Predicting the Outcomes of Oropharyngeal Surgery in Patients With Obstructive Sleep Apnea Using Tongue-Retaining Devices.

OBJECTIVE: To determine the efficacy of a tongue-retaining device (TRD) in predicting the outcomes of oropharyngeal surgery in patients with obstructive sleep apnea (OSA) before surgery. STUDY DESIGN: A prospective case-control study. SETTING: A single tertiary medical center. METHODS: Patients with moderate-severe OSA who underwent both uvulopalatopharyngoplasty and tongue base suspension between January 2022 and July 2022 were included. Each patient underwent a series of 3 overnight polysomnography. Objective outcomes include apnea-hypopnea index (AHI), minimal oxygen saturation, and reduction rate of AHI. The correlation between the reduction rate of AHI with TRD and surgery was analyzed with linear regression. RESULTS: The reduction rates of AHI were significantly different between the group using TRD (44 ± 24%) and the postoperative group (55 ± 21%). The cross-tabulation revealed a strong association between a positive response to TRD treatment and a positive response to surgery. The use of TRD to evaluate surgical response demonstrated a positive predictive value of 90% and a negative predictive value of 70%. A strong correlation between the decrease in AHI was observed in both TRD and surgery groups, which was demonstrated by a steep slope in the scatter plot and a significant simple linear regression line. CONCLUSION: Preoperative TRD response is an accurate tool for predicting the success of oropharyngeal surgery in managing OSA patients before surgical treatment. Furthermore, a quantifiable positive linear correlation exists between the efficacy of preoperative TRD treatment and surgery.

Controlled Decomposable Hydrogel Triggered with a Specific Enzyme.

In this study, superabsorbent polyelectrolyte hydrogels were synthesized by cross-linking a nondegradable poly (allylamine hydrochloride) (PAH) and a recombinant protein with a specific enzymatic cleavage site. The recombinant protein was produced by E. coli with the pET-32b(+) plasmid, which is featured with the thioredoxin (Trx) gene containing a thrombin recognition site and a T7/lac hybrid promoter for high expression of recombinant protein. The swelling test shows that the composite hydrogel still maintained a high swelling ratio to 900% when 15% recombinant protein was cross-linked with PAH. The degradation test shows that such a PAH composite hydrogel could be decomposed by the addition of specific enzyme thrombin, which might lead to new biomedical applications of hydrogels needed to be decomposable by specific time not determined by the time period.

Energy Efficiency of Inference Algorithms for Clinical Laboratory Data Sets: Green Artificial Intelligence Study.

BACKGROUND: The use of artificial intelligence (AI) in the medical domain has attracted considerable research interest. Inference applications in the medical domain require energy-efficient AI models. In contrast to other types of data in visual AI, data from medical laboratories usually comprise features with strong signals. Numerous energy optimization techniques have been developed to relieve the burden on the hardware required to deploy a complex learning model. However, the energy efficiency levels of different AI models used for medical applications have not been studied. OBJECTIVE: The aim of this study was to explore and compare the energy efficiency levels of commonly used machine learning algorithms-logistic regression (LR), k-nearest neighbor, support vector machine, random forest (RF), and extreme gradient boosting (XGB) algorithms, as well as four different variants of neural network (NN) algorithms-when applied to clinical laboratory datasets. METHODS: We applied the aforementioned algorithms to two distinct clinical laboratory data sets: a mass spectrometry data set regarding Staphylococcus aureus for predicting methicillin resistance (3338 cases; 268 features) and a urinalysis data set for predicting Trichomonas vaginalis infection (839,164 cases; 9 features). We compared the performance of the nine inference algorithms in terms of accuracy, area under the receiver operating characteristic curve (AUROC), time consumption, and power consumption. The time and power consumption levels were determined using performance counter data from Intel Power Gadget 3.5. RESULTS: The experimental results indicated that the RF and XGB algorithms achieved the two highest AUROC values for both data sets (84.7% and 83.9%, respectively, for the mass spectrometry data set; 91.1% and 91.4%, respectively, for the urinalysis data set). The XGB and LR algorithms exhibited the shortest inference time for both data sets (0.47 milliseconds for both in the mass spectrometry data set; 0.39 and 0.47 milliseconds, respectively, for the urinalysis data set). Compared with the RF algorithm, the XGB and LR algorithms exhibited a 45% and 53%-60% reduction in inference time for the mass spectrometry and urinalysis data sets, respectively. In terms of energy efficiency, the XGB algorithm exhibited the lowest power consumption for the mass spectrometry data set (9.42 Watts) and the LR algorithm exhibited the lowest power consumption for the urinalysis data set (9.98 Watts). Compared with a five-hidden-layer NN, the XGB and LR algorithms achieved 16%-24% and 9%-13% lower power consumption levels for the mass spectrometry and urinalysis data sets, respectively. In all experiments, the XGB algorithm exhibited the best performance in terms of accuracy, run time, and energy efficiency. CONCLUSIONS: The XGB algorithm achieved balanced performance levels in terms of AUROC, run time, and energy efficiency for the two clinical laboratory data sets. Considering the energy constraints in real-world scenarios, the XGB algorithm is ideal for medical AI applications.

