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1.
Sci Total Environ ; 712: 136557, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31931207

RESUMO

The bioaccumulation and trophic transfer of 12 Quinolones (QNs) have been studied in a macrophyte dominated lake-Baiyangdian Lake, China. QNs concentrations were detected in surface water, sediments, and 25 biological samples. The average concentrations of QNs varied from 3.01 ng/L for Oxolinic Acid (OXO) to 174 ng/L for Flumequine (FLU) in water, 3.28 ng/g (dry weight, dw) for OXO to 97.0 ng/g (dw) for FLU in sediments, and from 2.88 ng/g (dw) for Pipemidic Acid (PIP) to 37.7 ng/g (dw) for FLU in biological samples. The values of bioconcentration factors (BCFs) or bioaccumulation factors (BAFs) (in the range of 98.0-723 L/kg) and biota sediment accumulation factor (BSAFs) (in the range of 0.000300-0.124) were indicated that low bioaccumulation ability of target QNs in biological species. Due to the detected frequencies of FLU, Enrofloxacin (ENR), Norfloxacin (NOR), and Ofloxacin (OFL) were higher than 50%, the trophic magnification factors (TMFs) values for those QNs were calculated from three different habitats. The TMFs for those QNs were ranged from 0.840 to 1.10. Thereinto, ENR and NOR were appeared trophic magnification, while FLU and OFL were appeared trophic dilution in the food web of Baiyangdian Lake. Although the TMFs values of QNs were not showed significantly difference among three habitats, the TMFs values of those QNs showed significantly difference between the foodweb with macrophyte species and without macrophyte species. Except FLU, the other TMFs values of these QNs without macrophyte species (in the range of 0.700-1.01) were lower than the TMFs for QNs with macrophyte species. Finally, the results of human health risk for QNs suggested that consumption of fish from Baiyangdian Lake with a considerable risk, thus more standard and residue limits of QNs should be set to decrease the human health risk around this region. CAPSULE ABSTRACT: The spatial variation of bioaccumulation, trophic transfer, and human health risk for 12 QNs has been studied in the benthic foodweb from a macrophyte-dominated shallow lake.

2.
Disaster Med Public Health Prep ; : 1-5, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31939346

RESUMO

OBJECTIVE: We analyzed characteristics of tornado-related injuries and medical impact on a county-level hospital in China in June 23, 2016. The objective of this study was to describe and analyze local government rescue responses following the tornado. METHODS: County hospital medical records of 288 tornado-related injury patients were collected. Descriptive analyses to study injury characteristics and associated risk factors were performed. RESULTS: Of the studied population, 84% of the wounded were older than 45 years. Only 30 (10.4%) people were sent to the hospital for treatment within 3 hours following the disaster. Heavy objects or collapsing houses accounted for 191 (66.3%) of the documented injuries. The proportion of people with resulting brain injuries was 46.2% of the entire injured population, and the incidence of lower extremity injuries was 27.8%. A total of 89.6% of the wounded had skin and soft tissue injuries. Multiple injuries were found in 129 (44.8%) people and 156 had a single injury (54.2%), and 3 cases with acute stress disorder were admitted to the hospital. CONCLUSIONS: Preparation plans, including tornado warnings, prevention, and rescue, are a basic requirement for the mitigation of tornado-related injuries. Protection awareness of tornado disasters is also critical to ensure injury prevention.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31912872

RESUMO

PURPOSE: The aims of this study were to evaluate the effect of age at menarche (AM) on type 2 diabetes mellitus (T2DM) and to assess whether the fasting plasma glucose (FPG) and homeostasis model assessment (HOMA) index responses to AM and menopause status interact in Chinese rural adults. METHODS: A cross-sectional, population-based study including 23138 participants was performed. Logistic regression and multivariable linear regression were performed to investigate the relationship between AM and glucose status. Generalized linear model was utilized to calculate the interaction term of AM and menopause status on FPG and the HOMA index. Interaction plot was used to interpret the significant interaction effect. RESULTS: Women in the later menarche age group (≥ 18 years) had a 17.7% lower risk of T2DM (95% CI: 0.712, 0.951, P =0.008), after adjusting for multiple variables. Further adjustment for BMI completely attenuated this association (OR=0.884, 95% CI: 0.764, 1.024, P =0.099). A significant interaction effect of AM and menopause status on T2DM (P =0.004) was observed. The adverse effects of menopausal status on FPG and HOMA-2 of insulin resistance decreased with increasing menarche age, and the age ranges were limited to <18 and 9-19 years, respectively. CONCLUSIONS: Later menarche was associated with a lower risk of T2DM, and the association appears to be mediated by BMI. More importantly, the adverse effect of menopause status on T2DM was decreased along with increasing menarche age.

