Publications by authors named "Jia Li"

3,614 Publications

  • Page 1 of 1

AKR1C3 decreased CML sensitivity to Imatinib in bone marrow microenvironment via dysregulation of miR-379-5p.

Cell Signal 2021 May 10:110038. Epub 2021 May 10.

Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address:

Background: Drug resistance is an important cause of death for most patients with chronic myeloid leukemia (CML). The bone marrow microenvironment is believed to be mainly responsible for resistance to BCR-ABL tyrosine kinase inhibitors. The mechanism involved, however, is still unclear.

Methods: Bioinformatic analysis from GEO database of AKR1C3 was utilized to identify the AKR1C3 expression in CML cells under bone marrow microenvironment. Western blot and qPCR were performed to detect the AKR1C3 expression in two CML cell lines K562 and KU812 cultured +/- bone microenvironment derived stromal cells. CCK-8, soft agar colony assay, and Annexin V/PI assay were performed to detect the sensitivity of CML cells (K562 and KU812) to Imatinib under a gain of or loss of function of AKR1C3 treatment. The CML murine model intravenous inoculated with K562-OE-vector and K562-OE-AKR1C3 cells were established to estimate the effect of AKR1C3 inhibitor Indomethacin on Imatinib resistance. The bioinformatic analysis of miRNA databases was used to predict the potential miRNAs targeting AKR1C3. And the luciferase assay was utilized to validate the target relationship between miR-379-5p and AKR1C3. And, the soft agar colony assay and Annexin V/PI were used to validate the effect of miR-379-5p in AKR1C3 induced Imatinib resistance.

Results: In present study, we investigated AKR1C3 was highly expressed in CML under bone marrow microenvironment. AKR1C3 decreased Imatinib activity in K562 and KU812 cells, while inhibition of AKR1C3 could enhance Imatinib sensitivity in vitro study. Furthermore, murine model results showed combination use of AKR1C3 inhibitor Indomethacin effectively prolong mice survival, indicating that AKR1C3 is a promising target to enhance Imatinib treatment. Mechanically, AKR1C3 was found to be suppressed by miR-379-5p, which was down-expression in bone marrow microenvironment. Besides, we found miR-379-5p could bind AKR1C3 3'UTR but not degrade its mRNA level. Further, gain of miR-379-5p rescued the imatinib resistance induced by AKR1C3 overexpression in CML cells.

Conclusions: Altogether, our study identifies a novel signaling regulation of miR-379-5p/AKR1C3/EKR axis in regulating IM resistance in CML cell, and provides a scientific base for exploring AKR1C3 as a biomarker in impeding IM resistance in CML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2021.110038DOI Listing
May 2021

The polyamine regulator AMD1 up-regulates spermine levels to drive epidermal differentiation.

J Invest Dermatol 2021 May 10. Epub 2021 May 10.

Maintaining tissue homeostasis depends on a balance of cell proliferation, differentiation and apoptosis. Within the epidermis the levels of the polyamines putrescine, spermidine and spermine are altered in many different skin conditions yet their role in epidermal tissue homeostasis is poorly understood. We identify the polyamine regulator, AMD1, as a crucial regulator of keratinocyte differentiation. AMD1 protein is upregulated on differentiation and highly expressed in the suprabasal layers of the human epidermis. During keratinocyte differentiation, elevated AMD1 promotes decreased putrescine and increased spermine levels. Knockdown/inhibition of AMD1 results in reduced spermine levels and inhibition of keratinocyte differentiation. Supplementing AMD1-knockdown keratinocytes with exogenous spermidine/spermine rescued aberrant differentiation. We show that the polyamine shift is critical for the regulation of key transcription factors and signalling proteins that drive keratinocyte differentiation including KLF4 and ZNF750. These findings demonstrate that human keratinocytes use controlled changes in polyamine levels to modulate gene expression to drive cellular behaviour changes. Modulation of polyamine levels during epidermal differentiation could impact skin barrier formation or be used in the treatment of hyper-proliferative skin disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2021.01.039DOI Listing
May 2021

Whole genome sequencing of a snailfish from the Yap Trench (~7,000 m) clarifies the molecular mechanisms underlying adaptation to the deep sea.

PLoS Genet 2021 May 13;17(5):e1009530. Epub 2021 May 13.

Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.

Hadal environments (depths below 6,000 m) are characterized by extremely high hydrostatic pressures, low temperatures, a scarce food supply, and little light. The evolutionary adaptations that allow vertebrates to survive in this extreme environment are poorly understood. Here, we constructed a high-quality reference genome for Yap hadal snailfish (YHS), which was captured at a depth of ~7,000 m in the Yap Trench. The final YHS genome assembly was 731.75 Mb, with a contig N50 of 0.75 Mb and a scaffold N50 of 1.26 Mb. We predicted 24,329 protein-coding genes in the YHS genome, and 24,265 of these genes were successfully functionally annotated. Phylogenetic analyses suggested that YHS diverged from a Mariana Trench snailfish approximately 0.92 million years ago. Many genes associated with DNA repair show evidence of positive selection and have expanded copy numbers in the YHS genome, possibly helping to maintain the integrity of DNA under increased hydrostatic pressure. The levels of trimethylamine N-oxide (TMAO), a potent protein stabilizer, are much higher in the muscles of YHS than in those of shallow-water fish. This difference is perhaps due to the five copies of the TMAO-generating enzyme flavin-containing monooxygenase-3 gene (fmo3) in the YHS genome and the abundance of trimethylamine (TMA)-generating bacteria in the YHS gut. Thus, the high TMAO content might help YHS adapt to high hydrostatic pressure by improving protein stability. Additionally, the evolutionary features of the YHS genes encoding sensory-related proteins are consistent with the scarce food supply and darkness in the hadal environments. These results clarify the molecular mechanisms underlying the adaptation of hadal organisms to the deep-sea environment and provide valuable genomic resources for in-depth investigations of hadal biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009530DOI Listing
May 2021

