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1.
J Cell Mol Med ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185980

RESUMO

Long-term subjection to shift work increases the risk of cancer. The purpose of the present study was to explore the mechanism by which chronic circadian disruption impairs natural killer (NK) cell immunosurveillance. Mice were subjected to light-dark reverse every 4 days for 12 weeks to disrupt normal circadian rhythm. NK cell development and function were evaluated by flow cytometry. The mRNA and protein levels of period 1 (per1) and per2 were suppressed, while circadian locomotor output cycle kaput (CLOCK) was increased in the shifted mice, indicating successful generation of the circadian rhythm disruption mouse model. Chronic shift-lag promoted NK cell ageing, which is likely due to the reduction in Ly49 family receptor expression in shifted NK. We further studied the effects of circadian rhythm disruption on NK cell function. Chronic shift-lag inhibited NK cell secretion of granular CD107a and interferon gamma. Moreover, chronic shift-lag attenuated the clearance of MHC-I-deficient tumour cells by NK cells in vivo and promoted lung metastasis of B16F10 melanomas. Furthermore, chronic shift-lag reduced NK cell killing function, which may be due to the suppression of Eomes transcription factor expression, which inhibiting the transcription of CD122. In conclusion, our findings suggest that chronic circadian disruption attenuates NK cell cytolytic activity by decreasing the expression of CD122.

2.
Aging (Albany NY) ; 122020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33173017

RESUMO

MicroRNA 155 (miRNA-155) is frequently dysregulated in hepatocellular carcinoma (HCC) and other cancer types. Toll-like receptor 3 (TLR3), a putative miR-155 target, plays a key role in liver pathophysiology, and its downregulation in HCC cells is associated with apoptosis evasion and poor outcomes. Herein, we examined the ability of in situ self-assembled Au-antimiR-155 nanocomplexes (Au-antimiRNA NCs) to activate TLR3 signaling in HCC cells. Gene expression analysis confirmed an inverse relationship between miR-155 and TLR3 expression in HCC samples, and marked upregulation of miR-155 was observed in HCC cells but not in normal L02 hepatocytes. RNA immunoprecipitation confirmed physical interaction between miR-155 and TLR3, while negative regulation of TLR3 expression by miR-155 was demonstrated by luciferase reporter assays. Au-antimiR-155 NCs were self-assembled within HepG2 HCC cells, but not within control L02 cells. They efficiently silenced miR-155, thereby inhibiting proliferation and migration and inducing apoptosis in HepG2 cells. Molecular analyses suggested these effects are secondary to TLR3 signaling mediating NF-κB transcription, caspase-8 activation, and interleukin-1ß (IL-1ß) release. Our results provide a basis for future studies examining the in vivo applicability of this novel Au-antimiRNA NCs delivery system to halt HCC progression by activating pro-apoptotic TLR3 signaling.

3.
PLoS One ; 15(11): e0230035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186364

RESUMO

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

4.
Bioresour Technol ; 318: 124271, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33099099

RESUMO

Hydrothermal pretreatment can efficiently remove the residual antibiotics in oxytetracycline fermentation residue (OFR), but its effect on antibiotic resistance genes (ARGs) during composting remains unclear. This study compared the shifts in bacterial community and evolutions in ARGs and integrons during different composting processes of OFRs with and without hydrothermal pretreatment. The results demonstrated that hydrothermal pretreatment increased the bacterial alpha diversity at the initial phase, and increased the relative abundances of Proteobacteria and Actinobacteria but decreased that of Bacteroidetes at the final phase by inactivating mycelia and removing residual oxytetracycline. Composting process inevitably elevated the abundance and relative abundance of ARGs. However, the increase in ARGs was significantly reduced by hydrothermal pretreatment, because the removal of oxytetracycline decreased their potential host bacteria and inhibited their horizontal gene transfer. The results demonstrated that hydrothermal pretreatment is an efficient strategy to reduce the enrichment of ARGs during the OFR composting.