4.
J Environ Sci (China) ; 88: 370-384, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862078

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the atmosphere and they mostly stem from the imperfect combustion of fossil fuels and biofuels. PAHs are inherently associated with homogenous fine particles or distributed to different-sized particles during the aging of air masses. PAHs carried by fine particles undergo a long-range transport to remote areas while those adsorbed on coarse particles have a shorter lifetime in ambient air. More importantly, PAHs with higher molecular weights tend to be bound with finer particles and can deeply enter the lungs, posing severe health risks to humans. Thus, the environmental fate and health effects of particulate PAHs are strongly size-dependent. This review summarizes the size distributions of particulate PAHs freshly emitted from combustion sources as well as the distribution patterns of PAHs in ambient particles. It was found that PAHs from stationary sources are primarily bound to fine particles, which are slightly larger than particles to which PAHs from mobile sources are bound. In ambient air, particulate PAHs are distributed in larger size modes than those in the combustion fume, and the particle size decreases with PAH molecular weight increasing. The relevant mechanisms and influencing factors of particle size distribution changes are illustrated in this article, which are essentially attributed to combustion and ambient temperature as well as the physical and chemical properties of PAHs. Overall, the study on the particle size distribution of PAHs will contribute for a full understanding of the origin, atmospheric behaviors and health effects of particulate PAHs.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31872995

RESUMO

Na3V2(PO4)2O2F (NVPOF) is attracting great interest due to its large capacity and high working voltage. However, poor electronic conductivity limits the electrochemical performance of NVPOF. Herein, we fabricate N/P-dual-doped carbon-coated NVPOF microspheres (labeled as NVPOF@P/N/C) via a hydrothermal process followed by heat treatment. This microsphere-structured NVPOF@P/N/C composite has a relatively high tap density of 1.22 g/cm3. TEM and XPS results reveal that the dual-doped carbon layer is tightly coated on the NVPOF surface due to the bridging effect of P and has a good protective effect on NVPOF. Density functional theory (DFT) calculations confirm that a N/P-dual-doped carbon layer is advantageous to achieve higher electronic conductivity and lower migration activation energy than those of the undoped and single N- or P-doped carbon layer. As a cathode material for a sodium-ion battery (SIB), NVPOF@P/N/C exhibits high capacity (128 mAh/g at 0.5 C and 122 mAh/g at 2 C) and ultralong cycle performance (only 0.037% capacity fading rate per cycle in 500 cycles at 2 C). We believe that the NVPOF@P/N/C composite is appealing for high-performance SIBs with large energy density.

6.
Int J Mol Sci ; 20(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817671

RESUMO

Immunity is a defensive response that fights disease by identifying and destroying harmful substances or microbiological toxins. Several factors, including work-related stress, pollution, and immunosuppressive agents, contribute to low immunity and poor health. Native peptides, a new class of immunoregulatory agents, have the potential for treating immunodeficiencies, malignancies, and infections. However, the potential cytotoxicity and low immunoregulatory activity and stability of native peptides have prevented their development. Therefore, we designed three hybrid peptides (LTAa, LTAb, and LTAc) by combining a characteristic fragment of LL-37 with an active Tα1 center that included Tα1 (17-24), Tα1 (20-25), and Tα1 (20-27). The best hybrid peptide (LTAa), according to molecule docking and in vitro experiments, had improved immunoregulatory activity and stability with minimal cytotoxicity. We investigated the immunoregulatory effects and mechanisms of LTAa using a cyclophosphamide-immunosuppressed murine model. LTAa effectively reversed immunosuppression by enhancing immune organ development, activating peritoneal macrophage phagocytosis, regulating T lymphocyte subsets, and increasing cytokine (tumor necrosis factor-alpha, interleukin-6, and interleukin-1ß) and immunoglobulin (IgA, IgG, and IgM) contents. The immunomodulatory effects of LTAa may be associated with binding to the TLR4/MD-2 complex and activation of the NF-κB signaling pathway. Therefore, LTAa could be an effective therapeutic agent for improving immune function.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31834777

