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.
Hydrogels with multifunctional properties attracted intensively attention in the field of tissue engineering because of their excellent performance. Also, object-oriented design had been supposed to ...an effective and efficient method for material design as cell scaffold in the field of tissue engineering. Therefore, a scaffold-oriented injectable composite hydrogel was constructed by two components. One was pH-sensitive bifunctional nanoparticles for growth factor delivery to improve biofunctionability of hydrogel scaffold. The other was Diels-alder click crosslinked hyaluronic acid hydrogel as matrix. pH dependent release behavior of nanoparticle component was confirmed by results. And, its bioactivity was verified by
cell culture evaluation. In consideration of high-efficiency and effectiveness, low toxicity, controllability and reversibility, dynamic covalent and reversible Diels-alder click chemistry was used to design a HA hydrogel with two kinds of crosslinking points. The properties of hydrogel like gelation time and swelling ratio were influenced by pH value and polymer concentration. Composite hydrogel was formed by
polymerization, which exhibited acceptable mechanical property as a scaffold for biomedical field. Lastly,
evaluation from results of viability, DNA content and cell morphology confirmed that hydrogels could maintain cell activity and support cell growth. Compared with pure hydrogel, composite hydrogel possessed better properties.
The fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of ...resectable pancreatic cancer has not been elucidated.
A total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively.
The optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage.
FPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions.
The photoisomerization of azobenzene (AZO) makes it a potential type of photoswitch for the field of chemical engineering. However, the lack of stability and photobleaching characteristics of ...reversible photoisomerization have restricted further application of AZO as a photoswitch. Therefore, we have designed two polymers containing the AZO domain as macromolecular photoswitches and investigated their switching performance. The hydrophilic monomers hydroxyethyl methylacrylate (HEMA) and N-vinyl-2-pyrrolidone (NVP) were chosen to copolymerize with the AZO monomer to form HEMA-AZO copolymer and HEMA-NVP-AZO terpolymer. The domain content was calculated by integration of the peaks in the 1H NMR spectrum. Real-time UV spectra of polymer solutions upon UV light irradiation confirmed quick and successful trans-to-cis transition for the AZO domain. In reverse, the operable and controllable recovery processes upon white light were also verified by real-time UV spectra. Furthermore, repeated irradiation by UV light and white light for 20 times was used to check their fatigue resistance and recyclability. Importantly, recovery behaviors for the two polymers could be adjusted by solvent property, environment temperature, and light intensity. Higher environment temperature or higher light intensity resulted in shortened recovery time. The influence of solvent was only slightly different for the two polymers. Nanoassemblies, which were formed by HEMA-NVP-AZO terpolymer and poly(β-cyclodextrin)/poly(α-cyclodextrin), exhibited similar controllable switching performance to the pure polymer. In brief, the effectiveness and efficiency of the polymers as photoswitches have been confirmed by results in this work.
Light-responsive materials have attracted increasing interest in recent years on account of their adjustable on-off properties upon specific light. In consideration of reversible isomerization ...transition for azobenzene (AZO), it was designed as a light-responsive domain for nanoparticles in this research. At the same time, the interaction between AZO domain and β-cyclodextrin (β-CD) domain was designed as a driving force to assemble nanoparticles, which was fabricated by two polymers containing AZO domain and β-CD domain, respectively. The formed nanoparticles were confirmed by Dynamic Light Scattering (DLS) results and Transmission Electron Microscope (TEM) images. An obvious two-phase structure was formed in which the outer layer of nanoparticles was composed of PCD polymer, as verified by
1
HNMR spectroscopy. The efficient and effective light response of the nanoparticles, including quick responsive time, controllable and gradual recovered process and good fatigue resistance, was confirmed by UV-Vis spectroscopy. The size of the nanoparticle could be adjusted by polymer ratio and light irradiation, which was ascribed to its light-response property. Nanoparticles had irreversibly pH dependent characteristics. In order to explore its application as a nanocarrier, drug loading and
in vitro
release profile in different environment were investigated through control of stimuli including light or pH value. Folic acid (FA), as a kind of target fluorescent molecule with specific protein-binding property, was functionalized onto nanoparticles for precise delivery for anticancer drugs. Preliminary
in vitro
cell culture results confirmed efficient and effective curative effect for the nanocarrier on MCF-7 cells.