Assuntos
Compostagem , Oxitetraciclina , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Fermentação , Genes Bacterianos/genética , Esterco
5.
Medicine (Baltimore) ; 99(42): e22719, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080728

RESUMO

BACKGROUND: To compare perioperative outcomes and surgeon physical and mental stress when performing lobectomy through uniportal and multiportal video-assisted thoracoscopic surgery (VATS) on patients with non-small-cell lung cancer (NSCLC). METHODS: Patients aged 41 to 73 years with resectable NSCLC were randomly assigned via a computer-generated randomisation sequence to receive either uniportal VATS (UVATS) or multiportal VATS (MVATS) lobectomy and lymphadenectomy between December 2015 and October 2016. Overall, we randomly assigned 35 patients to the UVATS and 34 to the MVATS group. Patients and the investigators undertaking interventions, assessing short-term outcomes, performing ergonomic evaluations, and analyzing data were not masked to group assignment. RESULTS: Patient demographics of the 2 groups were comparable. The ergonomic evaluation considered eye blink rate and the NASA Task Load Index (NASA-TLX), better results were observed in UVATS than in MVATS. The operative time, number of lymph nodes harvested, chest tube duration, length of hospital stay, and lung function were not significantly different between the groups. Compared with MVATS lobectomy, UVATS lobectomy was associated with less intraoperative blood loss and less volume of total drainage in the 24 hours. No conversion, no reoperation, and no in-hospital mortality occurred in either group. CONCLUSIONS: UVATS lobectomy is a safe and programmable technique with some better perioperative outcomes and ergonomic results than MVATS. Further studies based on large numbers of patients and with long-term follow-up are required to confirm its benefits towards patients. TRIAL REGISTRATION: ClinicalTrials.gov ID:NCT02462356. Registered May 27, 2015.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/instrumentação , Cirurgia Torácica Vídeoassistida/instrumentação , Adulto , Idoso , Ergonomia , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
6.
Int J Nanomedicine ; 15: 7967-7977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116512

RESUMO

Background: Current drugs used for osteoporosis therapy show strong adverse effects. Stem cell-derived extracellular vesicles (EVs) provide another choice for osteoporosis therapy. Mouse mesenchymal stem cells (mMSCs)-derived EVs promote bone regeneration; however, their clinical application is limited due to non-specific tissue targeting. Alendronate specifically targets bone tissue via hydroxyapatite. Therefore, EVs were combined with alendronate to generate Ale-EVs by "click chemistry" to facilitate EVs targeting bone via alendronate/hydroxyapatite binding. Methods: Ale-EVs were characterized based on size using dynamic light scattering analysis and morphology was visualized by transmission electron microscopy. Hydroxyapatite affinity of Ale-EVs was detected by flow cytometry. Bone targeting of Ale-EVs was tested by ex vivo fluorescent imaging. Cell viability was assessed by using WST-8 reduction assay kit for testing the ability of Ale-EVs to promote mMSCs proliferation. Alkaline phosphatase experiment was used to detect ability of Ale-EVs to promote differentiation of mouse mesenchymal stem cells in vitro. Western blotting and Q-PCR assay were used to detect the early marker of osteogenic differentiation. Antiosteoporotic effects of Ale-EVs were detected in ovariectomy (OVX)-induced osteoporosis rat model. The safety of the Ale-EVs in vivo was measured by H&E staining and serum markers assay. Results: In vitro, Ale-EVs had high affinity with hydroxyapatite. Also, ex vivo data indicated that Ale-EVs-DiD treatment of mice induced strong fluorescece in bone tissues compared with EVs-DiD group. Furthermore, results suggested that Ale-EVs promoted the growth and differentiation of mouse MSCs. They also protected against osteoporosis in ovariectomy (OVX)-induced osteoporotic rats. Ale-EVs were well tolerated and no side effects were found, indicating that Ale-EVs specifically target bone and can be used as a new therapeutic in osteoporosis treatment. Conclusion: We used the Ale-N3 to modify mouse mesenchymal stem cells-derived extracellular vesicles by copper-free "click chemistry" to generate a Ale-EVs system. The Ale-EVs had a high affinity for bone and have great potential for clinical applications in osteoporosis therapy with low systemic toxicity.


