The aim of this study was to develop a noninvasive serological diagnostic approach in identifying and evaluating a panel of candidate autoantibodies to tumor‐associated antigens (TAAs) based on ...protein microarray technology for early detection of ovarian cancer (OC). Protein microarray based on 154 proteins encoded by 138 cancer driver genes was used to screen candidate anti‐TAA autoantibodies in a discovery cohort containing 17 OC and 27 normal controls (NC). Indirect enzyme‐linked immunosorbent assay (ELISA) was used to detect the content of candidate anti‐TAA autoantibodies in sera from 140 subjects in the training cohort. Differential anti‐TAA autoantibodies were further validated in the validation cohort with 328 subjects. Subsequently, 112 sera from the patients with ovarian benign diseases with 104 OC sera and 104 NC sera together were recruited to identify the specificity of representative autoantibodies to OC among ovarian diseases. Five TAAs (GNAS, NPM1, FUBP1, p53, and KRAS) were screened out in the discovery phase, in which four of them presented higher levels in OC than controls (P < .05) in the training cohort, which was consistent with the result in the subsequent validation cohort. An optimized panel of three anti‐TAA (GNAS, p53, and NPM1) autoantibodies was identified to have relatively high sensitivity (51.2%), specificity (86.0%), and accuracy (68.6%), respectively. This panel can identify 51% of OC patients with CA125 negative. This study supports our assumption that anti‐TAA autoantibodies can be considered as potential diagnostic biomarkers for detection of OC; especially a panel of three anti‐TAA autoantibodies could be a good tool in immunodiagnosis of OC.
We developed a noninvasive serological diagnostic approach of ovarian cancer (OC). Autoantibodies can be considered as potential biomarkers for the detection of OC. A panel of three anti‐TAA (GNAS, p53, and NPM1) autoantibodies was identified.
Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in the world and is influenced by various sociodemographic factors. This meta-analysis aims to determine the ...worldwide prevalence of POAG in the adult general population for the last 20 years, and explore variation in prevalence by age, gender and geographical location. An electronic literature search was performed using the PubMed, Embase, and Web of Science databases. Population-based cross-sectional or cohort studies published in the last 20 years (2000–2020) that reported prevalence of POAG were recruited. Relevant studies meeting defined eligibility criteria were selected and reviewed systematically by meta-analysis. The prevalence of POAG was analyzed according to various risk factors. A random effect model was used for the meta-analysis. Fifty publications with a total of 198,259 subjects were included in this meta-analysis. The worldwide overall prevalence of POAG was 2.4% (95% CI 2.0 ~ 2.8%). The prevalence increases with age. Men are found to be more susceptible to POAG than women (RR 1.28, p < 0.01). Africa is found to have the highest prevalence of POAG (4.0%) among all continents. The current estimated global population of POAG is 68.56 million (95% CI 59.99 ~ 79.98). POAG is a worldwide vision threatening disease with high prevalence for the last 20 years. The population-based prevalence of POAG varies widely across individual studies, due to variations in risk factors of age, gender, and population geographic location.
New mechanisms for the controlled growth of one‐dimensional (1D) metal–organic framework (MOF) nano‐ and superstructures under size‐confinement and surface‐directing effects have been discovered. ...Through applying interfacial synthesis templated by track‐etched polycarbonate (PCTE) membranes, congruent polycrystalline zeolitic imidazolate framework‐8 (ZIF‐8) solid nanorods and hollow nanotubes were found to form within 100 nm membrane pores, while single crystalline ZIF‐8 nanowires grew inside 30 nm pores, all of which possess large aspect ratios up to 60 and show preferential crystal orientation with the {100} planes aligned parallel to the long axis of the pore. Our findings provide a generalizable method for controlling size, morphology, and lattice orientation of MOF nanomaterials.
Templated interfacial synthesis was applied to metal–organic framework (MOF) growth under both size‐confinement and surface‐directing effects. This led to congruent polycrystalline MOF nanorods and nanotubes, and single crystalline nanowires with large aspect ratios up to 60 and controlled crystal lattice orientation.
Studies on erythropoietin regulation led to discovery of hypoxia-inducible factor 1 (HIF-1), a transcription factor which is central component of oxygen sensing mechanism in mammalian cells. The ...number of HIF-1 and hypoxia-regulated target genes has grown exponentially and includes genes that encode proteins with roles in erythropoiesis, angiogenesis, glycolytic pathway, glucose transport, metastasis, and cell survival. Thus, HIF-1 claimed the role of the master that orchestrates cellular responses to oxygen deprivation. In addition, HIF-1 is also activated or influenced through oxygen-independent mechanisms via growth factors, deregulated oncogenes, and/or tumor suppressors. Whereas HIF prolyl hydroxylases (PHDs) regulate HIF-1 (and subsequently identified HIF-2) during hypoxia, the PI3K, AKT and MAPK pathways mediate primarily non-hypoxic HIF regulation. Here we will focus primarily on pathways that lead to HIF activation via PI3K/AKT, and mTOR/p70S6K1. In addition, recent studies have revealed novel factors and mechanisms that regulate oxygen-independent HIF-1α and HIF-2α degradation. HIFs play important roles in many processes in health and disease. Consequently, HIFs and pathways (PI3K/AKT and mTOR/p70S6K1) that lead to normoxic HIF activation are considered potential therapeutic targets in these pathologies.
MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important roles in various cellular functions and tumor development. Recent studies have indicated that miR-21 is one of the ...important miRNAs associated with tumor growth and metastasis, but the role and molecular mechanism of miR-21 in regulating tumor angiogenesis remain to be elucidated. In this study, miR-21 was overexpressed by transfecting pre-miR-21 into human prostate cancer cells and tumor angiogenesis was assayed using chicken chorioallantoic membrane (CAM). We found that overexpression of miR-21 in DU145 cells increased the expression of HIF-1α and VEGF, and induced tumor angiogenesis. AKT and extracellular regulated kinases (ERK) 1/2 are activated by miR-21. Inhibition of miR-21 by the antigomir blocked this process. Overexpression of the miR-21 target, PTEN, also inhibited tumor angiogenesis by partially inactivating AKT and ERK and decreasing the expression of HIF-1 and VEGF. The AKT and ERK inhibitors, LY294002 and U0126, suppressed HIF-1α and VEGF expression and angiogenesis. Moreover, inhibition of HIF-1α expression alone abolished miR-21-inducing tumor angiogenesis, indicating that HIF-1α is required for miR-21-upregulated angiogenesis. Therefore, we demonstrate that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing HIF-1α and VEGF expression; HIF-1α is a key downstream target of miR-21 in regulating tumor angiogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and ...hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation. This phosphorylation enhances ATG14L-associated class III phosphatidylinositol 3-kinase VPS34 activity by increasing the binding of phosphatidylinositol to VPS34. ARD1-dependent PGK1 acetylation and PGK1-mediated Beclin1 S30 phosphorylation are required for glutamine deprivation- and hypoxia-induced autophagy and brain tumorigenesis. Furthermore, PGK1 K388 acetylation levels correlate with Beclin1 S30 phosphorylation levels and poor prognosis in glioblastoma patients. Our study unearths an important mechanism underlying cellular-stress-induced autophagy initiation in which the protein kinase activity of the metabolic enzyme PGK1 plays an instrumental role and reveals the significance of the mutual regulation of autophagy and cell metabolism in maintaining cell homeostasis.
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•Glutamine deprivation and hypoxia result in ARD1-dependent PGK1 K388 acetylation•PGK1 functioning as a protein kinase phosphorylates Beclin1 at S30•Beclin1 S30 phosphorylation enhances VPS34-Beclin1-ATG14L complex activity•Beclin1 S30 phosphorylation is required for autophagy initiation and tumorigenesis
Qian et al. demonstrate that glutamine deprivation and hypoxia inhibit mTOR and mTOR-dependent ARD1 S228 phosphorylation, which allows ARD1 to bind to PGK1 for PGK1 K388 acetylation. The acetylated PGK1 binds to and phosphorylates Beclin1 at S30, leading to activation of the VPS34-Beclin1 complex to initiate autophagosomal formation.
Abstract
The limited flux and selectivities of current carbon dioxide membranes and the high costs associated with conventional absorption-based CO
2
sequestration call for alternative CO
2
...separation approaches. Here we describe an enzymatically active, ultra-thin, biomimetic membrane enabling CO
2
capture and separation under ambient pressure and temperature conditions. The membrane comprises a ~18-nm-thick close-packed array of 8 nm diameter hydrophilic pores that stabilize water by capillary condensation and precisely accommodate the metalloenzyme carbonic anhydrase (CA). CA catalyzes the rapid interconversion of CO
2
and water into carbonic acid. By minimizing diffusional constraints, stabilizing and concentrating CA within the nanopore array to a concentration 10× greater than achievable in solution, our enzymatic liquid membrane separates CO
2
at room temperature and atmospheric pressure at a rate of 2600 GPU with CO
2
/N
2
and CO
2
/H
2
selectivities as high as 788 and 1500, respectively, the highest combined flux and selectivity yet reported for ambient condition operation.