Phase analysis on the error scaling of entangled qubits in a 53-qubit system.

We have studied carefully the behaviors of entangled qubits on the IBM Rochester with various connectivities and under a "noisy" environment. A phase trajectory analysis based on our measurements of the GHZ-like states is performed. Our results point to an important fact that entangled qubits are "protected" against environmental noise by a scaling property that impacts only the weighting of their amplitudes. The reproducibility of most measurements has been confirmed within a reasonably short gate operation time. But there still are a few combinations of qubits that show significant entanglement evolution in the form of transitions between quantum states. The phase trajectory of an entangled evolution, and the impact of the sudden death of GHZ-like states and the revival of newly excited states are analyzed in details. All observed trajectories of entangled qubits arise under the influences of the newly excited states in a "noisy" intermediate-scale quantum (NISQ) computer.

Cell detachment ratio on pH-responsive chitosan: A useful biometric for prognostic judgment and drug efficacy assessment in oncology.

The inherently unpredictable complexity of tumors impedes the widespread practice of the molecular biomarkers in outcome prediction. Alternatively, from the biophysical perspective, this study sought to investigate the applicability of the cell detachment ratio (CDR) derived from pH-responsive chitosan as a biometrical identifier for the disease state in cancer prognostic judgment and drug efficacy assessment. In the targeted therapy model, the repression of tumor dissemination in cells harboring aberrant ErbB signals (human non-small cell lung cancer cell line PC9 and breast cancer cell line BT474) were first demonstrated both in vitro and in vivo. Consequently, the corresponding CDR profile goes synchronously with the extent of cancer regression in response to the medication. Definitive integrins that drive the cell detachment were also verified through CDR examination following the integrin functional blockade. Conclusively, CDR is a promising clinical index for evaluation of the metastatic cell behaviors in terms of the cell detachment.

Regeneration of olfactory neuroepithelium in 3-methylindole-induced anosmic rats treated with intranasal chitosan.

Olfactory dysfunction significantly impairs the life quality of patients but without effective treatments to date. The previous report has demonstrated that chitosan mediates the differentiation of olfactory receptor neurons (ORNs) through insulin-like growth factors and insulin-like growth factor binding protein-2 axis in an in vitro model. However, whether chitosan can further treat olfactory dysfunction in vivo remains unexplored. This study aims to evaluate the therapeutic effect of chitosan on a 3-methylindole-induced anosmic rat model. Intraperitoneal injection of 3-methylindole is performed to induce anosmia in rats. Experimental results demonstrate that the food-finding duration after chitosan treatment gradually decrease to around 80 s, and both the olfactory neuroepithelium (ON) thickness and mature ORNs (expressing olfactory marker protein) are significantly restored. Furthermore, proliferating cells (expressing bromodeoxyuridine) are mainly co-expressed with immature ORNs (expressing ßIII tubulin) below the intermediate layer of the ON in the chitosan-treated group on day 28 following 3-methylindole treatment. Conversely, proliferating cells are scattered over the ON, and co-localized with immature ORNs and sustentacular cells (expressing keratin 18) in the sham group, and even immature ORNs go into apoptosis (expressing DNA fragmentation and cleaved caspase-3), possibly causing incomplete regeneration. Consequently, chitosan regenerates the ON by regulating olfactory neural homeostasis and reducing ORN apoptosis, and serves as a potential therapeutic intervention for olfactory dysfunction in the future.

Ultrasound-guided-fine-needle Aspiration Drainage and Percutaneous Ethanol Injection for Benign Neck Cysts.