Assuntos
Osso e Ossos/patologia , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoporose/patologia , Osteoporose/terapia , Animais , Regeneração Óssea , Diferenciação Celular , Sobrevivência Celular , Feminino , Humanos , Camundongos , Osteogênese , Osteoporose/fisiopatologia , Ratos
7.
Curr Drug Targets ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050859

RESUMO

Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition to these applications, it is increasingly becoming clear that the drug also has great potential in the field of cancer. Here, we briefly review current insights of aspirin's anti-tumor effects. These are multiple and vary from inhibiting the major cellular mTOR pathways, acting as a calorie-restricted mimetic by inhibition of energy production, suppressing platelet aggregation and granule release, inhibiting immune escape of tumor cells, to decreasing inflammatory responses. We consider these five mechanisms of action the most significant of aspirin's anti-tumor effects, whereby the anti-tumor effect may ultimately stem from its inhibition of energy metabolism, platelet function, and inflammatory response. As such, aspirin can play an important role to reduce the occurrence, proliferation, and metastasis of various types of tumors. However, most of the collected data are still based on epidemiological investi-gations. More direct and effective evidence is needed, and the side effects of aspirin intake need to be solved before this drug can be widely applied in cancer treatment.

8.
Thorac Cancer ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058505

RESUMO

BACKGROUND: In this study, we investigated the prognostic significance of a micropapillary (MP) component in patients with subcentimeter lung adenocarcinoma. METHODS: A total of 311 patients with subcentimeter lung adenocarcinoma who underwent surgical resection between January 2009 to December 2012 from seven medical centers were included. Recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: The five-year RFS was 79.8% in 97 (97/311, 31%) cases of adenocarcinoma with a MP component and 93.5% in the 214 (214/311, 69%) cases without. In multivariate analysis, MP was an independent risk factor for worse RFS (hazard ratio [HR], 3.73; 95% confidence interval [CI]: 1.87-7.42; P < 0.001) and OS (HR, 5.84; 95% CI: 2.20-15.49; P < 0.001). There was no significant difference among wedge resection, segmentectomy and lobectomy on RFS (P = 0.256) and OS (P = 0.103) in patients without MP. Regarding patients with a MP component, lobectomy achieved equivalent prognosis than segmentectomy, and both were better than wedge resection (P = 0.001). CONCLUSIONS: A MP component still suggest a poor prognosis in subcentimeter lung adenocarcinoma. Patients with subcentimeter lung adenocarcinoma with a MP component of 5% or greater treated with wedge resection were at higher risk of recurrence than patients treated with anatomical resection.

9.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120314965, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33115273

RESUMO

OBJECTIVE: Lp(a) (lipoprotein[a]) is an independent risk factor for cardiovascular diseases and plasma levels are primarily determined by variation at the LPA locus. We performed a genome-wide association study in the UK Biobank to determine whether additional loci influence Lp(a) levels. Approach and Results: We included 293 274 White British individuals in the discovery analysis. Approximately 93 095 623 variants were tested for association with natural log-transformed Lp(a) levels using linear regression models adjusted for age, sex, genotype batch, and 20 principal components of genetic ancestry. After quality control, 131 independent variants were associated at genome-wide significance (P≤5×10-8). In addition to validating previous associations at LPA, APOE, and CETP, we identified a novel variant at the APOH locus, encoding ß2GPI (beta2-glycoprotein I). The APOH variant rs8178824 was associated with increased Lp(a) levels (ß [95% CI] [ln nmol/L], 0.064 [0.047-0.081]; P=2.8×10-13) and demonstrated a stronger effect after adjustment for variation at the LPA locus (ß [95% CI] [ln nmol/L], 0.089 [0.076-0.10]; P=3.8×10-42). This association was replicated in a meta-analysis of 5465 European-ancestry individuals from the Framingham Offspring Study and Multi-Ethnic Study of Atherosclerosis (ß [95% CI] [ln mg/dL], 0.16 [0.044-0.28]; P=0.0071). CONCLUSIONS: In a large-scale genome-wide association study of Lp(a) levels, we identified APOH as a novel locus for Lp(a) in individuals of European ancestry. Additional studies are needed to determine the precise role of ß2GPI in influencing Lp(a) levels as well as its potential as a therapeutic target.

