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1.
Aging (Albany NY) ; 122020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385194

RESUMO

We investigated the effects of paternal characteristics, including age, body mass index (BMI), and semen parameters on chromosomal aberration-related miscarriages in couples that underwent treatment with assisted reproductive technology (ART). Single nucleotide polymorphism (SNP) array analysis showed chromosomal aberrations in 60.2% (557/925) of miscarried fetuses, including trisomy in 73.1% (407/557) of cases. There were higher chromosomal aberration rates in fetuses for men aged 20-24 years and ≥30 years compared with controls. After adjusting for age and BMI of the female partners, and the BMI and semen parameters of the males, there was no statistically significant effect of paternal age ≥30 years on the risk of chromosomal aberrations-related miscarriages. However, the odds of chromosomal abnormality-related miscarriage were 148% higher for the youngest fathers (age: 20-24 years) than fathers aged 25-29 years [adjusted odds ratio (OR): 2.48, 95% confidence interval (CI): 1.03-5.96; P=0.042]. Furthermore, high male BMI (adjusted OR: 1.56, 95% CI: 1.14-2.14; P=0.005) and low semen volume (adjusted OR: 2.09, 95% CI: 1.06-4.11; P=0.034) were associated with increased risk of chromosomal aberration-related miscarriages. These findings demonstrate that very young paternal age, high BMI, and low semen volume are associated with increased risk of chromosomal aberration-related miscarriages in couples undergoing ART treatment.

2.
ACS Nano ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32379422

RESUMO

Developing a convenient and effective method to prepare single-atom catalysts at mild synthetic conditions remains a challenging task. Herein, a voltage-gauged electrofiltration method was demonstrated to synthesize single-atom site catalysts at room temperature. Under regulation of the graphene oxide membrane, a bulk Fe plate was directly converted into Fe single atoms, and the diffusion rate of Fe ions was greatly reduced, resulting in an ultralow concentration of Fe2+ around the working electrode, which successfully prevented the growing of nuclei and aggregating of metal atoms. Monatomic Fe atoms are homogeneously anchored on the as-prepared nitrogen-doped carbon. Owing to the fast photoelectron injection from photosensitizers to atomically dispersed Fe sites through the highly conductive supported N-C, the Fe-SAs/N-C exhibits an outstanding photocatalytic activity toward CO2 aqueous reduction into syngas with a tunable CO/H2 ratio under visible light irradiation. The gas evolution rates for CO and H2 are 4500 and 4950 µmol g-1 h-1, respectively, and the tunable CO/H2 ratio is from 0.3 to 8.8. This article presents an efficient strategy to develop the single-atom site catalysts and bridges the gap between heterogeneous and homogeneous catalysts toward photocatalytic CO2 aqueous reduction into syngas.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32274921

RESUMO

Design and synthesis of advanced electrode materials with fast and stable ion storage are of importance for energy storage applications. Herein, we propose that introducing the heterogeneous interface in layer-structured mesocrystals is an efficient way to greatly improve the rate capability and cycle stability of lithium-ion battery (LIB) devices. NH4TiOF3 mesocrystals were employed as a typical model system to demonstrate the idea. The NH4TiOF3 mesocrystals were obtained via the hydrothermal reaction, and the NH4TiOF3/TiO2 interfaces were generated through calcining at different temperatures under an argon atmosphere. Phase composition, microstructure, and chemical analyses show that the as-prepared NH4TiOF3 mesocrystals possess "tablet-like" morphology, and the formation of the NH4TiOF3/TiO2 interface can be controlled by the calcination temperature. When evaluated as the anode for LIBs, the optimized sample (NH4TiOF3 calcined at 250 °C, NTF-250) shows excellent, fast, and stable lithium storage properties. Specifically, the NTF-250 electrode holds a reversible capacity of 159.5 mA h g-1 after 200 cycles at 0.2 A g-1. At a high current density of 20 A g-1, the electrode still maintains a reversible capacity of 89.6 mA h g-1 and reaches a reversible capacity of 128.6 mA h g-1 at a current density of 1 A g-1 after 2000 cycles. Theoretical and experimental studies show that the synergistic effects of the heterogeneous NH4TiOF3/anatase TiO2 interface in the layer-structured NH4TiOF3 mesocrystals lead to the upgraded electrochemical properties. Especially, the local build-in electric field induced by the nonuniform distribution of charge across the NH4TiOF3/anatase TiO2 interface facilitates the charge transport during the charging and discharging cycling. The current electrode design strategy paves a new way in boosting stable ion storage and thus is of great interest in energy storage and conversion.