RESUMO

Silica encapsulation effectively elevates the resistance of quantum dots (QDs) against water and oxygen. However, QDs-SiO2 composites present low thermal conductivity and strong thermal accumulation, leading to considerable fluorescent quenching of QDs in optoelectronic devices at high power. Here, a sandwich structural QDs-SiO2-BN nanoplate assembly material (QDs-SiO2-BNAs) is developed to reduce the thermal quenching and enhance the stability of QDs in LEDs. The QDs-SiO2-BNAs is fabricated by embedding QDs-SiO2 into the interlayer of layer-by-layer assembled BN nanoplates, and the BN nanoplates are pretreated by SiO2 encapsulation to strengthen the interaction with QDs-SiO2. This assembly structure endows the QDs with fast heat dissipation and double surface protection against air. The medium power QDs-converted LEDs (QD-LEDs) fabricated by directly on-chip packaging of the QDs-SiO2-BNAs gain 44.2 ℃ temperature reduction at 0.5 W in comparison with conventional QD-LEDs. After aging, the resulting QD-LEDs present degradation of only 1.2% under sustained driving for 250 hours. The QD-LEDs also pass the one-week reliability test at 85 ℃ / 85% RH with <±0.01 shift of the color coordinates, demonstrating the profound potential of the QDs-SiO2-BNAs in LED lighting and display applications.

8.
Front Physiol ; 10: 1430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824338

RESUMO

A 10-week feeding trial was conducted to investigate the effects of dietary bile acids (BA) on growth, glucose and lipid metabolism, liver histopathology, and the underlying regulation mechanism on AKT/FOXO1 (forkhead box O1) and cAMP/AMPK/SREBP1 (sterol regulatory element-binding protein 1) pathway in largemouth bass (Micropterus salmoides) fed with a high starch diet. Six experimental diets were prepared with BA levels at 0 (B0), 80 (B80), 160 (B160), 240 (B240), 300 (B300), and 600 (B600) mg/kg in a basal diet with 18.7% starch. Each diet was fed to six replicates with 30 fish (6.17 ± 0.03 g) in each tank. The highest weight gain rate (WGR) was observed in B300 group and the optimal level of BA was estimated at 475 mg/kg by a monistic cubic equation regression analysis. Dietary BA inclusion decreased hepatosomatic index (HSI) and hepatic lipid content significantly. The fish in B300 group clearly showed alleviated hepatic fibrosis, but more steatohepatitis symptoms diagnosed with various histopathological and immunofluorescence analysis. 10 out of 12 samples were observed hepatic fibrosis in B0 group while only two fibrosis samples in B300 group. The promoted liver histopathology by dietary BA was related to improved glucose and lipid metabolism. Dietary BA inhibited the expression of G6Pase by activating AKT and reducing FOXO1 transcription, which improved the regulation ability of gluconeogenesis, activated cAMP/AMPK and repressed SREBP1 transcription to inhibit hepatic lipogenesis, which prevented hepatic lipid accumulation. In conclusion, dietary BA enhanced the growth and alleviated liver fibrosis induced by a high starch diet to steatohepatitis/recovery symptom via improving glucose and lipid metabolism, which regulated by AKT/FOXO1 and cAMP/AMPK/SREBP1 pathway in largemouth bass.

