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1.
J Immunother Cancer ; 9(2)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33589528

RESUMO

BACKGROUND: Chemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC). METHODS: We analyzed prognostic value and immune contexture that associated with CXCL13+CD8+T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13+CD8+T cells and total CD8+T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC. RESULTS: Intratumoral CXCL13+CD8+T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13+CD8+T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8+T cells in high-level CXCL13+CD8+T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13+CD8+T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3+ regulatory T cells, TLS and decreased natural killer cells, GZMB+ cells. CONCLUSIONS: Intratumoral CXCL13+CD8+T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13+CD8+T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13+CD8+T cells abundance impaired total CD8+T cells' immune function. Intratumoral CXCL13+CD8+T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13+CD8+T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.

2.
J Int Med Res ; 49(2): 300060521993642, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33596700

RESUMO

BACKGROUND: We describe 2 unusual haemoglobin (Hb) Bart's hydrops cases that could not be explained by traditional factors.Case presentation: Two families with a diagnosis or history of foetal hydrops were enrolled. A suspension-array system was used to detect the 23 most frequent mutations in southern China. Multiplex ligation-dependent probe amplification (MLPA) was used to screen for possible deletions. Precise characterisation of the breakpoints of the novel variants and uniparental disomy analysis were performed using a single nucleotide polymorphism (SNP) array. Quantitative fluorescence PCR was used to eliminate maternal cell contamination and nonpaternity. In case 1, the suspension-array system indicated a maternal heterozygous (-SEA/) deletion, and the paternal sample was negative. The foetal hydrops was caused by the maternal (-SEA/) deletion and a de novo α-globin gene deletion (-193). In case 2, the paternal sample had a heterozygous (-SEA/) deletion, and MLPA and SNP array analysis revealed a large maternal deletion (-227) that encompassed the α-globin gene, which explained the history of Hb Bart's foetal hydrops. CONCLUSIONS: Our cases describe 2 new α0-thalassaemia deletions and illustrate the importance of using a combination of methods to detect rare types of α-thalassaemia.

3.
Front Public Health ; 9: 627312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614588

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in China. Although numerous studies have been conducted to determine the risk factors for COPD mortality such as ambient air pollution, the results are not fully consistent. Methods: This study included mortality analysis and a case-control design by using the data extracted from the Mortality Registration System in Jiading District, Shanghai. Traditional logistic regression, geographically weighted logistic regression (GWLR), and spatial scan statistical analysis were performed to explore the geographic variation of COPD mortality and the possible influencing factors. Results: Traditional logistic regression showed that extreme lower temperature in the month prior to death, shorter distance to highway, lower GDP level were associated with increased COPD mortality. GWRL model further demonstrated obvious geographical discrepancies for the above associations. We additionally identified a significant cluster of low COPD mortality (OR = 0.36, P = 0.002) in the southwest region of Jiading District with a radius of 3.55 km by using the Bernoulli model. The geographical variation in age-standardized mortality rate for COPD in Jiading District was explained to a certain degree by these factors. Conclusion: The risk of COPD mortality in Jiading District showed obvious geographical variation, which were partially explained by the geographical variations in effects of the extreme low temperature in the month prior to death, residential proximity to highway, and GDP level.

