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1.
Talanta ; 221: 121614, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076144

RESUMO

The cotton plant is an essential crop cultivated globally for its fiber and seeds. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to study the spatial distribution patterns of lipids in cottonseeds. 448 lipid ions were identified by LC-MS/MS, and 24 of which were precisely visualized by using MALDI-MSI. The lipids, including phosphatidylcholines (PC), phosphatidylethanolamines (PE) and triacylglycerols (TG) showed heterogeneous distribution patterns within the cotyledonary and radicle tissues. Additionally, the roles these lipids played in the metabolic pathways were analyzed, and relationship of the spatial distribution of LPC (lysophosphatidylcholine) and corresponding PC was studied. The unique distribution patterns of these lipid metabolites revealed by MSI can provide new insights into areas relating to the spatial compartmentation of lipid metabolism in plants. We believe that the results of MSI, if combined with transcriptomics and proteomics, may offer significant help in genetic engineering work.

2.
Sci Total Environ ; 751: 141620, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889456

RESUMO

With the development of the economy, anthropogenic emissions in the atmospheric environment increases, and air pollution has caused wide public concern. Vehicle exhaust is an important emission source in the atmosphere, and alkanes are the representative components in it. In this study, the optical properties of secondary organic aerosol (SOA) derived from several C12 alkanes (2-methylundecane, hexylcyclohexane, and cyclododecane) in the absence of NOX were determined. Absorption (imaginary part of the refractive index (RI), k) at 532 nm was negligible for all the derived SOA, and the scattering (real part of RI, n) of the SOA at 532 nm followed the order of cyclododecane SOA < hexylcyclohexane SOA < 2-methylundecane SOA, at both room- (25 °C) and low- (5 °C) temperature. The chemical compositions of the SOA formed were analyzed with an electrospray ionization time-of-flight mass spectrometer (ESI-TOF-MS). The mass spectra showed that the oligomers were generated in the reactions. It was shown that the different reaction pathways (due to various alkane structures) leaded to the difference in SOA chemical composition, which changed the RI values. The low-temperature condition promoted the progress of the oligomerization reaction so that the final RI values also changed. This work suggested that when estimating the radiative forcing of SOA using regional or global models, the structure of the precursors and reaction conditions should be taken into account.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118927, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32987271

RESUMO

A lysosomal-targeted near infrared (NIR) fluorescent probe for reactive oxygen species (ROS) was developed with highly sensitive ability. The different responding activity toward H2O2, OH, and HClO were investigated. Meanwhile, the probe has been successfully applied in detecting and imaging reactive oxygen species both in cells and in vivo.

4.
Sci Total Environ ; : 143029, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33129526

RESUMO

Plants are vital components of the nitrogen (N) cycling in the riparian zones. Understanding of N uptake strategies of riparian plants, including N sources and preference in N forms (ammonium (NH4+) vs. nitrate (NO3-)), is essential to advance our knowledge on the role that plants play in regulating nutrient biogeochemical cyclings in the riparian areas. In this study, stable N isotopes (δ15N) of three riparian plants, including Acorus calamus, Canna indica and Phragmites australis, and the δ15N of NH4+ and NO3- in different sources were measured during the plant growing season (June-September) in the Taihu Lake Basin. The dissolved inorganic N (DIN) from river water, groundwater, rainwater and soil were considered as the major N sources for plants in the riparian ecosystem. Our results indicated that soil was the largest source for plant N nutrition, with significantly different (P < 0.05) contributions from soil observed among plant species (80.5 ± 4.1, 73.9 ± 2.8 and 58.7 ± 6.1% for A. calamus, C. indica, and P. australis, respectively). Meanwhile, complex water networks, shallow water tables, and high DIN content in rainwater lead to nonignorable N contributions from river water, groundwater and rainwater to plants. Groundwater contributed more percentage of N to P. australis (12.8 ± 3.2%) than A. calamus (6.1 ± 1.9%) and C. indica (8.0 ± 1.5%), which is likely attributed to the deeper roots of P. australis. All plants showed similar N preference for NO3- during the growing season. External environmental conditions and plant characteristics and adaption to more abundant soil NO3- content are possible explanations. Our research could provide important information for vegetation selections during the process of riparian ecological restoration. Reasonable choice of vegetation is essential to plant growth and water quality management, especially in agricultural watersheds where N concentrations are relatively high in agricultural runoff due to the wide uses of N fertilizers.

