Parent-Implemented Behavior Interventions via Telehealth for Older Children and Adolescents.

Children and adolescents with intellectual and developmental disabilities (IDD) are more likely to engage in challenging and interfering behavior than their typically developing peers, which has been linked to many negative outcomes. The most effective interventions to address challenging and interfering behavior incorporate function-based assessments, which are used to develop individualized behavior interventions. Functional communication training (FCT) is an evidence-based practice to decrease challenging and interfering behavior that can be taught to parents using behavioral parent training (BPT); however, there are limited skilled professionals who can develop interventions and train parents. Telehealth can enable greater access to these professionals. This study used withdrawal designs to determine whether high parent treatment fidelity resulted in decreased challenging and interfering behavior and increased appropriate replacement behavior. Three participants (8-17 years) were included in the study, and their parents served as interventionists during mealtime, toothbrushing, and room cleaning. Data were analyzed using visual analysis. Each parent achieved high treatment fidelity with one session of BPT and bug-in-ear coaching. All participants had a decrease in challenging and interfering behavior and an increase in functional communication responses (FCRs) upon the introduction of the intervention with reliable reversals. All parents reported high social validity. Results and implications for practice and future research are discussed.

Life cycle assessment and techno-economic analysis of wood-based biorefineries for cellulosic ethanol production.

Poplar is widely used in the paper industry and accompanied by abundant branches waste, which is potential feedstock for bioethanol production. Acid-chlorite pretreatment can selectively remove lignin, thereby significantly increasing enzymatic efficiency. Moreover, lignin residues valorization via gasification-syngas fermentation can achieve higher fuel yield. Herein, environmental and economic aspects were conducted to assess technological routes, which guides further process optimization. Life cycle assessment results show that wood-based biorefineries especially coupling scenarios have significant advantages in reducing global warming potential in contrast to fossil-based automotive fuels. Normalization results indicate that acidification potential surpasses other indicators as the primary impact category. In terms of economic feasibility, coupling scenarios present better investment prospects. Bioethanol yield is the most critical factor affecting market competitiveness. Minimum ethanol selling price below ethanol international market price is promising with higher-levels technology. Further work should be focused on technological breakthrough, consumable reduction or replacement.

Trueness of intraoral scanning for different tooth-size arch-length deficiencies.

Background/purpose: As science and technology continue to advance, the utilization of intraoral scanners (IOSs) has become increasingly popular in the orthodontic workflow. The aim of this study was to discuss whether the degree of crowded arches affects scan accuracy. Materials and methods: Three different crowding levels of dental models (model MI: mild, model MO: moderate, and model SE: severe) were scanned using both an IOS and desktop scanner. Stereolithographic files were obtained and superimposed via CAD software to calculate differences between each measuring point of a model and the farthest corresponding point. The deviations from three models were compared with statistical analysis. Results: The trueness of different crowding arches showed that the deviation value of model SE was the maximum, followed by model MI, and model MO in the maxillary arch. In the mandibular arch, the order of the deviation from greatest to least was firstly model SE, then model MO, and model MI. Significant differences were observed among the maxillary models (P < 0.001), but there was no significant difference between models in the mandible (P = 0.669). Conclusion: The trueness of the three crowded arches is in the clinically acceptable range. The degree of crowding increases, the trueness of scanning at each position decreases. In the maxillary arch, more severe crowding corresponds to higher deviations. In the mandible, the degree of crowding is not explicitly related to the maximum deviation; therefore, the clinician should notice the deviation when using IOSs for crowding cases.

Promotion of osteogenic differentiation of stem cells and increase of bone-bonding ability in vivo using urease-treated titanium coated with calcium phosphate and gelatin.

