PFOR and/or PDH (iv) Aldh and AdhE, and (V) bifurcating, Fd-depen

PFOR and/or PDH (iv) Aldh and AdhE, and (V) bifurcating, Fd-dependent, and NAD(P)H dependent H2ases, that can be used for streamlining H2 and/or ethanol producing capabilities in sequenced and novel isolates. By linking genome content, reaction thermodynamics, and PF-6463922 cost end-product yields, we

offer potential targets for optimization of either ethanol or H2 yields via metabolic engineering. Deletion of LDH and PFL could potentially increase both H2 and ethanol yields. While deletion of ethanol producing pathways (aldH, adh, adhE), increasing flux through PFOR, overexpression of Fd -dependent H2ases, and elimination of potential H2-uptake (NAD(P)H-dependent) H2ases could lead to increased H2 production, eliminating H2 production and redirecting flux through PDH would be beneficial for ethanol production. Although gene and gene-product expression,

functional characterization, and metabolomic flux analysis remains critical in determining pathway utilization, insights regarding how genome content affects end-product yields can be used to direct metabolic engineering strategies and streamline the characterization of novel species with potential industrial applications. Acknowledgements This work was supported by funds provided by the Natural Sciences and Engineering Research Council of Canada (NSERC), through a Strategic Programs grant SNX-5422 supplier (STPGP 306944–04), by Genome Canada, through the Applied Genomics Research in Bioproducts or Crops (ABC) program for the grant titled, “Microbial Genomics for Biofuels and CoProducts from Biorefining Processes”, and by the Province of Manitoba, Agricultural and Rural Development Initiative (ARDI), grant 09–986. Electronic supplementary material Additional

file 1: Cofactor specificity (ATP or PP i ) of phosphofructokinases based on sequence alignments. Alignments of key residues determining ATP or PPi specificity, as determined by Bapteste et al. [74] and Bielen et al. [75], were performed using BioEdit v.7.0.9.0. The P. furiosus and Th. check details kodakarensis genes are very distinct (different COG and different KO) and are annotated as Archaeal phosphofructokinases. Abiraterone (PDF 178 KB) Additional file 2: Phylogenetic clustering of [NiFe] hydrogenases large (catalytic) subunits. Catalytic (large) subunits of [NiFe] H2ases were identified based upon the modular signatures as described by Calusinska et al. [16], Species considered in this manuscript are highlighted and corresponding H2ase gene loci are provided. (PDF 247 KB) Additional file 3: Phylogenetic clustering of [FeFe] hydrogenases large (catalytic) subunits. Catalytic (large) subunits of [FeFe] H2ases were identified based upon the modular signatures as described by Calusinska et al. [16]. Species considered in this manuscript are highlighted and corresponding H2ase gene loci are provided. (PDF 476 KB) References 1.

The current study will investigate whether a similar distribution

The current study will investigate whether a similar distribution pattern can also be observed in human subjects and whether this inhomogeneous distribution is concentrated around the tumour sites. Hepatic arterial injection with 99mTc-MAA and subsequent scintigraphic imaging is widely used to predict the biodistribution of 90Y microspheres, prior

to the actual radioembolization procedure. Its accuracy can however be disputed. In our centre, we have observed that patients with a borderline lung shunt fraction of 10% to 19%, as calculated using the 99mTc-MAA images (approximately Tipifarnib in vivo 24% of all patients, all of whom were instilled a by 50% reduced amount of radioactivity), had no signs of lung shunting on post- 90Y-RE Bremsstrahlung images. In these cases, it seems that the 99mTc-MAA-scan had false-positively predicted extrahepatic spread. This may be explained by the fact that 99mTc-MAA differs in many aspects from the microspheres that are used. Shape, size, density, in-vivo half-life, and number of 99mTc-MAA particles do not resemble the microspheres in any way [13, 31]. In addition, free technetium that is released from the MAA particles can disturb the (correct) assessment of extrahepatic spread. We hypothesize that

a small safety dose with low-activity PLX4032 solubility dmso 166Ho-PLLA-MS will be a more accurate predictor of distribution than 99mTc-MAA. The unique characteristics see more of 166Ho-microspheres, in theory, allow a more accurate prediction of

