Layperson assessment of smile lines and upper lip combined images in smile esthetics.

STATEMENT OF PROBLEM: The esthetic assessment of smile lines by laypersons is a subject of ongoing debate. However, smile lines often appear with different types of upper lip curvature, which further complicates the esthetic assessment process, and studies on this combination are lacking. PURPOSE: The purpose of this clinical study was to investigate a layperson's esthetic perception of smile lines and upper lip combined images. MATERIAL AND METHODS: Twenty-six smile images resulting from combinations of 3 upper lip types, 4 anterior smile line types, and 3 posterior smile line types were generated by an image editing software program. Eighty-three laypersons (39 men and 44 women; 18 to 35 years of age) completed rating images using a visual analog scale. Unattractive smiles were designated to be those with scores <50 and attractive ones with scores ≥50. Data were analyzed using 1-way analysis of variance and Bonferroni post hoc tests (α=.05). RESULTS: High anterior smile line with gingival display >4 mm obtained significantly lower scores of <50 when combined with all upper lip curvatures (upward: 28.29 ±22.79, straight: 38.74 ±23.00, downward: 30.67 ±22.25, P<.01). High anterior smile lines with gingival display ≤4 mm combined with upward and straight upper lip curvature images obtained significantly higher scores, and all were ≥50 (upward: 63.24 ±22.22, straight: 61.40 ±21.58, P<.01). CONCLUSIONS: From a layperson's perspective, high anterior smile lines with gingival display >4 mm combined with any lip type were determined to be unattractive. If gingival display was ≤4 mm combined with both upward and straight lip types, the smile was assessed as attractive.

Preparation and applications of keratin biomaterials from natural keratin wastes.

Keratin is a kind of natural polymer that is abundant in feathers, wool, and hair. Being one of the natural biomolecules, keratin has excellent biological activity, biocompatibility, biodegradability, favorable material mechanical properties, and natural abundance, which exhibit significant biological and biomedical application potentials. At present, the strategies commonly used for preparing keratin from hair, feathers, wool, etc. include physical, chemical, and enzymatic methods. The present article mainly reviews the structure, classification, preparation methods, and the main biological applications of keratin, and these applications cover wound healing, hemostasis, targeted release of tissue engineering drugs, and so on. It is expected to lay the foundations for its future in-depth investigations and wide applications of keratin biomaterials. KEY POINTS: • There are several pathways to prepare biologically active keratin from wool, feathers, and human hair, etc • Promoting blood coagulation by keratin is related to the adhesion and activation of platelets and the aggregation of fibrin • The biological applications of keratin, including wound healing and tissue engineering, are summarized.

Versatile Construction of Biomimetic Nanosensors for Electrochemical Monitoring of Intracellular Glutathione.

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large-scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs-poly(3,4-ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real-time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.

Soft Electrodes for Electrochemical and Electrophysiological Monitoring of Beating Cardiomyocytes.

Many cells in vivo have their inherent motions, which involve numerous biochemical and biophysical signals synergistically regulating cell behavior and function. However, existing methods offer little information about the concurrently chemical and physical responses of dynamically pulsing cells. Here, we report a soft electrode with an electrospun poly(3,4-ethylenedioxythiophene) (PEDOT)-based nanomesh to fully comply with spontaneous motions of cells. Moreover, this electrode demonstrated excellent electrical conductivity, electrochemical performance and cellular biocompatibility. Cardiomyocytes cultured thereon exhibited autonomous and rhythmic contractility, and synchronously induced mechanical deformation of the underlying electrode, which allowed real-time monitoring of nitric oxide release and electrophysiological activity of cardiomyocytes. This work provides a promising way toward recording chemical and electrical signals of biological systems with their natural motions.

Stretchable Electrochemical Sensors for Cell and Tissue Detection.

