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The question of whether all materials can solidify into the glassy form proposed by Turnbull half a century ago remains unsolved. Some of the simplest systems of monatomic metals have not been vitrified, especially the close-packed face-centred cubic metals. Here we report the vitrification of gold, which is notoriously difficult to be vitrified, and several similar close-packed face-centred cubic and hexagonal metals using a method of picosecond pulsed laser ablation in a liquid medium. The vitrification occurs through the rapid cooling during laser ablation and the inhibition of nucleation by the liquid medium. Using this method, a large number of atomic configurations, including glassy configurations, can be generated simultaneously, from which a stable glass state can be sampled. Simulations demonstrate that the favourable stability of monatomic metals stems from the strong topological frustration of icosahedra-like clusters. Our work breaks the limitation of the glass-forming ability of matter, indicating that vitrification is an intrinsic property of matter and providing a strategy for the preparation and design of metallic glasses from an atomic configuration perspective.
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Nanofiber is the critical building block for many biological systems to perform various functions. Artificial assembly of molecules into nanofibers in a controllable and reversible manner will create "smart" functions to mimic those of their natural analogues and fabricate new functional materials, but remains an open challenge especially for nature macromolecules. Herein, the controllable and reversible assembly of nanofiber (CSNF) from natural macromolecules with oppositely charged groups are successfully realized by protonation and deprotonation of charged groups. By controlling the electrostatic interaction via protonation and deprotonation, the size and morphology of the assembled nanostructures can be precisely controlled. A strong electrostatic interaction contributes to large nanofiber with high strength, while poor electrostatic interaction produces finer nanofiber or nanoparticle. And especially, the assembly, disassembly, and reassembly of the nanofiber occurs reversibly through protonation and deprotonation, thereby paving a new way for precisely controlling the assembly process and structure of nanofiber. The reversible assembly allows the nanostructure to dynamically reorganize in response to subtle perturbation of environment. The as-prepared CSNF is mechanical strong and can be used as a nano building block to fabricate high-strength film, wire, and straw. This study offers many opportunities for the biomimetic synthesis of new functional materials.
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BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.
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BACKGROUND: During the brewing of soy sauce, the conversion of multiple substances is driven by various microorganisms and their secreted enzyme systems. Soy sauce mash is an important source of enzyme systems during moromi fermentation, but the changes of enzyme systems in soy sauce mash during moromi fermentation are poorly understood. In order to explore the predominant enzyme systems existing during moromi fermentation and to explain the characteristics of the enzyme system changes, an enzymatic activities assay and 4D-label-free proteomics analysis were conducted on soy sauce mash at different stages of fermentation. RESULTS: The activities of hydrolytic enzymes in soy sauce mash decreased continuously throughout the fermentation process, while most of the characteristic physicochemical substances in soy sauce mash supernatant had already accumulated at the early stage of fermentation. Four hydrolytic enzymes were found to be positively correlated with important physicochemical indexes by principal component analysis and Pearson correlation analysis. The proteomics analysis revealed three highly upregulated enzymes and two enzymes that were present in important metabolic pathways throughout the fermentation process. Furthermore, it was found that Aspergillus oryzae was able to accumulate various nutrients in the soy sauce mash by downregulating most of its metabolic pathways. CONCLUSION: Enzymes present with excellent properties during the moromi fermentation period could be obtained from these results. Meanwhile, the characterization of the metabolic pathways of microorganisms during the moromi fermentation period was revealed. The results provide a basis for more scientific and purposeful improvement of moromi fermentation in the future. © 2024 Society of Chemical Industry.
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Fermentación , Proteómica , Alimentos de Soja , Alimentos de Soja/análisis , Alimentos de Soja/microbiología , Proteínas Fúngicas/metabolismo , Aspergillus oryzae/metabolismo , Aspergillus oryzae/enzimologíaRESUMEN
Tuning the selectivity of CO2 electroreduction reaction (CO2RR) solely by changing electrolyte is a very attractive topic. In this study, we conducted CO2RR in different aqueous electrolytes over bulk metal electrodes. It was discovered that controlled CO2RR could be achieved by modulating cations in the electrochemical double layer. Specifically, ionic liquid cations in the electrolyte significantly inhibits the hydrogen evolution reaction (HER), while yielding high Faraday efficiencies toward CO (FECO) or formate (FEformate) depending on the alkali metal cations. For example, the product could be switched from CO (FECO=97.3 %) to formate (FEformate=93.5 %) by changing the electrolyte from 0.1â M KBr-0.5â M 1-octyl-3-methylimidazolium bromide (OmimBr) to 0.1â M CsBr-0.5â M OmimBr aqueous solutions over pristine Cu foil electrode. In situ spectroscopy and theoretical calculations reveal that the ordered structure generated by the assembly of Omim+ under an applied negative potential alters the hydrogen bonding structure of the interfacial water, thereby inhibiting the HER. The difference in selectivity in the presence of different cations is attributed to the hydrogen bonding effect caused by Omim+, which alters the solvated structure of the alkali metal cations and thus affects the stabilization of intermediates of different pathways.
