There is a growing effort in the scientific community to design and fabricate versatile artificial nanomotors propelled by selfgenerated forces, because they have potential in the field of directed drug delivery, roving sensors, isolation and detection of targets, active biomimetic systems, and other emerging applications. [1] Inspired by the nanoscale linear biomotors (for example, kinesins), which can autonomously move in aqueous solution and are powered by spontaneous hydrolysis of biological energy units, substantial efforts towards the design of chemically powerful synthetic motors at the micro-and nanoscale have recently demonstrated the ability of converting chemical energy into autonomous motion based on a fuel solution (for example, aqueous hydrogen peroxide solution). [2][3][4] To explain the motion and energy transfer process in these chemically powered systems, several mechanisms, including bubble propulsion, [5] interfacial tension gradients, [6] self-electrophoresis, [7] self-diffusiophoresis, [8] osmotic propulsion, [9] ultrasound propulsion, [10] and polymerization reactions [11] were proposed.Among diverse synthetic microengines, chemically powered tubular micromotors prepared by the rolled-up technique and template electrosynthesis have displayed a high speed and the controllable directionality of the movement compared to bimetal nanorods or Janus microsphere motors. [12,13] These rocket-like microengines are capable of the pick-up, transportation, and release of various cargoes, including polymer particles, [14] nucleic acids, [15] cancer cells, [16] and bacteria. [17] However, they still have some inherent limitations, such as complex preparation technology, difficulty of surface modification, and poor biocompatibility or biodegradability. Moreover, it is required in many cases that synthetic motors can encapsulate, transport, and release targeted substances by themselves in an easy and controllable way and have good biocompatibility and biodegradability, particularly in both biomedical and environmental fields. Therefore, it still remains a challenge to develop new fabrication methods and expand the diversity of the building components.

BILN 2061 is a novel, specific hepatitis C virus (HCV) NS3 serine protease inhibitor discovered by Boehringer Ingelheim that has shown potent activity against HCV replicons in tissue culture and is currently under clinical investigation for the treatment of HCV infection. The poor fidelity of the HCV RNA-dependent RNA polymerase will likely lead to the development of drug-resistant viruses in treated patients. The development of resistance to BILN 2061 was studied by the in vitro passage of HCV genotype 1b replicon cells in the presence of a fixed concentration of the drug. Three weeks posttreatment, four colonies were expanded for genotypic and phenotypic characterization. The 50% inhibitory concentrations of BILN 2061 for these colonies were 72-to 1,228-fold higher than that for the wild-type replicon. Sequencing of the individual colonies identified several mutations in the NS3 serine protease gene. Molecular clones containing the single amino acid substitution A156T, R155Q, or D168V resulted in 357-fold, 24-fold, and 144-fold reductions in susceptibility to BILN 2061, respectively, compared to the level of susceptibility shown by the wild-type replicon. Modeling studies indicate that all three of these residues are located in close proximity to the inhibitor binding site. These findings, in addition to the three-dimensional structure analysis of the NS3/NS4A serine protease inhibitor complex, provide a strategic guide for the development of next-generation inhibitors of HCV NS3/NS4A serine protease.Hepatitis C virus (HCV) infection is believed to be the leading cause of chronic hepatitis, end-stage cirrhosis, and hepatocellular carcinoma, affecting over 4 million Americans and about 170 million people worldwide. Currently, the most effective treatment of HCV infection involves a combination of the nucleoside analog ribavirin with alpha interferon (IFN-␣). However, the regimen is prolonged and not well tolerated, and only approximately half of the genotype 1 HCV-infected individuals have a sustained virological response, although the response rate improves significantly (ϳ80%) when genotypes 2 and 3 are treated (7,29). An oral agent that offers promise as an efficacious alternative to IFN or that may be used in IFNcontaining regimens and that improves efficacy and/or the side effect profile is in great demand.The HCV genome is a 9.6-kb single-stranded RNA of positive polarity encoding a large polyprotein that is posttranslationally cleaved into structural and nonstructural proteins (3,12,23). The N-terminal domain (approximately 180 amino acids) of NS3 and the small hydrophobic NS4A protein compose a heterodimeric enzyme catalyzing the posttranslational processing of the HCV nonstructural proteins (1, 2, 23). Its structure has been extensively studied by X-ray crystallography (9, 30, 31) and nuclear magnetic resonance spectroscopy (1, 6). The proteolytic activity of NS3/NS4A serine protease is known to be essential for viral RNA replication (10,14). A recent study indicated that the NS3/NS4A serine protease a...