Azobenzene (AZO) has attracted increasing interest due to its reversible structural change upon a light stimulus. However, poor fatigue durability and the photobleaching phenomenon restricts its ...further application. Herein, the AZO domain as a pendent group, was incorporated into copolymers, which was synthesized by radical copolymerization in the research. Structure-properties of synthesized copolymer can be adjusted by monomer ratios. Emphatically, responsive properties of copolymer in different solutions were investigated. In the DMSO solution, copolymer exhibited effective structural change, stable rapid responsive time (1 min) upon UV light at room temperature, stable relative acceptable recovery time (100 min) upon white light at room temperature, and good fatigue resistance property. In an aqueous solution, even more controllable responsive properties and fatigue resistance properties for copolymer were verified by results. More pervasively, the recovery process could be controlled by light density and temperature. In order to clarify reasons for the difference between the AZO molecule and the AZO domain of copolymer, energy barrier or interactions between single atoms or even structural units was calculated using the density functional theory (DFT). Furthermore, the status of copolymer was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Finally, copolymer was further functionalized with bioactive protein (concanavalin, ConA) to reduce the cytotoxicity of the AZO molecule.
More and more studies show that inflammation, pain and insomnia have become the main common diseases. Effective treatments of inflammation, pain and insomnia have become an issue of primary concern ...in clinical practice. Oleuropein (OLE), the main phenolic component of Mediterranean extra virgin olive oil, has shown many pharmacological properties. In the present study, the anti-inflammatory effect of OLE was firstly evaluated using RAW264.7 macrophages subjected to stimulation with lipopolysaccharide (LPSC). The results obtained revealed that OLE caused significant and dose-dependent downregulation of nitric (NO), COX-2, inducible NO synthase iNOS, and the inflammation-associated cytokines IL-6 and TNF-α. From the mechanism, the expression of COX-2, cytokines IL-6 and TNF-α OLE is closely related to analgesic and sedation effect. Further evaluations showed significant analgesic and sedative effects of OLE in tail-flick test and sedation test conducted in SD rats in vivo. All these results indicate that OLE has anti-inflammatory, analgesic and sedative effects both in vitro and in vivo.
The application of azobenzene (AZO) as a kind of photo-switch is restricted by its excitation source,
i.e.
, UV light. Hence, visible light-driven azobenzene-based photo-switching is needed and has ...been designed in the work. In order to forecast the optimal triggered wavelength, the electrostatic potential, theoretical UV-vis spectra, as well as the energy gap for focused structures was calculated to describe the energy and orbit status of the molecules by DFT. According to the theoretical optimization results,
m
-Methyl Red (
m
-MR) containing copolymer was successfully synthesized as a visible light-driven photo-switch. Further, for performance evaluation, the efficiency and effectiveness of different excitation wavelengths was firstly evaluated for the copolymer using
m
-MR and
m
-Methyl Red acrylic anhydride (
m
-MRAA) as the controls. Compared with
m
-MR and
m
-MRAA, the copolymer exhibited outstanding characteristics as a photo-switch according to its response-recovery behavior. At the same time, blue light proved to be the most efficient excitation light source. Moreover, the equilibrium response time and recovery time showed some dependence on the excitation wavelength. Secondly, the influence of the light intensity on the isomerization transition was investigated. A relatively low light density could lead to a relatively low degree of the final
cis
form and needed more equilibrium time for
trans
to
cis
transformation but showed little effect on the recovery process. Thirdly, repeatable on/off irradiation was used to evaluate the fatigue resistance of the copolymer. Good fatigue resistance without photobleaching was verified from the results. Fourthly, the influence of the solvent on visible light-driven isomerization was also evaluated. Finally, the synthesized copolymer still had the characteristic of a pH indicator with a critical point at pH 5.0 and exhibited an obvious fluorescent characteristic.