the distribution with the use of scintigraphy and MRI. In this study, we chose to perform both an injection with 99mTc-MAA and administration of a safety dose of 166Ho-PLLA-MS. The respective distributions of the 99mTc-MAA and the 166Ho-PLLA-MS safety dose will be compared with the distribution of the treatment dose of 166Ho-PLLA-MS by quantitative analysis of the scintigraphic images. Both commercially available 4-Aminobutyrate aminotransferase 90Y-MS products are approved by the Food and Drug Administration (FDA) and European Medicines Agency as a medical device and not as a drug. Radioactive microspheres are a medical device since these implants do not achieve any of their primary intended purposes through chemical action within or on the body and are not dependent upon being metabolized for the achievement of their primary intended purpose. In accordance with the definition of a medical device by the FDA and in analogy with the 90Y-MS, we consider the 166Ho-PLLA-MS to be a medical device [32]. The Dutch medicine evaluation board has discussed this issue (13 July 2007) and has concluded that the microspheres are indeed to be considered as a medical device. One important issue concerning the resin-based SIR-Spheres ® is the relatively high number of particles instilled (>1,000 mg), since this may sometimes be associated with macroscopic embolization as observed during the fluoroscopic guidance [28, 33].

Curr Proteomics 2006, 3:271–282 10 2174/157016406780655586CrossR

Curr Proteomics 2006, 3:271–282. 10.2174/157016406780655586CrossRef 39. Myszka DG: Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors. Curr Opin Biotechnol 1997, 8:50–57. 10.1016/S0958-1669(97)80157-7CrossRef 40. Oshannessy DJ, Brighamburke M, Soneson KK, Hensley P, Brooks I: Determination of rate and equilibrium binding constants for macromolecular interactions using surface plasmon resonance: Dasatinib datasheet use of nonlinear least squares analysis methods. Anal Biochem 1993, 212:457–468. 10.1006/abio.1993.1355CrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions

N-FC participated in the design of the study and performed the statistical analysis and drafted the manuscript. T-YH carried out the immunoassays and performed the statistical analysis. H-CL and K-CL conceived the study and participated in its design and coordination. All authors read and approved the final manuscript.”
“Background Non-Hodgkin lymphoma (NHL) is a type of blood cancer, which presents not only as a solid tumor AZD0156 of lymphoid cells in lymph nodes and/or extranodal lymphatic organs such as spleen and bone marrow, but also as free lymphoma cells in circulating blood [1–3]. Particularly, most patients

can be cured with chemotherapy and/or radiation, which revealed the important status of chemotherapy in the treatment of NHL [4–6]. Currently, while various chemotherapeutic agents are validated to be effective in the treatment of lymphoma in preclinical studies,

clinical Rapamycin supplier applications are often limited for their side effects to normal tissues because of the systemic administration. As a result, finding more effective strategy to maximize the curative effect while minimizing the side effects of chemotherapy against lymphoma is of great importance and urgency [7, 8]. In the past decade, nanocarriers, including liposomes, polymeric nanoparticles, micelles, nanogels etc., with an appropriate diameter of tens to hundreds of nanometers, have received widespread attention for the specific delivery of bioactive reagents in the diagnosis and treatment of cancer [7, 9–12]. Encapsulation of bioactive reagents in nanocarriers can result in significant accumulation and retention in solid tumor tissues relative to administration of drug in conventional formulations selleck screening library through the enhanced permeability and retention (EPR) effect, which was firstly described by Maeda and colleagues [13–17]. What’s more, the drug loading nanocarriers owns high serum stability, which can contribute to long-time circulation in the blood vessels, resulting in long-lasting antitumor activities, especially for the killing of free malignant cells in circulating blood [12, 17, 18].

These deaths were mainly due to traumatic intracranial hemorrhage

These deaths were mainly due to traumatic intracranial hemorrhage and/or brain edema after operation. To avoid these accidents, we took the following measures: 1) 22# trochar was replaced by 24# trochar; 2) transplantation volume was reduced to 2 mm3; and 3) the tumor tissues were pushed as smoothly as possible. Take rate is not the only criterion in evaluation of an orthotopic animal model, while how close a model can replicate the original tumors is more essential. As brain metastasis and primary glioblastioma are two biologically different malignances in the central

nervous system, we Alvocidib ic50 selected them both as grafts in this study to assess this novel method. When compared between the two models, metastasis xenografts were evidently differentiated from glioblastoma xenograft in many aspects, however, when compared with their original malignances, both models demonstrated unquestionable similarity in histological structure features this website and growth patterns. Laurent et al. [10] performed both heterotransplantation AZD2014 concentration and orthotopic transplantation of human glioblastoma, and concluded that the organ-specific environment play a determining role in growth and invasive properties. In the current study, two different malignances were transplanted into the same organ; however, the resulting tumors didn’t demonstrate the similar growth patterns. So, it is more

