Flexibility Analysis of DNA Nanotubes with Prescribed Circumferences and Their Pearl-Necklace Assemblies with Gold Nanoclusters.

DNA has been demonstrated as a powerful platform for the construction of inorganic nanoparticles (NPs) into complex three-dimensional assemblies. Despite extensive research, the physical fundamental details of DNA nanostructures and their assemblies with NPs remain obscure. Here, we report the identification and quantification of the assembly details of programmable DNA nanotubes with monodisperse circumferences of a 4, 5, 6, 7, 8, or 10 DNA helix and their pearl-necklace-like assemblies with ultrasmall gold nanoparticles, Au25 nanoclusters (AuNCs), liganded by -S(CH2)nNH3+ (n = 3, 6, 11). The flexibilities of DNA nanotubes, analyzed via statistical polymer physics analysis through atomic force microscopy (AFM), demonstrate that ∼2.8 power exponentially increased with the DNA helix number. Moreover, the short-length liganded AuS(CH2)3NH3+ NCs were observed to be able to form pearl-necklace-like DNA-AuNC assemblies stiffened than neat DNA nanotubes, while long-length liganded AuS(CH2)6NH3+ and AuS(CH2)11NH3+ NCs could fragment DNA nanotubular structures, indicating that DNA-AuNC assembling can be precisely manipulated by customizing the hydrophobic domains of the AuNC nanointerfaces. We prove the advantages of polymer science concepts in unraveling useful intrinsic information on physical fundamental details of DNA-AuNC assembling, which facilitates DNA-metal nanocomposite construction.

Physical Mechanism of Amyloid-ß Peptide Chain Aggregation on Fluidic Lipid Nanotubules.

The question of how peptide chain aggregation is influenced by lipid membranes with varying shapes and structures is crucial for a detailed understanding of the neurotoxicity effect of the peptide chains. Not like the more usual spherical liposomes and planar lipid membranes, herein, we use lipid nanotubules as a model of important neuron synapse nanowire structures and devote particular attention to the effect of nanotubule fluidity on amyloid-ß peptide (Aß) chain aggregation. We apply single-molecule tracking (SMT) to elucidate how Aß chains diffuse and aggregate on lipid nanotubules with different fluidities. The physical mechanism implies that fluidic lipid nanotubules facilitate the super-diffusion of two-dimensional (2D)-mobile precursor Aß chains and promote their aggregation. This aggregation mechanism is retarded on less fluidic lipid nanotubules where the super-diffusion of 2D-mobile precursor Aß chains is restricted by "frozen" lipids with less mobility. This work provides a mechanistic explanation for Aß chain aggregation on fluidic lipid nanotubules.

Nanopatterned Polymer Surface Modulates Twist Polymorphism in a Single Amyloid Fibril.

The periodic twist behaviors of amyloid fibrils initiated and formed on block copolymer films with nanoscale features are studied. The discovery of twist variations even in a single amyloid fibril is reported: the fibril can vary its twist extents in response to the underlying nanopatterned surfaces by keeping its neighboring crossover sections right above the periodic nanodomains and tuning the distance between neighboring crossover sections based on either the periodic nanodomain distance or the fibril contour direction. This nanopattern-induced twist polymorphism arises from the fibril's two edges, exhibiting different hydrophobic interactions with the periodic nanodomains, as demonstrated by simulation studies. This work contributes to the understanding of surface effects on twist polymorphism in amyloid fibril structures that may be important to fibril polymorphism in amyloid pathologies and bioapplications of amyloid fibrils.

A mobile precursor determines protein resistance on nanostructured surfaces.