Electrochemical sensing based on conventional rigid electrodes has great restrictions for characterizing biomolecules in deformed cells or soft tissues. The recent emergence of stretchable sensors allows electrodes to conformally contact to curved surfaces and perfectly comply with the deformation of living cells and tissues. This provides a powerful strategy to monitor biomolecules from mechanically deformed cells, tissues, and organisms in real time, and opens up new opportunities to explore the mechanotransduction process. In this minireview, we first summarize the fabrication of stretchable electrodes with emphasis on the nanomaterial-enabled strategies. We then describe representative applications of stretchable sensors in the real-time monitoring of mechanically sensitive cells and tissues. Finally, we present the future possibilities and challenges of stretchable electrochemical sensing in cell, tissue, and in vivo detection.

Dual Stimuli-Responsive Supramolecular Self-Assemblies Based on the Host-Guest Interaction between ß-Cyclodextrin and Azobenzene for Cellular Drug Release.

Health has always been a hot topic of concern, whereas cancer is one of the largest security risks to human health. Although the existing drug delivery systems (DDSs) have been extensively reported and commercially applied, there are still some issues that have yet to be well-resolved, including the toxicity, side-effects, and targeted therapy efficiency of drugs. Consequently, it is still necessary to develop a novel, highly efficient, controlled and targeted DDS for cancer therapy. For this, a supramolecular polymer, ß-CD-g-PDMAEMA@Azo-PCL, was designed and developed through the host-guest inclusion complexation interactions between a host polymer, ß-cyclodextrin-graft-poly(2-(dimethylamino)ethyl methacrylate) (ß-CD-g-PDMAEMA), and a guest polymer, azobenzene modified poly(ε-caprolactone) (Azo-PCL), and was characterized by various analysis techniques. The supramolecular assembly was examined in various pH environments and/or under UV-vis irradiation, showing the formation of supramolecular assemblies from regular spherical shapes to irregular aggregates with various hydrodynamic diameters. The 2D NOESY NMR studies showed the formation of inclusion complexation between Azo-PCL and ß-CD-g-PDMAEMA and between ß-CD and the side groups of PDMAEMA. The supramolecular assemblies could encapsulate doxorubicin to form spherical core-shell drug-carrying micelles with an entrapment efficiency of 66.1%. The effects of external environment stimuli on the in vitro drug release were investigated, showing light- and pH-modulated drug release properties. The cytotoxicity assessment indicated that the blank supramolecular micelles were nontoxic, whereas the drug-loaded micelles exhibited comparable or even superior anticancer activity to the anticancer activity of free DOX and inhibition of cancer cell proliferation. Therefore, the developed supramolecular assemblies can potentially be used as drug-controlled release carriers.

Conductive Polymer Coated Scaffold to Integrate 3D Cell Culture with Electrochemical Sensing.

Remarkable progresses have been made in electrochemical monitoring of living cells based on one-dimensional (1D) or two-dimensional (2D) sensors, but the cells cultured on 2D substrate under these circumstances are departed from their three-dimensional (3D) microenvironments in vivo. Significant advances have been made in developing 3D culture scaffolds to simulate the 3D microenvironment yet most of them are insulated, which greatly restricts their application in electrochemical sensing. Herein, we propose a versatile strategy to endow 3D insulated culture scaffolds with electrochemical performance while granting their biocompatibility through conductive polymer coating. More specifically, 3D polydimethylsiloxane scaffold is uniformly coated by poly(3,4-ethylenedioxythiophene) and further modified by platinum nanoparticles. The integrated 3D device demonstrates desirable biocompatibility for long-term 3D cell culture and excellent electrocatalytic ability for electrochemical sensing. This allows real-time monitoring of reactive oxygen species release from cancer cells induced by a novel potential anticancer drug and reveals its promising application in cancer treatment. This work provides a new idea to construct 3D multifunctional electrochemical sensors, which will be of great significance for physiological and pathological research.

Bilayered membranes of Janus dendrimers with hybrid hydrogenated and fluorinated dendrons: microstructures and coassembly with lipids.