4.
Medicine (Baltimore) ; 100(7): e24668, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607804

RESUMO

ABSTRACT: We aimed to retrospectively analyze the clinical and computed tomography (CT) characteristics of young adults with Coronavirus Disease 2019 (COVID-19) pneumonia who were critically ill and to identify the features associated with non-survival.Thirty-eight COVID-19 patients (20-45 years old, 28 men) who had been admitted in the intensive care unit were included, including 18 non-survivors (group 1) and 20 survivors (group 2). Their clinical characteristics and initial and follow-up CT were compared between groups.In group 1, the days from illness onset to death were 21.1 ±â€Š10.3 days; 7 patients had underlying comorbidities. At admission, group 1 exhibited higher serum ferritin and interleukin-6 (IL-6) levels (1142.6 ±â€Š242.4 mg/L and 33.8 ±â€Š18.6 mmol/L) compared with group 2 (728.3 ±â€Š150.9 mg/L and 15.2 ±â€Š6.9 mmol/L, P < .01). Group 1 exhibited more rapidly progressive opacities and consolidation in follow-up CT (16.7 ±â€Š3.1 scores, 15.7 ±â€Š3.1 segments) than group 2 (11.4 ±â€Š4.0 scores, 10.3 ±â€Š4.6 segments, P < .01). The oxygenation index was lower (87.6 ±â€Š19.2 vs 99.1 ±â€Š20.4 mm Hg) and the mechanical ventilation duration was longer (14.7 ±â€Š6.9 vs 9.7 ±â€Š3.7 days) in group 1 compare with group 2 (P < .01).Compared with the survivors, the non-survivors showed higher serum ferritin and IL-6 levels, more rapidly progressive opacities in CT, lower oxygenation index, and longer mechanical ventilation durations. Special attention to ferritin/IL-6 levels and oxygenation index as well as early CT application and timely reexaminations are important to identify the individuals who may be at risk of becoming critically ill.


Assuntos
/diagnóstico , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Tomografia Computadorizada por Raios X/métodos , Adulto , Estado Terminal , Progressão da Doença , Feminino , Humanos , Masculino , Pneumonia Viral/virologia , Estudos Retrospectivos , Análise de Sobrevida
5.
Sci Rep ; 11(1): 4296, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619316

RESUMO

A deeper understanding of the causal links from education level to health outcomes may shed a light for disease prevention. In the present Mendelian randomization study, we found that genetically higher education level was associated with lower risk of major mental disorders and most somatic diseases, independent of intelligence. Higher education level adjusted for intelligence was associated with lower risk of suicide attempts, insomnia, major depressive disorder, heart failure, stroke, coronary artery disease, lung cancer, breast cancer, type 2 diabetes and rheumatoid arthritis but with higher risk of obsessive-compulsive disorder, anorexia nervosa, anxiety, bipolar disorder and prostate cancer. Higher education level was associated with reduced obesity and smoking, which mediated quite an extent of the associations between education level and health outcomes. These findings emphasize the importance of education to reduce the burden of common diseases.

6.
Plant Signal Behav ; : 1879533, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632077

RESUMO

Single treatment of plants with pathogens like Pseudomonas syringae can trigger systemic acquired resistance (SAR) that lasts several days to several weeks in Arabidopsis thaliana. Similar primed resistances were described for abiotic stresses like drought and heat stress. Most studies about plant resistance to ultraviolet (UV)-radiation used low UV-B radiations over a long period. These experimental designs make it difficult to distinguish acclimation effects from real cellular memory which facilitate transcriptional and other responses to a second UV-radiation after a latent phase. Here we present a novel UV-B priming system. We demonstrate that a single UV-B treatment, which causes neither visible damage nor accumulation of pigments, can stimulate resistance against UV-B stress. After a second damaging UV-B treatment, UV-primed plants showed significantly reduced damage in comparison to non-primed plants. Furthermore, the acquirement of the induced UV-B resistance was impaired in uvr8-6 mutants suggesting that the UV-B receptor is essential for UV-B stress memory in Arabidopsis. We discuss advantages and limits of our UV-B priming system which will be a powerful tool to investigate UV-B memory in future studies.