plausible and acceptable that it is the malignance itself but not environment that plays a determining role in the tumor growth patterns and other biological behaviors. With the identification of brain tumor stem cells from tumor mass or cell lines, it is reported that as rare as 102 CD133+ glioma cells could generate tumor mass, while as much as 106 CD133- glioma cells failed to form tumor mass after injected to the mouse brain. The fact that cell suspension injection of most established cell lines often yields well-circumscribed

intracranial tumors which are different from the original tumor, coupled with the complicated procedure of cell suspension injection precludes tumor stem cells as a desirable transplant [19–21]. In this study, the immunohistochemistry fantofarone with monoclone antibody against CD133 revealed that not only the original tumors, but the resulting tumors were positively stained for CD133. This result means the tumor tissues contained brain tumor stem cells and functioned as a tumor stem cell pool. It is reported that biological behaviors of tumor stem cells are highly dependent on their microenvironment [22, 23], in another word, CD133 negative tumor cells and stromal components also play an important role in the potential of tumor stem cells to re-establish the original tumor. Taken together, tumor stem cells, other tumor cells and stromal components make a concerted contribution to the growth of tumor mass in transplantation animal model.

Sci Transl Med 2:61ra91 doi:10 ​1126/​scitranslmed ​3001720 PubM

Sci Transl Med 2:61ra91. doi:10.​1126/​scitranslmed.​3001720 PubMedCrossRef Mantingh A, Breed ASPM, Beekhuis JR, Lith JMM van (eds) (1991) Screening in prenatal diagnosis. The Dutch Working Party on Prenatal Diagnosis, Utrecht Meijer S, Stemerding D, Hoppe R, Schielen P, Loeber G (2010) Prenatale

screening: een (on)getemd maatschappelijk probleem? [Prenatal screening: a (not yet) fully tamed problem?]. TSG 88:454–460CrossRef Nelis AP (1998) The introduction of DNA-diagnostic tests in the Netherlands: a regime analysis of the development of clinical genetics and DNA-diagnostic tests, 1970–1997. Twente University Press, Enschede NRC Handelsblad [Newspaper] (2008) Embryopolitiek [Embryopolitics]. June 2 Parliamentary documentation. Tweede kamer der Staten LDC000067 nmr Generaal (1989–1990a) Bevolkingsonderzoek neuraalbuisdefecten. Brief van de Staatssecretaris Selleck CBL0137 van Welzijn, Volksgezondheid en Cultuur [Population screening

neural tube defects. Letter from the State Secretary of Welfare, Health and Culture]. TK 21353:1 Parliamentary documentation. Tweede kamer der Staten Generaal (1989–1990b) Bevolkingsonderzoek neuraalbuisdefecten. Verslag van een mondeling overleg [Population screening neural tube defects. Report of the oral discussion]. TK 21353:2 Parliamentary documentation. Tweede kamer der Staten Generaal (1995–1996). Prenatale diagnostiek. Brief van de minister van Volksgezondheid, Welzijn en Sport [Prenatal diagnosis. Letter from the Minister of Health, Welfare and Sport]. TK 24624:1 Parliamentary documentation. Tweede Kamer der Staten Generaal (2003–2004a) find more Prenatale screening. Brief van de Staatssecretaris van Volksgezondheid, Welzijn en Sport (Prenatal

screening. Letter from the State Secretary of Health, Welfare and Sport), TK 29323:1 Parliamentary documentation. Tweede Kamer der Staten Generaal (2003–2004b) Stenogram begrotingsdebat 25,26,27 November 2003 [Shorthand report budget debate 25, 26, 27 November 2003]. TK 29200 Parliamentary documentation. Tweede Kamer der Staten Generaal (2003–2004c), Motie met het verzoek alle zwangere vrouwen de triple-dan wel Mannose-binding protein-associated serine protease quadruple test aan te bieden [Motion requesting offering triple or quadruple tests to all pregnant women]. TK 29200 XVI:102 Parliamentary documentation. Tweede Kamer der Staten-Generaal (1987–1988a) Preventie aangeboren afwijkingen. Nota [Prevention Congenital Anomalies. Report]. TK 20345:1,2 Parliamentary documentation. Tweede Kamer der Staten-Generaal (1987–1988b) Preventie aangeboren afwijkingen. Verslag van een mondeling overleg [Prevention congenital anomalies. Report oral discussion].TK 20345:3 Parliamentary documentation. Tweede Kamer der Staten-Generaal (1987–1988c) Preventie aangeboren afwijkingen. Brief van de Staatssecretaris van Welzijn Volksgezondheid en Cultuur [Prevention congenital anomalies.