A biomimetic membrane formed by hybrid Janus dendrimers (JDs) which contain hydrogenated and fluorinated dendrons was explored by dissipative particle dynamics simulations. The JD membrane is bilayered and shows a bicontinuous morphology which is also observed in nano-sized dendrimersomes. The thickness of the dendrimersome is significantly less than that of the planar membrane. The co-assembly of lipids with JDs to develop a hybrid membrane was studied as well. Lipids tend to locate in the hydrocarbon domain of the bicontinuous structure of the JD-rich membrane, while 2-dimensional micelles of JDs float in the leaflet of the lipid-rich membrane. The microstructure of the hybrid membrane was quantified by interdigitation lengths in the hydrocarbon, fluorocarbon, and lipid domains. Finally, the influence of lipid concentration on lipid fluidity was examined in terms of lipid diffusivity, which is found to be closely associated with the membrane microstructure.

Flexible Electrochemical Urea Sensor Based on Surface Molecularly Imprinted Nanotubes for Detection of Human Sweat.

Flexible electrochemical (EC) sensors have shown great prospect in epidermal detection for personal healthcare and disease diagnosis. However, no reports have been seen in flexible device for urea analysis in body fluids. Herein, we developed a flexible wearable EC sensor based on surface molecularly imprinted nanotubes for noninvasive urea monitoring with high selectivity in human sweat. The flexible EC sensor was prepared by electropolymerization of 3,4-ethylenedioxythiophene (EDOT) monomer on the hierarchical network of carbon nanotubes (CNTs) and gold nanotubes (Au NTs) to imprint template molecule urea. This sensor exhibited a good linear response toward physiologically relevant urea levels with negligible interferences from common coexisting species. Bending test revealed that this sensor possessed excellent mechanical tolerance and its EC performance was almost not affected by bending deformation. On-body results of human subjects showed that the flexible platform could distinctly respond to the urea levels in volunteer's sweat after aerobic exercise. The new flexible epidermal EC sensor can provide useful insights into noninvasive monitoring of urea levels in various biofluids, which is promising in the clinical diagnosis of diverse biomedical applications.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Dual-Stimuli-Responsive Paclitaxel Delivery Nanosystems from Chemically Conjugate Self-Assemblies for Carcinoma Treatment.

Diselenide-bond-linked poly(N-isopropylacrylamide)-paclitaxel chemical conjugates are synthesized as a drug release carrier. The conjugates can self-assemble into "core-shell" nanoscaled micelles in aqueous solution and show thermal and redox dual-responsiveness. The conjugates can afford a high encapsulation efficiency of up to 72.3%, and deliver hydrophobic anticancer drug paclitaxel in a temperature and oxidization or reduction stress-mode. The in vitro 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and in vivo anticancer assays are performed to assess the cytotoxicity and anticancer activity of the conjugates, suggesting that the developed conjugates can be used to treat carcinoma as a novel and highly efficient drug delivery system.

Esthetics and smile-related characteristics assessed by laypersons.

PURPOSE: This study aimed to identify the characteristics of full-smile images assessed by laypersons using visual analog scale measurement. MATERIALS AND METHODS: A total of 176 young Chinese subjects (88 males and 88 females; 20-35 years of age) with healthy dentogingival tissue were recruited to have their dynamic smiles captured using digital technology. A full-smile frame image of each subject was selected and evaluated by 22 laypersons (11 males and 11 females; 20-35 years of age) using visual analog scale measurement. Unattractive and attractive groups were designated according to the 25th percentile and 75th percentile of average visual analog scale score for the subjects, respectively. Eight smile variables were used to measure the characteristics of the full-smile images. Pearson's Chi-square test and unpaired t tests were used to analyze the data with significance level α = 0.05. RESULTS: The visual analog scale measurement scores of unattractive and attractive subgroups, respectively, were 37.89 ± 2.12 and 50.67 ± 2.75 (male subjects), and 37.14 ± 2.80 and 51.92 ± 1.99 (female subjects). VAS scores were significantly different between subgroups for both male and female subjects (P < .001). No significant differences were observed between male and female subjects (P > .05). CONCLUSIONS: Attractive full-smiles in young Chinese subjects demonstrated higher frequencies of average or low anterior smile line, average or low posterior smile line, upward upper lip curvature, and "broad and short" smile with high smile index. CLINICAL SIGNIFICANCE: The smile variables of anterior smile line, posterior smile line, upper lip curvature, and smile index are predominant factors of smile attractiveness, which should be given priority to consider and manage in the anterior esthetic treatment plan.