Image reconstruction with the chaotic fiber laser in scattering media.

Appl Opt 2021 May;60(13):4004-4012

The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.420441DOI Listing
May 2021

studies of deferasirox derivatives as potential organelle-targeting traceable anti-cancer therapeutics.

Chem Commun (Camb) 2021 May 12. Epub 2021 May 12.

Department of Chemistry, University of Texas at Austin, 105 E 24th street A5300, Austin, TX 78712-1224, USA.

We report here strategic functionalization of the FDA approved chelator deferasirox (1) in an effort to produce organelle-targeting iron chelators with enhanced activity against A549 lung cancer cells. Derivative 8 was found to have improved antiproliferative activity relative to 1. Fluorescent cell imaging revealed that compound 8 preferentially localises within the lysosome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc08156fDOI Listing
May 2021

Andrographolide Against Lung Cancer-New Pharmacological Insights Based on High-Throughput Metabolomics Analysis Combined with Network Pharmacology.

Front Pharmacol 2021 21;12:596652. Epub 2021 Apr 21.

Department of Respiratory and Critical Care, First Affiliated Hospital, Harbin Medical University, Harbin, China.

Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.596652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097142PMC
April 2021

A Biomimetic System for Studying Salicylate Dioxygenase.

ACS Symp Ser Am Chem Soc 2019 Jan 12;1317(4):71-83. Epub 2019 Jul 12.

Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, United States.

We report the characterization of [Fe(T1Et4iPrIP)(sal)] () (T1Et4iPrIP = tris(1-ethyl-4-isopropyl-imidazolyl)phosphine; sal = salicylate dianion), which serves as a model for substrate-bound salicylate dioxygenase (SDO). Complex crystallizes in the monoclinic space group 2/n with = 10.7853(12) Å, = 16.5060(19) Å, = 21.217(2) Å, = 94.489(2)°, and = 3765.5(7) Å. The structure consists of Fe bonded in distorted square pyramidal geometry ( = 0.32) with two salicylate oxygens and two T1Et4iPrIP nitrogens serving as the base and the apical position occupied by the other ligand nitrogen. [Fe(T1Et4iPrIP)(OTf)] (), the precursor for , catalyzes the cleavage of 1,4-dihydroxy-2-naphthoate in the presence of O. Complex is also capable of cleaving the salicylate aromatic ring in the presence of HO. The progression of this reaction toward product formation involves an Fe-phenoxide species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/bk-2019-1317.ch004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101989PMC
January 2019

Charge-Gradient Hydrogels Enable Direct Zero Liquid Discharge for Hypersaline Wastewater Management.

Adv Mater 2021 May 8:e2100141. Epub 2021 May 8.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Zero liquid discharge (ZLD), which maximizes water recovery and eliminates environmental impact, is an urgent wastewater management strategy for alleviating freshwater shortage. However, because of the high concentration of salts and broad-spectrum foulants in wastewater, a huge challenge for ZLD is lack of a robust membrane-based desalination technology that enables direct wastewater recovery without costly pretreatment processes. Here, a paradigm-shift membrane distillation (MD) strategy is presented, wherein the traditional hydrophobic porous membrane is replaced with a hydrophilic nonporous charge-gradient hydrogel (CGH) membrane that possesses hypersaline tolerance, fouling/scaling-free properties, and negligible vapor transfer resistance inside the membrane, simultaneously. Therefore, the CGH-based MD with high water flux enables direct desalination of hypersaline wastewater (130 g L ) containing broad-spectrum foulants (500 mg L ) during continuous long-term operation (200 h), and this technology paves a promising way to direct ZLD for wastewater management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202100141DOI Listing
May 2021

The efficacy and acceptability of hybrid electroconvulsive therapy compared with standard electroconvulsive therapy for schizophrenia patients: A parallel-group, double-blind, randomized, controlled trial.

Brain Stimul 2021 May 4;14(3):737-739. Epub 2021 May 4.

Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China; Department of Psychiatry, Shenzhen Kangning Hospital, and Shenzhen Mental Health Center, Shenzhen, Guangdong, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2021.04.017DOI Listing
May 2021

Tumour necrosis factor-α (TNF-α) enhances dietary carcinogen-induced DNA damage in colorectal cancer epithelial cells through activation of JNK signaling pathway.

Toxicology 2021 May 4;457:152806. Epub 2021 May 4.

