Commercially pure titanium (cp-Ti) is widely used in the field of long-term clinical oral implantology owing to its ability to allow close bone-implant apposition. The optimization of its function based on artificial proteins has become a key issue in the development of improved cp-Ti implants. Here, we set out to identify peptide aptamers with preferential adsorption towards titanium-based implants through the phage display methodology. Fifteen sequences were selected in the third round of biopanning. One sequence, ATWVSPY (named TBP1), had a 40% repetition rate and exhibited the strongest binding affinity to cp-Ti disks. Ten sequences were selected in the fourth round, among which the repetition rate is 80% for TBP1 and 20% for TBP2 (GVGLPHT). The peptide aptamers against cp-Ti disks can provide an alternative method of functional coating for biomaterial surfaces.

BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.

An original Ag nanoreactor capable of positively temperature-responsive and substrate-selective catalysis was prepared in this study. This nanoreactor was made of Ag nanoparticles encapsulated in a 4-nitrophenol (NP)-imprinted polymer matrix that exhibited a temperature-sensitive interpolymer interaction between poly(acrylamide)(PAAm) and (2-acrylamide-2-methylpropanesulfonic acid)(PAMPS). At relatively low temperatures (such as 20 degrees C), this nanoreactor did not demonstrate significant NP-selective catalysis due to the interpolymer complexation between PAAm and PAMPS, which caused shrinking in the imprinted networks. Conversely, at relatively high temperatures (such as 40 degrees C), this nanoreactor provided significant NP-selective catalysis resulting from the dissociation of the interpolymer complexes between PAAm and PAMPS. Unlike traditional Ag nanoreactors, which lack positively temperature-responsive catalysis or substrate-selective ability, this unique nanoreactor employed both the imprinting of the substrate molecule (i.e., NP) and a temperature-sensitive PAAm/PAMPS network, thereby making positively temperature-responsive, substrate-selective catalysis feasible.

To define whether repetitive exposures to low-dose radiation (LDR) can attenuate diabetes-induced testicular cell death, Type 1 diabetic rats were produced by single injection of streptozotocin (STZ). Once hyperglycemia was diagnosed, diabetic rats were treated with and without LDR (25 and 50 mGy X-rays) daily for 4 weeks. Eight and 12 weeks after diabetes onset, testicular apoptotic cell death was examined by flow cytometry with Annexin V/PI staining, Western blotting assay for caspase-3 cleavage, and TUNEL staining for localization of apoptotic cells. Diabetes induced a significant increase in testicular apoptotic cell death, which was able to be attenuated by repetitive exposures to LDR. Diabetes-induced testicular cell death was associated with increased mitochondrial dysfunction, shown by the decreased mitochondrial potential and increased expressions of Bax mRNA and protein. All these changes were significantly attenuated in certain extends by repetitive exposures to LDR. To investigate the mechanisms by which LDR attenuates diabetes-induced testicular apoptotic cell death, serum sex hormone (testosterone, luteinizing hormone and follicle stimulating hormone) levels, and both serum and testicular oxidative damage (lipid peroxides) and antioxidant contents (superoxide dismutase, catalase and glutathione) were measured. Serum sex hormones were significantly decreased in diabetic rats, but not significantly in diabetic rats with multiple exposures to LDR; Serum and testicular oxidative damage was significantly increased along with significant decreases in serum and testicular antioxidants in diabetic rats; however, these changes were significantly prevented by repetitive exposures to LDR. Furthermore, diabetic effects on the testicular oxidative damage and cell death were all attenuated by antioxidant N-acetylcysteine. These results suggest that diabetes-induced testicular cell death is probably mediated by increased oxidative stress. LDR protection from diabetes-induced testicular cell death is most likely mediated by its preserving antioxidants.