The application of azobenzene (AZO) as a kind of photo-switch is restricted by its excitation source,
i.e.
, UV light.
The control of intermetallic compounds (IMCs) is the key to achieve high-performance Al/Cu dissimilar joints. In the present study, the dissimilar metals of 6061-T6 Al and T2 pure Cu were joined by ...submerged friction stir welding (SFSW) technology. The results indicated that the peak temperature and dwelling time at high temperature were obviously reduced by applying additional water cooling in SFSW. In comparison to the joint fabricated by normal friction stir welding (FSW), the thickness of IMCs layer at the interface for the SFSW joint was much thinner and its distribution was more uniform, the formation of IMCs was effectively inhibited during the SFSW process. The Al2Cu phase was first formed at the Al/Cu interface, and then Al4Cu9 phase precipitated between Al2Cu phase and Cu. The tensile properties of the Al/Cu joints were significantly improved by the SFSW process. The maximum tensile strength of 255 MPa was obtained in the SFSW joint, which was 41.7% higher than that of the FSW joint. A higher joint efficiency of 91.1% was reached, which was due to the reduced stress concentration at the interface in SFSW caused by the thinner IMCs layer and lower welding heat input. The fracture occurs within Al2Cu phase or along the interface between Al and Al2Cu layer for the FSW joint. In contrast, the SFSW joint fractures at the HAZ on Cu side, showing favorable ductility.
In this research, the microstructure and micro mechanical property of linear friction welded joint for heteromorphic TC17 titanium alloy were investigated by nanoindentation testing and electron ...backscatter diffraction technique. The results show that the special microstructure in the weld zone (WZ) of the joint has great effects on its micro mechanical property. The WZ is composed of the transformed β phase, which exists in the form of equiaxed substructure, and the microstructure of the WZ can be divided into two parts along the centerline of the weld based on its main orientation. The WZ of the TC17 (α + β) side has the main orientation
⟨
112
⟩
and
⟨
111
⟩
, while the TC17 (β) side has the main orientation
⟨
101
⟩
. Meanwhile, more high angle grain boundaries (HAGB) are found in the WZ of the TC17 (α + β) side. These microstructure characteristics have a significant impact on the micro mechanical property of the WZ. Due to more HAGB are in the WZ of the TC17 (α + β) side than the TC17 (β) side, the interface strengthening effect is a slightly stronger in the TC17 (α + β) side, which leads to better elastic modulus, hardness, and fracture toughness. While the TC17 (α + β) side microstructure has the
101
⟨
111
⟩
and
112
⟨
111
⟩
slip modes that are easier activated under RD direction force, so the microstructure in the WZ of the TC17 (α + β) side has a smaller yield strength and a larger hardening exponent than that in the WZ of the TC17 (β) side. In addition, it was also found that the area in the edge of the WZ near thermo-mechanically affected zone of the TC17 (α + β) side (TC17 (α + β)-TMAZ) has the minimum micro mechanical property and is the weak area of the WZ, which is related to the lower degree of recrystallization compared to other areas of the WZ. This area has the smallest elastic modulus (146.4 MPa), hardness (3.4 GPa), yield strength (904 MPa), and fracture toughness (0.173 MPa*m1/2), while the hardening exponent is 0.107. The macro tensile fracture location also matches the weak area in the WZ of the joints. Besides, it was also found that the average yield strength and tensile strength of the joint are 1016 MPa and 1065 MPa, while the elastic modulus and elongation are 111.2 GPa and 2.1%. And the microhardness distribution of the joint presents a “w” shape, which is due to lower phase α/β interface content in the WZ of the LFW joint for heteromorphic TC17 alloy and leads to the minimum mechanical property.
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