Because of its excellent biocompatibility and low allergenicity, titanium has been widely used for bone replacement and tissue engineering. To produce a desirable composite with enhanced bone response and mechanical strength, in this study bioactive calcium phosphate (CaP) and gelatin composites were coated onto titanium (Ti) via a novel urease technique. The cellular responses to the CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on CaP/gel/Ti and CaP/Ti in vitro. The results showed that the optical density values, alkaline phosphatase expression and genes expression of MSCs on CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those on pure Ti (p < 0.05). CaP/gel/Ti and CaP/Ti rods (2 mm in diameter, 10 mm in length) were also implanted into femoral shaft of rabbits and pure Ti rods served as control (n = 10). Histological examination, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) measurements were performed at 4 and 8 weeks after the operation. The histological and SEM observations demonstrated clearly that more new bone formed on the surface of CaP/gel/Ti than in the other two groups at each time point. The CaP/gel/Ti bonded to the surrounding bone directly with no intervening soft tissue layer. An interfacial layer, containing Ti, Ca and P, was found to form at the interface between bone and the implant on all three groups by EDS analysis. However, the content of Ca, P in the surface of CaP/gel/Ti implants was more than in the other two groups at each time point. The CaP/gel/Ti modified by the urease method was not only beneficial for MSCs proliferation and osteogenic differentiation, but also favorable for bone bonding ability on Ti implants in vivo, suggesting that Ti functionalized with CaP and gelatin might have a great potential in clinical joint replacement or dental implants.

Biomaterials-enhanced bioactive agents to efficiently block spinal metastases of cancers.

The spine is the most common site of bone metastases, as 20%-40% of cancer patients suffer from spinal metastases. Treatments for spinal metastases are scarce and palliative, primarily aiming at relieving bone pain and preserving neurological function. The bioactive agents-mediated therapies are the most effective modalities for treating spinal metastases because they achieve systematic and specific tumor regression. However, the clinical applications of some bioactive agents are limited due to the lack of targeting capabilities, severe side effects, and vulnerability of drug resistance. Fortunately, advanced biomaterials have been developed as excipients to enhance these treatments, including chemotherapy, phototherapy, magnetic hyperthermia therapy, and combination therapy, by improving tumor targeting and enabling sustaining and stimuli-responsive release of various therapeutic agents. Herein, the review summarizes the development of biomaterials-mediated bioactive agents for enhanced treatments of spinal metastases and predicts future research trends.

Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma.

BACKGROUND: Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients, and available treatments are of little benefit. The objective of this trial was to determine whether acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy. METHODS: A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3×/wk on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates. Patients were followed for 6 months after the end of radiotherapy. RESULTS: Xerostomia Questionnaire scores for acupuncture were statistically significantly lower than for controls starting in week 3 through the 6 months (P = .003 at week 3, all other P < .0001), with clinically significant differences as follows: week 11, relative risk (RR) 0.63 (95% confidence interval [CI], 0.45-0.87); 6 months, RR 0.38 (95% CI, 0.19-0.76). Similar findings were seen for MDASI-HN scores. Group differences emerged as early as 3 weeks into treatment for saliva (unstimulated whole salivary flow rate, P = .0004), with greater saliva flow in the acupuncture group at week 7 (unstimulated whole salivary flow rate, P < .0001; stimulated whole salivary flow rate, P = .002) and 11 (unstimulated whole salivary flow rate, P < .02; stimulated whole salivary flow rate, P < .03) and at 6 months (stimulated whole salivary flow rate, P < .003). CONCLUSIONS: Acupuncture given concurrently with radiotherapy significantly reduced xerostomia and improved quality of life.

Immunosuppressive adenosine-targeted biomaterials for emerging cancer immunotherapy.

Immunotherapy has paved the way for the future of cancer therapy, but there are still significant challenges to be overcome, such as the occurrence of immune escape or suppression. Adenosine is essential in modulating the immune responses of immune cells and maintaining immune tolerance. Emerging adenosine pathway inhibitors are considered a breakthrough in cancer immunotherapy, with emphasis first being placed on the top-down blockade of adenosine signaling axis, followed by combination therapy. However, these therapeutic strategies rely on adenosine inhibitors, mainly small molecules or antibody proteins, which are limited by a single route of administration and off-target toxicity. Therefore, synergistic nanomedicine with accurate delivery targeting deeper tumors is focused on in preclinical studies. This review discusses how adenosine reshapes immunosuppressive microenvironments through its effects on immune cells, including lymphocytes and myeloid cells. Additionally, it will be the first discussion of a comprehensive strategy of biomaterials in modulating the adenosine signaling pathway, including inhibition of adenosine production, inhibition of adenosine binding to immune cells, and depletion of adenosine in the microenvironments. Furthermore, biomaterials integrating multiple therapeutic modalities with adenosine blocking are also discussed as a promising strategy for promoting cancer immunotherapy.

Effect of amylase activity on mechanical properties of dental composite resin.