7.
Sex Health ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632383

RESUMO

BACKGROUND: Elimination of HIV is a public health priority in China, but there has been reports of an upsurge in HIV among young people. A nationwide cross-sectional survey was conducted to assess the awareness of HIV knowledge, attitudes towards homosexuality and practice of sexual behaviours among Chinese aged 15-24 years. METHODS: The face-to-face survey was conducted from June to August 2017, collecting data on sociodemographic characteristics, HIV-related knowledge, attitudes towards homosexuality and practice of sexual behaviours among Chinese senior high school and university students. A generalised linear model (GLM) was used to assess the different levels of HIV knowledge between groups, and identify the key contributors to HIV knowledge scores. RESULTS: The survey was completed by 73.6% (1355/1840) of the students approached. The overall level of HIV-related knowledge was low (58.9%, 10.6/18); 48.0% (650/1355) supported same-sex marriage; and 6.9% (93/1355) self-identified as homosexual or bisexual. The major factors associated with higher scores [mean ± standard deviation (s.d.)] in HIV knowledge among students included: having received school-based HIV education (11.47 ± 3.51 vs 9.02 ± 4.14, P < 0.05); support for same-sex marriage (11.69 ± 3.33 vs 9.49 ± 4.29, P < 0.05) and older age (11.61 ± 2.78 vs 9.87 ± 4.17, P < 0.05). Compared with females, males were significantly more likely (all P < 0.05) to report masturbation (60.7% vs 7.6%), pornography experiences (77.4% vs 35.3%), sexual encounters (24.6% vs 12.3%), casual sex (37.0% vs 18.1%) and sex under the influence of alcohol (29.5% vs 12.8%). CONCLUSIONS: There is is still much room for improvement in terms of HIV/AIDS prevention and health education for Chinese young people, and more comprehensive and diverse models of education for HIV prevention are urgently needed.

8.
Sci Total Environ ; 763: 144616, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385844

RESUMO

The quantitative evaluations of nutrients delivered by submarine groundwater discharge (SGD) have been widely conducted worldwide, but sources of nutrients in the discharged submarine groundwater remain unclear. Identifying these sources of nutrients is essential to the protection and management of marine ecological environments. This study aims to evaluate the magnitudes of SGD and the associated nitrate in the Guangdong-Hongkong-Macao Greater Bay Area (GHM Greater Bay Area), China, and identify the sources of SGD-driven nitrate in this region using radioactive radium (Ra) isotopes (223Ra, 224Ra, and 228Ra) and stable nitrogen (N) and oxygen (O) isotope composition of nitrate (δ15N-NO3- and δ18O-NO3-). The results of the Ra mixing model show that the estimated SGD and the associated nitrate fluxes into the Greater Bay Area are (9.15 ± 1.26) × 108 m3/d and (3.77 ± 0.52) × 107 mol/d, respectively, both of which are comparable to the contributions from the Pearl River. Combing NO3- dual isotopic signatures of sampled coastal groundwater and five kinds of potential nitrate sources, we found that ammonium (NH4+) fertilizer and natural soil N are the two main sources of nitrate in discharged submarine groundwater and rivers. No anthropogenic inputs from manure or sewage waste were identified. This study provides significant insights into the establishment of effective management strategies for controlling SGD-nutrients into the bay and protecting the marine ecological environment.

9.
JAMA Oncol ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443541

RESUMO

Importance: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. Objective: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. Design, Setting, and Participants: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. Interventions: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. Main Outcomes and Measures: The primary end point was the rate of disease-free survival (DFS) at 3 years. Results: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. Conclusions and Relevance: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00806117.

10.
J Int Med Res ; 49(1): 300060520986668, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33478307

RESUMO

BACKGROUND: Congenital ventricular diverticulum is a rare abnormality that may occur as an isolated malformation. Most cases are accompanied by pericardial effusion. Prenatal counseling can be difficult because the prognosis is uncertain and there is no consensus approach to prenatal management.Case presentation: We describe a case of congenital cardiac diverticulum complicated by large pericardial effusion in one of monochorionic diamniotic twins. The case was diagnosed by ultrasonography at 21 weeks of gestation. Therapeutic pericardiocentesis at 22 weeks resulted in complete resolution of the effusion and led to a favorable fetal outcome. We summarize the interventions and pregnancy outcomes in cases of cardiac diverticula reported in the literature. CONCLUSIONS: Better awareness of clinical features, in utero therapies, and pregnancy outcomes could help define and improve prenatal management of congenital ventricular diverticula.

