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1.
Intest Res ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32224833

RESUMO

Background/Aims: Crohn's disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population's ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD. Methods: This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay. Results: The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, P<0.001). Serum AMH levels were comparable between CD patients and control group under 25 years of age (4.41±1.52 ng/mL vs. 3.49±2.10 ng/mL, P=0.06), however, serum AMH levels were significantly lower in CD patients over 25 years of age compared to control group (P<0.05). Multivariable analysis showed that an age greater than 25 (odds ratio [OR], 10.03; 95% confidence interval [CI], 1.90-52.93, P=0.007), active disease state (OR, 27.99; 95% CI, 6.13-127.95, P<0.001) and thalidomide use (OR, 15.66; 95% CI, 2.22-110.65, P=0.006) were independent risk factors associated with low ovarian reserve (serum AMH levels <2 ng/mL) in CD patients. Conclusions: Ovarian reserve is impaired in young women of reproductive age with CD. Age over 25 and an active disease state were both independently associated with low ovarian reserve. Thalidomide use could result in impaired ovarian reserve.

2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(0): 629-633, 2020 Mar 09.
Artigo em Chinês | MEDLINE | ID: mdl-32149484

RESUMO

Objective: To investigate the epidemiological characteristics of a family clustering of COVID-19. Methods: Field epidemiological survey was conducted. Result: Case 1 of the long-term residents from Hubei province was the source of infection of this family clustering. There were 6 cases (from case 2 to case 7) infected in the whole incubation period. The incubation period was more than 14 days for 3 of the second-generation cases. Routes of transmission include respiratory droplets (from case 1 transmitted to case 6, from case 1 to her family members) and closecontact (from case 1 to other cases in her family). All the age groups were generally susceptible, while elderly were easier to progress to critically ill. Besides respiratory symptoms, there were also gastrointestinal symptoms, of which diarrhea was the most common one. Conclusion: Family clustering had been an important part for COVID-19 cases.

3.
Environ Sci Technol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32131584

RESUMO

Secondary organic aerosol (SOA) constitutes a large fraction of organic aerosol worldwide, however, the formation mechanisms in polluted environments remain poorly understood. Here we observed fast daytime growth of oxygenated organic aerosol (OOA) (with formation rates up to 10 µg m-3 h-1) during low relative humidity (RH, daytime average 38 ± 19%), high RH (53 ± 19%), and fog periods (77 ± 13%, fog occurring during nighttime with RH reaching 100%). Evidence showed that photochemical aqueous-phase SOA (aqSOA) formation dominantly contributed to daytime OOA formation during the periods with nighttime fog, while both photochemical aqSOA and gas-phase SOA (gasSOA) formation were important during other periods with the former contributing more under high RH and the latter under low RH conditions, respectively. Compared to daytime photochemical aqSOA production, dark aqSOA formation was only observed during the fog period and contributed negligibly to the increase in OOA concentrations due to fog scavenging processes. The rapid daytime aging, as indicated by the rapid decrease in m,p-xylene/ethylbenzene ratios, promoted the daytime formation of precursors for aqSOA formation, e.g., carbonyls such as methylglyoxal. Photooxidants related to aqSOA formation such as OH radical and H2O2 also bear fast daytime growth features even under low solar radiative conditions. The simultaneous increases in ultraviolet radiation, photooxidant, and aqSOA precursor levels worked together to promote the daytime photochemical aqSOA formation. We also found that biomass burning emissions can promote photochemical aqSOA formation by adding to the levels of aqueous-phase photooxidants and aqSOA precursors. Therefore, future mitigation of air pollution in a polluted environment would benefit from stricter control on biomass burning especially under high RH conditions.