Conductive Polymer-Coated Carbon Nanotubes To Construct Stretchable and Transparent Electrochemical Sensors.

Carbon nanotube (CNT)-based flexible sensors have been intensively developed for physical sensing. However, great challenges remain in fabricating stretchable CNT films with high electrochemical performance for real-time chemical sensing, due to large sheet resistance of CNT film and further resistance increase caused by separation between each CNT during stretching. Herein, we develop a facile and versatile strategy to construct single-walled carbon nanotubes (SWNTs)-based stretchable and transparent electrochemical sensors, by coating and binding each SWNT with conductive polymer. As a polymer with high conductivity, good electrochemical activity, and biocompatibility, poly(3,4-ethylenedioxythiophene) (PEDOT) acting as a superior conductive coating and binder reduces contact resistance and greatly improves the electrochemical performance of SWNTs film. Furthermore, PEDOT protects the SWNTs junctions from separation during stretching, which endows the sensor with highly mechanical compliance and excellent electrochemical performance during big deformation. These unique features allow real-time monitoring of biochemical signals from mechanically stretched cells. This work represents an important step toward construction of a high performance CNTs-based stretchable electrochemical sensor, therefore broadening the way for stretchable sensors in a diversity of biomedical applications.

Dual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) copolymer micromicelles: surface RAFT synthesis, self-assembly and drug release applications.

BACKGROUND: Stimuli-responsive polymer materials are a new kind of intelligent materials based on the concept of bionics, which exhibits more significant changes in physicochemical properties upon triggered by tiny environment stimuli, hence providing a good carrier platform for antitumor drug delivery. RESULTS: Dual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) block copolymers (Fe3O4-g-PAA-b-PMAEFC) were engineered and synthesized through a two-step sequential reversible addition-fragmentation chain transfer polymerization route. The characterization was performed by FTIR, 1H NMR, SEC, XRD and TGA techniques. The self-assembly behavior in aqueous solution upon triggered by pH, magnetic and redox stimuli was investigated via zeta potentials, vibration sample magnetometer, cyclic voltammetry, fluorescent spectrometry, dynamic light scattering, XPS, TEM and SEM measurements. The experimental results indicated that the Fe3O4-g-PAA-b-PMAEFC copolymer materials could spontaneously assemble into hybrid magnetic copolymer micromicelles with core-shell structure, and exhibited superparamagnetism, redox and pH stimuli-responsive features. The hybrid copolymer micromicelles were stable and nontoxic, and could entrap hydrophobic anticancer drug, which was in turn swiftly and effectively delivered from the drug-loaded micromicelles at special microenvironments such as acidic pH and high reactive oxygen species. CONCLUSION: This class of stimuli-responsive copolymer materials is expected to find wide applications in medical science and biology, etc., especially in drug delivery system.

Stretchable Electrochemical Sensor for Real-Time Monitoring of Cells and Tissues.

Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real-time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching-free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.

[Limb torsion and developmental regression for one month after hand, foot and mouth disease in an infant].

A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered.

Carbon nanotube/gold nanoparticle composite-coated membrane as a facile plasmon-enhanced interface for sensitive SERS sensing.

