A
bstract
We find a class of novel black holes in higher derivative theory. The novel black holes follow behavior of Schwarzschild ones at large mass limit, while dramatically differentiate from ...Schwarzschild ones for little holes because of the effects which may root in quantum gravity. The temperature of the hole takes maximum for a specific mass, which is related to the new sale introduced in the higher derivative theory, and goes to zero at little mass limit. This property leads to a significant observation that the novel black hole may be a candidate for dark matters evading constraint from
γ
-ray burst.
: We have previously shown that high-mobility group box 1 (
) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of
in tumor development ...and progression remains largely unknown. In this study, we investigated the molecular mechanisms of
in PCa tumorigenesis.
: Gain-of-function and loss-of-function experiments were used to determine the biological functions of
both
and
. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between
and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of
and its relationship with Brahma-related gene 1 (
) was examined by immunohistochemistry.
: The results demonstrated that ectopic expression of
facilitated growth and metastasis of PCa by enhancing
signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of
showed the opposite effects. Mechanistically,
exerted these functions through its interaction with
which may augment
function and activate the
signaling pathway thereby promoting EMT. Importantly, both
and
expression was markedly increased in human PCa tissues.
: Taken together, these findings indicate that upregulation of
promotes PCa development
activation of
and accelerates metastasis through regulating
-mediated EMT.
could be used as a novel potential target for the treatment of PCa.
The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed ...that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.
This study is aimed at exploring the possible mechanism of action of the Suanzaoren decoction (SZRD) in the treatment of Parkinson’s disease with sleep disorder (PDSD) based on network pharmacology ...and molecular docking. Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the bioactive components and targets of SZRD, and their targets were standardized using the UniProt platform. The disease targets of “Parkinson’s disease (PD)” and “Sleep disorder (SD)” were collected by OMIM, GeneCards, and DisGeNET databases. Thereafter, the protein-protein interaction (PPI) network was constructed using the STRING platform and visualized by Cytoscape (3.7.2) software. Then, the DAVID platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Cytoscape (3.7.2) software was also used to construct the network of the “herb-component-target-pathway.” The core active ingredients and core action targets of the drug were verified by molecular docking using AutoDock software. A total of 135 Chinese herbal components and 41 corresponding targets were predicted for the treatment of PDSD using SZRD. Fifteen important signaling pathways were screened, such as the cancer pathway, TNF signaling pathway, PI3K-AKT signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway. The results of molecular docking showed that the main active compounds could bind to the representative targets and exhibit good affinity. This study revealed that SZRD has the characteristics and advantages of “multicomponent, multitarget, and multipathway” in the treatment of PDSD; among these, the combination of the main active components of quercetin and kaempferol with the key targets of AKT1, IL6, MAPK1, TP53, and VEGFA may be one of the important mechanisms. This study provides a theoretical basis for further study of the material basis and molecular mechanism of SZRD in the treatment of PDSD.
Open-framework chalcogenides with ion-exchange capacity are promising materials for removing hazardous heavy-metal ions and for capturing radioactive Cs+. However, research on the exchange mechanism ...is limited, especially for the framework chalcogenides that have multiple bridging anions. Generally, open-framework chalcogenides that have multiple bridging anions at the window or wall of the channels are rigid during the ion-exchange process. We show here that microporous sulfides with μ3-S2– (where μ3 = triple bridging mode) at the windows exhibit framework flexibility upon ion exchange. Three new microporous sulfides Na4Cu8Ge3S12·2H2O (1), Na3(Hen)Cu8Sn3S12 (where en = ethylenediamine) (2) and (dap)2(Hdap)4Cu8Ge3S18 (where dap = 1,2-diaminopropane) (3) were synthesized under solvothermal conditions. Compounds 1 and 2 contain a copper-rich framework composed of icosahedral Cu8S1216– units linked via monomeric GeS4 4– or SnS4 4– tetrahedral units, whereas compound 3 features an expanded framework composed of icosahedral Cu8S1216‑ units interconnected with dimeric Ge2S6 4– units. These compounds exhibit unusual ion-exchange properties. Specifically, the frameworks of 1 and 2 (with μ3-S at the small windows) show “breathing action” upon ion exchange of K+ or Rb+, which have relative large sizes, and compound 3 exhibits framework flexibility upon Cs+ ion exchange with both space group and channels changed.
•A hydrothermal method via surfactant template was used to prepare NiOOH nanosheets.•Physical bath deposition strategy was used to assemble nanosheets on EPGC electrode.•NiOOH/EPGC exhibits excellent ...electrocatalytic activities toward glucose and methanol.•Good analytical performance is obtained for detection of glucose and methanol.