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PURPOSE: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. METHODS: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. RESULTS: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. CONCLUSION: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.
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Fiber-reinforced hydrogels are a class of soft composite materials that have seen increased use across a wide variety of biomedical applications. However, existing fabrication techniques for these hydrogels are unable to realize biologically relevant macro/mesoscale geometries. To address this limitation, this paper presents a novel air-assisted, dual-polarity electrospinning printhead that converges high-strength electric fields, with low velocity air flow to remove the collector dependency seen with traditional far-field electrospinning setups. The use of this printhead in conjunction with different configurations of deformable collection templates has resulted in the production of three classes of fiber-reinforced hydrogel prototype geometries, viz., (i) tubular geometries with bifurcations and mesoscale texturing; (ii) hollow, nontubular geometries with single and dual-entrances; and (iii) three-dimensional (3D) printed flat geometries with varying fiber density. All three classes of prototype geometries were mechanically characterized to have properties that were in line with those observed in living soft tissues. With the realization of this printhead, biologically relevant macro/mesoscale geometries can be realized using fiber-reinforced hydrogels to aid a wide array of biomedical applications.
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HidrogelesRESUMEN
Silicon-based kinetic energy converters employing variable capacitors, also known as electrostatic vibration energy harvesters, hold promise as power sources for Internet of Things devices. However, for most wireless applications, such as wearable technology or environmental and structural monitoring, the ambient vibration is often at relatively low frequencies (1-100 Hz). Since the power output of electrostatic harvesters is positively correlated to the frequency of capacitance oscillation, typical electrostatic energy harvesters, designed to match the natural frequency of ambient vibrations, do not produce sufficient power output. Moreover, energy conversion is limited to a narrow range of input frequencies. To address these shortcomings, an impacted-based electrostatic energy harvester is explored experimentally. The impact refers to electrode collision and it triggers frequency upconversion, namely a secondary high-frequency free oscillation of the electrodes overlapping with primary device oscillation tuned to input vibration frequency. The main purpose of high-frequency oscillation is to enable additional energy conversion cycles since this will increase the energy output. The devices investigated were fabricated using a commercial microfabrication foundry process and were experimentally studied. These devices exhibit non-uniform cross-section electrodes and a springless mass. The non-uniform width electrodes were used to prevent pull-in following electrode collision. Springless masses from different materials and sizes, such as 0.5 mm diameter Tungsten carbide, 0.8 mm diameter Tungsten carbide, zirconium dioxide, and silicon nitride, were added in an attempt to force collisions over a range of applied frequencies that would not otherwise result in collisions. The results show that the system operates over a relatively wide frequency range (up to 700 Hz frequency range), with the lower limit far below the natural frequency of the device. The addition of the springless mass successfully increased the device bandwidth. For example, at a low peak-to-peak vibration acceleration of 0.5 g (peak-to-peak), the addition of a zirconium dioxide ball doubled the device's bandwidth. Testing with different balls indicates that the different sizes and material properties have different effects on the device's performance, altering its mechanical and electrical damping.
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Compuestos de Tungsteno , Vibración , Fenómenos FísicosRESUMEN
A series of petroleum coke (petcoke)-derived solid acid catalysts were prepared via nitric acid treatment with or without ball milling pretreatment. The inherent sulfur in petcoke was converted to sulfonic groups, which were active sites for the esterification of octanoic acid and methanol at 60 °C, with ester yields of 14-43%. More specifically, samples without ball milling treated at 120 °C for 3 h had a total acidity of 4.67 mmol/g, which was 1.6 times that of the samples treated at 80 °C, despite their -SO3H acidities being similar (~0.08 mmol/g). The samples treated for 24 h had higher -SO3H (0.10 mmol/g) and total acidity (5.25 mmol/g) but not increased catalytic activity. Ball milling increased the defects and exposed aromatic hydrogen groups on petcoke, which facilitated further acid oxidation (0.12 mmol -SO3H/g for both materials and total acidity of 5.18 mmol/g and 5.01 mmol/g for BP-N-3/120 and BP-N-8/90, respectively) and an increased ester yield. DFT calculations were used to analyze the pathways of sulfonic acid group formation, and the reaction pathway with NO2⢠was the most thermodynamically and kinetically favourable. The activities of the prepared catalysts were related to the number of -SO3H acid sites, the total acidity, and the oxygen content, with the latter two factors having a negative impact.
