Immobilization of Cd2+ in an aqueous environment using a two-step microbial-induced carbonate precipitation method.

Previous researches indicate that the potent toxicity of cadmium hinders the efficacy of the microbial-induced carbonate precipitation (MICP) process for bioremediation of Cd2+ in aqueous environment. Increasing urea and calcium resource doses, introducing synergists, and utilizing urease-producing consortia can improve bio-immobilization performance of MICP. However, such measures may incur cost increases and/or secondary contamination. This study first verifies the substantial biotoxicity of Cd2+ for urease activity and then analyzes the practical limitation of traditional MICP using Bacillus pasteurii for bioremediation of Cd2+ in an aqueous environment containing 1-40 mM Cd2+ by a series tube tests and numerical simulation. Subsequently, a two-step MICP method, which separates urea hydrolysis and heavy metal precipitation, is introduced in this study to eliminate the inhibitory effect of heavy metal on urease activity. The concentrations of ammonium, Cd2+, and pH were monitored over time. The results indicate that the urease expression in B. pasteurii can be significantly inhibited by Cd2+ particularly at the concentration ranging from 10 to 40 mM, leading to pretty low efficacy of traditional MICP for bioremediation of Cd2+ (Cd2+ removal rate as low as 21.55-38.47% when the initial Cd2+ concentration = 40 mM). In contrast, when the two-step MICP method is applied, the Cd2+ can be almost completely immobilized, even though the concentration ratio of urea to Cd2+ is as low as 1.5:1.0, which is close to the theory minimum concentration ratio for the complete precipitation of carbonate to cadmium ions(1.0:1.0). Therefore, the cost-effective, environmentally sustainable, and straightforward two-step MICP method holds great potential for application in the bioremediation of Cd2+-contaminated solutions in high concentration.

Machine Learning Enhanced Optical Microscopy for the Rapid Morphology Characterization of Silver Nanoparticles.

The rapid characterization of nanoparticles for morphological information such as size and shape is essential for material synthesis as they are the determining factors for the optical, mechanical, and chemical properties and related applications. In this paper, we report a computational imaging platform to characterize nanoparticle size and morphology under conventional optical microscopy. We established a machine learning model based on a series of images acquired by through-focus scanning optical microscopy (TSOM) on a conventional optical microscope. This model predicts the size of silver nanocubes with an estimation error below 5% on individual particles. At the ensemble level, the estimation error is 1.6% for the averaged size and 0.4 nm for the standard deviation. The method can also identify the tip morphology of silver nanowires from the mix of sharp-tip and blunt-tip samples at an accuracy of 82%. Furthermore, we demonstrated online monitoring for the evolution of the size distribution of nanoparticles during synthesis. This method can be potentially extended to more complicated nanomaterials such as anisotropic and dielectric nanoparticles.

Characteristics of tympanogram in symptomatic Eustachian tube dysfunction.

PURPOSE: To identify the characteristics of tympanogram in symptomatic Eustachian tube dysfunction (SETD) patients. METHODS: One hundred and twenty-four unilateral SETD patients presenting with type A tympanograms who underwent balloon dilation of the Eustachian tube (BDET) were recruited and assigned into effective BDET group and ineffective BDET group based on treatment effect. The unaffected ear in the same patient served as normal control. Fifty-one patients with sudden sensorineural hearing loss (SSHL) and 46 patients with Meniere's disease (MD) were selected for cases of non-ETD ear fullness. Demographics, 7-item Eustachian Tube Dysfunction Questionnaire score (ETDQ-7), and tympanograms were recorded and analyzed preoperatively and postoperatively. RESULTS: Of the 124 SETD patients included in the study 94 (75.8%) showed good response to BDET based on decreased ETDQ-7 scores. There were no significantly differences in the values of tympanometric peak pressure (TPP) between diseased ears and healthy ears in SETD patients, as well as in SSHL and MD patients. Instead, TPP shifts (the difference between two values of TPP obtained under a Valsalva and Toynbee maneuver) were remarkably reduced in affected ears compared with those in unaffected ears in effective BDET group at baseline. Moreover, TPP shifts in these SETD ears significantly raised and reached the levels in healthy ears postoperatively. CONCLUSIONS: This study demonstrated TPP shifts are decreased in a subset of SETD patients presenting with type A tympanograms and these patients are more likely to show good response to BDET.