10.
ACS Nano ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074660

RESUMO

Preparing transition-metal oxides in their two-dimensional (2D) form is the key to exploring their unrevealed low-dimensional properties, such as the p-type transparent superconductivity, topological Mott insulator state, existence of the condensed 2D electron/hole gas, and strain-tunable catalysis. However, existing approaches suffer from the specific constraint techniques and precursors that limit their product types. Here, we report a solution-based method to directly synthesize KNbO2 in 2D by an out-of-the-pot growth process at low temperature, which is observed directly in real time. The developed method can also be applied to other 2D ternary oxide syntheses, including CsNbO2 and composited NaxK1-xNbO2, and it can be extended to the preparation of self-assembled nanofilms. In addition, We demonstrate the emission of broadband photoluminescence (PL, λ ∼ 350-800 nm) from as-synthesized single-crystal 2D KNbO2 sheets down to a single unit cell thickness. The ultra-broadband emission is ascribed to the self-trapped excitation state (STEs) from the in-phase distortion of the NbO6 octahedrons in 2D NbO2- layers. Beyond the broader luminescent range and the robust material thermal stability of niobates, the absence of sample size restrictions and the large aspect ratio of the 2D oxide sheets will provide opportunities in miniaturizing and advancing 2D-materials integrated optoelectronic devices.

11.
Commun Biol ; 3(1): 612, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097765

RESUMO

Myostatin (MSTN), associated with the "double muscling" phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

12.
Aquat Toxicol ; 229: 105579, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33075615

RESUMO

Effective phytoremediation by aquatic plant such as duckweed could be applied to solve Cd pollution. In the present study, the impact of Graphene oxide (GO) on the accumulation of Cd in duckweed has been studied. The response of duckweed was also investigated, concluding growth, Cd2+ flux, and gene expression response. Results showed that GO promoted the accumulation of Cd in duckweed. After 6 h of Cd enrichment in duckweed, Cd content was about 1.4 times that of the control group at fronds and 1.25 times that of the control group at roots, meanwhile, Cd content in the water system was 0.67 times that of the control group. The Cd2+ influx increased significantly. 4471 genes were up-regulated and 3230 genes were down-regulated significantly as duckweed treated with GO under Cd treatment. Moreover, phagosome pathway was downregulated, some key proteins: Stx7, Rab7 and Tubastatin B (TUBB) were significantly downregulated with GO addition under Cd stress. Scanning electron microscope (SEM) observation showed that GO and Cd were attached on the cell surface of duckweed as white crystal. GO could be applied in phytoremediation by duckweed of Cd in aquatic system.

13.
Inorg Chem ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32929971

RESUMO

We synthesized and characterized three types of isostructural iodoargentates, [TM(phen)3]Ag2I4·3DMF (TM = Co (1), Ni (2), Zn (3)), [TM(phen)3]Ag3I5·DMF (TM = Co (4), Ni (5), Zn (6)), and [TM(phen)3]2Ag8I12·7DMF (TM = Co (7), Ni (8), Zn (9)) (phen = 1,10-phenanthroline, DMF = dimethylformamide) using transition-metal (TM) complexes as the structure-directing agents. Compounds 1-3 and compounds 4-6 feature zero-dimensional anionic [Ag4I8]4- and [Ag6I10]4- clusters, respectively. All of the [TM(phen)3]2+ cations in compounds 1-6 are arranged into a two-dimensional (2D) (6,3) net layer. Interestingly, compounds 1-3 are kinetically unstable in the mother solution, and they can be converted to compounds 4-6 via irreversible single-crystal to single-crystal transformation processes, respectively, with distinct changes in the crystal morphology and structure. Compounds 7-9 feature one-dimensional (1D) zigzag chains constructed from [Ag8I12]4- units. The UV-vis diffuse reflectance measurements demonstrate that compounds 1-9 possess the characteristics of semiconductors with band gaps of 2.58-2.71 eV and visible-light-irradiation-induced photocatalytic activities. Especially, compound 3 possesses higher photocatalytic degradation activity toward crystal violet (CV) and rhodamine B (RhB) in comparison to P25 under identical conditions. Moreover, the mechanism study reveals that the TM complex cations make a great contribution to the photocatalytic activity.