BACKGROUND: Ultrasound-guided-fine-needle aspiration drainage (US-FNAD) and US-percutaneous ethanol injection (US-PEI) have been widely used in the management of benign neck cysts. However, the long-term results of US-FNAD and US-PEI are not well elucidated. METHODS: We retrospectively collated patients under neck US examinations from March 2007 to December 2017 and investigated the recurrence after US-FNAD and US-PEI. Univariate and multivariate Cox regression analyses were used to assess significant risk factors for recurrence after US-FNAD. RESULTS: A total of 1075 patients were recruited, and their age was 50 ± 15 (mean ± standard deviation) years. A total of 862 patients had thyroid cysts, 118 patients had thyroglossal duct cysts (TGDC), twenty patients had branchial cleft cysts, 64 patients had parotid sialocysts, and 11 patients had plunging ranulas. Majority of the patients (97%, 1037/1075) reported significant symptom improvement immediately. However, 38% of the patients had recurrence with a median 3-year follow-up period. In a multivariate Cox regression analysis with adjustment for age and gender, plunging ranula (hazard ratio [HR]: 2.44, 95% confidence interval [CI]: 1.19-4.99) and lateral dimension size ≥ 0.8 cm (HR: 1.32, 95% CI: 1.04-1.67) after US-FNAD were independent risk factors for recurrence. There were 15 male and 19 female patients who received US-PEI therapy after repeated US-FNAD, of whom 23 patients had thyroid cysts, 6 had plunging ranulas, 4 had TGDC, and one had a branchial cleft cyst. The overall success rate was 94% (32/34), with a median follow-up period of 1.6 years. Two recurrent symptomatic patients had plunging ranulas. Some patients stated mild pain (21%, 7/34) and swelling sensation (26%, 9/34) after the injection. No major complications, such as vocal fold paresis or airway compression, were found. CONCLUSION: US-FNAD is an effective tool in the management of benign neck cysts with a 38% recurrence rate. Plunging ranulas have the highest rate of recurrence after FNAD. US-PEI is effective for most recurrent neck cysts after repeated US-FNAD.

Prediction of Unilateral Meniere's Disease Attack Using Inner Ear Test Battery.

OBJECTIVES: In the clinical setting, a variety of inner ear test results are obtained from patients with unilateral Meniere's disease (MD). In this study, the authors use inner ear test results as parameters to illustrate the relationship between inner ear function and vertigo attack frequency. DESIGN: We retrospectively enrolled 50 unilateral MD patients. In addition to clinical symptoms, the results of pure-tone audiometry and caloric, acoustic cervical vestibular-evoked myogenic potential (cVEMP), galvanic cVEMP, vibratory ocular VEMP (oVEMP), and galvanic oVEMP tests were collected via chart review. The multiple linear regression method was used to examine which independent variables have a statistically significant influence on vertigo attacks. RESULTS: In affected ears, the abnormal rate of the caloric, acoustic cVEMP, galvanic cVEMP, vibratory oVEMP, and galvanic oVEMP tests was 74%, 76%, 48%, 34%, and 30%, respectively. According to the regression model, the abnormal galvanic cVEMP response and abnormal galvanic oVEMP response had significantly negative correlations with the frequency of vertigo attacks after logarithmic transformation. A predictive model for disease attack frequency using significant parameters and their regression coefficients was proposed: (Equation is included in full-text article.) CONCLUSIONS:: Using the proposed model with galvanic VEMP, clinicians could develop better strategies to manage vertigo attacks in patients with MD.

Increased Cell Detachment Ratio of Mesenchymal-Type Lung Cancer Cells on pH-Responsive Chitosan through the ß3 Integrin.