Biomaterials are often engineered with nanostructured surfaces to control interactions with proteins and thus regulate their biofunctions. However, the mechanism of how nanostructured surfaces resist or attract proteins together with the underlying design rules remains poorly understood at a molecular level, greatly limiting attempts to develop high-performance biomaterials and devices through the rational design of nanostructures. Here, we study the dynamics of nonspecific protein adsorption on block copolymer nanostructures of varying adhesive domain areas in a resistant matrix. Using surface plasmon resonance and single molecule tracking techniques, we show that weakly adsorbed proteins with two-dimensional diffusivity are critical precursors to protein resistance on nanostructured surfaces. The adhesive domain areas must be more than tens or hundreds of times those of the protein footprints to slow down the 2D-mobility of the precursor proteins for their irreversible adsorption. This precursor model can be used to quantitatively analyze the kinetics of nonspecific protein adsorption on nanostructured surfaces. Our method is applicable to precisely manipulate protein adsorption and resistance on various nanostructured surfaces, e.g., amphiphilic, low-surface-energy, and charged nanostructures, for the design of protein-compatible materials.

Oriented Protein Nanoarrays on Block Copolymer Template.

Here, a simple yet robust method is developed to fabricate oriented protein nanoarrays by employing a block copolymer (BCP) template, which presents nano-scaled spot areas at high-density arrays. Unlike the conventional BCP nanolithography, the BCP platform described here resists nonspecific protein adsorption and prevents the denaturation of immobilized proteins in aqueous solution. The orderly arranged array areas are functionalized by linking chemistry which allows for the precise control of protein orientation. This approach allows us to generate potentially oriented protein nanoarrays at high-density array spots, which is useful for miniaturized nanoarrays within high-throughput proteomic applications.

Heterogeneous patterns on block copolymer thin film via solvent annealing: Effect on protein adsorption.

Heterogeneous patterns consisting of nanometer-scaled hydrophobic/hydrophilic domains were generated by self-assembly of poly(styrene)-block-poly(2-hydroxyethyl methacrylate) (PS-b-PHEMA) block copolymer thin film. The effect of the heterogeneity of the polymer film surface on the nonspecific adsorption of the protein human plasma fibrinogen (FBN, 5.0 × 5.0 × 47.5 nm(3)) was investigated. The kinetics of the FBN adsorption varies from a single-component Langmuir model on homogeneous hydrophilic PHEMA to a two-stage spreading relaxation model on homogeneous hydrophobic PS surface. On a heterogeneous PS-b-PHEMA surface with majority PS part, the initial FBN adsorption rate remains the same as that on the homogeneous PS surface. However, hydrophilic PHEMA microdomains on the heterogeneous surface slow down the second spreading stage of the FBN adsorption process, leading to a surface excess of adsorbed FBN molecules less than the presumed one simply calculated as adsorption onto multiple domains. Importantly, when the PS-b-PHEMA surface is annealed to form minority domelike PS domains (diameter: ∼50-100 nm) surrounded by a majority PHEMA matrix, such surface morphology proves to be strongly protein-repulsive. These interesting findings can be attributed to the enhancement of the spread FBN molecule in a mobile state by the heterogeneity of polymer film surface before irreversible adsorption occurs.

Forehead Flap for Simultaneous Reconstruction After Head and Neck Malignant Tumor Resection.

INTRODUCTION: Oncologic resection of the head and neck malignant tumor often results in complex reconstructive problems that require a reliable flap to restore both the form and function in single-stage operation. The free flap transfer has revolutionized head and neck reconstruction. However, forehead flap pedicled with superficial temporal artery (STA) or supraorbital artery (SOA)/supratrochlear artery (STrA) is a new option for reconstruction of head and neck with its own specific advantages. METHOD: The forehead flap was applied to reconstruct the defects of the posterior hypopharyngeal wall, external perioral skin and buccal mucosal, and nose and periorbital tissues after malignant tumor resection. Nine of the patients were reconstructed with forehead flap pedicled with STA, 7 of whom underwent postoperative radiation. Eight of the patients were pedicled with SOA (and/or STrA), 1 of whom underwent postoperative radiation. RESULTS: We applied this method in a total of 17 male patients. The mean age of patients was 61 years (range, 47-69 years) with a follow-up time of 12 to 180 months. The biggest defect covered by forehead flap pedicled with STA was measured 10.0 × 6.5 cm. The biggest defect covered by forehead flap pedicled with SOA and/or STrA was measured 9.0 × 7.0 cm. In all 17 patients, no vascular crisis happened and no partial or total flap necrosis was observed. All skin graft area and donor site healed well. No patient experienced flap strictures or fistulas after operation or after radiotherapy. No local recurrence developed during the follow-up time. Functions were assessed by specialist as optimal as no limitation of eyes or mouth opening, and no limitation of food swallowing. CONCLUSIONS: The forehead flap provides thin pliable tissue with reliable blood supply and high tolerance to radiotherapy. These advantages make it a valuable option to simultaneously reconstruct the defects after head and neck malignant tumor resection in certain selected patients.

