A facile one-pot method has been developed to synthesize uniform gold@mesoporous silica nanospheres （Au@MSNs）, which have a well-defined core-shell structure with ordered mesoporous silica as a ...shell. The resulting Au@MSNs have a high surface area （-521 rna/g） and uniform pore size （-2.5 nm） for the mesoporous silica shell. The diameter of the gold core can be regulated by adjusting the amount of HAuC14. The catalytic performance of the Au@MSNs was investigated using the reduction of 4-nitrophenol as a model reaction. The mesopores of the silica shells provide direct access for the reactant molecules to diffuse and subsequently interact with the gold cores. In addition, the Au@MSNs display the great advantage of sintering-resistance to 950 ℃ because the mesoporous silica shells inhibit aggregation or deformation of the gold cores. The high thermal stability enables the Au@MSNs to be employed in high-temperature catalytic reactions.
In mammalian cells, tumor suppressor p53 plays critical roles in the regulation of glucose metabolism, including glycolysis and oxidative phosphorylation, but whether and how p53 also regulates ...gluconeogenesis is less clear. Here, we report that p53 efficiently down-regulates the expression of phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), which encode rate-limiting enzymes in gluconeogenesis. Cell-based assays demonstrate the p53-dependent nuclear exclusion of forkhead box protein O1 (FoxO1), a key transcription factor that mediates activation of PCK1 and G6PC , with consequent alleviation of FoxO1-dependent gluconeogenesis. Further mechanistic studies show that p53 directly activates expression of the NAD ⁺-dependent histone deacetylase sirtuin 6 (SIRT6), whose interaction with FoxO1 leads to FoxO1 deacetylation and export to the cytoplasm. In support of these observations, p53-mediated FoxO1 nuclear exclusion, down-regulation of PCK1 and G6PC expression, and regulation of glucose levels were confirmed in C57BL/J6 mice and in liver-specific Sirt6 conditional knockout mice. Our results provide insights into mechanisms of metabolism-related p53 functions that may be relevant to tumor suppression.
In this paper, hierarchically ordered macro-/meso porous silica monoliths with 3D fcc packed macropores and 2D hexagonally arranged mesopores are synthesized by using polymer colloidal crystals as ...the hard template and block copolymer Pluronic P123 as a soft template. Through the impregnation of the colloidal crystal hard template with an acidic ethanol solution containing silica source and P123, the entrance size of macropores can be tailored by controlling the synthesis conditions. As the acid concentration increases, the resulting mesopore sizes tend to decrease slightly in the range of 4.7−3.6 nm, meanwhile, the macropore entrance size increase gradually from 0 to ca. 200 nm. These highly ordered macro-/mesoporous silica monoliths have a macropore of about 1.0 μm with tunable window size (0−200 nm), high surface area (ca. 330 m2/g) and large pore volume (∼ 0.36 cm3/g). Biomacromolecule adsorption results show that the porous silica monolith with the macropore entrance of about 50 nm has absorption capacity of ∼16.6 mg/g for bovine serum albumin (BSA, ∼10 nm in size), much higher than that (∼3.4 mg/g) of the porous silica materials without macropore entrance, and the porous materials with or without macropore entrances exhibit similar a adsorption capacity for cytochrome c (Cyt.c, dimension: ∼ 3 nm) (∼36.8 mg/g), suggesting that the large guest molecules can be excluded by the porous silica monoliths without the macopore entrances. These results indicate that, through engineering the pore connection and multimodal pore system, porous materials with hierarchically pores and tailorable window sizes can be created for size-selective applications, such as enrichment, nanofiltration, and drug delivery.
Osteoporosis is a major public health concern that significantly increases the risk of fractures. The aim of this study was to develop a Machine Learning based predictive model to screen individuals ...at high risk of osteoporosis based on chronic disease data, thus facilitating early detection and personalized management. A total of 10,000 complete patient records of primary healthcare data in the German Disease Analyzer database (IMS HEALTH) were included, of which 1293 diagnosed with osteoporosis and 8707 without the condition. The demographic characteristics and chronic disease data, including age, gender, lipid disorder, cancer, COPD, hypertension, heart failure, CHD, diabetes, chronic kidney disease, and stroke were collected from electronic health records. Ten different machine learning algorithms were employed to construct the predictive mode. The performance of the model was further validated and the relative importance of features in the model was analyzed. Out of the ten machine learning algorithms, the Stacker model based on Logistic Regression, AdaBoost Classifier, and Gradient Boosting Classifier demonstrated superior performance. The Stacker model demonstrated excellent performance through ten-fold cross-validation on the training set and ROC curve analysis on the test set. The confusion matrix, lift curve and calibration curves indicated that the Stacker model had optimal clinical utility. Further analysis on feature importance highlighted age, gender, lipid metabolism disorders, cancer, and COPD as the top five influential variables. In this study, a predictive model for osteoporosis based on chronic disease data was developed using machine learning. The model shows great potential in early detection and risk stratification of osteoporosis, ultimately facilitating personalized prevention and management strategies.
Self‐construction: A facile self‐templating strategy is presented for the synthesis of mesoporous carbon nanofibers by using zinc glycolate fibers as the built‐in template. The spectacular ...architectures show excellent performances as recommended electrode material for electrochemical capacitors.