avermitilis, including chromosomal arm replacement, internal

avermitilis, including chromosomal arm replacement, internal deletions and circularization. The chromosomal arm replacement in the bald mutant SA1-8 consisted of deletion of the 691-kb left terminus, and duplication of the 88-kb right terminus. The resulting new junction in fragment NA1 joined the partial coding regions of SAV546 (putative dehydrogenase) and SAV7499 (putative two-component system response regulator) at a 5-bp overlapping sequence. The internal deletions of fragments D and G1 appeared to be direct recombination events between two points. Fragment D was reduced 74-kb from

SAV7241 to SAV7304. No significant homology was found, since I-BET151 order the former was a putative ATP-dependent Clp protease, and the latter was a hypothetical protein. G1 had a 36-kb deletion, from SAV3792 ZD1839 research buy to SAV3823, and the left and right deletion termini overlapped only by 3-bp nucleotides.

The circular chromosome of SA1-6 joined SAV1302 (acetyl xylan esterase) and SAV7294 (amino acid transporter protein) with no overlapping sequence. Thus, all fusion sequences displayed minimal or no homology, indicating that the chromosome alteration has resulted from non-homologous recombination. Similarly, non-homologous (sometimes termed “”illegitimate”") recombination appeared to be involved in nearly all rearrangement events in previous studies of genetic instability in other Streptomyces species [5, 9, 12, 14, 21, 25], except for two homologous recombinations occurring between duplicated genes [8, 11]. This is reminiscent of breakpoint analysis of genome MK0683 rearrangements in Saccharomyces cerevisiae, in which non-homologous end-joining (NHEJ) Myosin appeared to be the major mechanism involved in gross chromosomal rearrangements, even in those strains in which homologous recombination is functional [26]. Homologs of the eukaryotic DNA-end-binding repair protein Ku, involved in NHEJ pathway, have been found in Streptomyces [27], suggesting the presence of this pathway. It would thus be of interest to determine the relationship between Ku protein and chromosome

instability in ku mutants of Streptomyces. This is the first report of an inner deletion event involving the central region of the Streptomyces chromosome, suggesting that each part of the Streptomyces chromosome may be the target for rearrangements. Previous reports indicated that the two chromosome ends were primary targets for a variety of rearrangements: deletion, amplification, replacement, and circularization [5, 9, 14, 25]. No essential genes located in the telomeric or subtelomeric regions of Streptomyces chromosome, and we are able to observe and characterize only those rearrangement events which did not affect the growth-dependent genes. This is the most likely reason as to why the majority of the rearrangements described in previous studies are located in the chromosome arms.

Sequence

Sequence PF-3084014 molecular weight and structural data comparisons allow the family of periplasmic chaperones to be divided into two subfamilies on the basis of the length of the loop connecting β-strand F1 with the donor G1 strand, the FGL and FGS subfamilies having a long and a short loop, respectively [15, 16]. This loop is an important structural element which, in the chaperone-subunit complex, extends the acceptor cleft binding motif of the chaperone G1 donor strand. In the FGS chaperones, the β-strand G1 stabilizes a subunit core by donating only three bulky hydrophobic residues [4, 7].

In the case of FGL chaperones, the G1 binding motif is typically extended by two additional, bulky, alternating hydrophobic residues from a loop region [5, 13]. In the FGL chaperones, the second subunit-binding motif involved in the

DSC mechanism is formed by three bulky hydrophopic residues located in the long N-terminal Vorinostat chemical structure sequence forming the β-strand A1 [5, 13]. The long F1-loop-G1 hairpin of these chaperones is stabilized by the disulfide bond conserved in the whole subfamily [17, 18]. The longer G1 and A1 binding motif of the FGL chaperones correlates with the extended structure of the subunits’ acceptor cleft [13]. The molecular differences in the structure and function of the FGL and the FGS chaperones presented here correlate with the structure of the adhesive organelles which they assemble [13]. Phloretin The FGL chaperones assemble organelles composed of only one type of protein subunit and, optionally, the second minor tip subunit [12, 13]. They