Double-nylon purse-string suture in closing postoperative wounds following endoscopic resection of large (≥ 3 cm) gastric submucosal tumors.

BACKGROUND: Endoscopic full-thickness resection (EFTR) of gastric submucosal tumors (SMTs) is safe and effective; however, postoperative wound management is equally important. Literature on suturing following EFTR for large (≥ 3 cm) SMTs is scarce and limited. AIM: To evaluate the efficacy and clinical value of double-nylon purse-string suture in closing postoperative wounds following EFTR of large (≥ 3 cm) SMTs. METHODS: We retrospectively analyzed the data of 85 patients with gastric SMTs in the fundus of the stomach or in the lesser curvature of the gastric body whose wounds were treated with double-nylon purse-string sutures after successful tumor resection at the Endoscopy Center of Renmin Hospital of Wuhan University. The operative, postoperative, and follow-up conditions of the patients were evaluated. RESULTS: All tumors were completely resected using EFTR. 36 (42.35%) patients had tumors located in the fundus of the stomach, and 49 (57.65%) had tumors located in the body of the stomach. All patients underwent suturing with double-nylon sutures after EFTR without laparoscopic assistance or further surgical treatment. Postoperative fever and stomach pain were reported in 13 (15.29%) and 14 (16.47%) patients, respectively. No serious adverse events occurred during the intraoperative or postoperative periods. A postoperative review of all patients revealed no residual or recurrent lesions. CONCLUSION: Double-nylon purse-string sutures can be used to successfully close wounds that cannot be completely closed with a single nylon suture, especially for large (≥ 3 cm) EFTR wounds in SMTs.

Two dimensional nanoarrays of individual protein molecules.

Protein molecules on solid surfaces are essential to a number of applications, such as biosensors, biomaterials, and drug delivery. In most approaches for protein immobilization, inter-molecular distances on the solid surface are not controlled and this may lead to aggregation and crowding. Here, a simple approach to immobilize individual protein molecules in a well-ordered 2D array is shown, using nanopatterns obtained from a polystyrene-block-poly(2-hydroxyethyl methacrylate) (PS-b-PHEMA) diblock copolymer thin film. This water-stable and protein-resistant polymer film contains hexagonally ordered PS cylindrical domains in a PHEMA matrix. The PS domains are activated by incorporating alkyne-functionalized PS and immobilizing azide-tagged proteins specifically onto each PS domain using "Click" chemistry. The nanometer size of the PS domain dictates that each domain can accommodate no more than one protein molecule, as verified by atomic force microscopy imaging. Immunoassay shows that the amount of specifically bound antibody scales with the number density of individual protein molecules on the 2D nanoarrays.

Biocompatibility of micro/nano structures on the surface of Ti6Al4V and Ti-based bulk metallic glasses induced by femtosecond laser.