The purpose of this study was to investigate the effect of amylase activity on the mechanical properties of three dental composite resin (Filtek Z350; Filtek Z250 and Polofil Supra). The specimens were immersed in amylase solution at four different activities (25, 50, 100 and 200 KIU/L) with an artificial saliva solution (AS) as a control. The flexural strength (FS) and elastic modulus (EM) were determined in a three-point bending test after immersion for periods up to 12 months. In addition, surface roughness and surface morphology also determined. The FS of Filtek Z350 reaching the lowest level of 67.86 MPa after AS immersion for one year. There was a general trend for FS to decrease following immersion in AS for all the tested materials. However, the amylase groups did not undergo a significant decrease in FS and EM, and there was a slight increase in FS and EM for Polofil Supra.

Comparison of the Anterior Tooth and Lip Esthetic Characteristics of Hani and Han Youth in China When Speaking.

OBJECTIVE: This study aims to measure and analyze the lip and tooth dynamic esthetic characteristics at rest and during speech in order to provide a reference for its esthetic design and restoration among the Hani and Han populations in Yunnan Province, China. METHODS: Subjects of Hani and Han ethnicity in Yunnan were selected using multistage stratified sampling and inclusive criteria. The lip and tooth dynamic esthetic characteristics of the subjects at rest and during the pinyin pronunciation of "me", "yi", "fu", and "si" were recorded using digital photography and analyzed with computer software. RESULTS: No statistical difference was detected between the Hani and Han groups in the upper central-incisor display, when pronouncing the pinyin "yi". Furthermore, there were no statistical differences in lip dynamic esthetic parameters between the Hani and Han groups, except for the distance between the upper and lower lips when pronouncing "si". There were three kinds of correlation between the upper central-incisor edge and lower lip: separation, contact, and overlap. CONCLUSION: The display of upper central incisors and the mouth width of Hani people are larger than those of Han people when at rest. When the pinyin "si" is pronounced, the display of upper central incisors and the upper-lower lip distance of Hani people is less than that of Han people due to labial muscle movement.

Generation of radially and azimuthally polarized light by optical transmission through concentric circular nanoslits in Ag films.

Optical transmission through concentric circular nanoslits is studied in experiments and numerical simulations. Polarized optical microscopic imaging shows that the optical transmission through these apertures is spatially inhomogeneous, exhibiting colored fan texture patterns. Numerical simulations show that these colored fan texture patterns originate from the cylindrical vector polarization of the transmitted beam. Specifically, the transmitted light is in-phase radially polarized at long wavelengths due to the predominant transmission of the transverse magnetic (TM) waveguide modes; and in-phase azimuthally polarized at short wavelengths due to the increased optical transmission of the transverse electric (TE) waveguide modes. Additionally, the transmission shows a peak at the wavelength of Wood anomaly and a dip at the resonant wavelength of surface plasmon excitation; and the transmitted light at these wavelengths is a mixture of azimuthally and radially polarized fields. These interesting optical transmission behaviors of circular nanoslits provide a miniaturized way to generating radially and azimuthally polarized light.

Bile acid transporter mediated STC/Soluplus self-assembled hybrid nanoparticles for enhancing the oral drug bioavailability.

The nano-particulate system for oral delivery faces a big challenge across the gastrointestinal bio-barriers. The aim was to explore the potential applications of bile acid transporter mediated the self-assembled hybrid nanoparticles (SHNPs) of sodium taurocholate (STC) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) for augmenting the oral delivery of poorly water-soluble drugs. Felodipine (FLDP) was chosen as a model drug. The self-assembly of STC with Soluplus to load FLDP and the microstructure of the SHNPs were confirmed using molecular simulation, STC determination by high performance liquid chromatography (HPLC) and transmission electron microscope. Results showed that STC was integrated with Soluplus on the surface of nanoparticles by hydrophobic interactions. The permeability of FLDP loaded STC/Soluplus SHNPs was STC dependent in the ileum, which was inhibited by the higher concentrations of STC and the inhibitor of apical sodium-dependent bile acid transporter (ASBT). STC/Soluplus (1:9) SHNPs significantly improved the drug loading of FLDP, achieved the highest permeability of FLDP and realized 1.6-fold of the area under the curve (AUC) of Soluplus self-assembled nanoparticles (SNPs). A water-quenching fluorescent probe P4 was loaded into the STC/Soluplus SHNPs, which verified that the SHNPs were transferred intactly across the ileum. In conclusion, STC/Soluplus SHNPs via ASBT are a potential strategy for enhancing the oral bioavailability of poorly water-soluble drugs.