The facile assembly of three-dimensional (3D) plasmonic substrates has been demonstrated. The assembly is based on the homogeneous decoration of multi-walled carbon nanotube/gold nanoparticle (CNT/AuNP) hybrid nanocomposites on a commercial polyvinylidene difluoride (PVDF) membrane, which is achieved via simple filtration. The CNT/AuNP hybrids with a unique 1D/0D structure remarkably improve the coverage and uniformity of plasmonic nanostructures on the membrane. The effective inter-particle and inter-tube coupling creates a multitude of hot spots within the probe area, and can produce a strong SERS effect. Moreover, the flexible membrane-based scaffold can efficiently collect and concentrate trace targets from large-volume sample solutions at milliliter-scale. The membrane-based SERS sensor shows high sensitivity and good reproducibility. The SERS sensor is employed to detect various molecular contaminants in aqueous samples, demonstrating its excellent field-testing capabilities for applications ranging from food safety to environmental monitoring.

Real-time monitoring of H2O2 release from single cells using nanoporous gold microelectrodes decorated with platinum nanoparticles.

Here, we report a self-supported nanoporous gold microelectrode decorated with well-dispersed and tiny platinum nanoparticles as an electrochemical nonenzymatic hydrogen peroxide biosensor. Nanoporous gold was fabricated by electrochemical alloying/dealloying and then small-sized platinum nanoparticles were electrodeposited uniformly on them. This novel hybrid nanostructure endows the sensor with high sensitivity and selectivity towards the reduction of hydrogen peroxide with a low detection limit of 0.3 nM. The sensor has been successfully applied for the measurement of H2O2 release from a single isolated human breast cancer cell, demonstrating its great potential for further physiological and pathological applications.

Revealing highly unbalanced energy barriers in the extension and contraction of the muscle-like motion of a [c2]daisy chain.

Nanoscale muscle-like materials have aroused great interest as they may provide controllable mechanical operations by artificial actuations. Molecular designs to achieve the desired motion at the macroscopic scale in experiments require atomic level understanding. By systematic quantum chemical and molecular dynamics calculations we reveal that the length change is not only due to the linear telescoping from the dibenzo[24]crown-8 recognition at two docking stations but also the folding/unfolding of two bulky stoppers. The extension and contraction processes of a [c2]daisy chain under acidic vs. basic conditions are exothermic but need to cross very different energy barriers, being at least double the height under acidic compared to basic conditions, hindering balanced cyclic motions at moderate excitation. Our result suggests that to realize the desired muscle-like motion one should adopt sufficiently high external excitation, using for example reasonably high temperature and further optimizing the solution used.

Assessment of dynamic smile and gingival contour in young Chinese people.

OBJECTIVES: This study aimed to classify the dynamic smile and to quantify the gingival line (GL), as well as apico-coronal displacement of the gingival zenith (GZ), in the maxillary anterior dentition in a young Chinese population. METHODS: Two-hundred young Chinese subjects (100 men and 100 women; 20-35 years of age) with healthy dentogingival tissue were recruited. The dynamic smile process was captured using a digital camera. The smile type, GL type, the vertical distance of the GZ between the canine and the central incisor on the same side and the GZ of the lateral incisor-GL relationship were measured using a self-developed smile-analysis method. The kappa statistics was used to examine the reliability of the data recorded by the rater. The Pearson chi-square test was used to analyse the differences between subjects regarding the frequencies of smile type and GL type at α = 0.05. RESULTS: Data revealed that 45.5% of subjects had a high smile and 45.5% had an average smile; 58.2% of the subjects presented an upwards GL. The GZ of canine teeth was 0.33 mm apical to the corresponding central incisor and no significant difference between both sides of the GZ was observed. The GZ of the lateral incisor was located coronal to the GL in 87.9% of samples. The vertical distance between the GZ of the lateral incisor and the GL was 0.59 mm and no statistically significant difference was detected. CONCLUSIONS: The most common findings were a high or average smile type, combined with an upward GL. In the majority of subjects, the GZ of the lateral incisor is coronal to the GL. The apico-coronal displacement of the GZ showed bilateral symmetry.