Section of Biomolecular Medicine. Electronic address:

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death. Benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazol [4,5-b] pyridine (PhIP) present in cooked meat are pro-carcinogens and considered to be potential risk factors for CRC. Their carcinogenic and mutagenic effects require metabolic activation primarily by cytochrome P450 1 family enzymes (CYPs); the expression of these enzymes can be modulated by aryl hydrocarbon receptor (AhR) activation and the tumour microenvironment, involving mediators of inflammation. In this study, we hypothesized that tumour necrosis factor-α (TNF-α), a key mediator of inflammation, modulates BaP- and PhIP-induced DNA damage in colon cancer epithelial cells. Importantly, we observed that TNF-α alone (0.1-100 pg/ml) induced DNA damage (micronuclei formation) in HCT-116 cells and co-treatment of TNF-α with BaP or PhIP showed higher levels of DNA damage compared to the individual single treatments. TNF-α alone or in combination with BaP or PhIP did not affect the expression levels of CYP1A1 and CYP1B1 (target genes of AhR signaling pathways). The DNA damage induced by TNF-α was elevated in p53 null HTC-116 cells compared to wild type cells, suggesting that TNF-α-induced DNA damage is suppressed by functional p53. In contrast, p53 status failed to affect BaP and PhIP induced micronucleus frequency. Furthermore, JNK and NF-κB signaling pathway were activated by TNF-α treatment but only inhibition of JNK significantly reduced TNF-α-induced DNA damage. Collectively, these findings suggest that TNF-α induced DNA damage involves JNK signaling pathway rather than AhR and NF-κB pathways in colon cancer epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2021.152806DOI Listing
May 2021

TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer.

PeerJ 2021 16;9:e11146. Epub 2021 Apr 16.

Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China.

Background: Gastric cancer (GC) is a heterogeneous disease that encompasses various molecular subtypes. The molecular mutation characteristics of circulating tumor DNA (ctDNA) in advanced gastric cancer (AGC), especially the clinical utility of TP53 mutation and MET amplification in ctDNA need to be further explored.

Objectives: The aim of this study was mainly to assess the clinical utility of TP53 mutation and MET amplification in ctDNA as biomarkers for monitoring disease progression of AGC.

Patients And Methods: We used multigene NGS-panel technology to study the characteristics of ctDNA gene mutations and screen the key mutant genes in AGC patients. The Kaplan-Meier method was used to calculate the survival probability and log-rank test was used to compare the survival curves of TP53 mutation and MET amplification in ctDNA of AGC patients. The survival time was set from the blood test time to the follow-up time to observe the relationship between the monitoring index and tumor prognosis.

Results: We performed mutation detection on ctDNA in 23 patients with AGC and identified the top 20 mutant genes. The five most frequently mutated genes were TP53 (55%), EGFR (20%), ERBB2 (20%), MET (15%) and APC (10%). TP53 was the most common mutated gene (55%) and MET had a higher frequency of mutations (15%) in our study. Kaplan-Meier analysis showed that patients with TP53 mutant in ctDNA had shorter overall survival (OS) than these with TP53 wild ( < 0.001). The Allele frequency (AF) of TP53 mutations in patient number 1 was higher in the second time (0.94%) than in the first time (0.36%); the AF of TP53 mutations in patient number 16 was from scratch (0∼0.26%). In addition, the AF of TP53 mutations in patients who survive was relatively low ( = 0.047). Simultaneously, Kaplan-Meier analysis showed that patients with MET amplification also had shorter OS than these with MET without amplification ( < 0.001).

Conclusion: TP53 and MET are the two common frequently mutant genes in ctDNA of AGC patients.TP53 mutation and MET amplification in ctDNA could predict disease progression of AGC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054733PMC
April 2021

Sesquiterpene coumarins from Ferula samarkandica Korovin and their bioactivity.

Phytochemistry 2021 May 3;187:112705. Epub 2021 May 3.

The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization and Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing South Road 40-1, Urumqi, 830011, China. Electronic address:

Phytochemical study on the ethanolic extract of the dried roots of Ferula samarkandica Korovin led to the isolation of nine undiscribed sesquiterpene coumarins, samarcandicins A-I, along with thirteen known sesquiterpene coumarins. Their structures were characterized by detailed spectroscopic analysis including NMR and HR-ESI-MS. Mogoltacin and nevskin exhibited high inhibitory activity against MV-4-11 cell with IC values of 3.94 ± 0.06 μM and 3.87 ± 0.10 μM, respectively, and nevskin and feshurin showed high inhibitory activity against mino cell with IC values of 1.48 ± 0.06 μM and 7.88 ± 0.60 μM, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2021.112705DOI Listing
May 2021

A systematic review and meta-analysis comparing arthroplasty and internal fixation in the treatment of elderly displaced femoral neck fractures.

OTA Int 2021 Mar 22;4(1):e087. Epub 2020 Dec 22.

Department of Orthopaedics.

Background: Currently, there are 2 mainstream treatments for displaced femoral neck fracture, including internal fixation and arthroplasty. However, there are still some controversial problems as to which treatment should be primarily chosen.