FXIIIa substrate peptide decorated BLZ945 nanoparticles for specifically remodeling tumor immunity.

Combretastatin A4 nanoparticles (CA4-NPs), which notably inhibit tumor growth, were found to cause tumor regrowth due to the intratumoral enrichment of M2-type macrophages after treatment. Since BLZ945, an inhibitor of CSF-1 receptor (CSF-1R), depletes and inhibits the proliferation of M2-type macrophages, it has the potential to relieve the immunosuppressive microenvironment and improve anti-tumor therapy of CA4-NPs. However, CSF-1R exists widely, not only in macrophages, and BLZ945 could cause potential hepatotoxicity. It is necessary to establish a tumor-targeting drug delivery system to reduce the off-target and side effects of BLZ945. In this study, FXIIIa substrate peptide A15 decorated BLZ945 nanoparticles (A15-BLZ-NPs) were developed, in which, BLZ945-poly(d,l-lactide) (BLZ945-PLA), produced by ring-opening polymerization, was encapsulated in poly(ethylene glycol)-poly(d,l-lactide) (PEG5k-PLA5k), and A15 was decorated on the surface PEG segment. A15-BLZ-NPs could crosslink with fibrin through elevated FXIIIa and specifically target intratumoral coagulation spots induced by CA4-NPs. In vivo studies showed that CA4-NPs induced enhanced distribution of BLZ945 in tumors, as the BLZ945 content was 3.75-fold in the CA4-NP + A15-BLZ-NP group compared to that of A15-BLZ-NP single treatment. Meanwhile, compared to the CA4-NP group, the combination treatment significantly reduced the proportion of M2-type macrophages (from 64.4% to 24.5%) and enriched cytotoxic T lymphocytes (from 1.5% to 18.9%) in tumors, suggesting that A15-BLZ-NPs remodeled and activated tumor immunity after CA4-NP treatment. Furthermore, the combined treatment effectively improved the tumor inhibition rate to 73.4%, which was significantly higher than that of CA4-NP (15.5%) or A15-BLZ-NP (23.9%) single treatment. This work established a novel combination strategy for anti-tumor therapy.

Topology control of human fibroblast cells monolayer by liquid crystal elastomer.

Eukaryotic cells in living tissues form dynamic patterns with spatially varying orientational order that affects important physiological processes such as apoptosis and cell migration. The challenge is how to impart a predesigned map of orientational order onto a growing tissue. Here, we demonstrate an approach to produce cell monolayers of human dermal fibroblasts with predesigned orientational patterns and topological defects using a photoaligned liquid crystal elastomer (LCE) that swells anisotropically in an aqueous medium. The patterns inscribed into the LCE are replicated by the tissue monolayer and cause a strong spatial variation of cells phenotype, their surface density, and number density fluctuations. Unbinding dynamics of defect pairs intrinsic to active matter is suppressed by anisotropic surface anchoring allowing the estimation of the elastic characteristics of the tissues. The demonstrated patterned LCE approach has potential to control the collective behavior of cells in living tissues, cell differentiation, and tissue morphogenesis.

The Dynamic Viscoelasticity of Dental Soft Polymer Material Containing Citrate Ester-Based Plasticizers.

The aim of this study was to investigate the dynamic viscoelasticity of dental soft polymer material containing citrate ester-based plasticizers. Three kinds of citrate ester-based plasticizer (Citroflex® C-2: TEC, Citroflex® A-2: ATEC, and Citroflex® A-4: ATBC), with the combination of 5 wt% ethyl alcohol, were used as the liquid phase. The dynamic viscoelastic properties of nine ethyl methacrylate polymers: (A, B, C, D, E, F, G, H, and I) were immersed in 37 °C distilled water for 0, 1, 3, 7, 14 and 30 days, respectively. The dynamic viscoelastic properties were measured at 37 °C with an automatic dynamic mechanical analyzer. The shear storage modulus (G'), shear loss modulus (G″), and loss tangent (tan δ) were determined at 1 Hz. These parameters were statistically analyzed by two-way and one-way ANOVA and Tukey's multiple comparison test at a predetermined significance level of 0.05. A significant difference was found among the materials in terms of the dynamic viscoelasticity. The materials containing citrate ester-based plasticizer ATBC showed the most stable dynamic viscoelasticity. Considering the limitations of this study, the results suggest that the inclusion of citrate ester-based plasticizer can improve the durability of dental soft polymer materials.