Chitosan is sensitive to environmental pH values due to its electric property. This study investigates whether the pH-responsive chitosan assay can provide a simple method to evaluate the aggressive behavior of cancer cells with cell detachment ratio. The epithelial-mesenchymal transition (EMT) is induced with transforming growth factor-ß1 (TGF-ß1) in the human non-small cell lung cancer cell line (A549). EMT-induced cells and untreated cells are cultured on chitosan substrates at pH 6.99 for 24 h, followed by pH 7.65 for 1 h. The cell detachment ratio (CDR) on pH-responsive chitosan rises with an increasing of the TGF-ß1 concentration. The protein array reveals that the expression levels of the α2, α3, α5, ß2, and ß3 integrins are higher in EMT-induced A549 cells than in untreated cells. A further inhibition assay shows that adding ß3 integrin blocking antibodies significantly decreases the CDR of EMT-induced cells from 32.7 ± 5.7% to 17.8 ± 2.1%. The CDR of mesenchymal-type lung cancer cells increases on pH-responsive chitosan through the ß3 integrin. Notably, the CDR can be theoretically predicted according to the individual CDR on the pH-responsive chitosan surface, irrespective of heterogeneous cell mixture. The pH-responsive chitosan assay serves as a simple in vitro model to investigate the aggressive behavior of lung cancer including the heterogeneous cell population.

Neuropeptide Y increases differentiation of human olfactory receptor neurons through the Y1 receptor.

Olfactory dysfunction significantly impedes the life quality of patients. Neuropeptide Y (NPY) is not only a neurotrophic factor in the rodent olfactory system but also an orexigenic peptide that regulates feeding behavior. NPY increases the olfactory receptor neurons (ORNs) responsivity during starvation; however, whether NPY can promote differentiation of human ORNs remains unexplored. This study investigates the effect of NPY on the differentiation of human olfactory neuroepithelial cells in vitro. Human olfactory neuroepithelium explants were cultured on tissue culture polystyrene dishes for 21 days. Then, cells were cultured with or without NPY at the concentration of 0.5 ng/mℓ for 7 days. The effects of treatment were assessed by phase contrast microscopy, immunocytochemistry and western blot analysis. The further mechanism was evaluated with NPY Y1 receptor-selected antagonist BIBP3226. NPY-treated olfactory neuroepithelial cells exhibited thin bipolar shape, low circularity, low spread area, and long processes. The expression levels of Ascl1, ßIII tubulin, GAP43 and OMP were significantly higher in NPY-treated cells than in controls (p < 0.05). NPY-treated olfactory neuroepithelial cells expressed more components of signal transduction apparatuses, Golf and ADCY3, than those without NPY treatment. Western blot analysis also further confirmed these findings (p < 0.05). Additionally, the expression levels of Ascl1, ßIII2 tubulin, GAP43, OMP, ADCY3, and Golf in BIBP3226 + NPY and controls were comparable (p > 0.05). NPY not only increases expressions of protein markers of human olfactory neuronal progenitor cells, but also promotes differentiation of ORN and enhances formation of components of olfactory-specific signal transduction pathway through Y1 receptors.

Regulation of chitosan-mediated differentiation of human olfactory receptor neurons by insulin-like growth factor binding protein-2.

Olfaction is normally taken for granted in our lives, not only assisting us to escape from dangers, but also increasing our quality of life. Although olfactory neuroepithelium (ON) can reconstitute its olfactory receptor neurons (ORNs) after injury, no adequate treatment for olfactory loss has yet emerged. The present study investigates the role of glycosaminoglycans (GAGs) in modulating olfactory neuronal homeostasis and elucidates the regulatory mechanism. This work isolates and cultures human olfactory neuroepithelial cells (HONCs) with various GAGs for 7 days, and find that chitosan promotes ORN maturation, expressing olfactory marker protein (OMP) and its functional components. Growth factor protein array, ELISA and western blot analysis reveal that insulin-like growth factor binding protein 2 (IGFBP2) shows a higher level in chitosan-treated HONCs than in controls. Biological activity of insulin-like growth factor-1 (IGF-1), IGF-2 and IGF-1 receptor (IGF1R) is further investigated. Experimental results indicate that IGF-1 and IGF-2 enhance the growth of immature ORNs, expressing ßIII tubulin, but decrease mature ORNs. Instead, down-regulation of phosphorylated IGF1R lifts the OMP expression, and lowers the ßIII tubulin expression, by incubation with the phosphorylated inhibitor of IGF1R, OSI-906. Finally, the effect of chitosan on ORN maturity is antagonized by concurrently adding IGFBP2 protease, matrix metallopeptidase-1. Overall, our data demonstrate that chitosan promotes ORN differentiation by raising the level of IGFBP2 to sequestrate the IGFs-IGF1R signaling. STATEMENT OF SIGNIFICANCE: Olfactory dysfunction serves as a crucial alarm in neurodegenerative diseases, and one of its causes is lacking of sufficient mature olfactory receptor neurons to detect odorants in the air. However, the clinical treatment for olfactory dysfunction is still controversial. Chitosan is the natural linear polysaccharide and exists in rat olfactory neuroepithelium. Previously, chitosan has been demonstrated to mediate the differentiation of olfactory receptor neurons in an in vitro rat model, but the mechanism is unknown. The study aims to evaluate the role and mechanism of chitosan in an in vitro human olfactory neurons model. Overall, these results reveal that chitosan is a potential agent for treating olfactory disorder by the maintenance of olfactory neural homeostasis. This is the first report to demonstrate that chitosan promotes differentiation of olfactory receptor neurons through increasing IGFBP2 to sequestrate the IGFs-IGF1R.

