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- ArticleYoshitomi T, Hirayama A, Nagasaki Y.Biomaterials. 2011 Nov;32(31):8021-8.The ultimate objective of nanoparticle-based therapy is to functionalize nanomedicines in a micro-disease environment without any side effects. Here, we reveal that our pH-responsive nitroxide radical-containing nanoparticles (RNP(pH)) disintegrate within the renal acidic lesion and act as scavengers of reactive oxygen species (ROS), leading to a relief of acute kidney injury (AKI). RNP(pH) was prepared using amphiphilic block copolymers possessing 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) moieties via amine linkage as a side chain of the hydrophobic segment. The self-assembled RNP(pH) disintegrated at pH below 7.0 because of a protonation of the amino groups in the hydrophobic core of the nanoparticles, thereby resulting in an improvement in ROS scavenging activity. Using a renal ischemia-reperfusion AKI model in mice, the therapeutic effect of RNP(pH) on ROS damage was evaluated. Unlike the RNP without pH-triggered disintegration (RNP(Non-pH)), the RNP(pH) showed extremely high ROS scavenging activity and renal protective effects. It is interesting to note that the side effect of nitroxide radicals was markedly suppressed due to the compartmentalization of nitroxide radicals in the core of RNP(pH) in untargeted area. The morphology changes in RNP(pH) were confirmed by analyzing electron spin resonance spectra, and these findings provide the evidence of the real therapeutic effect of the environment-sensitive specific disintegration of nanoparticles in vivo.
- ArticleLiu J, Li W, Zhang J, Ma Z, Wu X, Tang L.PeerJ. 2019;7:e8021.BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although multiple efforts have been made to understand the development of HCC, morbidity, and mortality rates remain high. In this study, we aimed to discover the mRNAs and long non-coding RNAs (lncRNAs) that contribute to the progression of HCC. We constructed a lncRNA-related competitive endogenous RNA (ceRNA) network to elucidate the molecular regulatory mechanism underlying HCC.
METHODS: A microarray dataset (GSE54238) containing information about both mRNAs and lncRNAs was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) in tumor tissues and non-cancerous tissues were identified using the limma package of the R software. The miRNAs that are targeted by DElncRNAs were predicted using miRcode, while the target mRNAs of miRNAs were retrieved from miRDB, miRTarBas, and TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the EnrichNet website. We constructed a protein-protein interaction (PPI) network of DEGs using STRING, and identified the hub genes using Cytoscape. Survival analysis of the hub genes and DElncRNAs was performed using the gene expression profiling interactive analysis database. The expression of molecules with prognostic values was validated on the UALCAN database. The hepatic expression of hub genes was examined using the Human Protein Atlas. The hub genes and DElncRNAs with prognostic values as well as the predictive miRNAs were selected to construct the ceRNA networks.
RESULTS: We found that 10 hub genes (KPNA2, MCM7, CKS2, KIF23, HMGB2, ZWINT, E2F1, MCM4, H2AFX, and EZH2) and four lncRNAs (FAM182B, SNHG6, SNHG1, and SNHG3) with prognostic values were overexpressed in the hepatic tumor samples. We also constructed a network containing 10 lncRNA-miRNA-mRNA pathways, which might be responsible for regulating the biological mechanisms underlying HCC.
CONCLUSION: We found that the 10 significantly overexpressed hub genes and four lncRNAs were negatively correlated with the prognosis of HCC. Further, we suggest that lncRNA SNHG1 and the SNHG3-related ceRNAs can be potential research targets for exploring the molecular mechanisms of HCC. - ArticleZhang X, Guo G, Wang G, Zhao J, Wang B, Yu X, Ding Y.Mol Med Rep. 2015 Dec;12(6):8021-31.Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan‑Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR‑510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low‑grade serous carcinoma (LGSC) and CCC specimens using RT‑qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2‑fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR‑510 and miR‑129‑3p were significantly downregulated, and that miR‑483‑5p and miR‑miR‑449a were significantly upregulated in CCC, compared with HGSC (P<0.05), which was consistent with the microarray results. Kaplan‑Meier analysis revealed low expression levels of miR‑510 and low expression levels of miR‑129‑3p, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymphatic metastasis and that HGSC was significantly associated with the poorer overall survival rates (P<0.05). The expression of miR‑510 was significantly higher in the LGSC and CCC tissues, compared with the HGSC and normal ovarian tissues. The results of the present study suggested that different subtypes of EOC have specific miRNA signatures, and that miR‑510 may be involved differently in HGSC and CCC. Thus, miR‑510 and miR‑129‑3p may be considered as potential novel candidate clinical biomarkers for predicting the outcome of EOC.
- ArticleTahir F, Bin Arif T, Ahmed J, Malik F, Khalid M.Cureus. 2020 May 08;12(5):e8021.Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.