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BACKGROUND: Soybeans and defatted soybeans, commonly used as protein ingredients, have different flavors of their fermented soy sauce. Clarifying the differences between the two soy sauces, as well as the formation mechanism, is an important prerequisite for improving the flavor of defatted soybean soy sauce. To this goal, the aroma characteristics of two soy sauces and their volatile profiles were compared by sensory evaluation and gas chromatography-mass spectrometry, and eight enzyme activities and volatile profiles of matured koji were determined. RESULTS: Sensory results showed that the acids, fruity and cooked potato-like attributes were higher in whole soybean fermented soy sauce, whereas defatted soybean soy sauce exhibited higher smoky and malty attributes, closely related to the contents of aroma-active compounds in soy sauce, such as isobutyl acetate, 2/3-methylbutanal, acetic acid and 2/3-methylbutanoic acid. The content of most volatiles in the matured kojis showed a consistent trend with that of soy sauce: alcohols, acids, furan(one)s and ketones. Interestingly, acid protease and cellulase activities were 3.3 and 1.6 times higher in the whole soybean koji than in defatted soybean koji, respectively, whereas neutral protease, aminopeptidase, glucoamylase and ß-glucosidase were approximately 2.0 times higher in defatted soybean koji. CONCLUSION: In summary, the flavor differences between soybean and defatted soybean fermented soy sauce were not only caused by the differences in the content of flavor precursors in the materials, but also closely related to the differences in the enzymatic profiles accumulated during the koji-making process. © 2022 Society of Chemical Industry.
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Alimentos de Soja , Alimentos de Soja/análisis , Glycine max/metabolismo , Fermentación , Odorantes/análisis , Péptido Hidrolasas/metabolismoRESUMEN
This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type â ¢(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type â collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.
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Fibrosis Pulmonar , Ratones , Masculino , Animales , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/inducido químicamente , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Fibronectinas/metabolismo , Vimentina/metabolismo , Cromatografía Liquida , Ratones Endogámicos C57BL , Espectrometría de Masas en Tándem , Estrés Oxidativo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , ARN Mensajero/metabolismoRESUMEN
The present study investigated the regulatory effect of tanshinone â ¡_A(TAâ ¡_A) on activator expression in human umbilical vein endothelial cells(HUVECs) and the effect on the phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt) signaling pathway in patients with antiphospholipid syndrome(APS). HUVECs cultured in vitro were divided into a medium group, a blank control group, an APS model group, an APS+LY5 group, an APS+LY10 group, an APS+LY20 group, an APS+TAâ ¡_A5 group, an APS+TAâ ¡_A10 group, an APS+TAâ ¡_A20 group, and an APS+TAâ ¡_A10+LY10 group. The effects of LY294002 and TAâ ¡_A at different concentrations on the secretion of interleukin-6(IL-6), interleukin-8(IL-8), and monocyte chemoattractant protein-1(MCP-1) by HUVECs were investigated. The effects on the mRNA expression of annexin A2(ANXA2), PI3 K, Akt, and E-cadherin(E-cad) were detected by quantitative polymerase chain reaction(qPCR), and Western blot was used to determine the effects on the protein expression of ANXA2, p-PI3 K/PI3 K, p-Akt/Akt, and E-cad. The results revealed that compared with the APS model group, the APS+TAâ ¡_A10 group showed statistically reduced IL-6 and MCP-1 and increased IL-8 in a concentration-dependent manner with the increase in TAâ ¡_A dose, while the APS+TAâ ¡_A10 group showed increased