9.
Oxid Med Cell Longev ; 2019: 1253289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885769

RESUMO

The study was aimed at investigating the effects of L-cystathionine on vascular endothelial cell apoptosis and its mechanisms. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. Apoptosis of vascular endothelial cells was induced by homocysteine. Apoptosis, mitochondrial superoxide anion, mitochondrial membrane potential, mitochondrial permeability transition pore (MPTP) opening, and caspase-9 and caspase-3 activities were examined. Expression of Bax, Bcl-2, and cleaved caspase-3 was tested and BTSA1, a Bax agonist, and HUVEC Bax overexpression was used in the study. Results showed that homocysteine obviously induced the apoptosis of HUVECs, and this effect was significantly attenuated by the pretreatment with L-cystathionine. Furthermore, L-cystathionine decreased the production of mitochondrial superoxide anion and the expression of Bax and restrained its translocation to mitochondria, increased mitochondrial membrane potential, inhibited mitochondrial permeability transition pore (MPTP) opening, suppressed the leakage of cytochrome c from mitochondria into the cytoplasm, and downregulated activities of caspase-9 and caspase-3. However, BTSA1, a Bax agonist, or Bax overexpression successfully abolished the inhibitory effect of L-cystathionine on Hcy-induced MPTP opening, caspase-9 and caspase-3 activation, and HUVEC apoptosis. Taken together, our results indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs.

10.
Sci Rep ; 9(1): 20239, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882926

RESUMO

Elucidation of the molecular mechanism related to the dedifferentiation and redifferentiation during tissue culture will be useful for optimizing regeneration system of tea plant. In this study, an integrated sRNAome and transcriptome analyses were carried out during phase changes of the stem explant culture. Among 198 miRNAs and 8001 predicted target genes, 178 differentially expressed miRNAs and 4264 potential targets were screened out from explants, primary calli, as well as regenerated roots and shoots. According to KEGG analysis of the potential targets, pathway of "aminoacyl-tRNA biosynthesis", "proteasome" and "glutathione metabolism" was of great significance during the dedifferentiation, and pathway of "porphyrin and chlorophyll metabolism", "mRNA surveillance pathway", "nucleotide excision repair" was indispensable for redifferentiation of the calli. Expression pattern of 12 miRNAs, including csn-micR390e, csn-miR156b-5p, csn-miR157d-5p, csn-miR156, csn-miR166a-3p, csn-miR166e, csn-miR167d, csn-miR393c-3p, csn-miR394, csn-miR396a-3p, csn-miR396 and csn-miR396e-3p, was validated by qRT-PCR among 57 differentially expressed phase-specific miRNAs. Validation also confirmed that regulatory module of csn-miR167d/ERF3, csn-miR156/SPB1, csn-miR166a-3p/ATHB15, csn-miR396/AIP15A, csn-miR157d-5p/GST and csn-miR393c-3p/ATG18b might play important roles in regulating the phase changes during tissue culture of stem explants.

11.
Nutrients ; 11(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731672

RESUMO

The relationship between dietary protein consumption and the risk of type 2 diabetes (T2D) has been inconsistent. The aim of this meta-analysis was to explore the relations between dietary protein consumption and the risk of T2D. We conducted systematic retrieval of prospective studies in PubMed, Embase, and Web of Science. Summary relative risks were compiled with a fixed effects model or a random effects model, and a restricted cubic spline regression model and generalized least squares analysis were used to evaluate the diet-T2D incidence relationship. T2D risk increased with increasing consumption of total protein and animal protein, red meat, processed meat, milk, and eggs, respectively, while plant protein and yogurt had an inverse relationship. A non-linear association with the risk for T2D was found for the consumption of plant protein, processed meat, milk, yogurt, and soy. This meta-analysis suggests that substitution of plant protein and yogurt for animal protein, especially red meat and processed meat, can reduce the risk for T2D.

12.
Pharmacology ; : 1-12, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694037

RESUMO

Bacterial infections remain the leading cause of death in children, the elderly, and immunocompromised patients. Andrographolide (AG), the main active component of the herb Andrographis paniculata, has been used for many years for anti-inflammatory and antibacterial infections. AG has an antibacterial effect on a wide variety of bacteria, which is reflected in the inhibition of bacterial pathogenic factors and the regulation of immunity to downregulate infectious inflammation caused by bacteria. In the current climate of frequently occurring antibiotic resistance, AG might be considered a promising lead for new antibacterial drug development. This review outlines the therapeutic potential of AG and its analogs in combating various bacterial infections, focusing on the mechanisms of action.

13.
Theranostics ; 9(25): 7648-7665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695792

RESUMO

Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous cell carcinoma (HNSC) is urgently required. Methods: Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed. Results: We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters. Conclusion: This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.