Femtosecond laser surface modification has been proved to be a versatile technology to create various functional materials by modifying solid surface properties. An interesting experimental phenomenon is found by exposing a Ti6Al4V alloy and Ti-based metallic glass to femtosecond laser irradiation. The research results show that the femtosecond laser induces different micro-nano structures on the surfaces of Ti6Al4V alloy and Ti-based metallic glass. Spherical structure and LIPSS (Laser-induced periodic surface structures) can be formed on the surface of Ti6Al4V alloy after femtosecond laser irradiation. On the surface of Ti-based metallic glass, LIPSS, SWPSS (Super-wavelength periodic surface structure) and neatly arranged microholes structures can be found. Under the same laser parameters, the micro-nano structures showed different evolution trends on the Ti6Al4V alloy and Ti-based metallic glass surfaces. The difference in surface structure between Ti6Al4V alloy and Ti-based metallic glass is since amorphous materials have no crystal lattice and a fixed melting temperature. In addition, there are differences in the biocompatibility of different surface structures. The size and distance of the micro-pits on the surface of different structures determine the ability of cells to adhesion, proliferate and differentiate. This conclusion has important significance for the application of Ti6Al4V alloy and Ti-based metallic glass in the field of biomedicine.

Evidence of a mobile precursor state in nonspecific protein adsorption.

We study the dynamics of nonspecific protein adsorption using nanometer-micrometer-scale patterns involving hydrophobic domains in hydrophilic matrices. We report the discovery of a critical requirement for the sizes of the hydrophobic/adhesive pads for protein adsorption: the area of each adhesive pad must be more than 2 orders of magnitude larger than the footprint of a protein molecule before irreversible adsorption occurs. We attribute this to the minimal surface area sampled by a mobile protein molecule in a precursor state before irreversible adsorption occurs. Kinetic analysis based on the precursor model quantitatively accounts for the experimental observation and reveals that the distance sampled by the mobile precursor state before irreversible adsorption increases with the size of the protein molecule.

ILC1s and ILC3s Exhibit Inflammatory Phenotype in Periodontal Ligament of Periodontitis Patients.

Innate lymphoid cells (ILCs) are emerging as important players in inflammatory diseases. The oral mucosal barrier harbors all ILC subsets, but how these cells regulate the immune responses in periodontal ligament tissue during periodontitis remains undefined. Here, we show that total ILCs are markedly increased in periodontal ligament of periodontitis patients compared with healthy controls. Among them, ILC1s and ILC3s, particularly NKp44+ILC3 subset, are the predominant subsets accumulated in the periodontal ligament. Remarkably, ILC1s and ILC3s from periodontitis patients produce more IL-17A and IFN-γ than that from healthy controls. Collectively, our results highlight the role of ILCs in regulating oral immunity and periodontal ligament inflammation and provide insights into targeting ILCs for the treatment of periodontitis.

Noninvasive detection of human dehydroepiandrosterone, progesterone and testosterone using LC-MS/MS revealed effects of birth control pills/devices and body weight on ovulatory prediction.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly used to measure steroids in human saliva. We studied the performance of a conventional LC-MS/MS for measuring dehydroepiandrosterone (DHEA), testosterone and progesterone in human saliva. These three steroids were co-extracted by liquid-liquid extraction and derivatized. Derivatives were resolved on a C18 column and quantified using an LC-MS/MS (AB Sciex API 2000) instrument. The assay's limits of quantification were 0.03 ng/mL for all three steroids. Inter-assay coefficients of variation were 16.6-18.8% (DHEA), 12.0-15.8% (testosterone), and 12.7-19.3% (progesterone). Assay linearity analysis showed R2 of 0.9926, 0.9750 and 0.9949 for DHEA, testosterone and progesterone, respectively. No carry-over between samplings was observed. An ion-enhancement effect of 11.6% for DHEA determination and ion-suppression effects of 13.9% and 20.7% for analysis of progesterone and testosterone, respectively, were determined. No interferences by 9 steroid analogs were detected. Spiked recoveries were 85.5% (DHEA), 86.5% (testosterone), and 92.6% (progesterone). Comparison with laboratory developed test (LDT)-LC-MS/MS methods by other New York State Department of Health certified laboratories revealed R2 = 0.9425 (DHEA, LC-MS/MS = 1.0267 LDT + 21.989), R2 = 0.9849 (testosterone, LC-MS/MS = 0.9447 LDT + 9.8037), and R2 = 0.9736 (progesterone, LC-MS/MS = 1.1196 LDT + 0.0985). Reference intervals for the 3 steroids in saliva for young males and females were estimated. Results of intra-individual salivary progesterone analysis indicated that caution should be exercised when using progesterone concentrations in predicting ovulation for females who are under treatment with birth control pills/devices or has body a weight of > 90 kg.