Physics-Guided Neural-Network-Based Inverse Design of a Photonic-Plasmonic Nanodevice for Superfocusing.

Controlling the nanoscale light-matter interaction using superfocusing hybrid photonic-plasmonic devices has attracted significant research interest in tackling existing challenges, including converting efficiencies, working bandwidths, and manufacturing complexities. With the growth in demand for efficient photonic-plasmonic input-output interfaces to improve plasmonic device performances, sophisticated designs with multiple optimization parameters are required, which comes with an unaffordable computation cost. Machine learning methods can significantly reduce the cost of computations compared to numerical simulations, but the input-output dimension mismatch remains a challenging problem. Here, we introduce a physics-guided two-stage machine learning network that uses the improved coupled-mode theory for optical waveguides to guide the learning module and improve the accuracy of predictive engines to 98.5%. A near-unity coupling efficiency with symmetry-breaking selectivity is predicted by the inverse design. By fabricating photonic-plasmonic couplers using the predicted profiles, we demonstrate that the excitation efficiency of 83% on the radially polarized surface plasmon mode can be achieved, which paves the way for super-resolution optical imaging.

The evolution rule of green innovation efficiency and its convergence of industrial enterprises in China.

The heterogeneity can greatly influence the green innovative development of industrial enterprises. Based on the stochastic frontier analysis model of heterogeneity, this paper measures the green innovative efficiency of industrial enterprises in China for the time period of 2008 to 2017, and concludes the following results: (a) in the production function estimation, the R&D expenditure of industrial enterprises is the main positive factor in influencing green innovation, while the energy consumption the main negative factor. The effects of R&D talents and environment quality are not obvious at both stages. (b) The overall green innovation efficiency of industrial enterprises is only 0.2981 at R&D stage with an efficiency loss of 0.7019, and the residual efficiency of green innovation is 0.9966 with persistent efficiency as 0.2991. The overall green innovation efficiency of industrial enterprises is only 0.3930 at new product sales stage with an efficiency loss of 0.607, and the residual efficiency of green innovation is 0.8196 with persistent efficiency as 0.4783. (c) In the sample period, there appears to be an apparent decreasing of green innovative efficiency level from R&D stage to new product sales stage. Besides, the distribution of both overall efficiency and persistent efficiency tend to disperse, and there are great differences among years which are expanded at different stages. (d) Certain "club convergence" exists in overall efficiency and persistent efficiency of green innovation. The structural problem at R&D stage is the main factor in influencing the green innovation overall efficiency. The residual factors such as time effect at new product sales stage affect new product transformation. In order to increase green innovation efficiency, considering development level of selves, regions can establish a "club" to set up an efficient and sharable patent transfer platform, and reduce new product transformation loss.

[Application of vestibular function examination battery in the staging of vestibular function in Meniere's disease].

Objective:To investigate the staging of vestibular organ damage in Meniere's disease, based on the vestibular function examination battery. Methods:Thirty-nine patients, clinically diagnosed as unilateral Meniere's disease, underwent audiologic test and vestibular function examination battery, including ocular vestibular evoked myogenic potential（oVEMP）, cervical vestibular evoke myogenic potential（cVEMP）, and caloric tests. Based on the results of the vestibular function examination battery, the vestibular function was divided into 4 stages. StageⅠ: oVEMP, cVEMP, and caloric tests were normal; stage Ⅱ: any one test of the three examinations was abnormal; stage Ⅲ: two of the three examinations were abnormal; Stage Ⅳ: All the three examinations were abnormal. Results:According to the vestibular function staging strategy in this study, patients in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were 7.7%（3/39）, 30.8%（12/39）, 33.3%（13/39）, 28.2%（11/39） respectively in the 39 Meniere's disease patients. However, according to the current clinical staging strategy of Meniere's disease, patients of stage1, 2, 3, 4 were 20.5%（8/39）, 43.6%（17/39）, 28.2%（11/39）, and 7.7%（3/39） respectively. 37.5%（3/8） patients in stage 1 and 64.7%（11/17） patients in stage 2 had two or more abnormal vestibular organs. While all the patients in stage 4 had abnormal semicircular canals, utricle, and saccule. The stage of vestibular function was correlated with the distribution of current clinical staging strategy of Meniere's disease（P<0.05）. Conclusion:The combination of oVEMP, cVEMP and caloric tests can divide the vestibular function into four stages, which can be used as a supplement to the traditional vestibular evaluation and clinical staging based on audiology in Meniere's disease.