Ecological understandings of soil bacterial community succession and assembly mechanism along elevational gradients in mountains remain not well understood. Here, by employing the high-throughput ...sequencing technique, we systematically examined soil bacterial diversity patterns, the driving factors, and community assembly mechanisms along the elevational gradients of 1800-4100 m on Gongga Mountain in China. Soil bacterial diversity showed an extraordinary stair-step pattern along the elevational gradients. There was an abrupt decrease of bacterial diversity between 2600 and 2800 m, while no significant change at either lower (1800-2600 m) or higher (2800-4100 m) elevations, which coincided with the variation in soil pH. In addition, the community structure differed significantly between the lower and higher elevations, which could be primarily attributed to shifts in soil pH and vegetation types. Although there was no direct effect of MAP and MAT on bacterial community structure, our partial least squares path modeling analysis indicated that bacterial communities were indirectly influenced by climate via the effect on vegetation and the derived effect on soil properties. As for bacterial community assembly mechanisms, the null model analysis suggested that environmental filtering played an overwhelming role in the assembly of bacterial communities in this region. In addition, variation partition analysis indicated that, at lower elevations, environmental attributes explained much larger fraction of the β-deviation than spatial attributes, while spatial attributes increased their contributions at higher elevations. Our results highlight the importance of environmental filtering, as well as elevation-related spatial attributes in structuring soil bacterial communities in mountain ecosystems.
This letter proposes an imaging receiver scheme for an indoor multiple-input-multiple-output (MIMO) visible light communication (VLC), in which a fisheye lens with ultrawide field-of-view is used for ...high-quality imaging, so it can realize omnidirectional receiving and provide high-spatial diversity for decoding of the MIMO signals. In addition, the fisheye lens projects planar and small-sized images, which means that the integration with compact planar receiver array is feasible. Using the polynomial projection model, the optical intensity on the receiving plane is obtained, which is in accordance with the experimental result and shows that the images of the light-emitting diodes are clearly separated. The simulation results indicate that low correlations of the channel matrix are achieved, so high spectral efficiency is realized with various receiver positions under indoor circumstance. Consequently, this fisheye-lens-based imaging receiver is a potential candidate for high-performance indoor MIMO VLC applications.
Invasive aspergillosis is a fungal infection that occurs mainly in immunocompromised patients. It is responsible for a high degree of mortality and is invariably unresponsive to conventional ...antifungal treatments. Histone deacetylase inhibitors can affect the cell cycle, apoptosis and differentiation. The histone deacetylase inhibitor vorinostat (SAHA) has recently received approval for the treatment of cutaneous T cell lymphoma. Here, we investigated the interactions of SAHA and itraconazole, voriconazole, and posaconazole against Aspergillus spp. in vitro using both planktonic cells and biofilms.
We investigated 20 clinical strains using broth microdilution checkerboard methods. The results showed synergy between SAHA and itraconazole, voriconazole, and posaconazole against 60, 40, and 25% of tested isolates of planktonic Aspergillus spp., respectively. Similar synergy was also observed against Aspergillus biofilms. The expression of the azole-associated multidrug efflux pumps MDR1, MDR2, MDR3 and MDR4, as well as that of HSP90, was measured by RT-PCR. The results indicated that the molecular mechanism of the observed synergistic effects in Aspergillus fumigatus may be partly associated with dampened expression of the efflux pump genes and, furthermore, that HSP90 suppression may be a major contributor to the observed synergistic effects of the drugs.
SAHA has potential as a secondary treatment to enhance the effects of azoles against both biofilm and planktonic cells of Aspergillus spp. in vitro. This effect occurs mostly by inhibition of HSP90 expression.
Cancer-associated fibroblasts (CAFs) are considered one of the most critical stromal cells that interact with pancreatic ductal adenocarcinoma (PDAC) and promote tumor growth, metastasis, and ...treatment resistance. Previous studies illustrated macroautophagy/autophagy contributes to CAF activation during tumor progression. Here in our study, we found that autophagy deficiency in CAFs impedes CAF activation by inhibiting proline biosynthesis and collagen production. Furthermore, we uncovered that autophagy promotes proline biosynthesis through mitophagy-mediated regulation of NADK2 (NAD kinase 2, mitochondrial), an enzyme responsible for production of mitochondrial NADP(H). Using an orthotopic mouse model of PDAC, we found that inhibiting mitophagy by targeting PRKN (parkin RBR E3 ubiquitin protein ligase) in the stroma reduced tumor weight. Thus, inhibition of CAFs mitophagy might be an attractive strategy for stroma-focused anti-cancer intervention.
Abbreviations: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ACTB/β-actin: actin, beta; ALDH18A1/P5CS: aldehyde dehydrogenase 18 family, member A1; ATG3: autophagy related 3; ATG5: autophagy related 5; BNIP3L: BCL2/adenovirus E1B interacting protein 3-like; CAFs:cancer-associated fibroblasts; COL1A1: collagen, type I, alpha 1; DES: desmin; ECM: extracellular matrix; FABP4: fatty acid binding protein 4, adipocyte; FAP/FAPα: fibroblast activation protein; IHC: immunohistochemical staining; LAMP1: lysosomal-associated membrane protein 1; NADK2: NAD kinase 2, mitochondrial; PC1: pro-collagen 1; PDAC: pancreatic ductal adenocarcinoma; PDGFR: platelet derived growth factor receptor; PDPN: podoplanin; PRKN: parkin RBR E3 ubiquitin protein ligase; PSCs: pancreatic stellate cells; VIM: vimentin; WT: wild-type
PDF
