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1.
J Hazard Mater ; 401: 123302, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32653782

RESUMO

In this study, reaction molecular dynamics were combined with experiments to gain in-depth understanding of the gaseous pyrolysis products generation mechanism and optimal paths during natural rubber (NR), styrene-butadiene rubber (SBR) and mixed rubbers (NR-SBR) for effective recovery of waste rubber. The results show that the pyrolysis temperature of NR increases gradually with SBR addition. The monomers produced during the initial stage of SBR pyrolysis are mainly 1,3-butadiene and styrene, in which the energy barriers of the formed H and CH2=CH in styrene are higher than those in 1,3-butadiene, and during further pyrolysis the main gas products are H2 and CH4. During co-pyrolysis of NR-SBR, the reaction paths show that increasing H2 yield and decreasing CH4 yield take place easily as SBR content rises. By contrast to pyrolysis of NR, the path of generating CH2=CH in SBR is more difficult while that of CH2=CH abstracting H occurred easily, leading to first enhancement in produced CH2=CH2 followed by a decline. Fixed bed experiments and gas chromatography (GC) analysis identify the main gas products of the three rubbers (NR, SBR, NR-SBR)as H2, CH4 and CH2=CH2 and the change of yield caused by the increase of SBR content are consistent with the simulation results.

2.
Talanta ; 221: 121453, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076076

RESUMO

Glycoalkaloids (GAs) are toxic secondary metabolites in potatoes, which are harmful to human body. The storage time has a great influence on the biosynthesis and distribution of GAs. In present study, an imaging mass microscope (iMScope) was used to investigate the distribution and changes of GAs in potato tubers under different storage time (0, 10, 15, 20, 30, 40 and 60 days). We established a growth model with logistic equation to evaluate the growth trends of four major GAs in sprout, periderm and medulla. The results showed that the growth rate and relative contents of four GAs in sprout and periderm were significantly higher than that in medulla. In addition, four GAs also presented different change trends. For dehydrosolanine and α-solanine, rapid growth period of these two GAs in sprout (about at the day 23, similar to these in medulla) was later than which period in periderm (about at the day 17), while rapid growth of dehydrochaconine and α-chaconine appeared at almost the same time (about at the day 20). Based on the biosynthesis and metabolism of GAs, we have made possible explanations for these results. This study is useful for comprehending the metabolism of GAs in different parts and monitoring food safety in potatoes.

3.
Talanta ; 221: 121606, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076136

RESUMO

Due to favourable efficiency and low cost, dual-response fluorescent probes play critical roles in the development of fluorescence assay system. Herein, a novel dual-response fluorescent probe (RDCN) was designed and synthesized for the detection of two environmental contaminants: hydrazine (N2H4) and cyanide (CN-). Probe RDCN exhibited discriminative sensing behaviors to N2H4 and CN- with different reaction mechanisms, allowing the high selectivity and sensitivity detection for N2H4 and CN-. The probe itself displayed red-emitting fluorescence as a result of strong intramolecular charge transfer (ICT) between diethylamino and dicyano. After mixing with hydrazine, a new corresponding hydrazone came into being with an intense yellow fluorescence. While, the probe could also largely switch to blue fluorescence in response to CN-. Furthermore, the probe RDCN was successfully employed to determine N2H4 and CN- in water samples with the detection limits of 0.08 µM and 0.33 µM, and to visualize N2H4 and CN- in live cells by means of different fluorescence channels (blue and yellow channels), revealing that probe RDCN has potential applications for discriminative detection N2H4 and CN- in biological environment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33006934

RESUMO

With the development of medical artificial intelligence, automatic magnetic resonance image (MRI) segmentation method is quite desirable. Inspired by the power of deep neural networks, a novel deep adversarial network, dilated block adversarial network (DBAN), is proposed to perform left ventricle, right ventricle and myocardium segmentation in short-axis cardiac MRI. DBAN contains a segmentor along with a discriminator. In the segmentor, the dilated block (DB) is proposed to capture and aggregate multi-scale features. The segmentor can produce segmentation probability maps while the discriminator can differentiate the segmentation probability map and the ground truth at the pixel level. In addition, confidence probability maps generated by the discriminator can guide the segmentor to modify segmentation probability maps. Extensive experiments demonstrate that DBAN has achieved the state-of-the-art performance on the ACDC dataset. Quantitative analyses indicate that cardiac function indices from DBAN are similar to those from clinical experts. Therefore, DBAN can be a potential candidate for short-axis cardiac MRI segmentation in clinical applications.