Assessment of Patient Outcomes After Adjuvant Vocal Fold Steroid Injection for Fibrosis After Microlaryngeal Surgery.

IMPORTANCE: Microlaryngeal surgery (MLS) is one of the most common procedures in laryngology; however, in cases of postoperative fibrosis, few remedial options are available. OBJECTIVE: To investigate the outcomes of vocal fold steroid injection (VFSI) as an adjuvant treatment for fibrosis after MLS. DESIGN, SETTING, AND PARTICIPANTS: Case series of 228 consecutive patients who underwent MLS for benign vocal lesions between January 2014 and December 2016 at a tertiary medical center. Adjuvant VFSI was performed in 25 patients (11%) with postoperative fibrosis, defined as severely decreased or absent mucosal wave on videolaryngostroboscopy (VLS) lasting for longer than 1 month postoperatively. Data were analyzed from July 1, 2018 to April 30, 2019. INTERVENTION: All adjuvant VFSIs were performed in the office under local anesthesia and were repeated monthly if the status of the mucosal wave did not return to normal or mildly decreased on the follow-up VLS. MAIN OUTCOMES AND MEASURES: The outcome parameters, namely, the 10-item Voice Handicap Index (VHI-10), smoothed cepstral peak prominence (CPP) of recorded voice samples, and mucosal wave status on VLS, were measured before and after MLS and after adjuvant VFSI. RESULTS: In this case series of 228 patients (72 men and 156 women; mean [SD] age, 42.8 [12.3] years), 25 had a decreased or absent mucosal wave after MLS, indicating postoperative fibrosis. Of these patients, 22 presented with deep-seated lesions that were removed using a microflap approach. After 1 course of adjuvant VFSI in 17 patients and 2 serial monthly injections in 8 patients, VFSI was associated with improved VHI-10 scores (mean, 24.4 points preoperatively, 22.1 points postoperatively, and 12.9 points after VFSI) that were comparable to the scores of the other 203 patients without vocal fold fibrosis after MLS (mean, 24.8 points preoperatively, 11.7 points postoperatively). Adjuvant VFSI was also associated with improved CPP (mean, 4.04 preoperatively, 4.23 postoperatively, and 5.11 after VFSI) that was comparable to the CPP of the other patients without postoperative fibrosis (mean, 4.33 preoperatively and 5.15 postoperatively). Overall, 19 (76%) of 25 patients with vocal fold fibrosis after MLS had normal (n = 11) or mildly decreased (n = 8) mucosal wave after adjuvant VFSI. CONCLUSIONS AND RELEVANCE: Adjuvant VFSI appeared to be associated with improvements in mucosal wave, voice quality, and subjective perception of dysphonia in patients with fibrosis after MLS, with outcomes comparable to those of the other patients without fibrosis. Adjuvant VFSI may be considered a rescue technique, reducing the rate of fibrosis after MLS from 11% to 3%.

Chitosan-hyaluronan: promotion of mucociliary differentiation of respiratory epithelial cells and development of olfactory receptor neurons.

