Background Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. Results Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. Conclusions Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making. Electronic supplementary material The online version of this article (10.1186/s40425-019-0650-9) contains supplementary material, which is available to authorized users.
The long-standing issues of low intrinsic electronic conductivity, slow lithium-ion diffusion and irreversible phase transitions on deep discharge prevent the high specific capacity/energy (443 mAh g À 1 and 1,550 Wh kg À 1 ) vanadium pentoxide from being used as the cathode material in practical battery applications. Here we develop a method to incorporate graphene sheets into vanadium pentoxide nanoribbons via the sol-gel process. The resulting graphene-modified nanostructured vanadium pentoxide hybrids contain only 2 wt. % graphene, yet exhibits extraordinary electrochemical performance: a specific capacity of 438 mAh g À 1 , approaching the theoretical value (443 mAh g À 1 ), a long cyclability and significantly enhanced rate capability. Such performance is the result of the combined effects of the graphene on structural stability, electronic conduction, vanadium redox reaction and lithium-ion diffusion supported by various experimental studies. This method provides a new avenue to create nanostructured metal oxide/graphene materials for advanced battery applications.
Graphene/polyaniline (PANI) nanocomposites were prepared by reducing graphene oxide with hydrazine in the presence of different amounts of polyaniline nanoparticles. In situ cryo-transmission electron microscope (TEM) images of a graphene oxide (GO)/PANI solution revealed that the PANI nanoparticles were anchored on the surface of the GO sheets. During the reduction, the as-adsorbed PANI nanoparticles were sandwiched between layers of graphene sheets. These PANI nanoparticles acted as spacers to create gaps between neighboring graphene sheets, resulting in a higher surface area compared to pure graphene. Graphene/PANI nanocomposites exhibited the high specific surface area of 891 m2/g. Utilizing this composite material, a supercapacitor with a specific capacitance of 257 F/g at a current density of 0.1 A/g has been achieved.
It has been found that the self-assembling peptide RADA 16-I forms a beta-sheet structure and self-assembles into nanofibers and scaffolds in favor of cell growth, hemostasis and tissue-injury repair. But its biophysical and morphological properties, especially for its beta-sheet and self-assembling properties in heat- and pH-denatured conditions, remain largely unclear. In order to better understand and design nanobiomaterials, we studied the self-assembly behaviors of RADA16-I using CD and atomic force microscopy (AFM) measurements in various pH and heat-denatured conditions. Here, we report that the peptide, when exposed to pH 1.0 and 4.0, was still able to assume a typical beta-sheet structure and self-assemble into long nanofiber, although its beta-sheet content was dramatically decreased by 10% in a pH 1.0 solution. However, the peptide, when exposed to pH 13.0, drastically lost its beta-sheet structure and assembled into different small-sized globular aggregates. Similarly, the peptide, when heat-denatured from 25 to 70 degrees C, was still able to assume a typical beta-sheet structure with 46% content, but self-assembled into small-sized globular aggregates at much higher temperature. Titration experiments showed that the peptide RADA16-I exists in three types of ionic species: acidic (fully protonated peptide), zwitterionic (electrically neutral peptide carrying partial positive and negative charges) and basic (fully deprotonated peptide) species, called 'super ions'. The unordered structure and beta-turn of these 'super ions' via hydrogen or ionic bonds, and heat Brownian motion under the above denatured conditions would directly affect the stability of the beta-sheet and nanofibers. These results help us in the design of future nanobiomaterials, such as biosensors, based on beta-sheets and environmental changes. These results also help understand the pathogenesis of the beta-sheet-mediated neuronal diseases such as Alzheimer's disease and the mechanism of hemostasis.
The interaction between components in hybrids is an indispensable factor in designing and fabricating composites with distinguished electromagnetic (EM) absorption performances. Herein, covalently bonded SiC/Co hybrid nanowires (NWs) have been fabricated, which present significantly enhanced EM absorption compared to a simple physical mixture of SiC and Co. The hybrids are characterized by transmission electron microscopy, X-ray diffraction, Raman spectroscopy, vector network analysis, and X-ray absorption near-edge spectroscopy at the Si K-edge, C K-edge, Co L 3,2 -edge and O K-edge. Microstructure analysis indicates the formation of Si-O-Co bonds between SiC NWs and magnetic Conanocrystals. Charge transfer takes place in the covalently bonded SiC/Co hybrid NWs. The induced synergistic coupling interaction in SiC/Co leads to an effective EM absorption band (RL < À10 dB) covering the frequency range of 10-16.6 GHz when the Co content is 25.1 wt% in the hybrid.
The dispersion of Nafion ionomer particles and Pt/C catalyst aggregates in liquid media was studied using both ultra-small-angle X-ray scattering (USAXS) and cryogenic TEM. A systematic approach was taken to study first the dispersion of each component (i.e., ionomer particles and Pt/C aggregates), then the combination of the components, and last the catalyst ink. Multiple-level curve fitting was used to extract the particle size, size distribution, and geometry of the Pt/C aggregates and the Nafion particles in liquid media from the scattering data. The results suggest that the particle size, size distribution, and geometry are not uniform throughout the systems but rather vary significantly. It was found that the interaction of each component (i.e., the Nafion ionomer particles and the Pt/C aggregates) occurs in the dispersion. Cryogenic TEM was used to observe the size and geometry of the particles in liquid directly and to validate the scattering results. The TEM results showed excellent agreement.
How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-CysPhe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable -turn and -sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form ''beads-on-a-thread'' type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine.-turn/-sheet ͉ hemostasis ͉ nanofibers ͉ hydrogel ͉ self-assembly D esign and fabrication of nanoscale biomaterials are critically important for the advancement of biomedical engineering. These include scaffolds for 3D cell and tissue culture, injured tissue repair, and controlled drug release. Biomaterials derived from synthetic or biological polymers have been used extensively for many biomedical applications over decades. Only recently, researchers have attempted to use structural motifs found in nature materials to design and fabricate nanobiomaterials for tissue engineering and regenerative medicine. It is known that many of fibrous proteins and peptides self-assemble into supramolecular structures by using -sheet structures, and one of the typical self-assembling peptides is the RADA16-I (1-9), termed as ionic self-complementary peptide. This kind of peptide has been designed by mimicking native protein motifs containing regular repeats of alternating oppositely charged residues separated by 1 or 2 hydrophobic residues. These residues interact with each other by at least three major forces: interand intramolecular forces such as hydrogen bonding, hydrophobic, and electrostatic interactions to drive molecular selfassembly process. Because charged amino acids play an important role in determining peptide molecular assembly through electrostatic interaction and hydrogen bonding, many of the self-assembling biomaterials are designed to ...
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