4.
Nat Plants ; 6(3): 202-208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32170285

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12b is a newly emerged genome engineering system. Here, we compared Cas12b from Alicyclobacillus acidoterrestris (Aac), Alicyclobacillus acidiphilus (Aa), Bacillus thermoamylovorans (Bth) and Bacillus hisashii (Bh) for genome engineering in rice, an important crop. We found AaCas12b was more efficient than AacCas12b and BthCas12b for targeted mutagenesis, which was further demonstrated in multiplexed genome editing. We also engineered the Cas12b systems for targeted transcriptional repression and activation. Our work establishes Cas12b as the third promising CRISPR system, after Cas9 and Cas12a, for plant genome engineering.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32159942

RESUMO

A biodegradable coronary stent is expected to eliminate the adverse events of an otherwise eternally implanting material after vessel remodeling. Both biocorrodible metals and biodegradable polymers have been tried as the matrix of the new-generation stent. Herein, we utilized a metal-polymer composite material to combine the advantages of the high mechanical strength of metals and the adjustable degradation rate of polymers to prepare the biodegradable stent. After coating polylactide (PLA) on the surface of iron, the degradation of iron was accelerated significantly owing to the decrease of local pH resulting from the hydrolysis of PLA, etc. We implanted the metal-polymer composite stent (MPS) into the porcine artery and examined its degradation in vivo, with the corresponding metal-based stent (MBS) as a control. Microcomputed tomography (micro-CT), coronary angiography (CA), and optical coherence tomography (OCT) were performed to observe the stents and vessels during the animal experiments. The MPS exhibited faster degradation than MBS, and the inflammatory response of MPS was acceptable 12 months after implantation. Additionally, we implanted another MPS after 1-year implantation of the first MPS to investigate the result of the MPS in the second implantation. The feasibility of the biodegradable MPS in second implantation in mammals was also confirmed.

6.
Aging (Albany NY) ; 122020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32203053

RESUMO

Renal fibrosis is a key factor in chronic kidney disease (CKD). Long non-coding RNAs (lncRNAs) play important roles in the physiological and pathological progression of human diseases. However, the roles and underlying mechanisms of lncRNAs in renal fibrosis still need to be discovered. In this study, we first displayed the increased lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in renal fibrosis in patients with obstructive nephropathy (ON). Then we found that transforming growth factor beta 1 (TGF-ß1) induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition, which promoted the viability, proliferation and migration of human renal proximal tubular epithelial (HK2) cells. Next, MALAT1/miR-145/focal adhesion kinase (FAK) pathway was confirmed to play an importment role in TGF-ß1-induced renal fibrosis. In addition, the MALAT1/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-ß1-induced renal fibrosis in vitro and in vivo. Furthermore, m6A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m6A modification on MALAT1.

7.
Theranostics ; 10(8): 3451-3473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206101

RESUMO

While protein arginine methyltransferases (PRMTs) and PRMT-catalyzed protein methylation have been well-known to be involved in a myriad of biological processes, their functions and the underlying molecular mechanisms in cancers, particularly in estrogen receptor alpha (ERα)-positive breast cancers, remain incompletely understood. Here we focused on investigating PRMT4 (also called coactivator associated arginine methyltransferase 1, CARM1) in ERα-positive breast cancers due to its high expression and the associated poor prognosis. Methods: ChIP-seq and RNA-seq were employed to identify the chromatin-binding landscape and transcriptional targets of CARM1, respectively, in the presence of estrogen in ERα-positive MCF7 breast cancer cells. High-resolution mass spectrometry analysis of enriched peptides from anti-monomethyl- and anti-asymmetric dimethyl-arginine antibodies in SILAC labeled wild-type and CARM1 knockout cells were performed to globally map CARM1 methylation substrates. Cell viability was measured by MTS and colony formation assay, and cell cycle was measured by FACS analysis. Cell migration and invasion capacities were examined by wound-healing and trans-well assay, respectively. Xenograft assay was used to analyze tumor growth in vivo. Results: CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment. Global mapping of CARM1 substrates revealed that CARM1 methylated a large cohort of proteins with diverse biological functions, including regulation of intracellular estrogen receptor-mediated signaling, chromatin organization and chromatin remodeling. A large number of CARM1 substrates were found to be exclusively hypermethylated by CARM1 on a cluster of arginine residues. Exemplified by MED12, hypermethylation of these proteins by CARM1 served as a molecular beacon for recruiting coactivator protein, tudor-domain-containing protein 3 (TDRD3), to CARM1-bound active enhancers to activate estrogen/ERα-target genes. In consistent with its critical role in estrogen/ERα-induced gene transcriptional activation, CARM1 was found to promote cell proliferation of ERα-positive breast cancer cells in vitro and tumor growth in mice. Conclusions: our study uncovered a "hypermethylation" strategy utilized by enhancer-bound CARM1 in gene transcriptional regulation, and suggested that CARM1 can server as a therapeutic target for breast cancer treatment.