4.
Nanoscale ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32159195

RESUMO

Cesium lead halide perovskite nanocrystals (PNCs) have aroused tremendous research attention because of their excellent optoelectronic properties. Herein, we developed a facile and green low-temperature strategy free of organic solvents, in which only pure water was adopted as the solvent, to synthesize CsPbBr3 NCs. Intriguingly, although formed with the assistance of water, the obtained CsPbBr3 NCs present a cubic crystal structure, photoluminescence quantum yield (PLQY) of 75%, and narrow emission line width for bright green emission. Furthermore, both electroluminescence (EL) and photoluminescence (PL)-based light-emitting diodes (LEDs) present intrinsic green emission originating from the as-prepared CsPbBr3 NCs. Hence, this work offered a novel eco-friendly avenue for the preparation of perovskite NCs for their practical applications in LEDs.

5.
Biomolecules ; 10(3)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204458

RESUMO

Alpha7 nicotinic acetylcholine receptors (α7nAChRs) are interesting not only because of their physiological effects, but because this receptor requires chaperones to traffic to cell surfaces (measured by alpha-bungarotoxin [αBGT] binding). While knockout (KO) animals and antibodies that react across species exist for tmem35a encoding the protein chaperone NACHO, commercially available antibodies against the chaperone RIC3 that allow Western blots across species have not been generally available. Further, no effects of deleting RIC3 function (ric3 KO) on α7nAChR expression are reported. Finally, antibodies against α7nAChRs have shown various deficiencies. We find mouse macrophages bind αBGT but lack NACHO. We also report on a new α7nAChR antibody and testing commercially available anti-RIC3 antibodies that react across species allowing Western blot analysis of in vitro cultures. These antibodies also react to specific RIC3 splice variants and single-nucleotide polymorphisms. Preliminary autoradiographic analysis reveals that ric3 KOs show subtle αBGT binding changes across different mouse brain regions, while tmem35a KOs show a complete loss of αBGT binding. These findings are inconsistent with effects observed in vitro, as RIC3 promotes αBGT binding to α7nAChRs expressed in HEK cells, even in the absence of NACHO. Collectively, additional regulatory factors are likely involved in the in vivo expression of α7nAChRs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32026450

RESUMO

Feature Integration Theory (FIT) set out the groundwork for much of the work in visual cognition since its publication. One of the most important legacies of this theory has been the emphasis on feature-specific processing. Nowadays, visual features are thought of as a sort of currency of visual attention (e.g., features can be attended, processing of attended features is enhanced), and attended features are thought to guide attention towards likely targets in a scene. Here we propose an alternative theory - the Target Contrast Signal Theory - based on the idea that when we search for a specific target, it is not the target-specific features that guide our attention towards the target; rather, what determines behavior is the result of an active comparison between the target template in mind and every element present in the scene. This comparison occurs in parallel and is aimed at rejecting from consideration items that peripheral vision can confidently reject as being non-targets. The speed at which each item is evaluated is determined by the overall contrast between that item and the target template. We present computational simulations to demonstrate the workings of the theory as well as eye-movement data that support core predictions of the theory. The theory is discussed in the context of FIT and other important theories of visual search.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32086726

RESUMO

During production of the article, Figure 4 was incorrectly used twice in the initial article, so it appeared both as Figure 4 and Figure 5 in the article.

8.
Clin Sci (Lond) ; 134(2): 123-138, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31922185

RESUMO

Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-ß and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.

9.
Nat Commun ; 11(1): 335, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953446

RESUMO

The sintering of supported metal nanoparticles is a major route to the deactivation of industrial heterogeneous catalysts, which largely increase the cost and decrease the productivity. Here, we discover that supported palladium/gold/platinum nanoparticles distributed at the interface of oxide supports and nitrogen-doped carbon shells would undergo an unexpected nitrogen-doped carbon atomization process against the sintering at high temperatures, during which the nanoparticles can be transformed into more active atomic species. The in situ transmission electron microscopy images reveal the abundant nitrogen defects in carbon shells provide atomic diffusion sites for the mobile atomistic palladium species detached from the palladium nanoparticles. More important, the catalytic activity of sintered and deactivated palladium catalyst can be recovered by this unique N-doped carbon atomization process. Our findings open up a window to preparation of sintering-resistant single atoms catalysts and regeneration of deactivated industrial catalysts.