mRNA and protein expression of ANXA2, PI3 K, Akt, and E-cad(P<0.05 or P<0.01) in a concentration-dependent manner with the increase in TAâ ¡_A dose. The findings indicated that the serum of APS patients could lead to the decreased mRNA and protein expression levels of ANXA2, PI3 K, Akt, and E-cad in HUVECs, increased secretion of IL-6 and MCP-1, and reduced secretion of IL-8, and activate vascular endothelial cells. In contrast, once the PI3 K/Akt signaling pathway was blocked, the mRNA and protein expression of ANXA2 and E-cad significantly decreased, IL-6 and MCP-1 secretion significantly increased, and IL-8 secretion was significantly reduced. It suggests that TAâ ¡_A regulates the activation of vascular endothelial cells in APS patients by activating the PI3 K/Akt signaling pathway.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Abietanos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Transducción de SeñalRESUMEN
In projected structure-activity relationship studies of the novel diheteroarylamide-based anti-HIV agent 2 (1C8), one objective was to evaluate the influence of incorporating the central amide motif in 2 into a five-membered pyrazolone ring, as found in 3. It was envisaged that compound 3 could be prepared through reaction of 3-hydrazino-5-nitrobenzisothiazole 5 with the methyl ester of 4-chloropyridine-3-carboxylic acid, followed by N-methylation of the pyridine nitrogen. However, the reaction of 3-methoxyl-5-nitrobenzisothiazole with hydrazine resulted in formation of ring-opened hydrazonate product 18. In the corresponding reaction with 3-chloro-5-nitrobenzisothiazole, a different rearrangement product 19 was formed, in which two 2,1-benzisothiazole units are joined by a sulfur bridge. Meisenheimer complex formation, favored by the presence of the 5-nitro substituent on the benzisothiazole ring, was postulated to be a key feature in the formation of these deep-seated rearrangement products. Support for the proposed formation of the pivotal Meisenheimer complexes and their subsequent evolution to the observed products in which the benzisothiazole sulfur atom is either expelled or maintained in the isomeric 2,1-benzisothiazole system was obtained by density function theory calculations.
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Amidas , Ácidos Carboxílicos , Hidrazinas , Relación Estructura-ActividadRESUMEN
BACKGROUND: Due to the lack of a sensitive, specific and rapid detection method, aetiological diagnosis of pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae, MP) is a constantly challenging issue. This retrospective study aimed to compare the diagnostic methods for Mycoplasma pneumoniae in children and evaluate their values. METHODS: From November 2018 to June 2019, 830 children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children's Medical Center. On the first day of hospitalization, sputum, throat swab and venous blood samples were collected to analyse MP-IgM (particle agglutination, PA), MP-IgM (immune colloidal gold technique, GICT), MP-DNA, MP-RNA (simultaneous amplification and testing, SAT) and MP-DNA (real-time polymerase chain reaction, RT-PCR). RESULTS: Among these 830 children, RT-PCR showed that the positive rate was 36.6% (304/830), in which the positive rate of macrolide resistance (A2063G mutation) accounted for 86.2% of cases (262/304). Using RT-PCR as the standard, MP-RNA (SAT) had the highest specificity (97.5%), and MP-IgM (PA) had the highest sensitivity (74.0%) and Youden index (53.7%). If MP-RNA (SAT) was combined with MP-IgM (PA), its Kappa value (0.602), sensitivity (84.2%), specificity (78.7%) and Youden index (62.9%) were higher than those of single M. pneumoniae detection. CONCLUSIONS: Our research indicated that a combination of MP-RNA (SAT) plus MP-IgM (PA) might lead to reliable results as an early diagnostic method for children with clinical manifestations of Mycoplasma pneumoniae pneumonia.