5.
J Genet ; 992020.
Artigo em Inglês | MEDLINE | ID: mdl-33168793

RESUMO

Gene rearrangements, such as anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), rearranged during transfection (RET) and neurotrophic receptor tyrosine kinase 1 (NTRK1), identified in cancer have been indicated to be robust therapeutic targets in lung carcinomas. However, a few studies have focussed on locally advanced rectal cancer (LARC). The discovery of novel gene fusions is also valuable for LARC research. We used mass spectrometry-based assays and RNA sequencing to detect both known ALK, ROS1, RET and NTRK1 rearrangements and novel gene fusions in LARC patients. FusionMap was also used to find gene fusions. None of the ALK, ROS1, RET or NTRK1 gene fusions were detected by mass spectrometry-based assays or RNA sequencing. Three fusion candidates, integrin subunit beta 7 (ITGB7)-ROS1, lamin A/C (LMNA)-NTRK1 and Golgi-associated PDZ and coiled-coil motif containing (GOPC)-keratin 8 (KRT8), showed relatively high junction-spanning reads by the FusionMap algorithm, but did not pass validation. These results suggest that no ALK, ROS1 or RET rearrangements were found in LARC.

6.
Oncol Rep ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169798

RESUMO

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that Fig. 6D contained images featuring overlapping data, which reportedly had been derived under different experimental conditions. Subsequently, further issues of data duplication were brought to light by another interested reader concerning the above article; first, certain of the images showing colony­forming assays in Fig. 4D were strikingly similar to images that had appeared in a previous publication by the same research group, and secondly, a couple of instances of data duplication were identified among the histopathological images presented within Fig. 7D. After having considered the various issues that have been brought to light with this paper, together with an appeal from the authors that a Corrigendum be published, the Editor of Oncology Reports has ruled that the article should be retracted from the publication on account of a lack of overall confidence in the presented data. Note that the authors were not in agreement that the number of errors reported and identified were sufficient to merit the retraction of the article. Additionally, the authors carefully checked the raw data and drew a conclusion that the final scientific conclusions were not affected. The Editor and the authors apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 2114­2126, 2018; DOI: 10.3892/or.2018.6297].

7.
J Virol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144319

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia that emerged in 2012. There is limited information on MERS-CoV pathogenesis, as data from patients are scarce and the generation of animal models reproducing MERS clinical manifestations has been challenging. Human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice and a mouse-adapted MERS-CoV (MERSMA-6-1-2) were recently described. hDPP4-KI mice infected with MERSMA-6-1-2 show pathological signs of respiratory disease, high viral titers in the lung, and death. In this work, a mouse-adapted MERS-CoV infectious cDNA was engineered by introducing non-synonymous mutations contained in the MERSMA-6-1-2 genome into a MERS-CoV infectious cDNA, leading to a recombinant mouse-adapted virus (rMERS-MA) that was virulent in hDDP4-KI mice. MERS-CoV adaptation to cell culture or mouse lungs led to mutations and deletions in genus-specific gene 5 that prevented full-length protein expression. In contrast, analysis of 476 MERS-CoV field isolates showed that gene 5 is highly stable in vivo, both in humans and camels. To study the role of protein 5, two additional viruses were engineered expressing a full-length gene 5 (rMERS-MA-5FL), or containing a complete gene 5 deletion (rMERS-MA-Δ5). rMERS-MA-5FL virus was unstable, as deletions appeared during passage in different tissue culture cells, highlighting MERS-CoV instability. The virulence of rMERS-MA-Δ5 was analyzed in a sublethal hDPP4-KI mouse model. Unexpectedly, all mice died after infection with rMERS-MA-Δ5 in contrast to those infected with the parental virus, which contains a 17-nt deletion and a stop codon in protein 5 at position 108. Interferon and pro-inflammatory cytokine expression was delayed and dysregulated in the lungs of rMERS-MA-Δ5 infected mice. Overall, these data indicated that rMERS-MA-Δ5 virus was more virulent than the parental one and suggest that the residual gene 5 sequence present in the mouse-adapted parental virus had a function in ameliorating severe MERS-CoV pathogenesis.IMPORTANCE Middle East respiratory coronavirus (MERS-CoV) is a zoonotic virus causing human infections with high mortality rate (∼35%). Animal models together with reverse genetics systems are essential to understand MERS-CoV pathogenesis. We developed a reverse genetics system for a mouse-adapted MERS-CoV that reproduces the virus behavior observed in humans. This system is highly useful to investigate the role of specific viral genes in pathogenesis. In addition, we described a virus lacking gene 5 expression that is more virulent than the parental one. The data provide novel functions in IFN modulation for gene 5 in the context of viral infection, and will help to develop novel antiviral strategies.

