•Geological-entropy-based hydraulic properties of DFN are investigated.•A unified relation between anisotropic permeability and entropy index is proposed.•There is a power-law relationship of ...hydraulic REV size versus entropy scale.
To investigate the intrinsic association between geometrical properties and permeability of anisotropic fractured media, a methodology of geological entropy is applied to anisotropic fracture networks for the evaluation of seepage fields. By integrating the synthetic effect of fracture geometrical parameters (e.g., trace length, spacing, dip angle, and aperture), the global connectivity of fracture networks is quantified by the entropy scale (Hs), while the directional entropy scale (Hs,α) is used to characterize the local geometrical anisotropy in arbitrary orientations. A series of hydraulic representative elementary volumes (REVs) of fracture patterns with various geometrical properties are acquired based on continuum analysis. The permeability in the continuum scale is obtained from steady-state flow simulations. Sensitivity analyses are performed to understand the geometrical dependence of permeability parameters regarding entropy indices. It is found that a systematic increase in trace length, spacing, and dip angle is correlated with an increase, decrease, and equilibrium in entropy, respectively, which corresponds to a change in hydraulic REV sizes that can be expressed as a power-law function related to the Hs. Moreover, Hs,α can well explain the permeability anisotropy resulting from the spatial order of fracture networks, and a unified mathematical relationship for the effective permeability coefficients in arbitrary orientations versus the Hs,α is proposed, independent of variations in fracture patterns and scales. The results indicate that geological entropy, related to the geometrical properties and spatial distribution of fractures, is appropriate to characterize the permeability of anisotropic systems.
With an extension of the geological entropy concept in porous media, the approach called directional entrogram is applied to link hydraulic behavior to the anisotropy of the 3D fracture networks. A ...metric called directional entropic scale is used to measure the anisotropy of spatial order in different directions. Compared with the traditional connectivity indexes based on the statistics of fracture geometry, the directional entropic scale is capable to quantify the anisotropy of connectivity and hydraulic conductivity in heterogeneous 3D fracture networks. According to the numerical analysis of directional entrogram and fluid flow in a number of the 3D fracture networks, the hydraulic conductivities and entropic scales in different directions both increase with spatial order (i.e., trace length decreasing and spacing increasing) and are independent of the dip angle. As a result, the nonlinear correlation between the hydraulic conductivities and entropic scales from different directions can be unified as quadratic polynomial function, which can shed light on the anisotropic effect of spatial order and global entropy on the heterogeneous hydraulic behaviors.
Glypican-3 (GPC3) has been widely recognized in the progression of liver tumors for several years. The relationship between overexpression of GPC3 and the poorer prognosis of patients with ...hepatocellular carcinoma (HCC) was performed by 2 meta-analyses. However, there were also some latest literatures that indicated different conclusions distinctly. It is necessary for us to carry out a meta-analysis by adding the latest data from current studies to explore the correlation between GPC3 and prognostic value in HCC.
We conducted a meta-analysis including a total of 14 studies to assess the potential prognostic significance of GPC3 expression for overall survival (OS) and disease-free survival (DFS). The expression of GPC3 was assessed by immunohistochemistry.
Fourteen studies with 2364 patients were incorporated in the meta-analysis. The combined hazard ratios (HRs) revealed that the overexpression of GPC3 could forecast a poor OS n = 2233 in 12 studies, HR = 1.40, 95% confidence interval (95% CI): 1.07-1.85, Z = 2.42, P = .02 and DFS (n = 1308 in 10 studies, HR = 1.61, 95% CI: 1.13-2.30, Z = 2.63, P = .008) in HCC patients. Subgroup treated by hepatectomy indicated that the pooled HR of OS was 1.43 (95% CI: 1.01-2.01, P = .04) and the combined HR of DFS was 1.59 (95% CI: 1.09-2.31, P = .02). The pooled odds ratios (ORs) showed that high GPC3 expression was also extensively associated with worse tumor differentiation, later tumor stage, presence of vascular invasion, and hepatitis B virus (HBV) infection. Subgroup analyses for GPC3 on HCC OS based on the studies categorized by regions, follow-up period, and sample size were also conducted.
The meta-analysis indicated that overexpression of GPC3 was significantly associated with poor prognosis in patients with HCC.