5.
Environ Res ; : 110331, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068576

RESUMO

The excess organic carbon is often added to meet denitrification requirements during municipal wastewater treatment, resulting in the carbon waste and increased risk of secondary pollution. In this study, microbial fuel cell (MFC) was coupled with an up-flow denitrification biofilter (BF), and the long-term performances of denitrification and power output were investigated under the different carbon source concentration. With sodium acetate (NaAc) of 600 mg/L and 300 mg/L, the favorable denitrification efficiencies were obtained (98.60%) and the stable current output was maintained (0.44 mA∼0.48 mA). By supplying NaAc of 150 mg/L, the high denitrification efficiency remained in a high range (89.31%) and the current output maintained at 0.12 mA, while, the denitrification efficiency dropped to 71.34% without coupling MFC. Electron balance analysis indicated that both nitrate removal and electron recovery efficiencies were higher in MFC-BF than that in BF, verifying the improved denitrification and carbon utilization performance. Coupling MFC significantly altered the bacterial community structure and composition, and while, the diversified abundance and distribution of bacterial genera were observed at the different locations. Compared with BF, the more exoelectrogenic genera (Desulfobacterium, Trichococcus) and genera holding both denitrifying and electrogenic functions (Dechloromonas, Geobacter) were found dominated in MFC-BF. Instead, the dominating genera in BF were Dechloromonas, Desulfomicrobium, Acidovorax and etc. By coupling MFC, the more complex and diversified network and the closer interaction relationships between the dominant potential functional genera were found. The study provides a feasible approach to effectively improve the denitrification efficiency and organic carbon recovery for deep denitrification process.

6.
Zool Res ; : 1-7, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058573

RESUMO

The restocking of the endangered Kanglang white minnow ( Anabarilius grahami) in Lake Fuxian, China, has been conducted for 13 years. However, few studies have reported on the effectiveness of the captive breeding and release of this species. Here, we investigated variations in morphology, including body shape and skeletal deformities, and genetic features among hatchery-born and recaptured A. grahami from Lake Fuxian. Results showed that current hatchery-reared fish displayed a stubbier body shape than their wild conspecifics from the 1980s. Furthermore, high skeletal deformity ratios were found in two aquafarms (Luchong, 50%; Haikou, 45.2%), and the release of malformed fish elevated the skeletal deformity rate of wild stocks found near the Lake Fuxian release sites (west coast, 19.0%; east coast, 12.5%). Based on variations in the cytochrome b (cyt b) gene, existing A. grahami populations showed relatively high haplotype diversity and low nucleotide diversity. Hatchery populations exhibited reduced genetic variations based on microsatellite markers and reintroduction led to markedly lower genetic diversity around the west coast release sites of Lake Fuxian. Analysis of molecular variance (AMOVA) of cyt b and microsatellite analysis showed that the greatest genetic variations were found within populations, and genetic distance and Bayesian clustering analysis showed that the 14 populations clustered into one group. Based on morphological and genetic tests, we discuss corresponding recommendations, including release size, feed formulations, breeding strategies, and release tags, to minimize potential risks and improve hatchery practices for better restocking of this species.