[Effect of porcelain thickness and substrate on optical properties of porcelain veneers for tetracycline stained teeth].

PURPOSE: To analyze the effect of porcelain layer thicknesses and substrates on color properties and translucency of IPS e.max LT porcelain laminate veneers used to restore tetracycline stained teeth. METHODS: Porcelain specimens with different core and veneer thickness (veneer/core thickness: 0.25 mm/0.25 mm, 0.50 mm/0.25 mm, 0.25 mm/0.50 mm, 0.50 mm/0.50 mm, and 0.25 mm/0.75 mm) were fabricated by heat-press layering technique. CIE L*a*b* parameters were measured under simulated tetracycline backgrounds and black and white backgrounds by a spectrophotometer, color differences ΔE001 between specimens on simulated tetracycline backgrounds and backgrounds themselves and ΔE002 between specimens on simulated tetracycline backgrounds and white background were calculated. The translucent parameter(TP) was also calculated. The data were submitted to statistical analysis with SPSS 17.0 software package. RESULTS: ΔE001 increased with increase of thickness of the core and veneer layer, but there was no significant difference between 0.25 mm and 0.50 mm core thickness groups with 0.50 mm veneer in thickness (P>0.01). Except for light grey, ΔE002 decreased over other substrates with increase of thickness of the core and veneer layer, but there was no significant difference between 0.50 mm and 0.75 mm core thickness groups with 0.25 mm veneer in thickness (P>0.01). Both ΔE001 and ΔE002 were significantly different over different substrates（P<0.01）. TP decreased as the increase of core and veneer thickness and TP was significantly different with different core and veneer thickness（P<0.01）. CONCLUSIONS: Both the core/veneer thickness and the substrate have significant influence on color matching and masking ability of IPS e.max LT porcelain laminate veneers used to restore tetracycline stained teeth. As for IPS e.max LT porcelain veneers, the color property was the best when yellowish tetracycline stained teeth were restored, while the light grey was worst. The thickness of core and veneer has significant influence on the translucency of porcelain laminate veneers.

Long non-coding RNA maternally expressed gene 3 inhibits osteogenic differentiation of human dental pulp stem cells via microRNA-543/smad ubiquitin regulatory factor 1/runt-related transcription factor 2 axis.

OBJECTIVE: The aim of the present study was to investigate the biological roles and underlying mechanism of the long non-coding RNA maternally expressed gene 3 (MEG3) on osteogenic differentiation of human dental pulp stem cells (hDPSCs). METHODS: The expression levels of MEG3, microRNA-543 (miR-543), osterix, osteopontin, osteocalcin and runt-related transcription factor 2 (RUNX2) were measured by quantitative real-time PCR (qRT-PCR). Alkaline phosphatase (ALP) activity assay and alizarin red S staining (ARS) were used to measure the impacts exerted by MEG3, miR-543 on osteogenic differentiation. Cell proliferation was measured by MTT assay. In addition, the targeted relationships between miR-543, MEG3, and Smad ubiquitin regulatory factor 1 (SMURF1) were assessed through dual luciferase reporter assay. RESULTS: During osteogenic induction, the expression of MEG3 was gradually reduced, whereas the expression of miR-543, osterix, osteopontin, osteocalcin and RUNX2 were gradually increased. Functional analysis implied that MEG3 overexpression or miR-543 inhibition reduced the cell proliferation, ALP activity, ARS levels, and decreased the expression of osteoblast-related proteins. Moreover, MEG3 promoted SMURF1 expression by directly targeting miR-543 as a competing endogenous RNA. Furthermore, overexpression of miR-543 or silencing SMURF1 could reverse the inhibitory effects of MEG3 on the osteogenic differentiation of hDPSCs. CONCLUSIONS: In conclusion, our study revealed that overexpression of MEG3 inhibited hDPSCs osteogenic differentiation via miR-543/SMURF1/RUNX2 regulatory network, which may contribute to the functional regulation and clinical applications of hDPSCs.