10.
Nat Biomed Eng ; 4(2): 159-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31659307

RESUMO

Mechanical mismatches between implanted electronics and biological tissues can lead to inaccurate readings and long-term tissue damage. Here, we show that functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can monitor multiple disease biomarkers in vivo. The flexible fibre bundles are injectable, have a low bending stiffness and display ultralow stress under compression. As proof-of-concept evidence of the sensing capabilities of these fibre bundles, we show that the fibre bundles enable the spatially resolved and real-time monitoring of H2O2 when implanted in tumours in mice, and that they can be integrated with a wireless transmission system on an adhesive skin patch to monitor calcium ions and glucose in the venous blood of cats for 28 d. The versatility of the helical fibre bundles as chemically functionalized electrochemical sensors makes them suitable for multiple sensing applications in biomedicine and healthcare.

11.
J Neuropathol Exp Neurol ; 79(1): 46-61, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31750928

RESUMO

This study investigated carbonylation of proteins with oxidative modification profiling in the striatum of aging and Parkinson disease (PD) rats, as well as the long-term effects of regular aerobic exercise on the carbonylation process and the damaging effects of PD vs habitual sedentary behavior. Regular aerobic exercise improved the PD rats' rotational behavior, increased tyrosine hydroxylase expression in both the striatum and substantia nigra pars compacta, and decreased α-synuclein expression significantly. Interestingly, apoptotic nuclei and autophagosomes were increased in the aerobic exercise PD rat striatum. Carbonylated protein Ca2+/calmodulin-dependent protein kinase alpha (CAMKIIα) was present in the middle-aged and aged groups but only in the sedentary, not the exercise, PD rat striatum. Notably, CAMKIIα was characterized by a 4-hydroxynonenal adduct. Regular aerobic exercise upregulated CAMKIIα expression level, activated the CAMK signaling pathway, and promoted the expression of autophagy markers Beclin1 and microtubule-associated proteins 1 A/1B light chain 3II. Aberrant carbonylation of CAMKII initiated age-related changes and might be useful as a potential biomarker of PD. Regular aerobic exercise alleviated protein carbonylation modification of CAMKIIα and regulated the CAMK signaling pathway, thereby affecting and regulating the homeostasis of apoptosis and autophagy in the striatum to alleviate the neurodegenerative process of PD lesions.

12.
Forensic Sci Int Genet ; 45: 102225, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31865225

RESUMO

Despite improvements in characterizing stutters of short tandem repeats (STRs), the relationships among the amounts of stutter variants and the relationships among motifs are not well understood yet. In the present study, 750 peripheral blood samples from human subjects were included to characterize the stutters of 58 STRs via the ForenSeq DNA Signature Prep Kit on a MiSeq FGx instrument. Alleles and corresponding stutter products were identified with a sequence simplification procedure. After screening, 26,921 alleles were included, that resulted in over 50 million reads, among which 8.69% were stutter products. Among these stutter products, 83.44% were N-1 stutters. Additionally, N-4, N-3, N-2, N0, N + 1, and N + 2 variants accounted for 0.11%, 0.77%, 6.45%, 3.01%, 5.95%, and 0.25% of the stutter products, respectively. For backward stutters, stutter products correlated best with the corresponding one-unit-longer stutter (or parental allele), which may represent a good predictor for backward stutters. For forward stutters, the N + 2 stutter correlated best with the N + 1 stutter, whereas the N + 1 stutter correlated best with the N-1 stutter rather than the expected parental allele, which indicated that the patterns were more complex for forward stutters. Additionally, some interesting findings were obtained for D21S11. For two adjacent contiguous motifs, co-stuttering patterns were observed where one motif tended to increase one repeat unit while the other motif decreased one repeat unit, whereas the inter-motif dependency was not significant for interrupted motifs. In conclusion, with massively parallel sequencing technology and our sequence simplification strategy, sequence variations within alleles and stutter products were identified, which was useful to determine the origin of stutters, identify more stutter variants, and explore the relationships among motifs. These findings may be helpful for allele designation, a deeper understanding of the mechanism of stutter, and improving resolution in forensic mixture analyses.

13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 339-345, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701719

RESUMO

OBJECTIVE: To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. METHODS: In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%~65% of the maximum oxygen consumption (V·O2max) to 70%~75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca2+/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. RESULTS: The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P< 0.01). The expression level of SYN1 in rats was up-regulated significantly (P<0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P<0.01), while the expression level of CaMK IIα in young rats was down-regulated (P<0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P< 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P<0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P<0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P<0.01), and mTOR was also significantly up-regulated in the aged group (P<0.05). CONCLUSION: Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.


Assuntos
Córtex Cerebral/fisiologia , Plasticidade Neuronal , Condicionamento Físico Animal , Resistência Física , Transdução de Sinais , Fatores Etários , Animais , Masculino , Ratos , Ratos Sprague-Dawley
14.
Anat Histol Embryol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724197

RESUMO

Mice models were used to study the pathogenesis of mice and human diseases. Although some mice models of allergic rhinitis and rhinosinusitis have been reported, no detailed anatomic, histological and computed tomographic comparative data of the normal murine sinus are available in the literature for new researchers to establish mice models. The purpose of this study was to clarify the histological and computed tomographic characteristics of the normal nasal sinus in BALB/c mice. Fifteen sinonasal specimens were collected. Five mice were subjected to micro-computed tomography imaging, and then dissected to observe its anatomic landmarks, and 10 mice were subjected to haematoxylin and eosin staining. Important anatomic landmarks were clearly demonstrated, including the ethmoturbinates, nasoturbinal, maxilloturbinate, ethmoid sinus, maxillary sinus, nasopharyngeal duct, nasolacrimal duct and vomeronasal organ. Full and typical sinonasal landmarks can be visualized by gross anatomy, micro-computed tomography imaging and haematoxylin and eosin staining, which will be useful for establishing the mouse models of nasal disease.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31726787

RESUMO

The healthy development of the city has received widespread attention in the world, and urban resilience is an important issue in the study of urban development. In order to better provide a useful reference for urban resilience and urban health development, this paper takes 56 cities in China as the research object, and selects 29 indicators from urban infrastructure, economy, ecology and society. The combination weight method, exploratory spatial data analysis (ESDA) and spatial measurement model are used to explore the spatial distribution of urban resilience and its influencing factors. From 2006 to 2017, the urban resilience of prefecture-level cities in the four provinces showed a wave-like rise. During the study period, the urban resilience values, measured as Moran's Is, were greater than 0.3300, showing a significantly positive correlation in regard to their spatial distribution. Regarding the local spatial correlation, the urban resilience of the study area had spatial agglomeration characteristics within the province, with a significant distribution of "cold hot spots" in the spatial distribution. From the perspective of the factors that affected urban resilience, the proportion of the actual use of foreign capital in GDP and carbon emissions per 10,000 CNY of GDP had a negative impact and GDP per square kilometer, the proportion of urban pension insurance coverage, the proportion of the population with higher education, and expenditure to maintain and build cities had a positive impact. The development strategy of urban resilience must be combined with the actual situation of the region, and the rational resilience performance evaluation system and the top-level design of urban resilience improvement should be formulated to comprehensively improve urban resilience.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31713142

RESUMO

Water-level regime alteration-associated redox fluctuation plays a primary role in governing exchange and transformation of nitrogen (N) in water-level fluctuation zones (WLFZs), while few understanding of how hydrological regimes under reservoir operation affected N cycling across the sediment-water interface (SWI), giving rise to uncertainties in reservoir N nutrient management. Batch microcosm simulation experiments with intact sediment cores from WLFZs of the Three Gorges Reservoir (TGR) were conducted for 24 days to identify holistic flooding-drying process mechanism on N-cycling patterns. Our results showed a distinct transition of N-cycling mode across the SWI, shifting from biological denitrogen loss dominated in initial period of flooding to enhance endogenous N retention. A dramatic source-sink switch of nitrous oxide (N2O) occurred in the first 1.5 days during the flooding period. However, combined accelerating migration of NH4+-N from sediment to overlying water, and subsequently enhanced transformation of NH4+-N to NO3--N formed from flooding to drying rotation, thereby increasing N loading to overlying water. The reason for this investigation could be attributed to intensive N loss through coupled nitrification and denitrification in oxic-anoxic microenvironments after flooding. With oxygen replenishment from atmosphere during drying phase, persistent ammonification of organic N in sediments provided sufficient source of NH4+-N for the formation of NO3--N fraction in a more oxic overlying water. Therefore, water-level regime alteration by reservoir operation was capable of weakening N removal from water body and lengthening internal N turnover time across redox-variable SWI. These findings elucidate new understanding of holistic hydrological regime mechanisms on N cycling across SWI and provide insight to biogenic N nutrient management for improving the green credentials of hydroelectric reservoir.