7.
J Dermatol Sci ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33059972

RESUMO

BACKGROUND: Radiation-induced skin injury is one of the main adverse effects and a dose-limiting factor of radiotherapy without feasible treatment. The underlying mechanism of this disease is still limited. OBJECTIVE: To investigate the potential molecular pathways and mechanisms of radiation-induced skin injury. METHODS: mRNA expression profiles were determined by Affymetrix Human HTA2.0 microarray.IFI6 overexpression and knockdown were mediated by lentivirus. The functional changes of skin cells were measured by flow cytometry, ROS probe and Edu probe. Protein distribution was detected by immunofluorescence experiment, and IFI6-interacting proteins were detected by immunoprecipitation (IP) combined with mass spectrometry. The global gene changes in IFI6-overexpressed skin cells after irradiation were detected by RNA-seq. RESULTS: mRNA expression profiling showed 50 upregulated and 13 down regulated genes and interferon alpha inducible protein 6 (IFI6) was top upregulated. Overexpression of IFI6 promoted cell proliferation and reduced cell apoptosis as well as ROS production following radiation, and conversely, increased the radiosensitivity of HaCaT and human skin fibroblast (WS1). IFI6 was translocated into nucleus in irradiated skin cells and the interacting relationship with mitochondrial single-stranded DNA-binding protein 1 (SSBP1), which could enhance the transcriptional activity of heat shock transcription factor 1 (HSF1).IFI6 augmented HSF1 activity following radiation in HaCaT and WS1 cells. RNA-seq analysis showed IFI6 modulated virus infection and cellular response to stress pathways, which may help to further explore how IFI6 regulate the transcriptional activity of HSF1. CONCLUSION: This study reveals that IFI6 is induced by ionizing radiation and confers radioprotection in skin cells.

8.
Cancer Res Treat ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017884

RESUMO

Purpose: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. Material and Methods: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. Results: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. Conclusion: CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

9.
CMAJ ; 192(40): E1138-E1145, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020121

RESUMO

BACKGROUND: Guideline recommendations may be affected by flaws in the process, inappropriate panel member selection or conduct, conflicts of interest and other factors. To our knowledge, no validated tool exists to evaluate guideline development from the perspective of those directly involved in the process. Our objective was to develop and validate a universal tool, the PANELVIEW instrument, to assess guideline processes, methods and outcomes from the perspective of the participating guideline panellists and group members. METHODS: We performed a systematic literature search and surveys of guideline groups (identified through contacting international organizations and convenience sampling of working panels) to inform item generation. Subsequent groups of guideline methodologists and panellists reviewed items for face validity and missing items. We used surveys, interviews and expert review for item reduction and phrasing. For reliability assessment and feedback, we tested the PANELVIEW tool in 8 international guideline groups. RESULTS: We surveyed 62 members from 13 guideline panels, contacted 19 organizations and reviewed 20 source documents to generate items. Fifty-three additional key informants provided feedback about phrasing of the items and response options. We reduced the number of items from 95 to 34 across domains that included administration, training, conflict of interest, group dynamics, chairing, evidence synthesis, formulating recommendations and publication. The tool takes about 10 minutes to complete and showed acceptable measurement properties. INTERPRETATION: The PANELVIEW instrument fills a gap by enabling guideline organizations to involve clinicians, patients and other participants in evaluating their guideline processes. The tool can inform quality improvement of existing or new guideline programs, focusing on insight into and transparency of the guideline development process, methods and outcomes.

10.
Blood Adv ; 4(19): 4693-4738, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33007077

RESUMO

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in ∼1 to 2 individuals per 1000 each year, corresponding to ∼300 000 to 600 000 events in the United States annually. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events. CONCLUSIONS: Strong recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range of 2.0 to 3.0 over a lower INR range for patients with VTE who use a vitamin K antagonist (VKA) for secondary prevention, and use of indefinite anticoagulation for patients with recurrent unprovoked VTE. Conditional recommendations include the preference for home treatment over hospital-based treatment for uncomplicated DVT and PE at low risk for complications and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.

11.
Aging (Albany NY) ; 122020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33099273

RESUMO

Foxg1 plays important roles in regeneration of hair cell (HC) in the cochlea of neonatal mouse. Here, we used Sox9-CreER to knock down Foxg1 in supporting cells (SCs) in the utricle in order to investigate the role of Foxg1 in HC regeneration in the utricle. We found Sox9 an ideal marker of utricle SCs and bred Sox9CreER/+Foxg1loxp/loxp mice to conditionally knock down Foxg1 in utricular SCs. Conditional knockdown (cKD) of Foxg1 in SCs at postnatal day one (P01) led to increased number of HCs at P08. These regenerated HCs had normal characteristics, and could survive to at least P30. Lineage tracing showed that a significant portion of newly regenerated HCs originated from SCs in Foxg1 cKD mice compared to the mice subjected to the same treatment, which suggested SCs trans-differentiate into HCs in the Foxg1 cKD mouse utricle. After neomycin treatment in vitro, more HCs were observed in Foxg1 cKD mice utricle compared to the control group. Together, these results suggest that Foxg1 cKD in utricular SCs may promote HC regeneration by inducing trans-differentiation of SCs. This research therefore provides theoretical basis for the effects of Foxg1 in trans-differentiation of SCs and regeneration of HCs in the mouse utricle.