8.
Sci Total Environ ; : 143633, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33223161

RESUMO

The source, distribution, migration, and fate of microplastics (MPs) in aquatic and terrestrial ecosystems have received much attention. However, the relevant reports in wetland ecosystems, the boundary area between water and land, are still rare. Where are the sources and sinks of MPs in the wetland? The latest researches have shown that the sources of MPs in wetlands include sewage discharge, surface runoff, and plastic wastes from aquaculture. Fibers and fragments are the most common shapes, and PE, PP, PS can be detected in water or sediment matrices, and biota of wetlands. The distribution is affected by hydrodynamic conditions, sediment properties, and vegetation coverage. Factors affecting the vertical migration of MPs include their own physical and chemical properties, the combination of substances that accelerate deposition (mineral adsorption and biological flocculation), and resuspension. Minerals tend to adsorb negatively charged MPs while algae aggregates have a preference for positively charged MPs. The wetlands vegetation can trap MPs and affect their migration. In water matrices, MPs are ingested by organisms and integrated into sediments, which makes them seem undetectable in the wetland ecosystem. Photodegradation and microbial degradation can further reduce the MPs in size. Although recent research has increased, we are still searching for a methodological harmonization of the detection practices and exploring the migration rules and fate patterns of MPs. Our work is the first comprehensive review of the source, distribution, migration, and fate of MPs in wetland ecosystems. It reveals the uniqueness of wetland habitat in the research of MPs and indicates the potential of wetlands acting as sources or sinks for MPs.

9.
Phys Chem Chem Phys ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226035

RESUMO

The tritium release behavior of the Li2TiO3 crystal has become an important index to evaluate its comprehensive performance as a solid breeder material in nuclear fusion reactors. The tritium diffusion on the surface (surface diffusion) and diffusion from the inside to the surface (hopping diffusion) in Li2TiO3 crystals with a 1/3-Li(001) surface are systematically investigated by the first-principles method. Possible adsorption sites, diffusion pathways and energy barriers of surface diffusion and hopping diffusion have been calculated and analyzed, respectively. Tritium atoms are found to diffuse preferentially along the [100] direction on the surface and two equivalent pathways across the surface were identified. The obtained activation energies are about 0.50 eV for surface diffusion and 1.56 eV for hopping diffusion. The local density of states and Bader charge for typical surface diffusion and hopping diffusion pathways are calculated and analyzed. The results reveal that the tritium (T) atom bonds with neighboring oxygen (O) atoms during the surface diffusion, while the T-O interaction is significantly weakened in the hopping diffusion which results in the higher activation energy than that of surface diffusion. In combination with our previous work, a complete tritium diffusion model for the Li2TiO3 crystal is proposed and the corresponding tritium diffusion coefficients are obtained. Our obtained activation energies are in the same range as previous experimental data and could provide theoretical support for the future related experiments.