AIE/FRET-based versatile PEG-Pep-TPE/DOX nanoparticles for cancer therapy and real-time drug release monitoring.

On account of the biological significance of self-assembling peptides in blocking the cellular mass exchange as well as impeding the formation for actin filaments resulting in program cell death, stimuli-responsive polypeptide nanoparticles have attracted more and more attention. In this work, we successfully fabricated doxorubicin-loaded polyethylene glycol-block-peptide (FFKY)-block-tetraphenylethylene (PEG-Pep-TPE/DOX) nanoparticles, where the aggregation-induced emission luminogens (AIEgen, TPE-CHO) can become a fluorescence resonance energy transfer (FRET) pair with the entrapped antitumor drug DOX to detect the release of drugs dynamically. This is the first successful attempt to detect and quantify the change of FRET signals in A549 cells via three methods to monitor the cellular uptake of nanoprobes and intracellular drug molecule release intuitively. As we proposed here, the combination of free DOX and the self-assembling peptide could achieve the synergistic anticancer efficacy. The multifunctional PEG-Pep-TPE/DOX nanoparticles may provide a new opportunity for combination cancer therapy and real-time detection of the drug release from stimuli-responsive nanomedicine.

A Mesoporous Nanoenzyme Derived from Metal-Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy.

Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (1 O2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H2 O2 , the hypoxic tumor microenvironment is relieved. Thus, Ce6-loaded NE serves as a H2 O2 -activated oxygen supplier to increase the local O2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T2 -weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF-derived mesoporous NE as a multifunctional theranostic agent in cancer therapy.

Liquid-Crystalline Hydroxyapatite/Polymer Nanorod Hybrids: Potential Bioplatform for Photodynamic Therapy and Cellular Scaffolds.

Recently, we found that self-organization of hydroxyapatite (HAp) with poly(acrylic acid) (PAA) leads to the formation of liquid-crystalline (LC) nanorod hybrids that form aligned films and show stimuli-responsive properties. Here, we demonstrate that these biocompatible HAp/PAA hybrid nanorods represent a platform technology as drug nanocarriers for photodynamic cancer therapy and as bioscaffolds for the control of cellular alignment and growth. To use hybrid nanorods as a drug nanocarrier, we introduced methylene blue (MB), a typical photosensitizer for photodynamic therapy, into the PAA nanolayer covering the surface of the HAp nanocrystals through electrostatic interactions. The stable MB-loaded HAp/PAA hybrid nanorods efficiently produced singlet oxygen from MB upon light irradiation and showed remarkable photodynamic therapeutic effects in cancer cells. Moreover, taking advantage of the mechanically responsive LC alignment properties of the HAp/PAA hybrid nanorods, macroscopically oriented bioscaffolds were prepared through a spin-coating process. The cells cultured on the oriented scaffolds showed cellular alignment and elongation along the oriented direction of the hybrid nanorods. The HAp/PAA hybrid nanorods demonstrate potential in drug delivery and tissue engineering. These unique LC HAp/PAA hybrid nanorods have significant potential as a platform for the development of various types of biomaterial.

Acid promoted cinnamyl ion mobility within peptide derived macrocycles.

We are developing methods that restrict the conformational mobility of peptides and related heteropolymers while simultaneously altering their properties. Our experiments occur as processes wherein a conserved, lipophilic reagent is activated in stages to form composite products with unprotected polyamides in parallel. For each starting oligomer, the goal is to create not one, but rather a collection of products. The intent is for those materials to retain molecular recognition elements of the biopolymer, yet display that functionality as part of stable, cyclic structures having defined shapes and enhanced membrane solubility/permeability. Here we describe reagent 2 and its two-step integration into peptides to afford macrocyclic ethers (e.g., 4 when starting with W-W-Y). When those materials are treated with protic acid in anhydrous solvent, the cinnamyl unit migrates from the oxygen of tyrosine to distribute throughout the structure, forming new products via carbon/carbon bonding. These changes occur concomitantly with acid-promoted rearrangements/cyclizations of the dienyne appendage to generate mixtures containing unique macrocycles such as 15. Similar amalgamations of 2 with more diverse peptides is a means to begin accessing complex peptidomimetics systematically. From a library of screening fractions generated in this way, we have identified a small molecule that selectively promotes hippocampal neurogenesis in the adult mouse brain.