal varies depending on the NH4+ concentration. At low NH4+-N concentrations (50 and 100 mg L-1), a field of 50 mT increased key enzyme activities and corresponding functional gene abundances. Additionally, it further improved functional bacterial abundances, which involved nitrifying and denitrifying bacteria at high NH4+ concentrations. These findings could provide guidance for the selection of optimum SMF intensity at different influent NH4+ concentrations.

16.
Nat Commun ; 11(1): 5302, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082346

RESUMO

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.

17.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33034614

RESUMO

PURPOSE: The aims of the present study were to explore immune-related genes (IRGs) in stage IV colorectal cancer (CRC) and construct a prognostic risk score model to predict patient overall survival (OS), providing a reference for individualized clinical treatment. METHODS: High-throughput RNA-sequencing, phenotype, and survival data from patients with stage IV CRC were downloaded from TCGA. Candidate genes were identified by screening for differentially expressed IRGs (DE-IRGs). Univariate Cox regression, LASSO, and multivariate Cox regression analyses were used to determine the final variables for construction of the prognostic risk score model. GSE17536 from the GEO database was used as an external validation dataset to evaluate the predictive power of the model. RESULTS: A total of 770 candidate DE-IRGs were obtained, and a prognostic risk score model was constructed by variable screening using the following 12 genes: FGFR4, LGR6, TRBV12-3, NUDT6, MET, PDIA2, ORM1, IGKV3D-20, THRB, WNT5A, FGF18, and CCR8. In the external validation set, the survival prediction C-index was 0.685, and the AUC values were 0.583, 0.731, and 0.837 for 1-, 2- and 3-year OS, respectively. Univariate and multivariate Cox regression analyses demonstrated that the risk score model was an independent prognostic factor for patients with stage IV CRC. High- and low-risk patient groups had significant differences in the expression of checkpoint coding genes (ICGs). CONCLUSION: The prognostic risk score model for stage IV CRC developed in the present study based on immune-related genes has acceptable predictive power, and is closely related to the expression of ICGs.

18.
Dev Cell ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33120014

RESUMO

Differentiation therapy utilizes our understanding of the hierarchy of cellular systems to pharmacologically induce a shift toward terminal commitment. While this approach has been a paradigm in treating certain hematological malignancies, efforts to translate this success to solid tumors have met with limited success. Mammary-specific activation of PKA in mouse models leads to aberrant differentiation and diminished self-renewing potential of the basal compartment, which harbors mammary repopulating cells. PKA activation results in tumors that are more benign, exhibiting reduced metastatic propensity, loss of tumor-initiating potential, and increased sensitivity to chemotherapy. Analysis of tumor histopathology revealed features of overt differentiation with papillary characteristics. Longitudinal single-cell profiling at the hyperplasia and tumor stages uncovered an altered path of tumor evolution whereby PKA curtails the emergence of aggressive subpopulations. Acting through the repression of SOX4, PKA activation promotes tumor differentiation and represents a possible adjuvant to chemotherapy for certain breast cancers.

19.
Oncol Rep ; 44(6): 2595-2609, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125108

RESUMO

Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA­loaded nanoliposomes (BA­NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA­NLs in fatty acid metabolism­mediated glycolysis, and investigate the role of key targets, such as acyl­CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase­1 (PFK­1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA­NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti­CRC function of BA­NLs. Moreover, the effects of BA­NLs were further validated by demonstrating that the key targets of HK2, PFK­1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA­NLs, which play key roles in the inhibition of glycolysis and fatty acid­mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.

20.
Med Gas Res ; 10(3): 130-133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33004711

RESUMO

The use of hydrogen for cancer control has made great progress in cytology and animal experiments. With the increasing number of hydrogen products on the market, larger numbers of advanced cancer patients have participated in clinical trials or received treatment at home after purchase. Our study reported a real-world survey from 82 patients with good cancer control using hydrogen products, including real world evidence from patients who received ineffective traditional treatment, patients who received traditional treatment that failed, or patients who refused traditional treatment. Two typical cases were reported herein. Subsequently, we included studies on the mechanism of hydrogen oncology. The mechanism of cancer control using hydrogen includes the inhibition of tumor cells and the activation of exhausted lymphocytes. Large-scale real world evidence has shown clinical value, and yet remains to be further developed and researched.

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