Methods: The relevant studies comparing arthroplasty with internal fixation were searched in the databases of PubMed, Embase, and Cochrane Library. Finally, 31 relevant randomized controlled trials were included in this meta-analysis. The quality of studies was evaluated and meta-analyses were performed using RevMan 5.3 software. We also assessed the heterogeneity among studies and publication bias via the I-squared index and forest plots.

Results: There was no significant difference between arthroplasty and internal fixation groups in patient mortality at both short-term and long-term points. However, patients treated with arthroplasty showed significantly lowered risks of reoperation both at short-term (5.6% vs 31.5%; relative risks (RR)  = 0.19; 95% CI, 0.13-0.28;  < .00001) and long-term follow-up (9.5% vs 45.9%; RR = 0.23; 95% CI, 0.17-0.33;  < .00001). Similarly, arthroplasty-treated patients demonstrated a significant decrease in the risk of postoperation complications at short-term (10.3% vs 34.4%; RR = 0.37, 95% CI, 0.24-0.57;  < .00001) and long-term follow-up (11.7% vs 42.5%; RR = 0.30, 95% CI, 0.16-0.57;  < .0002). Besides, patients in the arthroplasty group were associated with better alleviation of pain postoperation (18.3% vs 31.1%; RR = 0.50, 95% CI, 0.33-0.78;  = .002).In trial sequence analyses, all cumulative Z curves except that of mortality crossed the trial sequential monitoring boundaries and conventional boundaries, and required information size has been reached.

Conclusions: Arthroplasty leads to a lower rate of reoperation, a reduced risk of complications, and a better alleviation of postoperation pain both at short-term and long-term follow-up. Most importantly, and according to trial sequence analyses, more than enough evidence has been achieved that arthroplasty does show better outcomes than internal fixation in terms of reoperation rate, complications, and postoperation pain.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/OI9.0000000000000087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016607PMC
March 2021

A Finite Element Study on the Treatment of Thoracolumbar Fracture with a New Spinal Fixation System.

Biomed Res Int 2021 10;2021:8872514. Epub 2021 Apr 10.

Department of Orthopaedics, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.

Objective: In this study, the mechanical properties of the new spinal fixation system (NSFS) in the treatment of thoracolumbar fractures were evaluated by the finite element analysis method, so as to provide a mechanical theoretical basis for the later biomechanical experiments and clinical experiments.

Methods: T12-L2 bone model was constructed to simulate L1 vertebral fracture, and three models of internal fixation systems were established on the basis of universal spinal system (USS): Model A: posterior short-segment fixation including the fractured vertebra (PSFFV); Model B: short-segment pedicle screw fixation (SSPF); Model C: new spinal fixation system (NSFS). After assembling the internal fixation system and fracture model, the finite element analysis was carried out in the ANSYS Workbench 18.0 software, and the stress of nail rod system, fracture vertebral body stress, vertebral body mobility, and vertebral body displacement were recorded in the three models.

Results: The peak values of internal fixation stress, vertebral body stress, vertebral body maximum displacement, and vertebral body maximum activity in Model C were slightly smaller than those in Model B.

Conclusions: Compared with the traditional internal fixation system, the new spinal internal fixation system may have the mechanical advantage and can provide sufficient mechanical stability for thoracolumbar fractures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8872514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055395PMC
April 2021

Outcomes After Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries: A Tailored Approach in a Developing Setting.

Front Cardiovasc Med 2021 14;8:665038. Epub 2021 Apr 14.

Department of Cardiovascular Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is complex and diverse that has led to a variety of treatment strategies. Experience has been largely obtained in the advanced countries. The clinical diversity is greater in China. We evaluated our surgical approaches and outcomes of these patients. We reviewed 127 patients undergoing varied surgeries in our center in 2010-2019. Thirty patients underwent single-stage complete repair by unifocalizing MAPCAs and VSD closure (aged 3.9-131.4 months, median 22) with 3 (10%) early deaths. Ninety-seven underwent the first-stage rehabilitation strategy including systemic-to-pulmonary shunt in 29 (aged 0.5-144 month, median 8), and palliative RV-PA conduit in 68 (aged 2.2-209.6 months, median 14) with 5 (5.2%) early deaths. Eight-one patients (63.8%) eventually achieved complete repair with a median right/left ventricular (RV/LV) pressure ratio of 0.7 (ranged 0.4-1.0). Fourteen patients (11.0%) accepted palliation as final destination. Survival for the entire cohort was 89.5, 85.2, and 76.1% at 1, 5, and 10 years, respectively. Survival for those undergoing complete repair was 88.2 and 76.6% at 1 and 5 year, respectively. RV/LV pressure ratio ≥0.8 was risk factor for mortality (HR10.3, = 0.003). Our cohort, the largest from China, had distinctive clinical features with substantially wider age range and higher RV/LV pressure ratio. Using the combined approaches tailored to individual patients, complete repair was achieved in 64% of patients. The early and intermediate outcomes are acceptable compared to many of the previous reports.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.665038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079636PMC
April 2021

Differential diagnosis between small breast phyllodes tumors and fibroadenomas using artificial intelligence and ultrasound data.