14.
BMC Public Health ; 19(1): 1556, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767001

RESUMO

BACKGROUND: As extremely violent meteorological disasters, tornadoes often cause serious casualties. The study aims to analyze the characteristics and causes of tornado injuries in China under certain humanistic and geographical conditions. METHODS: A random sampling questionnaire survey was developed and distributed to tornado victims from two separate occurrences: an Enhanced Fujita 4 tornado in Yancheng, and a Fujita 3 tornado in Chifeng. The information of demographic characteristics, disaster environment, and individual behaviors in victims was collected. Chi-square test and binary logistic regression were used to analyze influencing factor of injuries. RESULTS: A total of 94 valid questionnaires (participation rate 95.9%) were finally collected in Yancheng tornado and 67 valid questionnaires (participation rate 93.1%) in Chifeng tornado. Residents' annual income (OR = 0.10, 95% CI 0.02-0.50, P = 0.005), degree of house collapse (OR = 183.12, 95% CI 8.04-4173.34, P = 0.001) have a significant impact on the probability of injury. Differences in tornado disaster drill awareness (P = 0.009), individual behaviors (P = 0.011) and fear level (P = 0.011) significantly affected the incidence of trauma. Whether victims were indoors or not has no statistical difference on injuries in China. CONCLUSIONS: Our study clarifies risk factors and is conducive to the expansion of the investigation in tornado casualties. The government should improve the wind-resistance of residential buildings. Victims should participate in disaster prevention drills to take effective disaster avoidance actions.

15.
Environ Toxicol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705742

RESUMO

Sterol is synthesized from cholesterol which is from the hydrolysis of stored cholesteryl esters. The process of maintaining cholesterol homeostasis is regulated by SREBP2-STARD4. Lots of researches demonstrated that male steroidogenesis could be interfered by di-n-butyl phthalate (DBP) or monobutyl phthalate (MBP). However, mechanisms of MBP exposure in this process have not been uncovered clearly. The objectiveof this study was to explore roles of SREBP2 and STARD4 in cholesteryl estersynthesis stimulated by MBP in mouse Leydig tumor cells (MLTC-1). MLTC-1 exposedto 10-8, 10-7, 10-6, 10-5 M MBP showed that levels of cholestery ester were increased significantly at 10-7 M MBP. Besides, cholesteryl ester synthesis stimulated by MBP was down-regulate when STARD4 or SREBP2 were inhibited. Activity of SREBP2 binding to the promoter of STARD4 was increased after MBP exposure. This study suggests that MBP can increase cholesteryl ester synthesis through SREBP2-STARD4 signal pathway in MLTC-1 cells.

16.
Environ Pollut ; : 113458, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31706758

RESUMO

The occurrence, distribution, and ecological risk of 10 quinolones (QNs) were investigated in the water and sediment samples from Baiyangdian Lake, China. The field samplings were conducted in April (dry season) and August (wet season) 2018, the results showed that QNs was extensively distributed in the Baiyangdian Lake. For the occurrence, Flumequine (FLU) and Ofloxacin (OFL) were the most detected QNs in Baiyangdian Lake. For the temporal variation, the sum concentration of QNs in water and sediment were ranged from 153 ng/L to 3093 ng/L and from 40.1 ng/g to 1475 ng/g in April, while ranged from 3.83 ng/L to 769 ng/L and from 20.3 ng/g to 373 ng/g in August. For the spatial variation, all of QNs exhibited significance difference in concentration at different sampling areas. Furthermore, PNEC plays an important role in ecological risk assessment, thus the PNECs of FLU and OFL were derived by assessment factors (AF), species sensitivity distribution (SSD), and AQUATOX model methods. The results showed that: PNECAFs, PNECSSDs, and PNECAQUATOXs were 18.7 µg/L, 196 µg/L, and 128 µg/L for FLU, respectively; and were 0.021 µg/L, 4.40 µg/L, and 3.00 µg/L for OFL, respectively. The PNECs for FLU and OFL derived by three approaches showed the rank of: PNECSSDs > PNECAQUATOXs > PNECAFs; while the risk quotients (RQs) followed the other rank of: RQSSDs < RQAQUATOXs < RQAFs. The results was indicated that the indirect ecological effects plays an important role in the derived PNECs for QNs, without considering the indirect ecological effects in natural ecosystem can lead to under-protective or over-protective PNECs (RQs) for chemicals. Therefore, AQUATOX model can be applied in deriving PNECs during the ecological risk assessment.

