The effect of surface nucleation modulation on the mechanical and biocompatibility of metal-polymer biomaterials.

The deployment of hernia repair patches in laparoscopic procedures is gradually increasing. In this technology, however, understanding the new phases of titanium from the parent phase on polymer substrates is essential to control the microstructural transition and material properties. It remains a challenging area of condensed matter physics to predict the kinetic and thermodynamic properties of metals on polymer substrates from the molecular scale due to the lack of understanding of the properties of the metal-polymer interface. However, this paper revealed the mechanism of nucleation on polymer substrates and proposed for the first record a time-dependent regulatory mechanism for the polymer-titanium interface. The interconnection between polymer surface chain entanglement, nucleation and growth patterns, crystal structure and surface roughness were effectively unified. The secondary regulation of mechanical properties was accomplished simultaneously to satisfy the requirement of biocompatibility. Titaniumized polypropylene patches prepared by time-dependent magnetron sputtering technology demonstrated excellent interfacial mechanical properties and biocompatibility. In addition, modulation by low-temperature plasma metal deposition opened a new pathway for biomaterials. This paper provides a solid theoretical basis for the research of titanium nanofilms on medical polypropylene substrates and the medical industry of implantable biomaterials, which will be of great value in the future.

Gas Diffusion Layer for Proton Exchange Membrane Fuel Cells: A Review.

Proton exchange membrane fuel cells (PEMFCs) are an attractive type of fuel cell that have received successful commercialization, benefitted from its unique advantages (including an all solid-state structure, a low operating temperature and low environmental impact). In general, the structure of PEMFCs can be regarded as a sequential stacking of functional layers, among which the gas diffusion layer (GDL) plays an important role in connecting bipolar plates and catalyst layers both physically and electrically, offering a route for gas diffusion and drainage and providing mechanical support to the membrane electrode assemblies. The GDL commonly contains two layers; one is a thick and rigid macroporous substrate (MPS) and the other is a thin microporous layer (MPL), both with special functions. This work provides a brief review on the GDL to explain its structure and functions, summarize recent progress and outline future perspectives.

Prognostic Bone Metastasis-Associated Immune-Related Genes Regulated by Transcription Factors in Mesothelioma.

Mesothelioma (MESO) is a mesothelial originate neoplasm with high morbidity and mortality. Despite advancement in technology, early diagnosis still lacks effectivity and is full of pitfalls. Approaches of cancer diagnosis and therapy utilizing immune biomarkers and transcription factors (TFs) have attracted more and more attention. But the molecular mechanism of these features in MESO bone metastasis has not been thoroughly studied. Utilizing high-throughput genome sequencing data and lists of specific gene subsets, we performed several data mining algorithm. Single-sample Gene Set Enrichment Analysis (ssGSEA) was applied to identify downstream immune cells. Potential pathways involved in MESO bone metastasis were identified using Gene Oncology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and Cox regression analysis. Ultimately, a model to help early diagnosis and to predict prognosis was constructed based on differentially expressed immune-related genes between bone metastatic and nonmetastatic MESO groups. In conclusion, immune-related gene SDC2, regulated by TFs TCF7L1 and POLR3D, had an important role on immune cell function and infiltration, providing novel biomarkers and therapeutic targets for metastatic MESO.

Erratum: Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.37220.].

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors.

Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tumor cells and the microenvironment. To overcome these limitations, we prepared a novel tumor-targeting delivery system based on the underlying mechanism of immune-targeted cell death that encapsulated granzyme B protein within a porous polymeric nanocapsule. Methods: A cell-penetrating peptide TAT was attached onto granzyme B (GrB) to enhance its transmembrane transport efficiency and potency to induce cell apoptosis. The endocytosis and internalization pathways of GrB-TAT (GrB-T) were analyzed in comparison with perforin by confocal microscopy and flow cytometry. Furthermore, the positively charged GrB-T was wrapped into nanoparticles by p-2-methacryloyloxy ethyl phosphorylcholine (PMPC)-modified HA (hyaluronic acid). The nanoparticles (called TCiGNPs) were characterized in terms of zeta potential and by transmission electron microscopy (TEM). The in vitro anti-tumor effects of GrB-T were examined by cell apoptosis assay and Western blotting analysis. The in vivo anti-tumor therapeutic efficacy of TCiGNPs was evaluated in a mouse tumor model. Results: The TAT peptide could play a role similar to perforin to mediate direct transmembrane transfer of GrB and improve GrB-induced cell apoptosis. The TCiGNPs were successfully synthesized and accumulated in the solid tumor through enhanced permeability and retention (EPR) effect. In the tumor microenvironment, TCiGNPs could be degraded by hyaluronidase and triggered the release of GrB-T. The TAT peptide enabled the translocation of GrB across the plasma membrane to induce tumor cell apoptosis in vivo.Conclusion: We successfully developed a granzyme B delivery system with a GrB-T core and a PMPC/HA shell that simulated CTL/NK cell-mediated cancer immunotherapy mechanism. The GrB delivery system holds great promise for cancer treatment analogous to the CTL/NK cell-induced immunotherapy.

Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy.

Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles. Methods: In this study, a pH-responsive superparamagnetic nanoparticles cluster (denoted as SMNC)-based method was developed for the precise and mild separation of blood TfR+ exosomes. Briefly, multiple superparamagnetic nanoparticles (SPMNs) labeled with transferrins (Tfs) could precisely bind to blood TfR+ exosomes to form an exosome-based cluster due to the specific recognition of TfR by Tf. They could realize the precise magnetic separation of blood TfR+ exosomes. More importantly, the pH-responsive dissociation characteristic of Tf and TfR led to the mild collapse of clusters to obtain pure blood TfR+ exosomes. Results: Blood TfR+ exosomes with high purity and in their original state were successfully obtained through the pH-responsive SMNC-based method. These can load Doxorubicin (DOX) with a loading capacity of ~10% and dramatically increase the tumor accumulation of DOX in tumor-bearing mice because of their innate passive-targeting ability. In addition, blood TfR+ exosomes changed the biodistribution of DOX leading to the reduction of side effects. Compared with free DOX, DOX-loaded blood TfR+ exosomes showed much better tumor inhibition effects on tumor-bearing mice. Conclusion: Taking advantage of the pH-responsive binding and disaggregation characteristics of Tf and TfR, the SMNC-based method can precisely separate blood TfR+ exosomes with high purity and in their original state. The resulting blood TfR+ exosomes showed excellent bio-safety and enable the efficient delivery of chemotherapeutics to tumors, facilitating the clinical translation of exosome-based drug delivery systems.

Correlation between Phase Behavior and Electrical Conductivity of 10 mol % Y-Doped BaZrO3: An Anomalous Dispersion Effect-Aided Synchrotron Radiation XRD Study Combined with TEM Observation and Electrochemical Analysis.

Y-doped BaZrO3 (BZY) has high proton conductivity and is a promising electrolyte candidate for fuel cells and electrolytic cells at an intermediate temperature range. However, the conductivity of BZY has a large discrepancy in the literature. In particular, for BaZr0.9Y0.1O3-δ (BZY10), the reported bulk conductivity varies in the range of more than 2 orders of magnitude. With the aim of revealing the reason, in this work, we conducted synchrotron radiation X-ray diffraction analysis on a BZY10. The X-ray was adjusted to 17.027 keV to approach the Y-K absorption edge (17.037 keV), and the anomalous dispersion effect was thereby activated for a precise distinction between Zr and Y. High-resolution scanning transmission electron microscopy observation and electrochemical measurements were also performed. Assisted by these experimental results, Rietveld refinement with greatly improved quality was thereby available to generate precise information on both the phase behavior and crystal structure. The results revealed that the BZY10 samples after sintering at 1600 °C for 8 to 200 h have a bimodal microstructure. They were not single phases, but mixtures of two perovskite phases differing slightly in Y contents. The Y contents in the two phases after sintering for 8 h were about 12.3 and 8.7 mol %, respectively, and finally became 10.6 and 9.2 mol %, respectively, after sintering for 200 h. In addition, the partition of Y over both the Ba and Zr sites was not suggested, although small Ba-deficiency around 0.05 formed in the sample sintered for 40 h or longer. But notably, the formation of the Ba vacancies is reasonably believed as the possible reason for the decrease in bulk and also grain boundary conductivities.