14.
Dig Dis Sci ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920660

RESUMO

BACKGROUND: Long non-coding RNAs have been acknowledged as the crucial regulators in the progression of human cancers, including gastric cancer (GC). Small nucleolar RNA host gene 10 (SNHG10) has been identified as an oncogene in several cancer types. Nonetheless, it is unclear whether SNHG10 exerts functions in GC cells. AIMS: The aims of the current study were to explore the function and underlying mechanism of SNHG10 in GC. METHODS: The expression levels of SNHG10, miR-495-3p and catenin beta 1 (CTNNB1) were detected by RT-qPCR. Loss-of-function assays, including CCK-8, colony formation assay, flow cytometry analysis and transwell assays, were conducted to verify the effect of SHNG10 on the proliferation, apoptosis, migration and invasion of GC cells. Mechanism experiments were performed to identify the downstream molecular mechanism of SNHG10. RESULTS: SNHG10 was expressed at a high level in GC cells. Knockdown of SNHG10 inhibited the proliferation, migration and invasion of GC cells. Silencing of SNHG10 led to the downregulation of core factors of WNT signaling pathway. Knockdown of SNHG10 could decline the expression of CTNNB1 through sequestering miR-495-3p. CONCLUSIONS: SNHG10 promotes the procession of GC through targeting miR-495-3p/CTNNB1 and activating WNT signaling pathway.

15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(8): 1018-1019, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32912422

RESUMO

Ampoule bottle is a small glass container for liquid medicine, with a capacity of 1-20 mL. It is often used to contain all kinds of liquid medicine for injection, vaccines, etc. Medical ampoules are related to all aspects of clinical work. In the process of operation, the opened ampoule bottle is often placed directly on the operating table. There are many shortcomings and deficiencies, for example, ampoules are easily to be overturned, causing environmental pollution, residual drug pollution, medical personnel exposure damage from their sharp ends, etc. For this reason, the medical staff from Northern Jiangsu People's Hospital designed a return box for ampoule bottle placement and obained a national utility model patent. The utility model has the advantages of being simple structured, convenient, safe and clean in the use process. The box can separate the opened ampoule bottles, reduce the waste of liquid medicine and drug pollution, effectively protect the ampoule bottle and avoid the injury of the medical staff. This new device is worth popularizing in clinical work.


Assuntos
Embalagem de Medicamentos , Vidro , Humanos , Injeções
16.
Diabetes Res Clin Pract ; 168: 108373, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827591

RESUMO

AIMS: To explore the associations between the microvascular/microstructural changes in the retina measured by optical coherence tomography angiography (OCTA) and renal function in type 2 diabetes patients with early chronic kidney disease (CKD). METHODS: This cross-sectional study, including 150 type 2 diabetes patients, was conducted from July 2017 to January 2019. We obtained retinal vessel density (VD) and retinal thickness using OCTA. The correlations between OCTA-derived parameters and CKD-related systemic data were assessed by multiple regression analyses. RESULTS: We found a significant decrease of VD in patients with CKD. Multiple regression analyses showed that: a) decreased eGFR (estimated glomerular filtration rate) was significantly correlated with decreased VD of superficial vascular complex (SVC) in macular area; b) increased UACR (urine albumin to creatinine ratio) was significantly associated with increased macular thickness; c) decreased HGB/HCT (Hemoglobin or Hematocrit) was significantly correlated with both decreased VD of SVC and increased retinal thickness in macular area. CONCLUSIONS: Decrease in the microcirculation of the retina and thickening of the macula associated with impaired renal function in type 2 diabetes. Our finding encourages the application of OCTA-derived metrics in diabetic eyes to monitor the progression of CKD.