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Infecciones Comunitarias Adquiridas , Neumonía por Mycoplasma , Antibacterianos , Niño , China , Infecciones Comunitarias Adquiridas/diagnóstico , Farmacorresistencia Bacteriana , Humanos , Macrólidos , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/diagnóstico , Estudios RetrospectivosRESUMEN
Elevated blood homocysteine (Hcy) is an independent risk factor for cardiovascular disease. A growing number of studies have evaluated the link between air pollution and blood Hcy levels, but the results are inconsistent. To date, no systematic review of the published studies has been conducted yet. We aimed to provide a comprehensive overview of these studies. We systematically searched three international databases (PubMed, Web of Science, and Embase) and four Chinese databases (Wanfang, CNKI, CBM, and VIP) for peer-reviewed epidemiological studies investigating associations between ambient air pollutants and Hcy levels published before December 2019. We screened literature, extracted data, assessed methodological quality, and evaluated the risk of bias of the included studies. Of 1157 identified articles, 10 were finally included in this systematic review. Most were cross-sectional studies and were performed in developed countries. Particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) and/or 10 µm (PM10) were investigated in all of the included studies. Overall, the evidence generally supports a positive association between higher PM concentrations and elevated Hcy levels. However, high heterogeneity in terms of study participants, study design, exposure duration, and particle components and sources, low methodological quality and probable high risk of bias in some studies, and limited literature number precluded us from drawing a robust conclusion. Associations between Hcy and gaseous pollutants were explored in only one or two studies, and the results were inconclusive. Additional, well-designed studies remain required to validate the association between air pollution and Hcy.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Estudios Transversales , Exposición a Riesgos Ambientales/análisis , Homocisteína , Humanos , Material Particulado/análisis , Material Particulado/toxicidadRESUMEN
An microRNA (miRNA) signature to predict the clinical outcome of pancreatic adenocarcinoma (PAAD) is still lacking. In the current study, we aimed at identifying and evaluating a prognostic miRNA signature for patients with PAAD. The miRNA expression profile and the clinical information regarding patients with PAAD were recruited from The Cancer Genome Atlas database. Differentially expressed miRNAs were identified between normal and tumor samples. By means of survival analysis, a 4-miRNA signature for predicting patients' with PAAD overall survival (OS) was constructed. Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of survival prediction. Furthermore, the biological function of the predicted miRNAs was evaluated using a bioinformatics approach. Four (hsa-mir-126, hsa-mir-3613, hsa-mir-424, and hsa-mir-4772) out of 17 differentially expressed miRNAs were associated to the OS of patients with PAAD. Moreover, the area under the curve (AUC) of the constructed 4-miRNA signature associated to patients' with PAAD 2-year survival was 0.789. The multivariate Cox's proportional hazards regression model suggested that this 4-miRNA signature was an independent prognostic factor of other clinical parameters in patients with PAAD. Further pathway enrichment analyses revealed that the miRNAs in the 4-miRNA signature might regulate genes that affect focal adhesion, Wnt signaling pathway, and PI3K-Akt signaling pathway. Thus, these findings indicated that the 4-miRNA signature might be an effective independent prognostic biomarker in the prediction of PAAD patients' survival.
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Biomarcadores de Tumor/biosíntesis , Regulación Neoplásica de la Expresión Génica , MicroARNs/biosíntesis , Neoplasias Pancreáticas , ARN Neoplásico/biosíntesis , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Tasa de Supervivencia , Neoplasias PancreáticasRESUMEN
In the original publication, the funding and conflict of interest statements were not correct.
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OBJECTIVE: To investigate the effect of marine fish collagen oligopeptide and calcium aspartate alone or in combination on bone mineral density in ovariectomized rats. METHODS: Sixty three-month-old SPF Wistar female rats were randomly divided into 6 groups according to their body weight: sham operation group, model control group(ovariectomy), calcium aspartate group(ovariectomy), marine fish collagen oligopeptide group(ovariectomy), aspartate calcium + marine fish collagen oligopeptide group(ovariectomy) and calcium carbonate control group(ovariectomy), 10 rats in each group. The sham operation group and the model control group were given the same volume of pure water by gavage, and the other groups were intragastrically administered with calcium aspartate(116. 7 mg/kg), marine fish collagen oligopeptide(250 mg/kg), calcium aspartate(116. 7 mg/kg) + marine fish collagen oligopeptide(250 mg/kg), calcium carbonate(35. 6 mg/kg), and the test substance was continuously administered for 90 days. After 90 days, the animals were sacrificed, and the liver and kidney of the rats were taken to calculate the organ coefficient and pathological examination. The rat femurs were taken to measure bone mineral density and bone calcium content and rat serum was used to determine serum calcium, phosphorus concentration and alkaline phosphatase(ALP) activity. RESULTS: Bone mineral density and bone calcium content in the model group were significantly lower than those in the sham operation group(P<0. 05), indicating that the osteoporosis model was successfully established by oophorectomy. There was no significant difference in the organ index of each group(P>0. 05), liver/kidney HE staining microscopic examination showed no abnormal changes, indicating the safety of the test substances. The bone mineral density of the aspartate calcium + marine fish collagen oligopeptide group was significantly greater than that of the model group(P<0. 05). The bone mineral density of the aspartate calcium group and the marine fish collagen oligopeptide group was larger than that of the model group, but there was no significant difference(P>0. 05). Compared with that in the model group, the calcium content of calcium aspartate + marine fish collagen oligopeptide group was significantly higher(P<0. 05). Compared with that in the calcium aspartate group, the calcium content of calcium aspartate + marine fish collagen oligopeptide group was higher(P<0. 05), there was no significant difference in serum calcium concentration between groups(P>0. 05). Compared with that in the model group, serum phosphorus concentration in the aspartate calcium group, marine fish collagen oligopeptide group, aspartate calcium + marine fish collagen oligopeptide group was significantly higher(P<0. 05) and ALP activity was significantly reduced(P<0. 05). CONCLUSION: The combination of calcium aspartate and marine fish collagen oligopeptide has a significant effect on increasing bone mineral density, also indicating that marine fish bone collagen oligopeptide could promote absorption of calcium aspartate.