- ArticleWang X, Liu M, Nogues IE, Chen T, Xiong X, Bonzel CL, Zhang H, Hong C, Xia Y, Dahal K, Costa L, Cui J, VA Million Veteran Program, Gaziano JM, Kim SC, Ho YL, Cho K, Cai T, Liao KP.Sci Rep. 2024 04 05;14(1):8021.The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10-3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10-131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype-phenotype screens in diverse populations.
- ArticlePadró JM, Pellegrino Vidal RB, Reta M.Anal Bioanal Chem. 2014 Dec;406(30):8021-31.The partition coefficients, P IL/w, of several compounds, some of them of biological and pharmacological interest, between water and room-temperature ionic liquids based on the imidazolium, pyridinium, and phosphonium cations, namely 1-octyl-3-methylimidazolium hexafluorophosphate, N-octylpyridinium tetrafluorophosphate, trihexyl(tetradecyl)phosphonium chloride, trihexyl(tetradecyl)phosphonium bromide, trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide, and trihexyl(tetradecyl)phosphonium dicyanamide, were accurately measured. In this way, we extended our database of partition coefficients in room-temperature ionic liquids previously reported. We employed the solvation parameter model with different probe molecules (the training set) to elucidate the chemical interactions involved in the partition process and discussed the most relevant differences among the three types of ionic liquids. The multiparametric equations obtained with the aforementioned model were used to predict the partition coefficients for compounds (the test set) not present in the training set, most being of biological and pharmacological interest. An excellent agreement between calculated and experimental log P IL/w values was obtained. Thus, the obtained equations can be used to predict, a priori, the extraction efficiency for any compound using these ionic liquids as extraction solvents in liquid-liquid extractions.
- ArticleLi L, Zhang L, Carmona U, Knez M.Chem Commun (Camb). 2014 Jul 28;50(59):8021-3.Light-chain apoferritin lacks ferroxidase activity, which can be supplemented with Pt-nanoparticles. The hybrid bioinorganic nanoparticle outperforms its heavy-chain pendant in terms of ferroxidase activity, mineralization ability and inhibition resistance. Being active in a cellular environment it regulates the iron homeostasis.
- ArticleHaikin Herzberger E, Levy O, Sun B, Miller N, Rahav R, Dana E, Raviv S, Hershko-Klement A, Wiser A.Sci Rep. 2023 05 17;13(1):8021.General anesthesia is frequently administered during oocyte retrieval. Its effects on the outcomes of IVF cycles are uncertain. This study investigated whether administration of general anesthesia (specifically propofol) during oocyte retrieval affects IVF outcomes. A total of 245 women undergoing IVF cycles were included in this retrospective cohort study. IVF outcomes of 129 women who underwent oocyte retrieval under propofol anesthesia and 116 without anesthesia were compared. Data were adjusted for age, BMI, estradiol on triggering day and total gonadotropin dose. The primary outcomes were fertilization, pregnancy and live birth rates. A secondary outcome was the efficiency of follicle retrieval associated with the use of anesthesia. Fertilization rate was lower in retrievals under anesthesia compared to without (53.4% ± 34.8 vs. 63.7% ± 33.6, respectively; p = 0.02). There was no significant difference in the ratio of expected to retrieved oocytes between retrievals with and without anesthesia (0.8 ± 0.4 vs. 0.8 ± 0.8, respectively, p = 0.96). The differences in pregnancy and live birth rates between the groups were not statistically significant. General anesthesia administered during oocyte retrieval may have adverse effects on the fertilization potential of oocytes. This impact on the developmental potential of oocytes may lead to negative IVF outcomes and should be investigated further.
- ArticleLin Y, Guan X, Su J, Chen S, Fu X, Xu X, Deng X, Chang J, Qin A, Shen A, Zhang L.Int J Nanomedicine. 2023;18:8001-8021.Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery.
- ArticleBogaerts T, Van Yperen-De Deyne A, Liu YY, Lynen F, Van Speybroeck V, Van Der Voort P.Chem Commun (Camb). 2013 Sep 21;49(73):8021-3.An enantioselective catalyst, consisting of a chiral Mn(III)salen complex entrapped in the MIL-101 metal organic framework, is reported. For the first time, we assemble a robust MOF-cage around a chiral complex. The heterogeneous catalyst shows the same selectivity as the homogeneous complex and is fully recyclable. Theoretical calculations provide insight into this retention of selectivity.