Multifunctional nano-micelles formed by amphiphilic gold-polycaprolactone-methoxy poly(ethylene glycol)(Au-PCL-MPEG) nanoparticles were synthesized and evaluated for potential drug delivery applications. Amphiphilic Au-PCL-MPEG nanoparticles were synthesized by the ring-opening polymerization of epsilon-caprolactone (epsilon-CL) using pre-synthesized 11-mercaptoundecanol stabilized Au (Au-MUD) nanoparticles in the presence of stannous octoate as a catalyst followed by esterification with MPEG-COOH. The amphiphilic Au-PCL-MPEG nanoparticles and the resulting nano-micelles formed in an aqueous solution have been characterized by a number of techniques, including 1H-NMR spectroscopy, transmission electron microscopy (TEM), fluorescent spectroscopy, and UV-vis spectroscopy. The critical aggregation concentration (CAC) of the micelles was 4 mg/l. The average size of the Au-PCL-MPEG nano-micelles below and above the CAC was 22 and 48 nm, respectively, as determined by the TEM. The controlled release of a model hydrophobic drug, 5-flurouracil, encapsulated in the Au-PCL-MEPG nanomicelles that lasted for more than four days was observed. In addition, due to the presence of Au nano-core, these Au-PCL-MPEG nanoparticles can potentially serve as a contrast agent for imaging (e.g., computed tomography (CT) imaging) and/or a nanoheater (e.g., in response to near infrared light) for photothermal therapy for cancer treatments.

OBJECTIVE: To investigate the morphological anatomical abnormalities of high congenital dislocation of hip in adults and provide anatomical basis for the total hip arthroplasty (THA). METHODS: From May 1997 to July 2008, 49 patients (57 hips) with high congenital dislocation of hip (Hartofilakidis type III) were treated. There were 6 males and 43 females with an average age of 29.4 years old (18-56 years old). The locations were left in 24 hips and right in 33 hips. The morphological parameters (including femoral length, isthmus, height of femoral head center, neck-shaft angle, medial head offset, anteversion angle, canal flare index, anteroposterior diameter of the true acetabulum, posterior thickness of the true acetabulum, depth of the true acetabulum) of suffering hips (dislocation group, n=57) were measured by preoperative X-ray, CT and intraoperative clinical observation and were compared with those of contralateral hips (control group, n=41). The intraoperative situations of hip were observed. RESULTS: The height of dislocation was (45.41 +/- 2.15) mm. The length difference of both lower extremities was (40.41 +/- 2.02) mm. In dislocation group, isthmus was shortened; height of femoral head center, neck-shaft angle and medial head offset were decreased; and anteversion angle was increased. CT showed that the canal flare index was larger than 4.7, femoral shape was funnel-shaped according to Noble classification. Anteroposterior diameter of the true acetabulum became smaller, posterior thickness of the true acetabulum became thicker, and depth of the true acetabulum was shallower. There were statistically significant differences in the morphological parameters of femur and acetabulum between two groups (P < 0.05). The intraoperative measurements showed that the anteroposterior diameter of acetabulum was (32.98 +/- 1.02) mm and the depth of acetabulum was (14.21 +/- 0.56) mm. There was no statistically significant difference between intraoperative measurements and preoperative measurements (P > 0.05). The acetabulum was full of fat and fibrous tissues. Running of the sciatic nerve in 40 cases were changed and it ran upward and laterally. CONCLUSION: When high congenital dislocation of the hip in adults is treated with THA, anatomical variation must be fully taken into account. The acetabulum is expanded toward posterosuperior, excessive reamed should be avoided to prevent femoral fractures, and appropriate or tailor-made prosthesis was selected.

Zirconium and hafnium complexes bearing new 1,2-ethanediyl- or 1,3-propanediyl-linked bis(beta-diketiminate) ligands,[{C(n)H(2n)-(BDI(Ar))(2)}MCl(2)](Ar = 2,6-Me(2)-C(6)H(3), 2,6-Cl(2)-C(6)H(3), 2,6-(i)Pr(2)-C(6)H(3); M = Zr, n = 2 (4a-c), n = 3 (5a-c); M = Hf, n = 2 (6b)), were synthesized via the reaction of MCl(4).2THF and one equivalent of dilithium salt of the corresponding ligand. Distorted trigonal prismatic and octahedral coordination geometries as well as C(1)-symmetric structures are found for zirconium complexes and in the solid state. Variable temperature (1)H NMR spectra indicated the fluxional nature of and in solution. Upon activation with methylaluminoxane (MAO), all these complexes except hafnium complex displayed moderate catalytic activities for ethylene polymerization. 1,2-Ethanediyl-linked complexes and are generally more active than their 1,3-propanediyl-linked analogues. The substituents at the ortho-positions of the phenyl rings have different effect on the catalytic activities of 1,2-ethanediyl-linked series or 1,3-propanediyl-linked series. It is noteworthy that even at a low Al/Zr molar ratio of 500, the catalytic activities of these zirconium complexes could be retained. Polyethylenes with broad molecular weight distributions (MWD = 15.3-20.3) were produced, which might result from the fluxional character of the zirconium complexes. The linear structure of obtained polyethylenes was further determined by (13)C NMR spectroscopy and DSC analysis.