Posterior atlantoaxial dislocation without fracture and neurologic deficit: a case report and the review of literature.

Traumatic posterior atlantoaxial dislocation without related fracture of the odontoid process is very rare, and only ten cases have been previously reported. The objective of this paper was to describe a case of traumatic posterior atlantoaxial dislocation without related fracture of the odontoid process, and its management with atlantoaxial transarticular screw fixation and bony fusion through an anterior retropharyngeal approach, and to review the relevant literature. The patient's medical and radiographic history is reviewed as well as the relevant medical literature. Posterior atlantoaxial dislocation was confirmed in a 48-year-old male struck by an automobile through conventional radiography, computed tomography and magnetic resonance imaging. No related fracture of the odontoid process or neurological deficit was found in this patient. Transarticular screw fixation of the atlantoaxial articulation through anterior retropharyngeal approach was performed after several unsuccessful attempts of closed reduction. At the latest follow-up, the lateral cervical spine radiography in flexion and extension demonstrated no instability of the atlantoaxial complex 21 months after the operation. In conclusion, patients with posterior atlantoaxial dislocation without fracture may survive with few or no-long term neurological deficit. Routine CT and MRI of the cervical spine should be carried out in patients with head or neck trauma to prevent missing of this rare clinical entity. Transarticular screw fixation of the atlantoaxial articulation through anterior retropharyngeal approach is safe and useful in case the management of dislocation is unsuccessful under closed reduction.

Kinetic study of Aß(1-42) amyloidosis in the presence of ganglioside-containing vesicles.

Alzheimer's disease (AD) is characterized by the amyloid-beta peptide (Aß) misfolding to form aberrant amyloid aggregates in the brain. Although recent evidence implicates that amyloid deposition in vivo is highly related to biomembranes, how the characteristic lipid components of neuronal membranes mediate this process remains to be fully elucidated. Herein, we established vesicle models to mimic exosomes and investigated their influence on the kinetics of Aß(1-42) amyloidosis. By using ternary vesicles composed of three brain lipids monosialoganglioside GM1, cholesterol and sphingomyelin, we found that GM1 could regulate peptide fibrillation by facilitating the conformational transition of Aß(1-42), and further quantitatively analyzed the influence of GM1-containing vesicles on the kinetics of Aß(1-42) fibrillation. In addition, GM1-containing vesicles induced the formation of Aß(1-42) fibrils at low concentrations, and these fibrils were toxic to PC12 cells. By analyzing the role of GM1 in this ternary mixture of membranes at the molecular level, we confirmed that GM1 clusters are presented as attachment sites for peptides, thus promoting the fibrillation of Aß(1-42).

Naturally available hypericin undergoes electron transfer for type I photodynamic and photothermal synergistic therapy.

Naturally available compounds with bioactivity are potential candidates for cancer treatment. In this paper, we isolated hypericin (HC) from Hypericum sinense L. and investigated its antitumor activity both in vitro and in vivo. The nanoparticles (NPs) of HC were prepared by a nanoprecipitation process with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000). With light irradiation, HC NPs not only undergo efficient electron transfer to generate the superoxide radical (O2-˙) and the hydroxyl radical (OH˙) as well as energy transfer producing singlet oxygen (1O2) for photodynamic therapy (PDT), but also non-radiative decay to produce heat for photothermal therapy (PTT) with a photothermal conversion efficiency of 29.3%. This synergistic therapy, therefore, largely boosts the phototherapy efficacy of HC NPs on human cervical cancer cells (HeLa), guaranteeing a low half maximal inhibitory concentration (IC50) of only 5.6 µg mL-1. Furthermore, in vivo studies suggest that HC NPs are capable of inhibiting tumor proliferation after laser irradiation, and the main organs remain healthy, including the heart, kidneys, liver, lungs and spleen. Our results indicate that HC NPs derived from nature with excellent phototherapy efficacies are biocompatible candidates for type I PDT/PTT synergistic cancer therapy.