17.
Circ Genom Precis Med ; 13(5): 387-395, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822252

RESUMO

BACKGROUND: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. METHODS: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. RESULTS: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. CONCLUSIONS: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

18.
J Biomech ; 110: 109938, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32827792

RESUMO

Root resorption is closely related to orthodontic force and affects orthodontic treatment with high incidence; however, the mechanism governing this effect is unclear. Microcracks are associated with bone resorption and may also play an important role in root resorption. This study aimed to assess the occurrence of microcracks on the root surface induced by orthodontic force, analyze the association between force and microcrack development, and propose potential measures to reduce microcracks. Different loads (0.5, 1, or 2 N) were applied between the left first molar and anterior teeth for different durations (1, 3, 7, or 14 days) in a rabbit model. The first molar was dissected and its surface was examined using scanning electron microscopy (SEM), which revealed the presence of microcracks on the compressed side of the root apices. The number, width, and length of microcracks were all positively correlated with the load magnitude and duration. The breaking strength of the root apex was tested by using a digital force tester. In addition, a finite element (FE) model was used to analyze the stress at the root apices and the crack propagation on the root surfaces. FE analysis calculated that the regions of maximum stress at the root apices were consistent with the microcrack regions observed via SEM. These results imply that orthodontic force can directly induce the occurrence and development of microcrack, and may contribute to further root resorption. Therefore, an appropriate interval and direction of orthodontic force may help reduce microcracks and prevent root resorption.

19.
Ann Palliat Med ; 9(5): 2970-2981, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787358

RESUMO

BACKGROUND: Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. METHODS: A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. RESULTS: We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. CONCLUSIONS: Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.

20.
Chemosphere ; 261: 127821, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32750621

RESUMO

Alkaline-thermal (AT) pretreatment is an economical and efficient pretreatment method to improve anaerobic biodegradability of biowaste. This study investigated the effect of AT pretreatment of spectinomycin mycelial residues (SMRs) for promoting anaerobic biodegradability along with the reduction of antibiotic resistance genes (ARGs), and thus obtained the optimal conditions of AT pretreatment. Biomethane potential (BMP) test was conducted to evaluate the anaerobic biodegradability of untreated and pretreated SMRs, and the fate of ARGs was tracked by quantitative polymerase chain reaction. Results showed that the modified Gompertz model fitted the results of BMP tests satisfactorily. Furthermore, AT pretreatment promoted BMP (B0) and reduced lag phase (λ) effectively. These were attributed to the solubilization of SMRs. The analyses of the changes in dissolved organic matter indicated that AT pretreatment could facilitate the solubilization of both biodegradable (e.g. protein) and recalcitrant matter (e.g. humic-like, analyzing by EEMs-PARAFAC), which had a significant corresponding positive (Person correlation, p < 0.01) and negative (Partial correlation, p < 0.01) influences on anaerobic biodegradability. However, the positive effects surpassed the negative effects, promoting the overall anaerobic biodegradability of SMRs. In addition, a considerable reduction of ARGs (by 0.62-1.36 log units) was observed at pH ≥ 12, attributed to the hydrolysis of phosphodiester bond of DNA in strong alkaline solution. Considering both anaerobic biodegradability and ARGs, the optimal AT condition was concluded as pH 12, temperature 90 °C and time 120 min.


Assuntos
Biodegradação Ambiental , Resistência Microbiana a Medicamentos/genética , Espectinomicina/química , Anaerobiose , Antibacterianos , Hidrólise , Metano , Esgotos , Temperatura
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