18.
Menopause ; 26(11): 1265-1271, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31688573

RESUMO

OBJECTIVE: The aim of the study was to determine if early menarche is associated with an increased risk of type 2 diabetes mellitus (T2DM) in rural Chinese women and to estimate the proportion that can be attributed to adiposity. METHODS: A total of 15,346 postmenopausal women were enrolled in this study. Logistic regression and restricted cubic spline analysis were performed to estimate the relationship between age at menarche and T2DM. Mediation analysis was used to investigate whether the association was mediated by body mass index (BMI). RESULTS: After adjusting for multiple confounders, the early menarche group (≤14 y) had a higher risk of T2DM (odds ratio [OR] = 1.21; 95% CI = 1.06-1.38; P = 0.004) compared with the reference group (16-17 y), whereas the late onset group (≥19 y) had a lower risk of T2DM (OR = 0.78; 95% CI = 0.66-0.92; P = 0.003). BMI partially mediated the association between age at menarche and T2DM, and the proportion of the effect was 28%. CONCLUSIONS: Early menarche increases the risk of T2DM, whereas later menarche decreases the risk. The association seems to be partially mediated by BMI.

19.
J Immunother Cancer ; 7(1): 298, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722750

RESUMO

BACKGROUND: Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). METHODS: The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. RESULTS: High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P < 0.001), disease-free (P = 0.002), and distant metastasis-free survival (P = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. CONCLUSIONS: We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.

20.
Front Plant Sci ; 10: 1148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608091

RESUMO

Optimizing flowering time is crucial for maximizing crop productivity, but gaps remain in the knowledge of the mechanisms underpinning temperate legume flowering. Medicago, like winter annual Arabidopsis, accelerates flowering after exposure to extended cold (vernalization, V) followed by long-day (LD) photoperiods. In Arabidopsis, photoperiodic flowering is triggered through CO, a photoperiodic switch that directly activates the FT gene encoding a mobile florigen and potent activator of flowering. In Arabidopsis, several CYCLING DOF FACTORs (CDFs), including AtCDF1, act redundantly to repress CO and thus FT expression, until their removal in LD by a blue-light-induced F-BOX1/GIGANTEA (FKF1/GI) complex. Medicago possesses a homolog of FT, MtFTa1, which acts as a strong activator of flowering. However, the regulation of MtFTa1 does not appear to involve a CO-like gene. Nevertheless, work in pea suggests that CDFs may still regulate flowering time in temperate legumes. Here, we analyze the function of Medicago MtCDF genes with a focus on MtCDFd1_1 in flowering time and development. MtCDFd1_1 causes strong delays to flowering when overexpressed in Arabidopsis and shows a cyclical diurnal expression in Medicago with peak expression at dawn, consistent with AtCDF genes like AtCDF1. However, MtCDFd1_1 lacks predicted GI or FKF1 binding domains, indicating possible differences in its regulation from AtCDF1. In Arabidopsis, CDFs act in a redundant manner, and the same is likely true of temperate legumes as no flowering time phenotypes were observed when MtCDFd1_1 or other MtCDFs were knocked out in Medicago Tnt1 lines. Nevertheless, overexpression of MtCDFd1_1 in Medicago plants resulted in late flowering relative to wild type in inductive vernalized long-day (VLD) conditions, but not in vernalized short days (VSDs), rendering them day neutral. Expression of MtCO-like genes was not affected in the transgenic lines, but LD-induced genes MtFTa1, MtFTb1, MtFTb2, and MtSOC1a showed reduced expression. Plants carrying both the Mtfta1 mutation and 35S:MtCDFd1_1 flowered no later than the Mtfta1 plants. This indicates that 35S:MtCDFd1_1 likely influences flowering in VLD via repressive effects on MtFTa1 expression. Overall, our study implicates MtCDF genes in photoperiodic regulation in Medicago by working redundantly to repress FT-like genes, particularly MtFTa1, but in a CO-independent manner, indicating differences from the Arabidopsis model.

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