Carbonized bamboo‐derived carbon nanodots (CNDs) as efficient additives for application in perovskite solar cells (PSCs) are reported. These carboxylic acid‐ and hydroxyl‐rich CNDs interact with the ...perovskite through hydrogen bonds and, thereby, promote the carriers' lifetimes and realize high‐performance p–i–n PSCs having the structure indium tin oxide/NiOx/CH3NH3PbI3 (MAPbI3)/PC61BM/BCP/Ag. As a result of interactions between the CNDs and the perovskite, the presence of the nonvolatile CND additive increases the power conversion efficiency (PCE) of the PSC from 14.48% ± 0.39% to 16.47% ± 0.26%. Furthermore, adding urea, a Lewis base, increases the PCE to 20.2%—the result of a significant increase in the crystal size and a lower content of grain boundary defects and, therefore, longer carrier lifetimes. Cells containing these two additives (without encapsulation) exhibit excellent shelf‐life and air‐stability, maintaining their high PCEs after storage in air—at a temperature of 25 °C and a humidity of 40%—for over 500 h. This performance is among of the best ever reported for p–i–n PSC devices incorporating carbon‐based additives.
High‐performance air‐stable perovskite solar cells are obtained after embedding carbon nanodots and urea into the perovskite. The best device performance features a power conversion efficiency of 20.2%, with negligible hysteresis. The devices displays excellent air‐stability for over 500 h without any encapsulation under 40% humidity (25 °C).
There is ample evidence that retinal dopamine (DA) is involved in the biochemical signaling cascade that controls emmetropization, but it is unknown how its release depends on the spectral ...composition of ambient light. We have studied DA release, refractive development, and growth in chicken eyes that were exposed to light of different spectral bands, and had either normal vision or were covered by frosted diffusers to induce myopia.
Experiment 1: After spending the night in the dark, chicks were exposed to white room light (spectral range, 430-630 nm) or kept in the dark. Additional chicks were unilaterally exposed to blue (peak at 470 nm), red (620 nm), or UV lighting (375 nm) for 30 minutes and their fellow eyes covered with black occluders to minimize light exposure. Experiment 2: In the second experiment, chicks wore diffusers over one eye to induce deprivation myopia and were raised for 5 days in either white room light or in lighting supplied by UV, blue, or red light-emitting diodes (LEDs). Refractive states were recorded daily with infrared photoretinoscopy, and ocular dimensions at the start and end of the experiment with A-scan ultrasonography. DA and its metabolites were measured in retina and vitreous by high pressure liquid chromatography-electrochemical detection (HPLC-ED) in all cases.
Compared to chicks kept in the dark, retinal DA and vitreal 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were clearly elevated after 30 minutes in white light. Vitreal DOPAC was also increased in red, blue, and UV lighting, compared to the fellow eyes covered with black occluders (black occluder versus blue light: 1.31 ± 0.32 vs. 1.70 ± 0.37; red: 1.26 ± 0.33 vs. 1.64 ± 0.38; UV: 1.13 ± 0.19 vs. 1.63 ± 0.21 ng/0.1 g wet weight). Chickens developed significantly less deprivation myopia, with shorter eyes, when raised under UV and blue lighting for 5 days, compared to under red and white light. Eyes with normal vision became more hyperopic in blue and UV lighting. Vitreal DOPAC levels were lowest after 5 days of exposure to UV lighting.
Red, blue, and UV lighting all stimulated the release of retinal DA, but there were wavelength-dependent differences in DA release and metabolism. Less deprivation myopia developed in UV and blue lighting, compared to white and red light. The application of these findings to humans is limited by the fact that, different from chicks, humans have very low sensitivity in the near-UV region of the spectrum.
As one important component of sulfur cathodes, the carbon host plays a key role in the electrochemical performance of lithium‐sulfur (Li‐S) batteries. In this paper, a mesoporous nitrogen‐doped ...carbon (MPNC)‐sulfur nanocomposite is reported as a novel cathode for advanced Li‐S batteries. The nitrogen doping in the MPNC material can effectively promote chemical adsorption between sulfur atoms and oxygen functional groups on the carbon, as verified by X‐ray absorption near edge structure spectroscopy, and the mechanism by which nitrogen enables the behavior is further revealed by density functional theory calculations. Based on the advantages of the porous structure and nitrogen doping, the MPNC‐sulfur cathodes show excellent cycling stability (95% retention within 100 cycles) at a high current density of 0.7 mAh cm‐2 with a high sulfur loading (4.2 mg S cm‐2) and a sulfur content (70 wt%). A high areal capacity (≈3.3 mAh cm‐2) is demonstrated by using the novel cathode, which is crucial for the practical application of Li‐S batteries. It is believed that the important role of nitrogen doping promoted chemical adsorption can be extended for development of other high performance carbon‐sulfur composite cathodes for Li‐S batteries.
The nitrogen‐doped mesoporous carbon material is found to chemically adsorb sulfur, and the related mechanism is revealed by experimental survey and density functional theory calculation. Taking full advantages of chemical adsorption of sulfur, MPNC‐S cathode delivered an excellent capacity retention (95% within 100 cycles), high Coulombic efficiency (>96%), as well as high areal capacity of above 3 mAh cm‐2.
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