12.
Org Biomol Chem ; 18(40): 8179-8185, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33026031

RESUMO

A practical visible-light-induced aerobic oxidative dehydrogenative coupling reaction of glycine derivatives with olefins has been developed to efficiently synthesize quinoline-2-carboxylates. This metal-free process proceeds smoothly under mild conditions and exhibits good tolerance of functional groups. Given the low cost of the catalyst and feedstock materials, the mild reaction conditions and the absence of hazardous byproducts, this protocol should find broad applications in the synthesis of quinoline-2-carboxylate derivatives.

13.
Front Immunol ; 11: 579043, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072123

RESUMO

Autoimmune diseases are conditions that emerge from abnormal immune responses to natural parts of the body. Extracellular vesicles (EVs) are membranous structures found in almost all types of cells. Because EVs often transport "cargo" between cells, their ability to crosstalk may be an important communication pathway within the body. The pathophysiological role of EVs is increasingly recognized in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Type 1 diabetes, and autoimmune thyroid disease. EVs are considered as biomarkers of these diseases. This article outlines existing knowledge on the biogenesis of EVs, their role as messegers in cellular communication and the function in T/B cell differentiation and maturation, and focusing on their potential application in autoimmune diseases.

14.
IET Syst Biol ; 14(5): 297-306, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33095751

RESUMO

Extensive experimental evidence has been demonstrated that the dynamics of CDK1-APC feedback loop play crucial roles in regulating cell cycle processes, but the dynamical mechanisms underlying the regulation of this loop are still not completely understood. Here, the authors systematically investigated the stability and bifurcation criteria for a delayed CDK1-APC feedback loop. They showed that the maximum reaction rate of CDK1 inactivation by APC can drive sustained oscillations of CDK1 activity ([inline-formula removed]) and APC activity ([inline-formula removed]), and the amplitude of these oscillations is increasing with the increase of the reaction rate over a wide range; a certain range of the self-activation rate for CDK1 is also significant for generating these oscillations, for too high or too low rates the oscillations cannot be generated. Moreover, they derived the sufficient conditions to determine the stability and Hopf bifurcations, and found that the sum of time delays required for activating CDK1 and APC can induce [inline-formula removed] and [inline-formula removed] to be oscillatory, even when the [inline-formula removed] and [inline-formula removed] settle in a definite stable steady state. Furthermore, they presented an explicit algorithm for the properties of periodic oscillations. Finally, numerical simulations have been presented to justify the validity of theoretical analysis.

15.
Cell Death Dis ; 11(10): 913, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33099575

RESUMO

Atg7 is an indispensable factor that plays a role in canonical nonselective autophagy. Here we show that genetic ablation of Atg7 in outer hair cells (OHCs) in mice caused stereocilium damage, somatic electromotility disturbances, and presynaptic ribbon degeneration over time, which led to the gradual wholesale loss of OHCs and subsequent early-onset profound hearing loss. Impaired autophagy disrupted OHC mitochondrial function and triggered the accumulation of dysfunctional mitochondria that would otherwise be eliminated in a timely manner. Atg7-independent autophagy/mitophagy processes could not compensate for Atg7 deficiency and failed to rescue the terminally differentiated, non-proliferating OHCs. Our results show that OHCs orchestrate intricate nonselective and selective autophagic/mitophagy pathways working in concert to maintain cellular homeostasis. Overall, our results demonstrate that Atg7-dependent autophagy plays a pivotal cytoprotective role in preserving OHCs and maintaining hearing function.