Gold (Au) nanoparticles (NPs) stabilized with a monolayer of folate-conjugated poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol) copolymer (Au-P(LA-DOX)-b-PEG-OH/FA) was synthesized as a tumor-targeted drug delivery carrier. The Au-P(LA-DOX)-b-PEG-OH/FA NPs consist of an Au core, a hydrophobic poly(l-aspartate-doxorubicin)(P(LA-DOX)) inner shell, and a hydrophilic poly(ethylene glycol) and folate-conjugated poly(ethylene glycol) outer shell (PEG-OH/FA). The anticancer drug, doxorubicin (DOX), was covalently conjugated onto the hydrophobic inner shell by acid-cleavable hydrazone linkage. The DOX loading level was determined to be 17wt%. The Au-P(LA-DOX)-b-PEG-OH/FA NPs formed stable unimolecular micelles in aqueous solution. The size of the Au-P(LA-DOX)-b-PEG-OH/FA micelles were determined as 24-52 and 10-25nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The conjugated DOX was released from the Au-P(LA-DOX)-b-PEG-OH/FA micelles much more rapidly at pH 5.3 and 6.6 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Cellular uptake of the Au-P(LA-DOX)-b-PEG-OH/FA micelles facilitated by the folate-receptor-mediated endocytosis process was higher than that of the micelles without folate. This was consistent with the higher cytotoxicity observed with the Au-P(LA-DOX)-b-PEG-OH/FA micelles against the 4T1 mouse mammary carcinoma cell line. These results suggest that Au-P(LA-DOX)-b-PEG-OH/FA NPs could be used as a carrier with pH-triggered drug releasing properties for tumor-targeted drug delivery.

Folate-conjugated unimolecular micelles based on amphiphilic hyperbranched block copolymer, Boltorn((R)) H40-poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol)/FA-conjugated poly(ethylene glycol)(H40-P(LA-DOX)-b-PEG-OH/FA), were synthesized as a carrier for tumor-targeted drug delivery. The anticancer drug DOX was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms by pH-sensitive hydrazone linkage. The size of the unimolecular micelles was determined as approximately 17-36 and 10-20nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The release profiles of the DOX from the H40-P(LA-DOX)-b-PEG-OH/FA micelles showed a strong dependence on the environmental pH values. The DOX release rate increased in the acidic medium due to the acid-cleavable hydrazone linkage between the DOX and micelles. Cellular uptake of the H40-P(LA-DOX)-b-PEG-OH/FA micelles was found to be higher than that of the H40-P(LA-DOX)-b-PEG-OH micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. Degradation studies showed that the H40-P(LA-DOX)-b-PEG-OH/FA copolymer hydrolytically degraded into polymer fragments within six weeks. These results suggest that H40-P(LA-DOX)-b-PEG-OH/FA micelles could be a promising nanocarrier with excellent in vivo stability for targeting the drugs to cancer cells and releasing the drug molecules inside the cells by sensing the acidic environment of the endosomal compartments.

Electromagnetically induced transparency in a three-level Lambda-type molecular system with nonzero permanent dipole moments is investigated. It is shown that in the (2+2)-transition processes, when the sign of d(21), the difference in permanent dipole moments of the probe transition, is positive, perfect electromagnetically induced transparency with steep normal dispersion could be obtained under specific conditions. In contrast, when the sign of d(21) is negative, surprisingly gain without inversion with steep anomalous dispersion could be attained.