Quant Imaging Med Surg 2021 May;11(5):2052-2061

Department of Ultrasound, Peking University People's Hospital, Beijing, China.

Background: It is challenging to differentiate between phyllodes tumors (PTs) and fibroadenomas (FAs). Artificial intelligence (AI) can provide quantitative information regarding the morphology and textural features of lesions. This study attempted to use AI to evaluate the ultrasonic images of PTs and FAs and to explore the diagnostic performance of AI features in the differential diagnosis of PTs and FAs.

Methods: A total of 40 PTs and 290 FAs <5 cm in maximum diameter found in female patients were retrospectively analyzed. All tumors were segmented by doctors, and the features of the lesions were collated, including circularity, height-to-width ratio, margin spicules, margin coarseness (MC), margin indistinctness, margin lobulation (ML), internal calcification, angle between the long axis of the lesion and skin, energy, grey entropy, and grey mean. The differences between PTs and FAs were analyzed, and the diagnostic performance of AI features in the differential diagnosis of PTs and FAs was evaluated.

Results: Statistically significant differences (P<0.05) were found in the height-to-width ratio, ML, energy, and grey entropy between the PTs and FAs. Receiver operating characteristic (ROC) curve analysis of single features showed that the area under the curve [(AUC) 0.759] of grey entropy was the largest among the four features with statistically significant differences, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.925, 0.459, 0.978, and 0.190, respectively. When considering the combinations of the features, the combination of height-to-width ratio, margin indistinctness, ML, energy, grey entropy, and internal calcification was the most optimal of the combinations of features with an AUC of 0.868, and a sensitivity, specificity, PPV, and NPV of 0.734, 0.900, 0.982, and 0.316, respectively.

Conclusions: Quantitative analysis of AI can identify subtle differences in the morphology and textural features between small PTs and FAs. Comprehensive consideration of multiple features is important for the differential diagnosis of PTs and FAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047381PMC
May 2021

Protective and Risk Factors for Medical and Nursing Staff Suffering From Psychological Symptoms During COVID-19.

Front Psychol 2021 16;12:603553. Epub 2021 Apr 16.

Department of Neurology, Hainan General Hospital, Haikou, China.

With the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in China, the general public but also medical staff were confronted with psychological challenges, suffering from the highly infectious and unknown characteristics of COVID-19. In this study, we surveyed psychological symptoms including anxiety, depression, and sleep disorders in medical staff. A questionnaire star/WeChat link-based survey assessing the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9 depression, the Insomnia Severity Index, Social Support scales in addition to lifestyle, and income level was conducted and included 8,288 medical staff from 24 provinces in China. Pearson Chi-square and Mann-Whitney -tests were used to evaluate single risk factors and significant differences in psychological symptoms before and during the outbreak of COVID-19. Binary logistic regression analyses were conducted for the risk factors of anxiety, depression, and sleep disorder symptoms. Medical staff had a high incidence of psychological symptoms, which was more prominent during the COVID-19 epidemic. Comparatively, females, nurses, first-line department, never exercised, and low income were risk factors for psychological symptoms. Social support including objective support, subjective support, support utility, and regular sports over 3 times per week were protective and manageable elements that could protect from and manage the psychological symptoms of medical staff. The susceptibility of psychological symptoms among medical staff should be of concern to policymakers and the public in the long-term, and the aggravation of mental health problems of medical staff could be eased by providing adequate social support during and after the COVID-19 outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.603553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086510PMC
April 2021

Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats.

Biomed Res Int 2021 7;2021:6655225. Epub 2021 Apr 7.

Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6655225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049797PMC
April 2021

AKR1B10 protects against UVC-induced DNA damage in breast cancer cells.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr 29. Epub 2021 Apr 29.

Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen 518000, China.

The cellular response to DNA damage is crucial for maintaining the integrity and stability of molecular structure. To maintain genome stability, DNA-damaged cells should be arrested so that mutations can be repaired before replication. Although several key components required for this arrest have been discovered, the majority of the pathways are still unclear. Through a number of assays, including cell viability, colony formation, and apotheosis assay, we found that AKR1B10 protected cells from UVC-induced DNA damage. Surprisingly, UVC-induced γH2AX foci and DNA double-strand breaks in the AKR1B10-overexpressing cells were ∼4-5 folds lower than those in the control group. The expression levels of AKR1B10, p53, chk1, chk2, nuclear factor (NF)-κB, and p65 showed dynamic changes in response to UVC irradiation. Our results suggested that AKR1B10 is involved in the pathway of cell cycle checkpoint and NF-κB in DNA damage. Taken together, our results suggest that AKR1B10 is involved in the repair of the DNA double-strand break, which provides a new insight into the role of AKR1B10 in DNA damage repair and indicates a new trail in tumorigenesis and cancer drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/abbs/gmab045DOI Listing
April 2021

Agricultural co-operatives participating in supply chain integration in China: A qualitative comparative analysis.

PLoS One 2021 28;16(4):e0250018. Epub 2021 Apr 28.

School of Finance and Economics, Zhejiang Dongfang Polytechnics, Wenzhou, Zhejiang, China.