are characterized by a thin fimbrial, amorphous or capsule-like morphology. Each subunit of these homopolymeric structures possesses the host-cell receptor binding site or sites; thus, they are polyadhesins. In contrast, the FGS chaperones assemble AG-881 datasheet heteropolymeric, well-structured adhesive pili composed of up to seven different subunits [10, 19]. Pili are monoadhesins, as they possess only one receptor binding subunit located at the tip of the organelle. In addition, the division of chaperones and adhesive organelles into the FGS and FGL families also correlates with the phylogenetic analysis based on the usher ancestry. The FGL organelles belong to the γ3-monophyletic group, while the FGS can be divided into five clades: γ1, γ2, γ4, κ and π [20]. The adhesive organelles of the chaperone-usher type are unique virulence factors specific only to Gram-negative -pathogenic bacteria. The conservation of this mechanism renders it a good potential target for the development of antibacterial agents [21, 22]. The pilicides originally proposed by Svensson et al. in 2001 are a class of low molecular weight agents, derivatives of a dihydrothiazolo ring-fused 2-pyridone scaffold which block formation of pili by affecting the function of chaperone [22].

We are currently confirming our findings by studying the correlat

We are currently confirming our findings by studying the correlation between the sensitivity of patients’ glioblastoma cells and the patient’s survival. Poster No. 64 Development Citarinostat of a New Brain Metastasis Model in the Nude Rat Jian Wang1, Inderjit Kaur Daphu 1 , Paal-Henning Pedersen2, Hrvoje Miletic1, Randi Hovland3, Sverre Mørk4, Rolf Bjerkvig1, Frits Thorsen1 1 Department of Biomedicine, University of Bergen, Bergen, Norway, 2 Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway, 3 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital,

Bergen, Norway, 4 Department of Pathology, Haukeland University Hospital, Bergen, Norway Brain metastasis is a common cause of mortality in cancer patients, and associated with poor prognosis. In order to better understand the complex metastatic process and Apoptosis inhibitor the interaction between metastases

and the microenvironment, we developed a new animal model, where human brain metastases were xenografted into the brains of immunodeficient rats. Tumor take was achieved in 7 out of 9 human brain metastases implanted. By MR imaging, the animal brain metastases showed similar radiological features as observed clinically. Histological comparisons between the primary tumors from the patients, the patient brain metastases and the xenografted brain metastases showed similar growth patterns. An immunohistochemical PRKD3 study showed similar marker expressions between the patient tumors and the corresponding animal brain tumors. A DNA copy Androgen Receptor pathway Antagonists number analysis showed several chromosomal deletions and amplifications, but only one change, gain of 2q, was exclusively found in the animal brain metastases. In conclusion, we have developed a representative in vivo model for studying metastatic brain cancer,

which will be used to assess responses to treatment. This model was refined by establishing a cell line (H1) from one of the brain metastases (primary: melanoma). In order to follow systemic spread of the cell line in vivo, we generated two new cell lines by transfecting with either dsRed or H1 GFP-Luc reporter genes. The transgene-positive cells were selected by fluorescence activated cell sorting to obtain homogenously fluorescent cell lines. A pilot study showed that the H1/dsRed cells were tumorigenic when implanted intracranially and subcutaneously in matrigel, in nod/SCID eGFP positive mice. A bioluminescence assay using optical imaging on H1/GFP-Luc cells was done in vitro, which showed a strong luciferase activity in the cells. Currently the H1/GFP-Luc cells is injected intracardially, to study the ability of systemic homing of these cells into the brain of nod/SCID mice. Poster No.

Lu

Recombination frequencies in NER-deficient H. pylori mutants after natural transformation We next examined the role of the H. pylori NER system in recombination. Each mutant strain was individually transformed with genomic DNA extracted from H. pylori strain J99-R3. This strain contains a point mutation (A1618T) that confers Rif click here resistance

which can be used as a selection marker to recover recombinant clones (Additional file 2: Figure S2). Recombinant clones were distinguished from spontaneous mutants by partial rpoB sequence analysis. The uvrA mutant exhibited a highly significant decrease of the recombination frequency in comparison to the wild type (Figure 2B). A decreased mean recombination frequency was also determined for the uvrB deficient mutant, MEK162 ic50 however, the difference between the uvrB mutant and wild type did not reach statistical significance (BF =14, “strong evidence”). There was no significant