8.
Int J Mol Sci ; 21(6)2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32209971

RESUMO

Vacuolar invertase is involved in sugar metabolism and plays a crucial role in plant growth and development, thus regulating seed size. However, information linking vacuolar invertase and seed size in rice is limited. Here we characterized a small grain mutant sg2 (grain size on chromosome 2) that showed a reduced in grain size and 1000-grain weight compared to the wild type. Map-based cloning and genetic complementation showed that OsINV3 is responsible for the observed phenotype. Loss-of-function of OsINV3 resulted in grains of smaller size when compared to the wild type, while overexpression showed increased grain size. We also obtained a T-DNA insertion mutant of OsINV2, which is a homolog of OsINV3 and generated double knockout (KO) mutants of OsINV2 and OsINV3 using CRISPR/Cas9. Genetic data showed that OsINV2, that has no effect on grain size by itself, reduces grain length and width in the absence of OsINV3. Altered sugar content with increased sucrose and decreased hexose levels, as well as changes vacuolar invertase activities and starch constitution in INV3KO, INV2KO, INV3KOINV2KO mutants indicate that OsINV2 and OsINV3 affect sucrose metabolism in sink organs. In summary, we identified OsINV3 as a positive regulator of grain size in rice, and while OsINV2 has no function on grain size by itself. In the absence of OsINV3, it is possible to detect a role of OsINV2 in the regulation of grain size. Both OsINV3 and OsINV2 are involved in sucrose metabolism, and thus regulate grain size. Our findings increase our understanding of the role of OsINV3 and its homolog, OsINV2, in grain size development and also suggest a potential strategy to improve grain yield in rice.

9.
Nat Commun ; 11(1): 736, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024823

RESUMO

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32055881

RESUMO

PURPOSE: To assess the natural evolution of the osseous reaction following arthroscopic double-row rotator cuff repair with PEEK anchors and to analyze its correlation with clinical shoulder function. METHODS: Between 2015 and 2017, 159 patients received arthroscopic double-row rotator cuff repair with PEEK anchors and underwent serial clinical and radiological follow-up (3, 6, 12, and 24 months). Radiological results were analyzed by tendon integrity, bone marrow edema, and peri-implant osteolysis. Clinical shoulder function was evaluated with the Constant score. RESULTS: One-hundred and seventeen patients were enrolled; among them, 63% demonstrated bone marrow edema around the anchors on postoperative 3-month MRI. The edema area percentage was 41% ± 7%. At 6 months, edema was only seen in 12% of cases, with an area percentage of 18% ± 5%. At 12 and 24 months, edema was rarely present. Fluid signals around the anchor were observed in 17.6%, 42.7%, 33.3%, and 21.0% of patients at 3, 6, 12, and 24 months, respectively; the tunnel widening values were 1.1 ± 0.4 mm, 1.8 ± 0.5 mm, 2.3 ± 0.6 mm, and 2.2 ± 0.7 mm at each follow-up, respectively. The sign of osteolysis was significantly more obvious around the lateral anchor than around the medial anchor. The presence of an osseous reaction was not correlated with worse clinical outcome. CONCLUSION: Osseous reactions following arthroscopic rotator cuff repair are common and significant even with PEEK anchors. Bone marrow edema does not last more than 6 months in patients without complications. Peri-implant osteolysis is more evident around the lateral anchor than around the medial anchor and improves gradually over time. The sign of osteolysis is not correlated with clinical shoulder function. Based on these findings, surgeons should be cautious about bone marrow edema lasting more than 6 months following arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: Level IV.

11.
Nature ; 578(7793): 129-136, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32025019

RESUMO

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.

12.
Clin Interv Aging ; 15: 225-237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110002

RESUMO

Background and Objective: Activities of daily living (ADL) disability seriously affects the quality of life in the elderly. This study aims to examine the prevalence of ADL disability and its possible correlation with lipid profile indicators (LDL-C, TG and HDL-C) among female centenarians in Hainan, China. Methods: A cross-section of complete sample study including 822 female centenarians was conducted from the China Hainan Centenarians Cohort Study (CHCCS) from June 2014 to December 2016. Barthel index was used to estimate ADL disability and multivariate logistic regression model was used to explore the relationship between lipid profile indicator and ADL disability. Results: A total of 822 female centenarians were recruited in Hainan province, and the median age was 102 (IQR: 101-104) years, and 244 (29.7%) centenarians had ADL disability. After adjustment, 1 mmol/L increment in LDL-C, TG and HDL-C were associated with 26.4% (aOR=0.736, 95% CI:0.592-0.915), 29.8% (aOR=0.702, 95% CI:0.521-0.948) and 60.5% (aOR=0.395, 95% CI:0.257-0.610) decline in ADL disability of female centenarian, respectively. The prevalence of ADL disability showed downward trend with the increase of the quintile of LDL-C, TG and HDL-C (Ptrend<0.05). Increment of HDL-C levels had the strongest protective effect against ADL disability. Conclusion: We concluded that a new possible association of higher normal lipid profile indicators, especially HDL-C, might have a protective effect on ADL disability among female centenarians.

13.
Faraday Discuss ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108211

RESUMO

In this article, we present a kind of dual-emission fluorescent nanothermometer, which is made of europium (Eu3+)-doped silicon nanoparticles (Eu@SiNPs), allowing the detection of intracellular temperature in living cells with high accuracy. In particular, the presented SiNP-based thermometer features dual-emission fluorescence (blue (455 nm) and red (620 nm) emission), negligible toxicity (cell viability of treated cells remains above 90% during 24 h of treatment) and robust photostability in living cells (i.e., preserving >90% of fluorescence intensity after 45 min of continuous UV irradiation). More significantly, the fluorescence intensity of the Eu@SiNPs exhibits a linear ratiometric temperature response in a broad range from 25 to 70 °C. Taking advantage of these attractive merits, the Eu@SiNP-based nanothermometer is able to accurately (∼4.5% change per °C) determine dynamic changes in intracellular temperature in a quantitative and long-term (i.e., 30 min) manner.

14.
J Dig Dis ; 21(2): 98-103, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916702

RESUMO

OBJECTIVE: To explore the relationship between hepatic cytochrome P450 2C19 (CYP2C19) gene polymorphisms and the effectiveness and safety of thalidomide in the treatment of patients with immune-related bowel disease (IRBD). METHODS: CYP2C19 variants in 79 patients treated with thalidomide were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The clinical response and adverse events of the thalidomide treatment were recorded. The potential influences of the CYP2C19 genotype polymorphisms on the clinical efficacy and adverse events of thalidomide were then investigated. RESULTS: Altogether 79 patients with IRBD (70 with Crohn's disease, three with ulcerative colitis and six with Behcet's disease) receiving thalidomide therapy were recruited from January 2013 to February 2015 in a tertiary IBD center in China. Overall, 21.5% (17/79) of these patients had CYP2C19 poor metabolizers genotype (PM). The overall response rate and the incidence of adverse events of CYP2C19 extensive metabolizers genotype were not significantly different from that of the PM when IRBD patients were treated with thalidomide (P = 0.517 and 0.816, respectively). CONCLUSION: CYP2C19 polymorphisms do not seem to be associated with efficacy of thalidomide and the incidence of adverse events in treating IRBD.