Developing a biomaterial that promotes regeneration of both respiratory epithelium (RE) and olfactory neuroepithelium (ON) improves the surgical outcome of endoscopic sinus surgery. Although chitosan (CS) inhibits mucociliary differentiation of RE, it has been reported to regenerate ON. In addition, hyaluronic acid (HA) has been demonstrated to promote regeneration of RE. Whether the composite CS + HA would simultaneously benefit RE and ON remains unexplored. Human nasal respiratory epithelial cells (RECs) and olfactory neuroepithelial cells (ONCs) are respectively obtained from the RE and the ON. They are cultured in vitro and divided into groups undergoing four treatments, control, CS, HA, and CS + HA and assessed by scanning electron microscope, immunocytochemistry, and Western blots following indicated growth conditions. RECs keep polygonal morphology with mucociliary differentiation in the CS + HA group. The levels of E-cadherin, zonula occludens-1, mucin 5AC, and forkhead box protein J1 are significantly higher in the CS + HA group than in the CS alone group. In addition, ONCs express lower cytokeratin 18 (CK18) and higher olfactory marker protein (OMP) in the CS + HA group than in HA alone group. ONCs express more signal transduction apparatuses, adenylate cyclase 3, in CS and CS + HA groups than in HA and controls. Chitosan-hyaluronan plays a part in promoting differentiation of ORNs and facilitating mucociliary differentiation of RECs. This composite is a promising biomaterial for the sinonasal application.

The diagnostic performance of ultrasonography and computerized tomography in differentiating superficial from deep lobe parotid tumours.

OBJECTIVES: To validate and compare ultrasound (US) versus computerized tomography (CT) criteria in the localisation of superficial/deep lobe tumours of the parotid gland. DESIGN AND SETTING: This was a retrospective study of diagnostic tests performed from January 2008 to June 2017. PARTICIPANTS: We included adult patients who were referred for a neck ultrasonography examination due to parotid tumours, and who subsequently underwent parotid surgery. MAIN OUTCOME MEASURES: We assessed the location of parotid tumours, comparing the minimum fascia-tumour distance (MFTD) criterion on an US with eight CT criteria. We analysed receiver operating characteristic (ROC) curves of the MFTD for malignant, benign, and all parotid tumours, and compared the accuracy, sensitivity, and specificity of the optimal MFTD with those of CT anatomical criteria. RESULTS: A total of 166 parotid tumours were included. The mean (SD) MFTD in superficial lobe tumours was significantly shorter than that of deep lobe tumours (1.2 [0.7] vs 2.8 [1.9] mm, effect size: 1.84; 95% CI, 1.27-2.41). The areas under the ROC curve were 0.63 for malignant tumours and 0.88 for benign tumours. The optimal MFTD cut point was 2.4 mm for the 154 benign parotid tumours, and the accuracy, sensitivity and specificity were 90%, 80% and 91%, respectively. For the 136 benign parotid tumours that underwent CT examination, three criteria had an accuracy of over 90% (FNline, tMasseter and Conn's arc), but the sensitivities were all below 50%. CONCLUSIONS: Minimum fascia-tumour distance is more feasible for benign tumours than for malignant tumours for the localisation of parotid tumours. For benign parotid tumours, US is enough to guide operations.

Hyaluronan antagonizes the differentiation effect of TGF-ß1 on nasal epithelial cells through down-regulation of TGF-ß type I receptor.

Although hyaluronan (HA)-based biomaterials have been proposed to promote mucociliary differentiation of nasal epithelial cells (NECs), the mechanism by which HA affects the growth and differentiation of NECs has not been thoroughly explored. This study investigates the effect and mechanism of HA on the differentiation of NECs. The experiment cultures human NECs in four conditions, namely controls, transforming growth factor (TGF)-ß1, TGF-ß1 + HA and HA groups. In the TGF group, the NECs become irregular shape without formation of tight junction and mucociliary differentiation of NECs is inhibited. Epithelial-mesenchymal transition (EMT) of NECs also occurs in the TGF group. However, with addition of HA in TGF groups, NECs reveal the mucociliary phenotypes of epithelial cells with tight junction expression. Incubation of TGF-ß1 in an NEC culture leads to an increase in phosphorylated type 1 TGF-ß receptors (p-TßRI). This increase is attenuated when NECs are cultured in the presence of HA. Similar expressions are observed in phosphorylated smad2/smad3. Additionally, HA-dependent inhibition of TGF-ß1 signalling is inhibited by co-incubation with a blocking antibody to CD44. Experimental results indicate that HA can antagonize TGF-ß1 effect on EMT and mucociliary differentiation of NECs by down-regulation of TßR I, which is via CD44.

Poly (ethylene-co-vinyl alcohol) is a suitable substrate for human olfactory neuroepithelial cell differentiation in vitro through a defined regulatory pathway.