Agro-food supply chain integration (ASCI) plays a growingly important role in the stable and sustainable development of agriculture. However, it is challenging for core firms to integrate the small-scale and scatted farmers due to complex transaction processes and volatile relationships in China. Agricultural co-operatives are organizations that unite farmers' power and help them achieve economic benefits. Our research focuses on ASCI from the perspective of co-operatives. A comprehensive cooperative framework, including trinity co-operatives and trinity federations, is conducted to figure out the position and process of agricultural co-operatives in ASCI, while QCA provides detailed collaborative patterns for agricultural co-operatives to adopt. Results show that agricultural co-operatives can achieve high economic and social/environmental performance when participating in ASCI. This study further completes the ASCI literature and offers many managerial and academic implications to co-operatives' members and policy-makers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250018PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081254PMC
April 2021

ARHGAP20 Expression Inhibited HCC Progression by Regulating the PI3K-AKT Signaling Pathway.

J Hepatocell Carcinoma 2021 21;8:271-284. Epub 2021 Apr 21.

Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, 514000, People's Republic of China.

Introduction: One of the most common cancers is hepatocellular carcinoma (HCC), which is an aggressive cancer that is associated with high mortality. The expression and role of ARHGAP20 in HCC remain unclear.

Materials And Methods: The expression and clinical role of ARHGAP20 were investigated using online databases and HCC samples from Meizhou People's Hospital. Wound healing assays, transwell migration/invasion assays, and lung metastasis models were performed using nude mice. Gene set enrichment analyses were used to further explore the potential mechanisms.

Results: Inspired by expression analyses of three different public databases (ie, TIMER, Oncomine, and HCCDB database), we confirmed that ARHGAP20 was downregulated in clinical HCC tumors compared with normal controls. ARHGAP20 expression inhibited HCC migration and invasion in vitro and in vivo. Based on GSEA results, we tested markers of the PI3K-AKT signaling pathway. Interestingly, while ARHGAP20 upregulation suppressed HCC migration/invasion and phosphorylation of AKT/PI3K molecules, exposure to the PI3K-AKT pathway agonist rhIGF-1 partially rescued these phenomena. ARHGAP20 also showed a close correlation with certain components in the HCC immune microenvironment. Furthermore, we revealed that downregulated ARHGAP20 was significantly correlated with larger tumor size and vascular invasion, and could be used as an adverse independent prognostic factor for HCC OS but not RFS.

Conclusion: ARHGAP20 was identified for the first time as a tumor suppressor gene that could inhibit HCC progression by regulating the PI3K-AKT signaling pathway and the immune microenvironment in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JHC.S298554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071084PMC
April 2021

Probing the Mechanism for 2,4'-Dihydroxyacetophenone Dioxygenase Using Biomimetic Iron Complexes.

Inorg Chem 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, Oakland University, Rochester, Michigan 48309-4477, United States.

In this study, we report the synthesis and characterization of [Fe(T1Et4iPrIP)(2-OH-AP)(OTf)](OTf) (), [Fe(T1Et4iPrIP)(2-O-AP)](OTf) (), and [Fe(T1Et4iPrIP)(DMF)](OTf) () (T1Et4iPrIP = tris(1-ethyl-4-isopropyl-imidazolyl)phosphine; 2-OH-AP = 2-hydroxyacetophenone, and 2-O-AP = monodeprotonated 2-hydroxyacetophenone). Both and serve as model complexes for the enzyme-substrate adduct for the nonheme enzyme 2,4'-dihydroacetophenone (DHAP) dioxygenase or DAD, while serves as a model for the ferric form of DAD. Complexes - have been characterized by X-ray crystallography which reveals T1Et4iPrIP to bind iron in a tridentate fashion. Complex additionally contains a bidentate 2-OH-AP ligand and a monodentate triflate ligand yielding distorted octahedral geometry, while possesses a bidentate 2-O-AP ligand and exhibits distorted trigonal bipyramidal geometry (τ = 0.56). Complex displays distorted octahedral geometry with 3 DMF ligands completing the ligand set. The UV-vis spectrum of matches more closely to the DAD-substrate spectrum than , and therefore, it is believed that the substrate for DAD is bound in the protonated form. TD-DFT studies indicate that visible absorption bands for and are due to MLCT bands. Complexes and are capable of oxidizing the coordinated substrate mimics in a stoichiometric and catalytic fashion in the presence of O. Complex does not convert 2-OH-AP to products under the same catalytic conditions; however, it becomes anaerobically reduced in the presence of 2 equiv 2-OH-AP to .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.1c00167DOI Listing
April 2021

Analysis of risk factors for unplanned reoperation following primary repair of gastrointestinal disorders in neonates.

BMC Anesthesiol 2021 Apr 23;21(1):128. Epub 2021 Apr 23.

Department of Anesthesiology, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women's & Children's Central Hospital, No.1617, Riyue Avenue, Qingyang District, Chengdu, 610091, P.R. China.

Background: The aim of our study was to identify the factors associated with unplanned reoperations among neonates who had undergone primary repair of gastrointestinal disorders.