Facile Strategy to Generate Aligned Polymer Nanofibers: Effects on Cell Adhesion.

Structure of polymer fiber membranes plays a vital role in controlling cell responses as applied to immobilize targets for specific cell interactions. Electrospinning is a simple and powerful method to prepare polymer fiber membranes with scales from nano- to micrometers. In this report, a facile yet versatile strategy has been developed for fabricating polymer nanofiber membranes with well-aligned structures using a glass sheet between the needle and a static drum as the collector. Effects of solution concentration, polymer molecular weight, applied voltage, and collection distance on the morphologies of the formed fibers were systematically studied. Adhesion of cells (e.g., mouse melanoma cells B16-F10 and fibroblast cells NIH-3T3) on the fiber membrane has been further investigated. Our results show that cell morphologies varied from elongated to spherical on the random fiber membrane when the pore area of membrane decreased. In contrast, on the membrane with aligned morphology, when decreasing the gap width of fiber membrane, cell is found to keep elongated state and spread along the alignment direction. This work provides a facile yet effective strategy to engineer surface structures of the fiber membranes for controlling cell adhesion.

The synthesis and mercury-recognizing skill of two emission "turn-on" rhodamine derivatives excited by rare earth up-conversion lattice.

The present paper focused on the synthesis and Hg(II)-sensing behavior of two rhodamine derived probes. Up-conversion NaYF4 nanocrystals were constructed and applied as the excitation host so that those probes could be lightened by the 980 nm excited up-conversion emission, aiming at better probe photostability. The efficient energy transfer between the up-conversion host and the probes was analyzed and confirmed by spectral analysis and emission decay lifetime comparison. The probes followed a simple complexation stoichiometry of 1:1 with Hg(II) ions. Then two sensing composite systems containing the up-conversion host and the probes were established. Their sensing performance, including spectral response, Stern-Volmer plots, emission stability and selectivity, was explored in detail. It was found that the probe emission linearly increased with increasing Hg(II) ions while was immune to other common metal ions, showing emission "turn-on" effect towards Hg(II) ions with good selectivity.

Malignant ameloblastoma (metastatic ameloblastoma) in the lung: 3 cases of misdiagnosis as primary lung tumor with a unique growth pattern.

Malignant ameloblastoma (metastatic ameloblastoma, MA) is currently defined as a distinct pathologic entity, MA, despite its histologically benign appearance. According to the new criteria, the histological and clinical features of MA are more homogenous. Here, we report three cases of histologically confirmed pulmonary MA. Two of the three patients complained of chest pain as the primary symptom, and the other case was detected upon the evaluation of pulmonary nodules found during a health examination after a local recurrence of mandible ameloblastoma. All three patients were female with an average age of 48 years. The intervals between the primary ameloblastoma and metastasis to the lung were 14 years, 19 years and 10 years, averaging 14.3 years. Prior to metastasis to the lung, only one patient experienced local recurrences, at 5 and 19 years after the primary tumor resection, while the other two patients both remained disease-free. Computed tomography (CT) or X-ray evaluation demonstrated multiple bilateral lung nodules ranging in size from several millimeters up to 2 cm. Histologically, the pulmonary metastatic tumors showed a unique growth pattern: the tumor cells grew among the interstitial alveoli but did not appear to destructively infiltrate the surrounding tissue. Immunohistochemically, the MA cells expressed squamous differentiation markers, such as CK10/13 and p63, while the alveolar epithelial cells stained for TTF1 and PE10. In this paper, we discuss the clinical behavior, differential diagnosis and unique growth pattern of pulmonary MA.