difference between the recombination frequency of the uvrC mutant and the wild type (Figure 2B). The introduction of an intact copy of the uvrA gene into the uvrA mutant restored the recombination frequency to wild type levels. In contrast, the uvrD deletion mutant (ΔuvrD) showed a hyper-recombinational phenotype (Figure 2B) that is in agreement with previous studies in E. coli[26] and in H. pylori[23]. Characterization of the donor DNA imports after recombination in NER-deficient mutants One of the characteristics of H. pylori is the import of relatively short fragments of donor DNA into the recipient chromosome after natural transformation. see more In order to understand whether components of the NER system play a role in the control of the length of DNA fragments replaced after natural transformation, and in the

formation of interspersed ID-8 sequences of the recipient (ISR), single recombination events were further characterized. For this, Rif resistant clones obtained using the in vitro transformation assay were randomly selected and a 1663 bp fragment in the rpoB locus was sequenced. Recombinant nucleotide sequences were aligned with both donor and recipient sequences to identify the different import parameters used for graphic comparisons of the polymorphisms (Figure 3). Maximum likelihood estimations (MLE) of the import size were calculated and the total number of ISR found among the isolates was counted. Statistical significance of the results was evaluated using a Bayesian approach (see Methods). Since the uvrA mutant showed a strongly reduced recombination frequency, an allele-specific PCR was used in a pre-screening step to distinguish between spontaneous mutants and recombinant clones. Figure 3 Import patterns after transformation of recipient strain 26695 wild type (wt, left panel) and  uvrC  mutant (right panel) with DNA of Rif resistant strain J99-R3. Each row represents a 1663 bp partial rpoB sequence.

J Electro Mater 2009, 38:586–595 CrossRef 37

J Electro Mater 2009, 38:586–595.CrossRef 37. Tideglusib supplier Li S, Bi H, Cui B, Zhang F, Du Y, Jiang X, Yang C, Yu Q, Zhu Y: Anomalous magnetic properties in Co 3 O 4 nanoparticles covered with polymer decomposition residues. J Appl Phys 2004, 95:7420–7422.CrossRef 38. Zhang S, Pelligra CI, Keskar G, Majewski PW, Ren F, Pfefferle LD, Osuji CO: Liquid crystalline

order and magnetocrystalline anisotropy in magnetically doped semiconducting ZnO nanowires. ACS Nano 2011, 5:8357–8364.CrossRef 39. Pelligra CI, Majewski PW, Osuji CO: Large area vertical alignment of ZnO nanowires in semiconducting polymer thin films directed by magnetic fields. Nanoscale 2013, 5:10511–10517.CrossRef 40. Singhal RK, Dhawan MS, Gaur SK, Dolia SN, Kumar S, Shripathi T, Deshpande UP, Xing YT, Saitovitch E, Garg KB: Selleck BTK inhibitor Room-temperature

ferromagnetism in Mn-doped dilute ZnO semiconductor: an electronic structure study using X-ray ARRY-438162 photoemission. J Alloys Compd 2009, 477:379–385.CrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions BSK and SL designed and planned the experiments. BSK performed powder and nanowire synthesis and measurements. BSK, SL, and SYJ performed data analysis and interpretation. WKK, JHP, and YCC assisted with sample characterization and contributed to measurement discussions. JK, CRC, and SYJ wrote the manuscript with help from the co-authors. All authors discussed the results and reviewed the manuscript. All authors

read and approved the final manuscript.”
“Background Nowadays, the rapid development of microfluidic/nanofluidic systems has been seen in many applications such as fluid mixing [1, 2], drug delivery [3], ion transporters [4], and DNA translocators [5]. The micro/nanochannels are the key components in the microfluidic/nanofluidic systems. Recently, more complex nanochannels (e.g., with some Cediranib (AZD2171) nanostructures at the bottom) are designed to study the influences on the flowing characteristic of fluid in the nano/microchannels [2]. The successful fabrication of these micro/nanochannels urgently needs to be solved. At present, the nanochannel fabrication methods mainly include focused ion beam milling [5], nanoimprint lithography [6], electron beam drilling [7], and wet chemical etching [8]. However, the complexity and/or cost of these methods greatly restrict the nanochannel fabrication, especially for the nanochannel with complex nanostructures at the bottom. Since atomic force microscopy (AFM) was invented, the AFM tip-based nanomachining method had emerged as one of the essential technologies for nanostructure fabrication [9]. A lot of works have already been carried out to fabricate nanochannels on the surfaces of different kinds of materials using this method [10–15]. For example, Zhang et al. [13] presented an AFM-based high-rate tunable nanolithography technique to scratch nanochannels on PMMA surfaces. Kawasegi et al.