Methods: A retrospective chart review was conducted for neonates who underwent primary gastrointestinal surgery between July 2018 and September 2020. The neonates were divided into two cohort, depending on whether they had an unplanned reoperation. The primary outcome was the occurrence of unplanned reoperation. The risk factors that associated the occurrence of unplanned reoperation were examined.

Main Results: Two hundred ninety-six neonates fulfilled the eligibility criteria. The incidence of unplanned reoperation was 9.8%. Analyses of all patients with respect of developing unplanned reoperation showed that the length of operative time was an independent risk factor [Odds Ratio 1.02; 95% confidence interval 1.00, 1.04; p = 0.03]. Patients with unplanned reoperation had a longer postoperative hospital length-of-stay [19.9 ± 14.7 vs. 44.1 ± 32.1 days; p<0.01].

Conclusion: The current study is the first analysis of risk factors associated with an unplanned reoperation in neonates undergoing primary repair of gastrointestinal disorders. The length of operative time is the only risk factor for an unplanned reoperation, and the unplanned reoperation can directly prolong the postoperative hospital length-of-stay.

Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx with No. ChiCTR2000040260 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-021-01345-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063406PMC
April 2021

SAUR15 Promotes Lateral and Adventitious Root Development via Activating H+-ATPases and Auxin Biosynthesis.

Plant Physiol 2020 Oct;184(2):837-851

State Key Laboratory of Grassland Agro-ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs; College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, People's Republic of China.

SMALL AUXIN-UP RNAs (SAURs) comprise the largest family of early auxin response genes. Some SAURs have been reported to play important roles in plant growth and development, but their functional relationships with auxin signaling remain unestablished. Here, we report Arabidopsis (Arabidopsis thaliana) SAUR15 acts downstream of the auxin response factors ARF6,8 and ARF7,19 to regulate auxin signaling-mediated lateral root (LR) and adventitious root (AR) formation. The loss-of-function mutant saur15-1 exhibits fewer LRs and ARs. By contrast, plants overexpressing SAUR15 exhibit more LRs and ARs. We find that the SAUR15 promoter contains four tandem auxin-responsive elements, which are directly bound by ARF6 and ARF7 and are essential for SAUR15 expression. LR and AR impairment in arf6 and arf7 mutants is partially reduced by ectopic expression of SAUR15. Additionally, we demonstrate that the ARF6,7-upregulated SAUR15 promotes LR and AR development using two mechanisms. On the one hand, SAUR15 interacts with PP2C-D subfamily type 2C protein phosphatases to inhibit their activities, thereby stimulating plasma membrane H+-ATPases, which drives cell expansion and facilitates LR and AR formation. On the other hand, SAUR15 promotes auxin accumulation, potentially by inducing the expression of auxin biosynthesis genes. A resulting increase in free auxin concentration likely triggers LR and AR formation, forming a feedback loop. Our study provides insights and a better understanding of how SAURs function at the molecular level in regulating auxin-mediated LR and AR development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1104/pp.19.01250DOI Listing
October 2020

Expanding of ST11 Carbapenemase-Producing Subclones in a Chinese Hospital, Shenzhen, China.

Infect Drug Resist 2021 13;14:1415-1422. Epub 2021 Apr 13.

Shenzhen People's Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, Guangdong, People's Republic of China.

Background: ST11 is the most prevalent sequence type of clinical in China.

Methods: We investigated the characteristics of the ST11 subclones using core genome multi-locus sequence typing (cgMLST). Ninety-three carbapenemase-producing isolates were collected at Shenzhen People's Hospital. Then, whole-genome sequencing and cgMLST were used to discriminate apparent subclones within the ST11 group.

Results: We analyzed the prevalence and genetic relationships of these subclones. ST11 and carbapenemase (KPC-2) were the predominant genotype and carbapenemase, respectively, in the clinical carbapenemase-producing strains. cgMLST scheme genotyping divided the ST11 group into two clades across seven complex types (CTs). CT1313 was the most prevalent subclone. The deletion of and a high frequency of SNPs in genes associated with the stress- and SOS-responses were found in CT1291 and CT2405 over time, respectively.

Conclusion: Our results indicated that the subclones of the ST11 group had different patterns of prevalence. Highly discriminatory genotyping techniques, such as cgMLST scheme, should be used in further molecular epidemiology investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S299478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053513PMC
April 2021

DP1 prostanoid receptor activation increases the severity of an acute lower respiratory viral infection in mice via TNF-α-induced immunopathology.

Mucosal Immunol 2021 Apr 20. Epub 2021 Apr 20.

Respiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.

Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of infant hospitalization and mortality. We previously identified that prostaglandin D2 (PGD2), released following RSV infection of primary human airway epithelial cells or pneumonia virus of mice (PVM) infection of neonatal mice, elicits pro- or antiviral innate immune responses as a consequence of D-type prostanoid receptor 2 (DP2) or DP1 activation, respectively. Here, we sought to determine whether treatment with the DP1 agonist BW245c decreases the severity of bronchiolitis in PVM-infected neonatal mice. Consistent with previous findings, BW245c treatment increased IFN-λ production and decreased viral load in week 1 of the infection. However, unexpectedly, BW245c treatment increased mortality in week 2 of the infection. This increased morbidity was associated with viral spread to the parenchyma, an increased cellular infiltrate of TNF-α-producing cells (neutrophils, monocytes, and CD4 T cells), and the heightened production of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. These phenotypes, as well as the increased mortality, were significantly attenuated following the administration of anti-TNF-α to PVM-infected, BW245c-treated mice. In summary, pharmacological activation of the DP1 receptor in PVM-infected neonatal mice boosts antiviral innate and adaptive immunity, however, this is ultimately detrimental, as a consequence of increased TNF-α-induced morbidity and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41385-021-00405-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057290PMC
April 2021

Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson's disease models.