16.
Ann Thorac Surg ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33096070

RESUMO

BACKGROUND: The clinical predictors of distal aortic remodeling (DAR) after various procedures for extensive acute aortic dissection are not fully understood. METHODS: From 2008 to 2018, a total of 122 candidates with extensive acute type A and B aortic dissections survived operations of total arch replacement + frozen elephant trunk (n=36), ascending aortic replacement + supra-aortic debranching + retrograde stenting (hybrid procedure, n=25) and total endovascular repair (n=61). DAR was assessed at four thoracoabdominal aortic levels, based on true lumen expansion, false lumen patency, maximal aortic area and blood supply of major branches. Univariate and multivariate logistic and mixed-effect models were performed to delineate patterns and risks of DAR at mid-term follow-up. RESULTS: At 3.9 years, 13 (10.7%) aorta-related adverse events (including 3 [2.5%] aortic-related deaths) and 8 (6.6%) aortic re-interventions occurred. Follow-up computed tomography angiography was performed in all patients at 3.3 years (interquartile range, 2.7-4.4 years). Degree of DAR, being relatively independent among aortic levels, was maximal at the pulmonary bifurcation level (90.2% complete false lumen thrombosis) and decreased along the distal aorta. Analyses of longitudinal data indicated that baseline overall false lumen patency was the only available factor to predict DAR at all four aortic levels. Dissection type, surgical technique, implant size and medication did not sufficiently influence DAR at mid-term follow-up. CONCLUSIONS: After distinct operations for extensive acute aortic dissection, DAR beyond the stent graft coverage is a local, anatomical behavior independent of dissection type or proximal management.

17.
J Natl Cancer Inst ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.

18.
Nat Commun ; 11(1): 4980, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020477

RESUMO

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.


Assuntos
Neoplasias/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Carcinogênese , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Sumoilação , Proteína Supressora de Tumor p53/genética , Ubiquitinação
19.
J Neuroinflammation ; 17(1): 320, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33100215

RESUMO

BACKGROUND: Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function. METHODS: Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8-12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU)+/DCX+ cells, BrdU+/neuronal nuclei (NeuN)+ neurons, and BrdU+/GFAP+ glial cells in the dentate gyrus were assessed by immunofluorescence. RESULTS: CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU+/DCX+ cells and BrdU+/NeuN+ neurons, and increased numbers of BrdU+/GFAP+ cells. SOX2OT knockdown partially inhibited the effects of CLP on levels of SOX2 and neuronal markers, neuronal populations in the hippocampus, and cognitive function. SOX2 deficiency recapitulated the effects of SOX2OT knockdown. CONCLUSION: SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.

20.
Dis Markers ; 2020: 6486031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101544

RESUMO

Objective: To evaluate the diagnostic value of apolipoprotein E (APOE) gene in Alzheimer's disease (AD). Methods: Databases including PubMed, EMBASE, Google Scholar, Wanfang Med online, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) were searched for literatures in English or Chinese. No limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve (SROC) and Fagan's Nomogram were drawn, and metaregression and subgroup analysis were used to explore the source of heterogeneity. Results: A total of 13 studies, including 2662 cases and 8843 controls, were analyzed. The combined sensitivity (SEN) was 0.62 (95% CI (0.58-0.66)), specificity (SPE) was 0.84 (95% CI (0.81-0.86)), the positive likelihood ratio was 3.8 (95% CI (3.3-4.3)), and the negative likelihood ratio was 0.45 (95% CI (0.41-0.49)). The area under the ROC curve was 0.80, and the diagnostic ratio (DOR) was 8. Neither publication bias was detected in Deeks' funnel plot, nor threshold effect was shown in the SROC. Metaregression analysis showed that the diagnostic methods, experimental design, and sample size contributed to the heterogeneity in SEN, while the diagnostic methods, experimental design, blind evaluation on test results, and sample size contributed to the heterogeneity in SPE. When the pretest probability was set as 50%, the posterior probability in Fagan's Nomogram was 79%, the positive likelihood ratio (LRP) was 5, and the negative likelihood ratio (LRN) was 0.42. Conclusions: AD could neither be confirmed nor excluded by the APOE genotype test. The sensitivity and specificity of the APOE gene test were relatively low in the diagnosis of AD. The diagnostic value of APOE ε4 gene in AD was moderate; it might play an important role in the prevention of AD.

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