Phosphodiesterase 4D interacting protein (PDE4DIP) is a centrosome/Golgi protein associated with cyclic nucleotide phosphodiesterases. PDE4DIP is commonly mutated in human cancers, and its alteration ...in mice leads to a predisposition to intestinal cancer. However, the biological function of PDE4DIP in human cancer remains obscure. Here, we report for the first time the oncogenic role of PDE4DIP in colorectal cancer (CRC) growth and adaptive MEK inhibitor (MEKi) resistance. We show that the expression of PDE4DIP is upregulated in CRC tissues and associated with the clinical characteristics and poor prognosis of CRC patients. Knockdown of PDE4DIP impairs the growth of KRAS-mutant CRC cells by inhibiting the core RAS signaling pathway. PDE4DIP plays an essential role in the full activation of oncogenic RAS/ERK signaling by suppressing the expression of the RAS GTPase-activating protein (RasGAP) neurofibromin (NF1). Mechanistically, PDE4DIP promotes the recruitment of PLCγ/PKCε to the Golgi apparatus, leading to constitutive activation of PKCε, which triggers the degradation of NF1. Upregulation of PDE4DIP results in adaptive MEKi resistance in KRAS-mutant CRC by reactivating the RAS/ERK pathway. Our work reveals a novel functional link between PDE4DIP and NF1/RAS signal transduction and suggests that targeting PDE4DIP is a promising therapeutic strategy for KRAS-mutant CRC.
Strategy management alludes to the organizational and environmental factors that shape firms’ propensities to make research and development (R&D) investments. We complement this literature by ...building on vicarious learning to explain how a firm determines its own R&D investment level based on the R&D investment patterns of partners and competitors. Using panel data on firms publicly traded in China, we show an inverted U-shaped relationship between a firm’s R&D investment pattern and the R&D investment patterns of its partners and competitors. Convergence is driven by imitation and legitimation while divergence is explained by risk perception. We conclude that competitors represent a more valuable reference than partners. Our findings advance research on vicarious learning and the antecedents of R&D investments, underscoring the role of interdependence in influencing firms’ R&D investment decisions.
•Achieving CoFe alloy & Co + Fe2C in Co-Fe bimetallic catalysts by a strategic precursor addition.•Ensuring consistent metal size and support properties for each catalyst.•Investigating the ...performance mechanism of three active phases in FTS.•Leveraging Co-Fe interaction in CoFe alloy to optimize CO/H2 adsorption behaviors.•Enhancing FTS performance through increased strongly adsorbed CO and improved CO/H2 ratio.
In the realm of Fischer-Tropsch synthesis (FTS), the escalating cost of cobalt has spurred interest in Co-Fe bimetallic catalysts as substitutes for monometallic Co catalysts. Unfortunately, it is difficult to clarify specific functions and interactions of the two phases, as investigating catalysts in a unified dimension of both metal and support is still a challenge. Herein, we realize precise control over synthesizing nitrogen-doped carbon materials supported bimetallic catalysts containing CoFe alloy and Co + Fe2C dual active phases. The catalysts are comprehensively characterized to address the above problem by excluding the influence of metal sizes and support properties. Our findings reveal that compared to metallic Co alone and Co + Fe2C dual active phases, the Co-Fe interaction in CoFe alloy with electron transfer from Fe to Co optimizes reactant adsorption behaviors through achieving a larger number of strongly adsorbed CO per active site to increase the density of C* adsorbates and a higher surface CO/H2 ratio to inhibit the hydrogenation of CHx* intermediates for chain termination, as well as an appropriate ability for CO adsorption/ dissociation. These advantages collectively enhance both CO activation and C-C coupling, and consequently, the CoFe/NC (CoFe alloy) catalyst exhibits the superior catalytic performance in the cobalt space–time yield in C5+ products (3011.2 gC5+ kgCo−1h−1), which surpasses the Co/NC (monometallic Co) and Co + Fe/NC (Co + Fe2C dual active phases) by 2.2 times and 2.4 times, respectively. This study serves as a promising route for the development of efficient and low-cost bimetallic catalysts through the strategic arrangement of multiple active phases for various reactions.
Objective
This study aimed to elucidate the underlying mechanisms of ameloblastoma (AM) through integrated bioinformatics analysis.
Methods
We downloaded two microarrays of AMs from the GEO database ...and identified differentially expressed genes (DEGs) by integrated bioinformatics analysis. The enrichment analysis of DEGs was conducted to characterize GO and KEGG pathways. Protein‐protein interaction (PPI) network and hub genes were screened via STRING and Cytoscape. CIBERSORT algorithm was utilized to analyze immune infiltration in AMs. We also verified the diagnostic and therapeutic value of hub genes.