Exploring structural variations of hydrogen-bonding patterns in cellulose during mechanical pulp refining of tobacco stems.

Hydrogen bonding and mechanical refining are closely correlated. In this work, structural variations of hydrogen bonding patterns in cellulose during mechanical pulp refining, including the hydrogen bonding energy and distance as well as the content of hydrogen bonds, have been explored by using the second derivative FTIR spectra and deconvolving spectra in the OH stretching vibrational region. Results show that except for the bond distance, both the hydrogen bonding energy and the content of hydrogen bonds exhibit a significant variation at an increasing beating degree. The calculated hydrogen bonding energies for intermolecular O6H⋯O3' decrease by 12.9%, while those of intramolecular O3H⋯O5 and O2H⋯O6 vary little. Evolutions of the content of certain hydrogen bonds differ depending on the different refining stage. It is suggested that along with the role of water, hydration and swelling, internal/external fibrillation and delamination are strongly related to the structural variations of hydrogen bonding patterns in cellulose during mechanical pulp refining.

Exosomes separated based on the "STOP" criteria for tumor-targeted drug delivery.

Exosomes, a class of natural nanoparticles, have recently been used for drug delivery. To move from bench to bedside, exosomes should meet the "STOP" criteria: (1) high Safety; (2) good Targeting ability; (3) rapid Obtainment; and (4) high Purity. To the best of our knowledge, however, no studies on exosomes that can satisfy all the abovementioned criteria have been reported to date. In this study, an optimized superparamagnetic nanoparticle cluster (SMNC)-based method was used to easily achieve the abovementioned objective. Multiple superparamagnetic nanoparticles (SPMNs) labeled by holo-transferrin with PEG spacers anchor onto an exosome to form an upgraded exosome-based superparamagnetic nanoparticle cluster (denoted SMNC-EXO-PLUS). SMNC-EXO-PLUSs separated exosomes from healthy animal blood to ensure high safety, and their formation based on the specific binding of SPMNs to exosomes endowed exosomes with high purity. In addition, SMNC-EXO-PLUSs possessed strong magnetic response, realizing their rapid obtainment and good targeting ability. The results demonstrated that the cell viability was maintained as high as 88% in a 1000 µg mL-1 SMNC-EXO-PLUS solution, and the time interval from the extraction of blood to the acquisition of purified exosomes could be reduced to 3.5 h. Furthermore, the effects of in vivo tumor inhibition of drug-loaded SMNC-EXO-PLUSs (denoted as D-SMNC-EXO-PLUSs) were pronounced. Based on the "STOP" criteria, we exploited a new exosome-related drug delivery vehicle, dramatically promoting the clinical translation of exosomes.

The effects of surface charge on the intra-tumor penetration of drug delivery vehicles with tumor progression.

The limited penetration of drug delivery vehicles in tumors reduces their therapeutic efficacy, which is a major obstacle. Thus, great efforts have already been paid to regulate both tumor tissue and the physicochemical properties of drug delivery vehicles to achieve deeper penetration. However, the principles for regulating these properties remain unclear. Herein, we investigated the performance of nanocapsules in different tumor stages, and particularly focused on the difference in the performance of nanocapsules with different surface charges. Our in vivo and in vitro results showed that when the tumor was small in the early stage, the electropositive nanocapsules could penetrate much deeper than the electronegative nanocapsules; however, when the tumor was quite large in the late stage, the electronegative nanocapsules would penetrate further into the tissue. This study proposes a potential strategy for tumor therapy by selecting drug delivery vehicles with an appropriate surface charge based on the tumor development stages.

Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy.

Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy.