Van der Waals heterostructures formed by assembling different two-dimensional atomic crystals into stacks can lead to many new phenomena and device functionalities. In particular, ...graphene/boron-nitride heterostructures have emerged as a very promising system for band engineering of graphene. However, the intrinsic value and origin of the bandgap in such heterostructures remain unresolved. Here we report the observation of an intrinsic bandgap in epitaxial graphene/boron-nitride heterostructures with zero crystallographic alignment angle. Magneto-optical spectroscopy provides a direct probe of the Landau level transitions in this system and reveals a bandgap of ~38 meV (440 K). Moreover, the Landau level transitions are characterized by effective Fermi velocities with a critical dependence on specific transitions and magnetic field. These findings highlight the important role of many-body interactions in determining the fundamental properties of graphene heterostructures.
Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and has a high mortality rate worldwide. Sorafenib is the only systemic treatment demonstrating a statistically significant but ...modest overall survival benefit. We previously have identified the aurora kinases (AURKs) and FMS-like tyrosine kinase 3 (FLT3) multikinase inhibitor DBPR114 exhibiting broad spectrum anti-tumor effects in both leukemia and solid tumors. The purpose of this study was to evaluate the therapeutic potential of DBPR114 in the treatment of advanced HCC.
Human HCC cell lines with histopathology/genetic background similar to human HCC tumors were used for in vitro and in vivo studies. Human umbilical vein endothelial cells (HUVEC) were used to evaluate the drug effect on endothelial tube formation. Western blotting, immunohistochemical staining, and mRNA sequencing were employed to investigate the mechanisms of drug action. Xenograft models of sorafenib-refractory and sorafenib-acquired resistant HCC were used to evaluate the tumor response to DBPR114.
DBPR114 was active against HCC tumor cell proliferation independent of p53 alteration status and tumor grade in vitro. DBPR114-mediated growth inhibition in HCC cells was associated with apoptosis induction, cell cycle arrest, and polyploidy formation. Further analysis indicated that DBPR114 reduced the phosphorylation levels of AURKs and its substrate histone H3. Moreover, the levels of several active-state receptor tyrosine kinases were downregulated by DBPR114, verifying the mechanisms of DBPR114 action as a multikinase inhibitor in HCC cells. DBPR114 also exhibited anti-angiogenic effect, as demonstrated by inhibiting tumor formation in HUVEC cells. In vivo, DBPR114 induced statistically significant tumor growth inhibition compared with the vehicle control in multiple HCC tumor xenograft models. Histologic analysis revealed that the DBPR114 treatment reduced cell proliferation, and induced apoptotic cell death and multinucleated cell formation. Consistent with the histological findings, gene expression analysis revealed that DBPR114-modulated genes were mostly related to the G2/M checkpoint and mitotic spindle assembly. DBPR114 was efficacious against sorafenib-intrinsic and -acquired resistant HCC tumors. Notably, DBPR114 significantly delayed posttreatment tumor regrowth and prolonged survival compared with the regorafenib group.
Our results indicated that targeting AURK signaling could be a new effective molecular-targeted agent in the treatment of patients with HCC.
Due to their organized structures, remarkable stiffness, and nice biocompatibility and biodegradability, amyloid fibrils serve as building blocks for versatile sustainable materials. Silver ...nanoparticles (AgNPs) are commonly used as the nano-catalysts for various electrochemical reactions. Given their large specific surface area and high surface energy, AgNPs exhibit high aggregation propensity, which hampers their electrocatalytic performance. Food protein wastes have been identified to be associated with climate change and environmental impacts, and a surplus of whey proteins in dairy industries causes high biological and chemical demands, and greenhouse gas emissions. This study is aimed at constructing sustainable electrode surface modifiers using AgNP-deposited whey protein amyloid fibrils (AgNP/WPI-AFs). AgNP/WPI-AFs were synthesized and characterized via spectroscopic techniques, electron microscopy, and X-ray diffraction. Next, the electrocatalytic performance of AgNP/WPI-AF modified electrode was assessed via para-nitrophenol (p-NP) reduction combined with various electrochemical analyses. Moreover, the reaction mechanism of p-NP electrocatalysis on the surface of AgNP/WPI-AF modified electrode was investigated. The detection range, limit of detection, sensitivity, and selectivity of the AgNP/WPI-AF modified electrode were evaluated accordingly. This work not only demonstrates an alternative for whey valorization but also highlights the feasibility of using amyloid-based hybrid materials as the electrode surface modifier for electrochemical sensing purposes.
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•Silver nanoparticles-deposited whey protein fibrils (AgNP/WPI-AFs) were prepared.•Electrode modified by AgNP/WPI-AFs was used for the detection of p-nitrophenol.•NP/AF-modified electrode has better electrocatalytic activity than bare electrode.•Detection limit and sensitivity of NP/AF-modified electrode were determined.•NP/AF-modified electrode shows nice selectivity, reproducibility, and stability.
The properties of amyloid fibrils, e.g., unique structural characteristics and superior biocompatibility, make them a promising vehicle for drug delivery. Here, carboxymethyl cellulose (CMC) and whey ...protein isolate amyloid fibril (WPI-AF) were used to synthesize amyloid-based hybrid membranes as vehicles for the delivery of cationic and hydrophobic drugs (e.g., methylene blue (MB) and riboflavin (RF)). The CMC/WPI-AF membranes were synthesized via chemical crosslinking coupled with phase inversion. The zeta potential and scanning electron microscopy results revealed a negative charge and a pleated surface microstructure with a high content of WPI-AF. FTIR analysis showed that the CMC and WPI-AF were cross-linked via glutaraldehyde and the interacting forces between membrane and MB or RF was found to be electrostatic interaction and hydrogen bonding, respectively. Next, the in vitro drug release from membranes was monitored using UV-vis spectrophotometry. Additionally, two empirical models were used to analyze the drug release data and relevant rate constant and parameters were determined accordingly. Moreover, our results indicated that in vitro drug release rates depended on the drug-matrix interactions and transport mechanism, which could be controlled by altering the WPI-AF content in membrane. This research provides an excellent example of utilizing two-dimensional amyloid-based materials for drug delivery.
Amyloid fibrillogenesis of proteins have been considered as the major cause behind several degenerative diseases. Nanoparticles have been found to have great potential as a substrate for designing ...amyloid fibril inhibitors and/or modulators. This is mainly due to its ideal characteristics, such as small size, high surface area-to volume ratio, and modifiable surface. This study is aimed at examining the influence of amino acid-modified silver nanoparticles on amyloid fibril formation. We first synthesized and characterized the proline- and cysteine-functionalized silver nanoparticles (Pro-AgNP and Cys-AgNP). Next, the effects of functionalized silver nanoparticles on amyloid fibrillogenesis and structural changes of hen lysozyme were examined using various spectroscopic and biophysical tools. Our results showed that Pro-AgNP/Cys-AgNP dose-dependently suppressed lysozyme amyloid fibrillogenesis, whereas negligible fibril-inhibiting effect was observed in the bare AgNP or proline/cysteine. Moreover, reduced solvent exposure and α-to-β transition were detected in lysozyme upon the addition of Pro-AgNP/Cys-AgNP. Finally, the nature of interactions between lysozyme and Pro-AgNP/Cys-AgNP was further examined using fluorescence quenching and molecular docking. By altering the properties of nanoparticles to design suitable nanoprobes, we have shown that amyloid fibrillogenesis can be controlled.
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•Proline-/cysteine-modified silver nanoparticles (Pro-/Cys-AgNP) were prepared.•Pro-AgNP/Cys-AgNP dose-dependently suppresses lysozyme amyloid fibril formation.•Pro-AgNP/Cys-AgNP affect the structure or conformation of hen lysozyme.•Quenching of lysozyme fluorescence by Pro-/Cys-AgNP belongs to the static type.•Nature of Pro-/Cys-AgNP-lysozyme interaction was studied via molecular docking.
Abstract
Objective
To explore the effect of acute normovolemic hemodilution (ANH) on the anesthetic effect, plasma concentration, and postoperative recovery quality in elderly patients undergoing ...spinal surgery.
Methods
A total of 60 cases of elderly patients aged 65 to 75 years who underwent elective multilevel spinal surgery were assigned randomly into the ANH group (n = 30) and control group (n = 30). Hemodynamic and blood gas analysis indexes were observed and recorded before ANH (T
1
), after ANH (T
2
), immediately after postoperative autologous blood transfusion (T
3
), 10 min (T
4
), 20 min (T
5
), 30 min (T
6
), 40 min (T
7
), and 50 min (T
8
) after the transfusion, and at the end of the transfusion (i.e., 60 min; T
9
). At T
3 ~ 9
, bispectral index (BIS) and train-of-four (TOF) stimulation were recorded and the plasma propofol/cisatracurium concentration was determined. The extubation time and recovery quality were recorded.
Results
The ANH group presented a lower MAP value and a higher SVV value at T
2
, and shorter extubation and orientation recovery time (
P
< 0.05) compared with the control group. BIS values at T
8
and T
9
were lower in the ANH group than those in the control group (
P
< 0.05). TOF values at T
7 ~ 9
were lower in the ANH group than those in the control group (
P
< 0.05). There were no statistically significant differences in the postoperative plasma concentrations of propofol and cisatracurium between the groups (
P
> 0.05).