Aging (Albany NY) 2021 Apr 20;13(8):11738-11751. Epub 2021 Apr 20.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in 6-OHDA-treated PC12 cells. , we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either or .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109056PMC
April 2021

Diversity and spatial distribution of endophytic fungi in Cinnamomum longepaniculatum of Yibin, China.

Arch Microbiol 2021 Apr 20. Epub 2021 Apr 20.

College of Life Sciences and Food Engineering, Key Lab of Aromatic Plant Resources Exploitation and Utilization in Sichuan Higher Education, Yibin University, Yibin Sichuan, 644000, China.

Cinnamomum longepaniculatum (Gamble) N. Chao is an important woody incense plant that contains volatile terpenoids and has been extensively cultivated in Yibin, China. However, the relationship between endophytic fungal diversity and C. longepaniculatum species remains unclear. Here, fungal taxa in different tissue samples were analyzed using Illumina-based sequencing of ITS1 region of fungal rDNA genes. Results showed that 476 OTUs were identified in all tissues of C. longepaniculatum, with 78 OTUs common among all tissues. Similarity cluster analysis indicated that these OTUs belong to 5 phyla and at least 18 genera, with a large number of OTUs remaining unidentified at family and genus levels. The fungal community in seeds exhibited the greatest richness and diversity, followed by those in branches, leaves, and roots, respectively. Unclassified Chaetosphaeriales (91.66%), Passalora (57.17%), and unclassified Ascomycota (58.79%) OTUs dominated in root, branch, and leaf communities, respectively, and other common groups in the branch community included unclassified Ascomycota (12.13%), Houjia (10.38%), and Pseudoveronaea (5.43%), whereas other common groups in leaf community included Passalora (11.43%) and Uwebraunia (8.58%). Meanwhile, the seed community was dominated by unclassified Ascomycota (16.98%), unclassified Pleosporaceae (15.46%), and Talaromyces (12.50%) and also included high proportions of unclassified Nectriaceae (7.68%), Aspergillus (6.95%), Pestalotiopsis (6.02%), and Paraconiothyrium (5.11%) and several seed-specific taxa, including Peniophora, Cryptodiscus, and Penicillium. These findings suggest that Yibin-native C. longepaniculatum harbors rich and diverse endophytic communities that may represent an underexplored reservoir of biological resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00203-021-02325-3DOI Listing
April 2021

Preferential CEBP binding to T:G mismatches and increased C-to-T human somatic mutations.

Nucleic Acids Res 2021 Apr 20. Epub 2021 Apr 20.

Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

DNA cytosine methylation in mammals modulates gene expression and chromatin accessibility. It also impacts mutation rates, via spontaneous oxidative deamination of 5-methylcytosine (5mC) to thymine. In most cases the resulting T:G mismatches are repaired, following T excision by one of the thymine DNA glycosylases, TDG or MBD4. We found that C-to-T mutations are enriched in the binding sites of CCAAT/enhancer binding proteins (CEBP). Within a CEBP site, the presence of a T:G mismatch increased CEBPβ binding affinity by a factor of >60 relative to the normal C:G base pair. This enhanced binding to a mismatch inhibits its repair by both TDG and MBD4 in vitro. Furthermore, repair of the deamination product of unmethylated cytosine, which yields a U:G DNA mismatch that is normally repaired via uracil DNA glycosylase, is also inhibited by CEBPβ binding. Passage of a replication fork over either a T:G or U:G mismatch, before repair can occur, results in a C-to-T mutation in one of the daughter duplexes. Our study thus provides a plausible mechanism for accumulation of C-to-T human somatic mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab276DOI Listing
April 2021

The role of iron homeostasis in adipocyte metabolism.

Food Funct 2021 Apr 20. Epub 2021 Apr 20.

Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, College of Animal Science, Zhejiang University, Hangzhou, China.

Iron plays a vital role in the metabolism of adipose tissue. On the one hand, iron is essential for differentiation, endocrine, energy supply and other physiological functions of adipocytes. Iron homeostasis affects the progression of many chronic metabolic diseases such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In adipose tissue, iron deficiency is associated with obesity, mainly due to inflammation. Nevertheless, excessive iron in adipose tissue leads to decreased insulin sensitivity owing to mitochondrial dysfunction and adipokine changes. On the other hand, iron has an effect on the thermogenesis of adipocytes. Iron deficiency affects the production of beige fat and the direction of the differentiation of brown fat. In this review, we summarize the current understanding of the crosstalk between iron homeostasis and metabolism in adipose tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo03442hDOI Listing
April 2021