10.
Orthop Surg ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200562

RESUMO

OBJECTIVE: To evaluate the strain-rate-dependent viscoelastic properties of the intervertebral disc by in vitro experiments. METHOD: The biomechanical experiments were conducted from September 2019 to December 2019. The lumbar spines of sheep were purchased within 4-6 hours from the local slaughterhouse, and the intervertebral disc samples were divided into three groups. In rupture group, the samples were used to test the mechanical behavior of the intervertebral disc rupture at different strain rates. In fatigue injury group, the samples were used to test the mechanical behavior of fatigue injury on the intervertebral disc under different strain rates. In internal displacement group, the samples were used to test the internal displacement distribution of the intervertebral disc at different strain rates by applying an optimized digital image correlation (DIC) technique. RESULTS: Both the yielding and cracking phenomenon occurs at fast and medium loading rates, while only the yielding phenomenon occurs at a slow loading rate. The yield stress, compressive strength, and elastic modulus all increase with the increase of the strain rate, while the yield strain decreases with the increase of the strain rate. The logarithm of the elastic modulus in the intervertebral disc is approximately linear with the logarithm of the strain rate under different strain rates. Both before and after fatigue loading, the stiffness in the loading and unloading curves of the intervertebral disc is inconsistent, forming a hysteresis loop, which is caused by the viscoelastic effect. The strain rate has no significant effect on the internal displacement distribution of the intervertebral disc. Based on the experimental data, the constitutive relationship of the intervertebral disc at different strain rates is obtained. The fitting curves are well coupled with the experimental data, while the fitting parameters are approximately linear with the logarithm of the strain rate. CONCLUSIONS: These experiments indicate that the strain rate has a significant effect on the mechanical behavior of the intervertebral disc rupture and fatigue injury, while the constitutive equation can predict the rate-dependent mechanical behavior of lumbar intervertebral disc under flexion very well. These results have important theoretical guiding significance for preventing lumbar disc herniation in daily life.

11.
Sensors (Basel) ; 20(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207829

RESUMO

The accurate terrain classification in real time is of great importance to an autonomous robot working in field, because the robot could avoid non-geometric hazards, adjust control scheme, or improve localization accuracy, with the aid of terrain classification. In this paper, we investigate the vibration-based terrain classification (VTC) in a dynamic environment, and propose a novel learning framework, named DyVTC, which tackles online-collected unlabeled data with concept drift. In the DyVTC framework, the exterior disagreement (ex-disagreement) and interior disagreement (in-disagreement) are proposed novely based on the feature diversity and intrinsic temporal correlation, respectively. Such a disagreement mechanism is utilized to design a pseudo-labeling algorithm, which shows its compelling advantages in extracting key samples and labeling; and consequently, the classification accuracy could be retrieved by incremental learning in a changing environment. Since two sets of features are extracted from frequency and time domain to generate disagreements, we also name the proposed method feature-temporal disagreement adaptation (FTDA). The real-world experiment shows that the proposed DyVTC could reach an accuracy of 89.5%, but the traditional time- and frequency-domain terrain classification methods could only reach 48.8% and 71.5%, respectively, in a dynamic environment.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33216251

RESUMO

A 22-year-old female with SDHB-positive who presented with palpitation and hypertension after adrenalectomy was performed 18F-FDG PET/CT to detect the primary ectopic pheochromocytoma (PCC) and rule out metastasis. PET/CT is useful for detecting and localizing the primary ectopic PCC.

13.
Andrologia ; : e13888, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167063

RESUMO

The association of single nucleotide polymorphisms (SNPs) in heat shock protein 90 (HSP90) genes with idiopathic male infertility remains unclear. In this study, the five selected SNPs in HSP90AA1 namely rs10133307, rs10873531, rs11547523, rs11621560 and rs7145597 were genotyped in 116 idiopathic infertile males and 185 ethnically matched fertile males using the Sequenom MassARRAY assay. The role of these SNPs in male infertility was then studied using multiple genetic models. We observed that genotype distribution (p = .028) and allelic frequency (p = .032) of rs11547523 were significantly different between the infertile and fertile groups. In particular, A genotype of rs11547523 was associated with an increased risk of infertility in the allele (OR = 2.508, p = .048), dominant (OR = 2.733, p = .030) and additive models (OR = 0.366, p = .031). However, there were no significant differences in semen parameters including seminal volume (p = .452), sperm concentration (p = .727), total sperm number (p = .588), motility (p = .282) and morphology (p = .975) between A and A/G genotypes of rs11547523. These results indicate that rs11547523 in HSP90AA1 may be associated with idiopathic male infertility in the Chinese population. The outcome of this study contributes to the development of the diagnosis of male infertility.