17.
Clin Sci (Lond) ; 133(22): 2301-2315, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31722010

RESUMO

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.

18.
J BUON ; 24(4): 1700-1705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646828

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the common types of cancer that originate from the nasopharyngeal region. Recurrence and early metastasis represent major problems associated with NPC mortality. These are mainly caused by various molecular changes that take place during the conversion of normal stem cells into treatment-resistant stem cells. The aim of our study was to investigate the proliferative behavior of cancer stem cells in different stages of NPC and to identify the functional roles of SPLUNC1 and MLL3 associated with cancer stem cells. METHODS: We successfully developed a NPC mouse model using C666-1 cells. Immunohistochemistry and Western blotting were used to analyze the expression of SOX2, SPLUNC1 and MLL3. RESULTS: Null BALB/c mice developed initial and aggressive stages of NPC in 3 and 10 weeks, respectively. Histological results showed that the proliferative ability of cells increased as the tumor progressed to the next level. The SOX2 protein showed a peculiar pattern of upregulation in aggressive NPC when compared with control tissues and initial NPC. Remarkably, our study found that SPLUNC1 and MLL3 expression showed upregulation in initial NPC, which indicates their role in the tumor resistance mechanism even if their expression was downregulated in aggressive NPC. CONCLUSIONS: Our results conclude that SPLUNC1 and MLL3 expression control the resistance mechanism of cancer stem cells in initial NPC, but their downregulation in aggressive stages contributes to developing resistance in nasopharyngeal cancer stem cells.

19.
Materials (Basel) ; 12(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640231

RESUMO

To investigate the relationship between inclusions and bending fatigue behaviors in 20Cr2Ni4 steel under different stress concentrations. This paper designs a new experimental method to prefabricate different size stress concentrations near the inclusions, and then conducts a new type of bending fatigue test to study the inclusions and their surrounding stress distributions in 20Cr2Ni4 steel. A microhardness tester was combined with laser etching equipment to realize the prefabrication of different stress concentrations at arbitrary positions around any inclusion on the gear steel surface. This method provides an experimental basis for the quantitative analysis of the relationship between stress distribution and fatigue life around the inclusions of heavy-duty gear steels. We also predict the bending fatigue lives of heavy-duty gear steels with different types of inclusions, stress states, and spatial distributions. Then, based on the prefabricated notch parameters and the state of inclusions in the steel, a mathematical model of quantitative analysis is proposed, which can accurately predict the fatigue limit of heavy-duty gear steel. The research results can be applied to the actual use of heavy-duty gears and to the accurate life estimation based on the state of gear stress, thereby providing a quantitative reference model for subsequent gear steel production and gear part processing.

20.
Am J Cancer Res ; 9(9): 1922-1937, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598395

RESUMO

Activation of the PI3K/mTOR pathways is significantly correlated with a poor prognosis in nasopharyngeal carcinoma (NPC). Inhibition of these pathways was reported to be effective in restoring radiosensitivity. In this study, the activity of the novel ATP-competitive, orally bioavailable mTOR inhibitor AZD8055 was found to inhibit the phosphorylated mTOR and NPC cells proliferation. The IC50 doses in CNE1 and CNE2 cell lines were 60 and 100 nanomolar, respectively. AZD8055 significantly enhanced the inhibitions of cell growth and colony formation induced by irradiation (P < 0.05 for all). AZD8055 at the IC50 doses prolonged G2/M arrest (P < 0.05) and promoted the apoptosis (P < 0.01) induced by irradiation and autophagy in NPC cells. Blocking autophagy weaken the cell growth inhibition and decreased apoptosis induced by AZD8055 combined with irradiation. Treatment with AZD8055 at 5, 10 and 20 mg/kg/d significantly enhanced NPC cell radiosensitivity in vivo and significantly induced apoptosis and autophagy in tumor tissues, Neither 5 nor 20 mg/kg/d AZD8055 induced significantly pro-apoptosis bax expressions in mouse livers and kidneys. 5 mg/kg/d produced good radiosensitivity but had little impact on body weight. We concluded that AZD8055 was a promising candidate radiosensitizer for NPC.

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