Results
Overall, 776 DEGs were identified in AMs through bioinformatics analysis. The function enrichment analysis shed light on pathways involved in AMs. Subsequently, we screened six hub genes via PPI network. Furthermore, we evaluated immune infiltration in AMs and found that macrophages may be participating in the progression of AMs. The upregulated expression of FN1 was related to the macrophages M2 polarization. Finally, ROC analysis indicated that six hub genes had high diagnostic value for AMs and 11 drugs interacted with upregulated hub genes were identified by screening the DGIdb database.
Conclusion
This study revealed the underlying mechanisms of pathogenesis and biological behavior of AMs and provided candidate targets for the diagnosis and treatment of AMs.
The noncircular synchronous belt drive mechanism has demonstrated certain achievements and has been used in special fields. Research regarding noncircular synchronous belt drive mechanisms has ...focused on optimization design and kinematic analysis in China, whereas two pulley noncircular synchronous belt transmissions have been developed overseas. However, owing to the noncircular characteristics of the belt pulley, the real-time variation in the belt length slack during the transmission of the noncircular synchronous belt is significant, resulting in high probabilities of skipping and vibration. In this study, a noncircular tensioning pulley is added to create a stable three-pulley noncircular synchronous belt driving mechanism and a good synchronous belt tensioning, with no skipping; hence, the non-uniform output characteristic of the driven pulley is consistent with the theoretical value. In the circular noncircular noncircular three-pulley noncircular synchronous belt mechanism, the pitch curve of the driving synchronous belt pulley is circular, whereas those of the driven synchronous belt and tensioning pulleys are noncircular. To minimize the slack of the belt length of the synchronous belt and the constraint of the concavity and circumference of the tensioning pulley, an automatic optimization model of the tensioning pulley pitch curve is established. The motion simulation, analysis, and optimization code for a three-belt-pulley noncircular synchronous belt drive mechanism is written, and the variation in belt length slack under different speed ratios is analyzed based on several examples. The testbed for a circular–noncircular–noncircular three-pulley noncircular synchronous belt transmission mechanism is developed. The test shows that the three-pulley noncircular synchronous belt drives well. This study proposes an automatic optimization algorithm for the tensioning pulley pitch curve of a noncircular synchronous belt transmission mechanism; it yields a stable transmission of the noncircular synchronous belt transmission mechanism as well as non-uniform output characteristics.
The effects of molecular size on SiO
2
deposition regulated surface barriers and zeolite catalysis are probed, taking
n
-pentane isomerization and benzene alkylation with ethylene as model reactions. ...Chemical liquid deposition of SiO
2
on the parent ZSM-5 sample only modifies its external surface slightly and passivates a small proportion of Brønsted acid sites. The apparent diffusivities increase significantly at 363–393K after SiO
2
deposition, indicating SiO
2
on ZSM-5 crystals reduces surface barriers at low temperatures. The conversion for
n
-pentane isomerization increases by up to 26% after SiO
2
deposition, while the conversion for benzene alkylation decreases by up to 19%. Obviously, the positive effect of SiO
2
deposition can be balanced out by the pore confinement effect at high temperatures, which is stronger for a larger molecule. This work provides a unique understanding of molecular size effects on surface barriers, which should serve to guide the design of zeolite catalysts.
Graphical Abstract
The family of graphene has attracted increasing attention on account of their large specific surface area and good mechanical properties in the biomedical field. However, some characteristics like ...targeted delivery property and drug delivery capacity could not satisfy the need of a drug carrier. Herein, a graphene oxide (GO) nanocarrier was designed by modification of a folic acid (FA) derivative and a β-cyclodextrin (β-CD) derivative in order to improve two properties, respectively. In the first step, reactive or crosslinkable FA and aldehydic β-CD (β-CD-CHO) were designed and synthesized for further modification. In the second step, synthesized functional molecules were coupled onto GO sheets one by one to obtain the GO nanocarrier. IR spectra and XRD results were used to identify the chemical and structural information before and after modification for the GO nanocarrier. The final GO nanocarrier exhibited a typical thin wrinkled sheet morphology of the GO sheet without any influence by two functional molecules. Finally, in vitro evaluation was used to clarify the drug loading and controlling capacity of the nanocarrier as a drug delivery system. The results revealed that the GO nanocarrier had a better CPT loading capacity and showed better controllability for CPT release.
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