15.
BMJ Open ; 10(1): e026560, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31924626

RESUMO

OBJECTIVE: To investigate the relationship between upper and lower limb muscle strength and the health-related quality of life (HRQoL) of a Chinese rural, elderly population. DESIGN: A population-based, cross-sectional study. SETTING: Miyun, Beijing, China. PARTICIPANTS: The participants of this study were 2083 (834 men and 1249 women) older adults from a rural area, (average age of ≥60 years), living in Miyun county, located on the outskirts of Beijing. Data were collected between May and October 2014. Handgrip strength and timed up and go tests (TUGT) were conducted to measure the muscle strength of their upper and lower limbs, respectively. The Euro Quality of Life (Euroqol) (EQ-5D)-Visual Analogue Scale was used to evaluate participants' HRQoL. RESULTS: A significant association between handgrip strength and the EQ-5D index (ß=0.015 per SD, 95% CI: 0.008 to 0.023, p<0.001) was discovered, following adjustments. The association between handgrip strength and the EQ-5D index in the ≥80 years group was found to be stronger than that of the 60-79 years group, following adjustment (ß per SD: 0.013 vs 0.035). Similar results were observed when comparing the non-chronic disease group, in terms of TUGT time, against those with chronic diseases. CONCLUSIONS: There was a significant relationship between muscle strength (measured via handgrip strength and TUGT time) and HRQoL (measured via EQ-5D index and VAS score) in the Chinese rural elderly population. Furthermore, this relationship was stronger in the older population (aged ≥80 years), and in those participants diagnosed with chronic diseases.

16.
Exp Cell Res ; 387(1): 111754, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805276

RESUMO

Benign prostatic hyperplasia (BPH) is a common disease in older men, and there is evidence that obesity is a causal factor. It is currently unclear whether the hormone leptin, which is positively correlated to obesity, is involved in BPH. The aim of this study was to determine the effect of leptin on testosterone-induced BPH in mice and to explore possible underlying mechanisms. Testosterone (3 mg/kg) was injected into wild-type and leptin-deficient ob/ob male mice for 14 consecutive days, and prostate tissues were subjected to various analyses. Additionally, BPH epithelial-1 (BPH-1) cells were treated with leptin to further investigate the underlying mechanisms. Leptin deficiency attenuated testosterone-induced morphological and pathological changes of BPH in mice. Furthermore, leptin deficiency alleviated the process of epithelial-mesenchymal transition (EMT) and suppressed the downregulation of bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) in testosterone-treated mice. The in vitro data revealed that leptin significantly increased the expression of the EMT-associated marker vimentin but decreased the expression of E-cadherin, and that upregulation of BAMBI mitigated the intensity of leptin-induced EMT responses. Our results suggest that leptin can promote EMT in BPH through downregulating BAMBI. Suppressing leptin might be a potential therapeutic approach in preventing BPH development and progression.

17.
Bioresour Technol ; 297: 122417, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759856

RESUMO

This study evaluates the effect of replacement of N2 with CO2 as atmosphere in catalytic pyrolysis of waste lignocellulosics with acidic and metal-modified zeolites, respectively, on the 16 EPA priority pollutant polycyclic aromatic hydrocarbons (PAHs) in bio-oils. By coupling solid phase extraction pretreatment with single ion monitoring detection, it is found that the replacement alleviates PAHs in bio-oil concerning synchronously abating the 16 PAHs with low, medium and high molecular weights, and the benzo[a]pyrene equivalent toxicity of bio-oil decreases. Meanwhile, CO2 decreases the content of small oxygenates, e.g. furans, ketones, acids, and increases phenolics and aromatics affording more stable and valuable bio-oils. Moreover, CO2 enhances carbon conversion efficiency, especially in combination with Fe-modified zeolite, which presents a synergistic effect. This study indicates the practical application of CO2 as an atmosphere in catalytic pyrolysis to improve the bio-oil quality by suppressing PAHs formation and adjusting compound constituent.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Atmosfera , Dióxido de Carbono , Nitrogênio , Pirólise
18.
Endocrine ; 67(3): 587-596, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845180