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Ácido Aspártico , Densidad Ósea , Animales , Calcio , Colágeno , Femenino , Humanos , Oligopéptidos , Ovariectomía , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Observational studies on the association between fish and poultry intake and the risk of total cancer mortality have been reported with mixed results. Thus, we aimed to assess this association by conducting a meta-analysis of prospective studies. We performed a literature search on PubMed database through February 1, 2017 to identify relative prospective studies. A random-effects model was used to calculate the summary estimates. We identified fourteen prospective studies involving 2,378,204 participants and 96,712 cancer mortality events. Comparing the highest category of consumption with lowest category, pooled relative risk (RR) of total cancer mortality was 0.99 (95% confidence interval [CI], 0.94-1.05) for fish (10 studies) and 0.96 (95% CI, 0.93-1.00) for poultry (8 studies), respectively. However, we failed to identify any dose-response association based on a limited number of eligible studies, with a pooled RR of 0.98 (95% CI, 0.92-1.05) and 0.97 (95% CI, 0.88-1.07) for each 100 g per day increment in fish and poultry consumption, respectively. In summary, this meta-analysis indicates that consumption of either fish or poultry is not substantially associated with lower risk of total cancer mortality. The observed weak inverse association for high poultry consumption needs to be verified in additional large prospective studies.
Asunto(s)
Productos Pesqueros , Neoplasias/mortalidad , Aves de Corral , Animales , Dieta , Humanos , Estudios ProspectivosRESUMEN
The aim of this study was to investigate the effect of wogonoside (WGS) on the cisplatin (cDDP) resistance in human gastric carcinoma SGC7901/cDDP cells and its possible mechanism. The drug-resistant SGC7901/cDDP cells were established by stepwise exposure to cDDP. CCK-8 assay was employed to detect the cytotoxic effect of WGS and cDDP on SGC7901/cDDP cells, and the combined effect of WGS and cDDP was analyzed by Chou-Talalay method. Flow cytometry was used to determine the apoptosis and reactive oxygen species (ROS). Nuclear factor erythroid-2 related factor 2 (Nrf2) gene was knocked down by using the short hairpin RNA (shRNA) approach. The protein levels of Nrf2, NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S transferase-π (GST-π), multidrug resistance-associated protein 1 (MRP1), cleaved Capase-3, p-Akt and Akt were detected by Western blotting. The result showed that after various concentrations of WGS and/or cDDP treatment for 48 h, the cell viability was remarkably reduced in a dose-dependent manner (P < 0.05). When the inhibition rate exceeded 16%, the combination of WGS and cDDP produced a synergistic effect. The protein levels of p-Akt, Nrf2 and MRP1 in SGC7901/cDDP cells were higher than those in SGC7901 cells (P < 0.05). WGS and LY294002 (PI3K inhibitor) both remarkably decreased the phosphorylation level of Akt (P < 0.05), down-regulated the protein level of Nrf2 (P < 0.05), increased the content of ROS (P < 0.05), up-regulated the protein level of cleaved Caspase-3 (P < 0.05), and induced apoptosis (P < 0.05). Meanwhile, N-acetyl-L-cysteine (NAC) decreased apoptosis and oxidative stress reaction induced by WGS (P < 0.05). WGS and Nrf2 gene silencing both down-regulated the protein levels of NQO1, GST-π and MRP1 (P < 0.05). These results suggest that WGS may reverse cDDP resistance in SGC7901/cDDP cells through blocking the PI3K/Akt/Nrf2/ARE signaling pathway, thus enhancing the cytotoxicity of cDDP and inducing oxidative stress reaction and apoptosis.