The aqueous NiOOH nanosheets were synthesized using a hydrothermal method via a surfactant template under mild reaction conditions. The as-prepared products were characterized by atomic force microscopy (AFM), X-ray diffraction (XRD) and scanning electron microscopy (SEM), the results of which indicated that ultrathin and porous NiOOH nanosheets with a thickness of only several nanometers have been obtained. The obtained NiOOH nanosheets were subsequently assembled on electrochemically pretreated glassy carbon (EPGC) electrode through a simple physical bath deposition method to form NiOOH/EPGC electrode. SEM, energy dispersive X-ray spectroscopy (EDX) and electrochemical impedance spectroscopy (EIS) proved the successful assembly of NiOOH on EPGC surface. The effective deposition of NiOOH electrocatalyst on electrode is believed to result from the higher surface area and higher surface concentration of CO functional groups existing on EPGC surface. Glucose and methanol were selected as model molecules to investigate the electrocatalytic performance of NiOOH/EPGC electrode. The electrochemical experiments revealed that a favorable activity of the NiOOH/EPGC electrode toward electrooxidation of glucose and methanol has been found. The present NiOOH/EPGC based amperometric sensor exhibited a rapid and highly sensitive response to glucose and methanol, which might find promising applications in medical applications, biological fuel cells and food industries.
Two new 3D hybrid framework iodides, Hmta(Hmta)Ag4I4 (1; Hmta = hexamethylenetetramine) and (Hmta)2Ag8I6I2 (2), have been synthesized under solvothermal conditions. Compound 1 consists of a ...neutral 3D framework built up from alternation of the tetrahedral Ag4I4 unit and Hmta with dia-b topology. Compound 2 features a 3D cationic framework with flu topology, constructed by cationic Ag8I62+ units linked with Hmta. Tetrahedral Hmta plays crucial structure-directing roles in the formation of these 3D frameworks with high symmetry. The temperature-dependent photoluminescent measurement reveals luminescent thermochromism of the compounds, the emission maximum of which shows a gradual blue shift with increasing temperature. The results indicate that 1 is a promising wavelength- and intensity-dependent luminescent thermometer applicable in two different temperature ranges.
Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies ...have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H2O2) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2. Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People's Hospital, China (approval No. 2018PHC081) on December 18, 2018.
Wilson disease (WD) is a rare hereditary copper metabolism disorder, wherein cognitive impairment is a common clinical symptom. Chrysophanol (CHR) is an active compound with neuroprotective effects. ...The study aims to investigate the neuroprotective effect of CHR in WD and attempted to understand the potential mechanisms. Network pharmacology analysis was applied to predict the core target genes of CHR against cognitive impairment in WD. The rats fed with copper-laden diet for 12 weeks, and the effect of CHR on the copper content in liver and 24-h urine, the learning and memory ability, the morphological changes and the apoptosis level of neurons in hippocampal CA1 region, the expression level of Bax, Bcl-2, Cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT proteins were detected. Network pharmacology analysis showed that cell apoptosis and PI3K-AKT signaling pathway might be the main participants in CHR against cognitive impairment in WD. The experiments showed that CHR could reduce the copper content in liver, increase the copper content in 24-h urine, improve the ability of the learning and memory, alleviate the damage and apoptosis level of hippocampal neurons, down-regulate the expression of Bax, Cleaved Caspase-3, and up-regulate the expressions of Bcl-2, p-PI3K/PI3K, p-AKT/AKT. These results suggested that CHR could alleviate cognitive impairment in WD by inhibiting cell apoptosis and triggering the PI3K-AKT signaling pathway.
Graphical abstract
Luminescent thermochromic materials with a dramatic shift of emission band under different temperatures are highly desirable in temperature sensing fields. However, the design of the synthesis of ...such compounds remains a great challenge. In this work, two new luminescent thermochromic silver iodides, (emIm)Ag3I4 (1) and (emIm)Ag2I3 (2) (emIm = 1-ethyl-3-methyl imidazole), have been synthesized under solvothermal conditions. Compound 1 features a Ag3I4− anionic layer, while compound 2 possesses an infinite Ag2I3− chain structure, both of which are charge balanced by emIm+ cations. Particularly, they display luminescent thermochromism with a significant wavelength shift of emission maximum with temperature change. They represent rare examples of infinite layered or chain silver iodides that show luminescent thermochromism. Furthermore, the results indicate that compounds 1 and 2 are promising wavelength-dependent luminescent thermometers.
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