RESUMO

PURPOSE: Fatty acid binding protein 4 (FABP4) has been demonstrated to be secreted from adipocytes in an unconventional pathway associated with lipolysis. Circulating FABP4 is elevated in metabolic disorders and has been shown to affect various peripheral cells such as pancreatic ß-cells, hepatocytes and macrophages, but its effects on adipocytes remains unclear. The aim of this study was to investigate the effects of exogenous FABP4 (eFABP4) on adipocyte differentiation and function. METHODS: 3T3-L1 pre-adipocytes or mature adipocytes were treated with recombinant FABP4 in the absence or presence of FABP4 inhibitor I-9/p38 MAPK inhibitor SB203580; Meanwhile male C57BL/6J mice were subcutaneously injected twice a day with recombinant FABP4 (0.35 mg/kg) with or without I-9 (50 mg/kg) for 2 weeks. The effects of eFABP4 on differentiation, lipolysis and inflammation were determined by triglyceride measurement or lipolysis assay, western blotting, or RT-qPCR analysis. RESULTS: eFABP4 treatment significantly reduced intracellular triglyceride content and decreased expression of adipogenic markers peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), intracellular FABP4, and adiponectin in 3T3-L1 cells. Besides, eFABP4 promoted lipolysis and inflammation in differentiated 3T3-L1 adipocytes as well as in adipose tissue of eFABP4-treated C57BL/6J mice, with elevated gene expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and elevated protein expression of adipose triglyceride lipase (ATGL), phosphorylation of hormone-sensitive lipase (HSL) (Ser-660), p38, and nuclear factor-kappa B (NF-κB). The pro-inflammatory and pro-lipolytic effects of eFABP4 could be reversed by SB203580/I-9. CONCLUSIONS: These findings indicate that eFABP4 interferes with adipocyte differentiation, induces p38/HSL mediated lipolysis and p38/NF-κB mediated inflammation in adipocytes in vitro and in vivo.

19.
J Phys Condens Matter ; 32(3): 035501, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31585446

RESUMO

Planar bismuthene grown on SiC substrate provides a promising candidate to engineer van der Waals double-layer (DL) made of two dimensional (2D) topological insulators. We perform systematical calculations in DL hydrogenated bismuthene (H-Bi) that can be used to simulate the experimentally grown planar bismuthene to explore realizable 2D topological insulator van der Waals DL. Two possible geometry configurations of AA- and AB-stacked DL H-Bi are investigated. Due to pseudo Jahn-Teller effect, AB-stacked DL H-Bi has a strong interlayer coupling interaction and shows buckled lattice. Particularly, both AA- and AB-stacked DL H-Bi are topologically trivial rather than topologically nontrivial. The physical origin of the trivial topology is clarified by analyzing orbital composition. We discuss how the electronic properties are modified by interlayer coupling, external strain, and metal atom intercalation. It is also found that, for AB-stacked DL H-Bi, metal atom intercalation gives rise to novel multiple Rashba splitting near the valence band top, which is expected to manipulate the same spin in different planar bismuthene layers. Our results present various and tunable electronic properties of van der Waals DL H-Bi and allow for probing into multiple Rashba effect in 2D inversion-asymmetric topological insulators.

20.
Hematology ; 25(1): 26-33, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861969

RESUMO

Objectives: Although anemia is a widespread condition that leads to an increase in morbidity and mortality, particularly as people age, little information on anemia in centenarians is available. The objective of this study was to determine the prevalence of anemia and examine the relationship between anemia and a decline in kidney function in Chinese centenarians.Methods: We conducted a population-based cross-sectional study of a sample of 1002 Chinese centenarians (180 men and 822 women) from 2014 to 2016. Anemia was defined as a hemoglobin level of <130 g/L for men and <120 g/L for women.Results: The prevalence of anemia and severe anemia (<100 g/L) were 68.5% (men, 76.1%; women, 66.8%) and 19.6% (men, 16.1%; women, 20.3%), respectively. The risk of anemia and estimated glomerular filtration rate (eGFR) showed a nonlinear relationship (nonlinear P = 0.021). The interaction analysis revealed that ethnicity and diabetes mellitus played a role in the association between the eGFR (<60 mL/min/1.73 m2) and anemia.Conclusion: Anemia is highly prevalent in Chinese centenarians, particularly among men. Decreased kidney function was an independent determinant of anemia, especially in Han participants and participants with diabetes mellitus. The possibility of decreased kidney function needs to be considered in the evaluation and treatment of anemia in centenarians.

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