- ArticleAnalysis of carbon emissions from land cover change during 2000 to 2020 in Shandong Province, China.Zhu L, Xing H, Hou D.Sci Rep. 2022 05 16;12(1):8021.Land cover change affects the carbon emissions of ecosystems in some way. The qualitative and quantitative understanding of carbon emissions from human activities (e.g., land cover change, industrial production, etc.) is highly significant for realizing the objective of carbon neutrality. Therefore, this paper used GlobeLand30 land cover maps, annual average normalised difference vegetation index (NDVI) data, annual average net ecosystem productivity (NEP) data and statistical yearbook data from 2000 to 2020 to explore the relationship between land cover change and carbon emissions. Specifically, it included land cover change, carbon storage changes influenced by land cover change, spatial and temporal analysis of carbon sources and sinks, land use intensity change and anthropogenic carbon emissions. The results of the study show that the main land cover changes in Shandong province during 2000-2020 was cultivated land conversion to artificial surfaces. Among them, the area of cultivated land converted to artificial surfaces from 2000 to 2010 was 4930.62 km2, and the proportion of cultivated land converted to artificial surfaces from 2010 to 2020 was as high as 78.35%. The total carbon stock of vegetation affected by land cover change decreased by 463.96 × 104 t and 193.50 × 104 t in 2000-2010 and 2010-2020 respectively. The spatial and temporal distribution of carbon sources and sinks differed more markedly from 2000 to 2020, and land use intensity changes in Shandong Province showed an upward trend. Of the total energy production, industry has the largest energy consumption, followed closely by total energy consumption in transportation, storage and postal services.
- ArticleLatunde-Dada S, Bott R, Hampton K, Leszczyszyn OI.Anal Chem. 2015 Aug 04;87(15):8021-5.Taylor dispersion analysis (TDA) is a fast and simple method for determining hydrodynamic radii. The method is applicable under conditions that allow the solute molecules to diffuse appreciably across the cross section of the flow before its measurement. This mitigates the effects of early stage convection on the dispersion and thus imposes a lower bound on the value of the diffusion coefficient measurable at a given flow speed. In this paper, we use the exact solution to the dispersion problem to analyze solutes outside the limits of TDA. Furthermore, by modeling the early stage convection, we analyze a mixture of two solutes with significantly different sizes that mimics heavily aggregated samples. The results obtained from the fits in both cases were in good agreement to the expected values. This demonstrates the potential of the model to extend dispersion analysis to regimes well outside the TDA limits such as the analysis of large molecules and the use of high flow-rates.
- ArticleGeneration of microswimmers from passive Brownian particles in a spherically aberrated optical trap.Mondal A, Roy B, Banerjee A.Opt Express. 2015 Mar 23;23(6):8021-8.We induce spontaneous motion that is both directed and complex in micron-sized asymmetric Brownian particles in a spherically aberrated optical trap to generate microswimmers. The aberrated optical trap is prepared in a slightly modified optical tweezers configuration where we use a refractive index mismatched cover slip leading to the formation of an annular intensity distribution near the trap focal plane. Asymmetric scattering from a micro-particle trapped in this annular trap gives rise to a net tangential force on the particle causing it to revolve spontaneously in the intensity ring. The rate of revolution can be controlled from sub-Hz to a few Hz by changing the intensity of the trapping light. Theoretical simulations performed using finite-difference time-domain method verify the experimental observations. We also experimentally demonstrate simultaneous spin and revolution of a micro-swimmer which shows that complex motion can be achieved by designing a suitable shape of a micro-swimmer in the optical potential.
- ArticleSousa CEB, Medeiros CMS, Pereira RF, Neto AA, Neto MAV.Heliyon. 2021 Sep;7(9):e08021.The vast majority of goat skin processed by traditional tanneries comes from small rural producers. Thus, with the predominance of rustic creation, slaughter, and skinning methods, the batches of hides processed by tanneries have a very heterogeneous quality. Thus, there is a need to categorize the samples according to the quantity and location of defects. The categorization process is subjective and strongly influenced by the experience of the professional classifier, causing a lack of homogeneity in the composition of the goat hide lots for sale. Aiming to reduce failures in the categorization of goatskin samples, the authors investigate the application of computer vision and artificial intelligence on a set of previously categorized wet blue goatskin photographic samples. That said, is analyzed the capacity of different classifiers, with different paradigms, in detecting defects in goatskin samples and in categorizing these samples among seven possible quality levels. A hit rate of 95.9% was achieved in detecting defects and 93.3% in categorizing quality levels. The results suggest that the proposed methodology can be used as a decision aid tool in the qualification process of goat leather samples, which can reduce sample labeling errors.
- ArticleWang X, Yang P, Zheng J, Liu P, Wei C, Guo J, Zhang Y, Zhao D.Sci Rep. 2021 04 13;11(1):8021.At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.