High rates of genetic variation ensure the survival of RNA viruses. Although this variation is thought to result from error-prone replication, RNA viruses must also maintain highly conserved genomic segments. A balance between conserved and variable viral elements is especially important in order for viruses to avoid "error catastrophe." Ribavirin has been shown to induce error catastrophe in other RNA viruses. We therefore used a novel hepatitis C virus (HCV) replication system to determine relative mutation frequencies in variable and conserved regions of the HCV genome, and we further evaluated these frequencies in response to ribavirin. We sequenced the 5 untranslated region (5 UTR) and the core, E2 HVR-1, NS5A, and NS5B regions of replicating HCV RNA isolated from cells transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis delta virus ribozyme to control 3 cleavage. We found quasispecies in the E2 HVR-1 and NS5B regions of untreated replicating viral RNAs but not in conserved 5 UTR, core, or NS5A regions, demonstrating that important cis elements regulate mutation rates within specific viral segments. Neither T7-driven replication nor sequencing artifacts produced these nucleotide substitutions in control experiments. Ribavirin broadly increased error generation, especially in otherwise invariant regions, indicating that it acts as an HCV RNA mutagen in vivo. Similar results were obtained in hepatocyte-derived cell lines. These results demonstrate the potential utility of our system for the study of intrinsic factors regulating genetic variation in HCV. Our results further suggest that ribavirin acts clinically by promoting nonviable HCV RNA mutation rates. Finally, the latter result suggests that our replication model may be useful for identifying agents capable of driving replicating virus into error catastrophe.Genetic variation provides a selective advantage for RNA virus populations, promoting escape from immune selection and rapid adaptation to novel environments (8). The absence of proofreading-repair mechanisms in RNA replicases and transcriptases is thought to contribute to mutation rates in the range of 10 Ϫ3 to 10 Ϫ5 substitutions per nucleotide per round of RNA replication (32). However, two factors exert a counterbalancing pressure against excessive genetic variation. A high degree of conservation of viral genomic sequences must be maintained for interactions with specific cellular proteins, as in the case of internal ribosomal entry. Excessive error rates can also contribute to net loss of fitness by leading to "error catastrophes" that threaten the viability of populations of quasispecies present in viral swarms. While the RNA genome of hepatitis C virus (HCV) contains hypervariable regions that are thought to contribute to immune escape, little is known about their intrinsic origins or their control in the absence of immune or drug selection.The extraordinary genetic diversity of HCV is reflected in its in vivo generation of quasispecies, whic...

www.angewandte.org gami, [6] and other types of unconventional nucleic acids (Figure 1), [3c, 7] that can replace traditional proteases and antibodies, possess independent structural functions, and perform specific biological non-genetic functions. [3a-c, 4a,b, 8] The concept of FNA was also used to generalize the nongenetic functions of nucleic acids (Figure 1). [9] Meanwhile, research on the combination and functions of FNAs, such as DNAzymes, aptazymes, and aptamers, and nanomaterials, Wentao Xu studied at China Agricultural University (BS 2001, PhD 2006) and conducted postdoctoral research there before joining the faculty. He is currently an associate professor in the College of Food Science and Nutritional Engineering at China Agricultural University. His research interest is functional nucleic acid biosensors and nanomaterials. Wanchong He obtained his BS degree from Huazhong Agricultural University in 2017. He is now a PhD candidate in the College of Food Science and Nutritional Engineering at China Agricultural University. His research interest is functional nucleic acid biosensors.

Current wound sealing systems such as nanoparticle‐based gluing of tissues allow almost immediate wound sealing. The assistance of a laser beam allows the wound sealing with higher controllability due to the collagen fiber melting which is defined by loss of tertiary protein structure and restoration upon cooling. Usually one employs dyes to paint onto the wound, if water absorption bands are absent. In case of strong bleeding or internal wounds such applications are not feasible due to low welding depth in case of water absorption bands, dyes washing off, or the dyes becoming diluted within the wound. One possible solution of these drawbacks is to use autonomously movable particles composing of biocompatible gold and magnetite nanoparticles and biocompatible polyelectrolyte complexes. In this paper a proof of principle study is presented on the utilization of thermophoretic Janus particles and capsules employed as dyes for infrared laser‐assisted tissue welding. This approach proves to be efficient in sealing the wound on the mouse in vivo. The temperature measurement of single particle level proves successful photothermal heating, while the mechanical characterizations of welded liver, skin, and meat confirm mechanical restoration of the welded biological samples.