11.
Chemosphere ; 272: 129650, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33486452

RESUMO

Oil and natural gas (O&G) extraction operations emit hazardous volatile organic compounds (VOCs) in quantities that have adverse effects on human health. Our current understanding of the exposure risks associated with upstream O&G exploitations remains limited, and very few quantitative on-site remediation strategies have been proposed. To this end, we assessed the health risks associated with the emission of hazardous VOCs and presented a set of remediation goals for the city of Calgary, which is a major center of the Canadian oil industry. Results from probabilistic risk assessment (PRA) suggested that although VOCs had a negligible impact on chronic non-cancer-associated risk, inhalation-associated cancer risk remained a significant concern. Carbon tetrachloride, benzene, and 1,3-butadiene were the dominant VOCs, representing 88% of the integrated inhalation cancer risk (= 7.8 × 10-5); background, solid fuel combustion, and O&G extraction were among the primary sources that posed the greatest threat to human health. Results of a Monte Carlo simulation revealed that the probability of developing cancer due to inhalation of hazardous VOCs was ∼13.1% on clean air days and 45.9% on days with significant levels of air pollution. Preliminary remediation goals (PRGs) included reductions of 24.2-65.1% and 11.4-50.9% targeting priority VOCs and their sources, respectively. Taken together, our findings suggest that stringent control of the sources of VOCs, particularly fossil fuel combustion, is an urgent priority. PRA coupled with PRGs provides informative risk assessments and suggests quantitative remediation strategies that can be applied toward improved management of hazardous pollutants.

12.
Commun Biol ; 4(1): 121, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500522

RESUMO

Detecting vascular endothelial growth factor C (VEGF-C), a kind of tumor biomarker, is of significant clinical importance in evaluating the prognosis of patients with cancer. However, laboratory analyses are usually not suitable for point-of-care testing because they are expensive and time consuming. In response to these challenges, we fabricated an origami paper-based microfluidic electrochemical device. To improve the specificity of VEGF-C detection, nanocomposites, synthesized by new methylene blue (NMB), amino-functional single-walled carbon nanotubes (NH2-SWCNTs), and gold nanoparticles (AuNPs), were used to modify the surface of working electrodes. Results of electrochemical detection showed that the immunosensor had excellent linearity, ranging from 0.01 to 100 ng mL-1 (R2 = 0.988), and the limit of detection was 10 pg mL-1. To confirm the high specificity of the device under real-world conditions, we evaluated the device using clinical serum samples from our hospital. The results demonstrated that the device had an excellent performance and could provide a platform for real-time detection of cancers.

13.
Bioresour Technol ; 324: 124668, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33453520

RESUMO

A one-stage airlift internal circulation biofilm reactor was continuously operated for 668 days to treat 50 mg/L of ammonia wastewater to pursue the long-term stability of partial nitritation and anammox (PNA) process. The operational performance and microbial community structure of the biofilm and the flocs were investigated. A nitrogen removal efficiency (NRE) of 70% was obtained successfully at a dissolved oxygen (DO) of 0.05-0.15 mg/L by regulating aeration rate. The microbial analysis indicated Candidatus Brocadia (29.5%) and Nitrosomonas (6.8%) were dominant in both biofilms and flocs. It was found that DO control and aeration rate were the key factors in performance stability, and a stable performance could be recovered and maintained under oxygen-limiting conditions. Further, the achievement of activated ammonia oxidation bacteria (AOB), dominated anammox bacteria (AMX), suppressed NOB, and controlled heterotrophic bacteria (HB) in the biofilms played a major role in the long-term stable operation.


Assuntos
Compostos de Amônio , Microbiota , Amônia , Biofilmes , Reatores Biológicos , Nitrogênio , Oxirredução
14.
Medicine (Baltimore) ; 99(49): e23324, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285709

RESUMO

The aim of this study was to identify the main risk factors for health-care-associated infections (HAIs) following cardiac surgery and to establish an effective early warning model for HAIs to enable intervention in an earlier stage.In total, 2227 patients, including 222 patients with postoperative diagnosis of HAIs and 2005 patients with no-HAIs, were continuously enrolled in Beijing Anzhen Hospital, Beijing, China. Propensity score matching was used and 222 matched pairs were created. The risk factors were analyzed with the methods of univariate and multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to test the accuracy of the HAIs early warning model.After propensity score matching, operation time, clamping time, intubation time, urinary catheter time, central venous catheter time, ≥3 blood transfusions, re-endotracheal intubation, length of hospital stay, and length of intensive care unit stay, still showed significant differences between the 2 groups. After logistic model analysis, the independent risk factors for HAIs were medium to high complexity, intubation time, urinary catheter time, and central venous catheter time. The ROC showed the area under curve was 0.985 (confidence interval: 0.975-0.996). When the probability was 0.529, the model had the highest prediction rate, the corresponding sensitivity was 0.946, and the specificity was 0.968.According to the results, the early warning model containing medium to high complexity, intubation time, urinary catheter time, and central venous catheter time enables more accurate predictions and can be used to guide early intervention after pediatric cardiac surgery.

15.
Scand J Immunol ; : e13006, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275792

RESUMO

Tumor infiltrating mast cells (TIMs) have been reported to play functional roles in the tumor microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumor infiltrating lymphocytes (TILs) in mRCC patients treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 mRCC patients; TIMs (mast cells density positive to tryptase), along with CD8+ and CD4+ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log-rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression-free survival (OS, p=0.008, and PFS, p=0.016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS and (HR=0.624, 95% CI: 0.420-0.927, p=0.020) and PFS (HR=0.658, 95% CI: 0.466-0.930, p=0.019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one- and two-year OS (p=0.002 and p=0.004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (p=0.008 andp=0.001, respectively). Thus, better OS in mRCC patients exhibiting an high mast cell density population may be attributed to the co-existence of CD8+ and CD4+ TILs, which have anti-tumor effects on activation status.

16.
Sci Rep ; 10(1): 21254, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277510

RESUMO

Patients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and graph theoretical network analyses, respectively, of resting-state functional Magnetic Resonance Imaging (rs-fMRI) in T2DM patients with and without MCI, so as to facilitate early diagnose. Twenty-five T2DM patients with MCI (DM-MCI), 25 T2DM patients with normal cognition (DM-NC), 27 healthy controls were enrolled. Whole-brain ReHo values were calculated and topological properties of functional networks were analyzed. The DM-MCI group exhibited decreased ReHo in the left inferior/middle occipital gyrus and right inferior temporal gyrus, and increased ReHo in frontal gyrus compared to the DM-NCs. Significant correlations were found between ReHo values and clinical measurements. The DM-MCI group illustrated greater clustering coefficient/local efficiency and altered nodal characteristics (efficiency, degree and betweenness), which increased in certain occipital, temporal and parietal regions but decreased in the right inferior temporal gyrus, compared to the DM-NCs. The altered ReHo and impaired network organization may underlie the impaired cognitive functions in T2DM and suggesting a compensation mechanism. These rs-fMRI measures have the potential as biomarkers of disease progression in diabetic encephalopathy.

17.
Immun Inflamm Dis ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33277966

RESUMO

BACKGROUND: Altered lipid metabolism is involved in the development of many tumors. However, the role of dissimilar lipid metabolism in head and neck squamous cell carcinoma (HNSCC) is not fully established. AIMS: Here, we sought to determine the prognostic value of lipid metabolism-related genes in HNSCC. METHODS: RNA-seq data and clinical features of 545 HNSCC cases were obtained from The Cancer Genome Atlas database. A regulatory network of transcription factors-lipid metabolism genes and a risk prognostic model of lipid metabolism-related genes was developed using bioinformatics and Cox regression modeling. We used tumor immune estimation resource to analyze immune cell infiltration in patients with HNSCC based on the prognostic index (PI) of lipid metabolism-related genes. RESULTS: A total of 136 differentially expressed lipid metabolism genes were identified. Of these, 23 are related to prognosis. In addition to predicting HNSCC prognosis, 11 lipid metabolism-related genes (ARSI, CYP27B1, CYP2D6, DGKG, DHCR7, LPIN1, PHYH, PIP5K1B, PLA2G2D, RDH16, and TRIB3) also affect HNSCC clinical features (stage, gender, and pathological stage). The PI of lipid metabolism-related genes embodied the state of HNSCC tumor immune microenvironment.

18.
Mol Biol Evol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33316072

RESUMO

Avian genomes are small and lack some genes that are conserved in the genomes of most other vertebrates including nonavian sauropsids. One hypothesis stated that paralogs may provide biochemical or physiological compensation for certain gene losses; however, no functional evidence has been reported to date. By integrating evolutionary analysis, physiological genomics, and experimental gene interference, we clearly demonstrate functional compensation for gene loss. A large-scale phylogenetic analysis of over 1,400 SLC2 gene sequences identifies six new SLC2 genes from nonmammalian vertebrates and divides the SLC2 gene family into four classes. Vertebrates retain class III SLC2 genes but partially lack the more recent duplicates of classes I and II. Birds appear to have completely lost the SLC2A4 gene that encodes an important insulin-sensitive GLUT in mammals. We found strong evidence for positive selection, indicating that the N-termini of SLC2A4 and SLC2A12 have undergone diversifying selection in birds and mammals, and there is a significant correlation between SLC2A12 functionality and basal metabolic rates in endotherms. Physiological genomics have uncovered that SLC2A12 expression and allelic variants are associated with insulin sensitivity and blood glucose levels in wild birds. Functional tests have indicated that SLC2A12 abrogation causes hyperglycemia, insulin resistance, and high relative activity, thus increasing energy expenditures that resemble a diabetic phenotype. These analyses suggest that the SLC2A12 gene not only functionally compensates insulin response for SLC2A4 loss but also affects daily physical behavior and basal metabolic rate during bird evolution, highlighting that older genes retain a higher level of functional diversification.

19.
PLoS Genet ; 16(12): e1009270, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370292

RESUMO

Skeletal muscle plays a central role in regulating glucose uptake and body metabolism; however, highland hypoxia is a severe challenge to aerobic metabolism in small endotherms. Therefore, understanding the physiological and genetic convergence of muscle hypoxia tolerance has a potential broad range of medical implications. Here we report and experimentally validate a common physiological mechanism across multiple high-altitude songbirds that improvement in insulin sensitivity contributes to glucose homeostasis, low oxygen consumption, and relative activity, and thus increases body weight. By contrast, low-altitude songbirds exhibit muscle loss, glucose intolerance, and increase energy expenditures under hypoxia. This adaptive mechanism is attributable to convergent missense mutations in the BNIP3L gene, and METTL8 gene that activates MEF2C expression in highlanders, which in turn increases hypoxia tolerance. Together, our findings from wild high-altitude songbirds suggest convergent physiological and genetic mechanisms of skeletal muscle in hypoxia resistance, which highlights the potentially medical implications of hypoxia-related metabolic diseases.


Assuntos
Adaptação Fisiológica , Altitude , Evolução Molecular , Consumo de Oxigênio , Transcriptoma , Animais , Peso Corporal , Tentilhões , Glucose/metabolismo , Homeostase , Insulina/metabolismo , Músculo Esquelético/metabolismo
20.
Proc Natl Acad Sci U S A ; 117(48): 30276-30284, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168745

RESUMO

Two fundamental constraints limit the number of characters in text that can be displayed at one time-print size and display size. These dual constraints conflict in two important situations-when people with normal vision read text on small digital displays, and when people with low vision read magnified text. Here, we describe a unified framework for evaluating the joint impact of these constraints on reading performance. We measured reading speed as a function of print size for three digital formats (laptop, tablet, and cellphone) for 30 normally sighted and 10 low-vision participants. Our results showed that a minimum number of characters per line is required to achieve a criterion of 80% of maximum reading speed: 13 characters for normally sighted and eight characters for low-vision readers. This critical number of characters is nearly constant across font and display format. Possible reasons for this required number of characters are discussed. Combining these character count constraints with the requirements for adequate print size reveals that an individual's use of a small digital display or the need for magnified print can shrink or entirely eliminate the range of print size necessary for achieving maximum reading speed.

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