Conclusion
During orthopedic surgery, the plasma concentration of elderly patients is increased after autologous blood transfusion of ANH, and the depth of anesthesia and muscle relaxant effect are strengthened, thus leading to delayed recovery of respiratory function and extubation.
Development of a novel fluorescence enhancement probe for detection of Sn2+ in organisms, with high selectivity and sensitivity, is of great interest but remains a great challenge. Herein, an ...ICT-based fluorescence probe TPPB was rationally developed to act as an ‘enhancement’ luminescent and “naked-eye” indicator for Sn2+ detection. Importantly, spectroscopic studies indicated that TPPB was a fluorescence enhancement sensor for Sn2+ with rapid response, low detection limit (0.116 μM) and excellent binding constant (1.6 × 104 M−1). The mechanism of TPPB response to Sn2+ was further proved by 1H NMR titration, and enhancement calculations. Furthermore, TPPB is applied as a fluorescence probe for imaging in Hela cells, indicated that it can be potentially applied for Sn2+ sensing in biological fields.
The effects of surface treatment of flax fibers featuring vinyltrimethoxy silane (VTMO) and maleic anhydride-polypropylene (MAPP) on the mechanical properties of flax/PP composites were investigated. ...α-polypropylene (α-PP) and β-polypropylene (β-PP) were used as matrices for measuring the mechanical properties of the flax fiber/polypropylene (flax/PP) composites. Flax/PP composites composed of double-covered uncommingled yarn (DCUY) were prepared using a film-stacking technique. The influence of surface treatment on the tensile, flexural, impact, and water uptake properties of Flax/PP composites were investigated. MAPP treatment was suitable for flax/PP composites in terms of superior tensile and impact properties. VTMO treatment showed superior flexural properties and less influence on the impact properties after moisture absorption.
In this study, a polyacrylonitrile nanofiber membrane was first hydrolyzed and then functionalized with tris(hydroxymethyl)aminomethane (P-Tris), then used as an affinity nanofiber membrane for ...lysozyme adsorption in membrane chromatography. The dynamic adsorption behavior of lysozyme was investigated in a flow system under various operating parameters, including adsorption pHs, initial feed lysozyme concentration, loading flow rate, and the number of stacked membrane layers. Four different kinetic models, pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion kinetic models, were applied to experimental data from breakthrough curves of lysozyme. The results showed that the dynamic adsorption results were fitted well with the pseudo-second-order kinetic model. The breakthrough curve experimental results show significant differences in the breakthrough time, the dynamic binding capacity, the length of the mass transfer zone, and the utilization rate of the membrane bed under different operating parameters. Four dynamic adsorption models (i.e., Bohart–Adams, Thomas, Yoon–Nelson, and BDST models) were used to analyze the breakthrough curve characteristics of the dynamic adsorption experiments. Among them, the Yoon–Nelson model was the best model to fit the breakthrough curve. However, some of the theoretical results based on the Thomas and Bohart–Adams model analyses of the breakthrough curve fit well with the experimental data, with an error percentage of <5%. The Bohart–Adams model has the largest difference from the experimental results; hence it is not suitable for breakthrough curve analysis. These results significantly impact dynamic kinetics studies and breakthrough curve characteristic analysis in membrane bed chromatography.
Breast cancer-derived vascular endothelial growth factor-C (VEGF-C) has been shown to enhance lymphangiogenesis in lymph nodes to accelerate cancer metastasis. However, the remodeling of lymph node ...microenvironments by VEGF-C remains elusive. By in vivo selection, we established a subline (named as "LC") with strong lymphatic tropism and high VEGF-C expression from the human MDA-MB-231 breast cancer cell line. Co-culture with LC cells or treatment with LC-conditioned medium upregulated the expression of CXC chemokines in lymphatic endothelial cells (LECs), which could be inhibited by pre-incubation with VEGF-C-neutralizing antibodies and VEGFR3 inhibitors. The chemokines produced by LECs enhanced recruitment of myeloid-derived suppressor cells (MDSCs) to tumor-draining and distant lymph nodes in tumor-bearing mice. Treatment with a CXCR2 inhibitor after tumor cell inoculation dramatically decreased the number of MDSCs in lymph nodes, suggesting the importance of the chemokine/CXCR2 signaling axis in MDSC recruitment. In addition, LEC-released chemokines also stimulated the expression of serum amyloid A1 (SAA1) in cancer cells, enhancing their lymphatic invasion by increasing VE-cadherin phosphorylation, junction disruption, and vascular permeability of LECs. Clinical sample validation confirmed that SAA1 expression was associated with increased lymph node metastasis. Collectively, we reveal a novel mechanism by which cancer cell-derived VEGF-C remodels lymphovascular microenvironments by regulating chemokine production in LECs to promote cancer invasion and MDSC recruitment. Our results also suggest that inhibition of CXCR2 is effective in treating lymphatic metastasis.
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