14.
Anal Chim Acta ; 1139: 79-87, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190712

RESUMO

Targeted proteomics has advantages over earlier conventional technologies for protein detection. We developed and validated an LC/MRM-MS-based targeted proteomic method combined with immunoaffinity precipitation for the enrichment and detection of low abundance chemerin isoforms in human biofluids. After tryptic digestion, each chemerin isoform was characterized by isoform-specific peptides, and the absolute quantification was achieved by using stable isotope-labeled peptides as internal standards. In serum, follicular fluid and synovial fluid, a total of 6 chemerin isoforms were identified and quantified, among which a novel natural isoform 153Q was discovered for the first time. The relative content of the six chemerin isoforms in human serum was 157S ≫ 156F ≫ 158K > 154F ≥ 155A > 153Q in the ratio of 25:17:5:2.5:2.2:1, respectively. The absolute contents were in the range of 88-3.5 ng/mL. This distribution remained consistent among the 3 biofluids analyzed. Total chemerin were found to be increased in both polycystic ovary syndrome (serum and follicular fluid) and rheumatoid arthritis (serum) patients. However, chemerin isoform analysis revealed that only 156F & 157S were increased in the former, while 155A, 156F & 157S were increased in the latter. This demonstrates the potential of this method in detailed characterization of changes in chemerin isoforms that may be of clinical relevance.

15.
Pak J Pharm Sci ; 33(3): 909-913, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-33191212

RESUMO

Food supplements can modulate the composition of human intestinal microflora due to the potential capacity of improving the host health. Chitosan (CS) possesses diverse biological and pharmacological effects and has been used as a new source of prebiotic. In this study, ERIC (Enterobacterial Repetitive Intergenic Consensus)-PCR and viable counts methods were combined to explore the prebiotic-like effects of CS on the intestinal microflora in mice. Mice were divided into 3 groups randomly, and treated with water, 1g/kg of CS, 0.25g/kg of CS, respectively for 24 days. Subsequently, they were treated with levofloxacin (65mg/kg) for 6 days. Viable counts method indicated the growth of Lactobacillus was promoted with CS treatment while at the same time Enterobacteria and Enterococcus were inhibited. ERIC-PCR fingerprint, UPGMA dendrogram, PCA and diversity analysis showed that the intestinal microflora composition was changed with antibiotics treatment, and that samples were significantly separated from those of the control and long-term CS-treated groups. Together, our results demonstrated that CS could be regarded as a potential food supplement for protecting intestinal microflora and regulate imbalance.

16.
Nature ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166988

RESUMO

The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs1. Studies in animals experimentally infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. Although COVID-19 severity ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 mice that we originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early times after infection. Notably, although pre-treatment with convalescent plasma prevented notable clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

17.
Medicine (Baltimore) ; 99(45): e23032, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157954

RESUMO

RATIONALE: Primitive neuroectodermal tumor (PNET) of the urinary bladder is a highly aggressive tumor with high local recurrence and distant metastasis rates in cases of incomplete excision. We report a case of a young female patient, in whom early laparoscopic radical cystectomy combined with standard lymph node dissection and a modified vincristine, doxorubicin hydrochloride, and cyclophosphamide (VAC) chemotherapy regimen was controversial. Because PNET of the urinary bladder is a rare malignancy, the standard treatment regimen has not yet been established. It is not clear whether surgery combined with postoperative chemotherapy for PNET patients may be superior to surgery alone on long term survival. PATIENT CONCERNS: The patient was a 45-year-old Chinese woman who complained of lower urinary tract symptoms, including urgency, frequency, and difficulty in urination, for 2 months. DIAGNOSES: PNET. INTERVENTIONS: The patient underwent laparoscopic radical cystectomy and standard lymph node dissection, combined with modified VAC chemotherapy regimens. OUTCOMES: After undergoing radical surgery in 2018, the patient completed 6 courses of adjuvant chemotherapy. Abdominal and thorax computed tomography scanning was performed 3, 6, 9, and 12 months after the surgery was completely free of tumor. The patient is still alive with no signs of recurrent disease 2 years after diagnosis. LESSONS: Radical surgery and standard lymphadenectomy combined with adjuvant chemotherapy may be essential to improve the prognosis of PNET of the urinary bladder.


Assuntos
Cistectomia/métodos , Tumores Neuroectodérmicos Primitivos/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Quimioterapia Adjuvante/métodos , Criança , Terapia Combinada , Ciclofosfamida/normas , Dactinomicina/normas , Feminino , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/cirurgia , Resultado do Tratamento , Vincristina/normas
18.
Nat Commun ; 11(1): 5898, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214551

RESUMO

O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.

19.
Nat Commun ; 11(1): 5843, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203843

RESUMO

Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell-cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.

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