Olfactory dysfunction significantly influences patients' life quality, but currently has no adequate treatment. Poly (ethylene-co-vinyl alcohol) (EVAL) mediates cell adhesion, growth and modulates differentiation of neural stem cells. However, whether EVAL is a suitable substrate to establish an in vitro culture system that can promote development and differentiation of human olfactory neuroepithelial cells (HONCs) remains unexplored. This study isolates and cultures HONCs on controls and EVAL films for 21 days. The effects of treatment are assessed using immunocytochemistry, microarray analysis, quantitative PCR, ELISA and western blots following culturing. Most of the cell morphology on controls is epithelial and expresses markers of sustentacular cells (SCs), cadherin-1 and cytokeratin18, whereas the main population on EVAL presents as morphology with extended thin processes and possesses markers of mature olfactory sensory neurons (OSNs), olfactory marker protein (OMP). Microarray analyses reveal neuropeptide Y (NPY) and amphiregulin (AREG) are the two important regulating factors on EVAL films. HONCs cultured on EVAL films enhance the development of mature OSNs through NPY signaling, and significantly decrease the growth of SCs by blocking epidermal growth factor receptor (EGFR) activation. EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future. STATEMENT OF SIGNIFICANCE: Olfaction not only contributes to enjoyments of food, but provides a clue to escape from dangerous environmental hazards. However, loss of smell is commonly progressive and there is no good prognostic approach for olfactory dysfunction. Here, we use poly (ethylene-co-vinyl alcohol) (EVAL) to establish an in vitro culture system that promotes development and differentiation of human olfactory neuroepithelial cells. We show that EVAL not only enhances the development of mature olfactory sensory neurons through neuronpeptide Y signaling, but significantly protects the olfactory neuroepithelium from metaplasia by inhibiting EGFR activation. Therefore, EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future.

Promotion of olfactory receptor neuron differentiation of olfactory neuroepithelial cells by using chitosan solution.

BACKGROUND: Olfactory dysfunction significantly influences patients' quality of life. Chitosan has been reported to support neuron and Schwann cell growth and even leads to orient axonal growth. However, researchers have yet to explore whether chitosan solution can promote differentiation of olfactory receptor neurons of the olfactory neuroepithelium and be used for treating olfactory dysfunction. OBJECTIVE: To evaluate the effect of chitosan solution on the differentiation of olfactory neuroepithelial cells. METHOD: Olfactory neuroepithelial cells were isolated from embryonic day 17 of Wistar rats and then cultured with and without soluble chitosan for 9 days. The concentration of chitosan solution was set at 0.1 mg/mL. The effects of treatment were assessed by immunocytochemistry and Western blot after culturing. RESULTS: The morphologic analysis indicated that olfactory neuroepithelial cells treated with chitosan exhibited bipolar shape with asymmetric processes. In addition, from days 3 to 9, the expression level of ßIII tubulin gradually reduced, but the expression level of olfactory marker protein significantly rose at day 9 in the chitosan groups (p < 0.05). Importantly, chitosan-treated olfactory neuroepithelial cells expressed more signal transduction apparatuses, olfactory neuron specific-G protein and adenylate cyclase 3, than those without chitosan treatment at day 9. Western blot analysis also further confirmed the results (p < 0.05). CONCLUSION: Experimental results revealed that soluble chitosan promoted differentiation of olfactory neuroepithelial cells based on its role in olfactory receptor neuron differentiation, neurite outgrowth, and signal transduction apparatus expressions.

Electronic Coupling between Graphene and Topological Insulator Induced Anomalous Magnetotransport Properties.

It has been theoretically proposed that the spin textures of surface states in a topological insulator can be directly transferred to graphene by means of the proximity effect, which is very important for realizing a two-dimensional topological insulator based on graphene. Here we report the anomalous magnetotransport properties of graphene-topological insulator Bi2Se3 heterojunctions, which are sensitive to the electronic coupling between graphene and the topological surface state. The coupling between the pz orbitals of graphene and the p orbitals of the surface states on the Bi2Se3 bottom surface can be enhanced by applying a perpendicular negative magnetic field, resulting in a giant negative magnetoresistance at the Dirac point up to about -91%. An obvious resistance dip in the transfer curve at the Dirac point is also observed in the hybrid devices, which is consistent with theoretical predictions of the distorted Dirac bands with nontrivial spin textures inherited from the Bi2Se3 surface states.