- ArticleBakker E.Anal Chem. 2014 Aug 19;86(16):8021-4.The group of Egorov has recently proposed an elegant method to determine unbiased selectivity coefficients of ion-selective electrodes (Egorov et al. Anal. Chem. 2014, 86, 3693). Once the electrode is exposed to a solution containing only interfering ions, the time-dependent experimental selectivity coefficients are plotted as a function of the inverse fourth root of time and extrapolated to zero. The principal assumption of the approach is the progression of the diffusion layer in the membrane phase with square root of time. This letter critically evaluates the usefulness of this methodology by finite element analysis. The results suggest that the improvement of observed selectivity values are highly significant for an initially uniform distribution of primary ions across the membrane, strongly supporting the methodology. When strong inward ion fluxes of primary ions are present instead, a modification of the method by extrapolation of logarithmic selectivity coefficients appears to give the best results.
- ArticleHartmann S, Beasley A, Mozhayeva D, Engelhard C, Witte K.Sci Rep. 2020 05 15;10(1):8021.One major environmental problem of our time are emerging contaminants in the aquatic environment. While nanoparticles exhibit attractive features such as antimicrobial properties in the case of silver nanoparticles (AgNPs), earlier studies suggest that NPs are not completely filtered out at wastewater treatment plants and may therefore be continuously introduced into the aquatic environment. Although adverse effects of AgNPs on aquatic organisms have been extensively studied, there is still a lack of knowledge on how this chemical stressor interacts with natural cues on the maternal and subsequent generation of aquatic organisms. We tested whether AgNPs (NM-300K, 14.9 ± 2.4 nm, concentration range: 2.5 µg/L - 20 µg/L) affect the kairomone-induced adaptive anti-predator defence mechanism in maternal Daphnia and their offspring. While maternal Daphnia developed typical anti-predator defence mechanisms when exposed to kairomones and AgNPs, their offspring could not develop such adaptive defensive traits. The lack of this defence mechanism in offspring could have dramatic negative consequences (e.g. reduced Daphnia population) for the entire complex food web in the aquatic ecosystem. For a realistic risk assessment, it is extremely important to test combinations of chemical stressors because aquatic organisms are exposed to several natural and artificial chemical stressors at the same time.
- ArticleGalperin I, Javeed A, Luig H, Lochnit G, Rühl M.Appl Microbiol Biotechnol. 2016 Sep;100(18):8021-30.Aryl-alcohol oxidases (AAOs) are enzymes supporting the degradation of lignin by fungal derived class II peroxidases produced by white-rot fungi. AAOs are able to generate H2O2 as a by-product via oxidation of an aryl-alcohol into its correspondent aldehyde. In this study, an AAO was heterologously expressed in a basidiomycete host for the first time. The gene for an AAO of the white-rot fungus Pleurotus sapidus, a close relative to the oyster mushroom Pleurotus ostreatus, was cloned into an expression vector and put under control of the promotor of the glyceraldehyde-3-phosphate dehydrogenase gene 2 (gpdII) of the button mushroom Agaricus bisporus. The expression vector was transformed into the model basidiomycete Coprinopsis cinerea, and several positive transformants were obtained. The best producing transformants were grown in shake-flasks and in a stirred tank reactor reaching enzymatic activities of up to 125 U L(-1) using veratryl alcohol as a substrate. The purified AAO was biochemically characterized and compared to the previously described native and recombinant AAOs from other Pleurotus species. In addition, a two-enzyme system comprising a dye-decolorizing peroxidase (DyP) from Mycetinis scorodonius and the P. sapidus AAO was successfully employed to bleach the anthraquinone dye Reactive Blue 5.
- ArticleHartung F, Jamrozik A, Rosen ME, Aguirre G, Sarwer DB, Chatterjee A.Sci Rep. 2019 05 29;9(1):8021.Faces are among the most salient and relevant visual and social stimuli that humans encounter. Attractive faces are associated with positive character traits and social skills and automatically evoke larger neural responses than faces of average attractiveness in ventral occipito-temporal cortical areas. Little is known about the behavioral and neural responses to disfigured faces. In two experiments, we tested the hypotheses that people harbor a disfigured is bad bias and that ventral visual neural responses, known to be amplified to attractive faces, represent an attentional effect to facial salience rather than to their rewarding properties. In our behavioral study (N = 79), we confirmed the existence of an implicit 'disfigured is bad' bias. In our functional MRI experiment (N = 31), neural responses to photographs of disfigured faces before treatment evoked greater neural responses within ventral occipito-temporal cortex and diminished responses within anterior cingulate cortex. The occipito-temporal activity supports the hypothesis that these areas are sensitive to attentional, rather than reward properties of faces. The relative deactivation in anterior cingulate cortex, informed by our behavioral study, may reflect suppressed empathy and social cognition and indicate evidence of a possible neural mechanism underlying dehumanization.
- ArticleImani-Saber Z, Ghafouri-Fard S.Asian Pac J Cancer Prev. 2014;15(19):8021-8.The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha (RARα). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.