Reconfigurable polymer-templated liquid crystal holographic gratings via visible-light recording.

Polymer-templated nematic liquid crystal (LC) holographic gratings via visible-light recording are presented in the presence of reactive mesogens (RMs) and rose bengal (RB)/N-phenylglycine (NPG) photoinitiation systems. By optimizing the concentration of RMs in the polymer-templated LC gratings, the template after being washed out can be refilled with suitable fluidic components. And the dependence of the first-order diffraction efficiency (DE) on the concentration of RB and NPG molecules was discussed in detail. The polarization-dependency of diffraction properties was also investigated. It is revealed that the diffractive behaviors of polymer-templated LC gratings can be dynamically reconfigured by varying temperature or refilling organic solutions with different refractive index (RI). Furthermore, the potential for recording holograms using green light is explored. We expect that the reconfigurable polymer-templated LC gratings fabricated via visible-light interference would provide a facile approach to regulate the diffraction properties of holographic gratings apart from electric field, thus paving a way towards a class of novel anti-counterfeiting devices.

Local Versus General Anesthesia for Balloon Dilation of the Eustachian Tube: A Single-Center Retrospective Study in a Chinese Population.

OBJECTIVE: To compare local anesthesia (LA) versus general anesthesia (GA) for balloon dilation of the Eustachian tube (BDET) using the Bielefeld Dilation System in a Chinese population with obstructive Eustachian tube dysfunction (OETD). METHODS: A total of 49 patients with OETD undergoing BDET under either LA or GA were included in the present study. Intraoperative blood pressure, heart rate, and pain sensation were recorded. The surgical outcome was assessed by Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) symptom scores and positive Valsalva maneuver at baseline, 1 day, 2-, 4-, 12-, 24-, and 52-week follow-up. RESULTS: Balloon dilation of the Eustachian tube procedures were successfully completed in all patients without adverse effects. The visual analog scale score for maximal pain during the surgical procedure in the LA group was 6.1 ± 1.0. Intraoperative blood pressure and heart rate were higher in the LA group compared with the GA group. The duration and costs of surgery were significantly reduced in the LA group compared with the GA group. Normalization of ETDQ-7 scores at 12-week and 52-week follow-up was observed in 71.9% (23/32) and 63.3% (19/30) of patients in the LA group, respectively, which was comparable to that of the GA group. Although improvement in positive Valsalva maneuver was observed in both groups after BDET, more patients reported positive Valsalva maneuver in the GA group compared with the LA group at 12-week and 52-week follow-up. In total, 96.0% (24/25) of patients in the LA group and 95.8% (23/24) of patients in the GA group would choose LA if BDET was needed again. CONCLUSION: Balloon dilation of the Eustachian tube under LA is safe and feasible in a Chinese population. The surgical outcome of BDET is comparable between under LA and GA during 52-week follow-up. Further studies are needed to address management of intraoperative pain and determine longer follow-up outcome for BDET under LA.

Characteristics of 43 multiple auricular deformity case families and auricle morphology in 463 microtia patients in South China.

BACKGROUND: Earlier studies have suggested that microtia is a genetic disease with a worldwide incidence of microtia is between 0.83/10,000 and 17.40/10,000. For microtia, auricle morphology is the most crucial characteristic. However, no studies have been performed to characterize the genetic similarity of microtia and auricle morphology similarity. For the sporadic patients, the relationship between the gestational age of parents and the incidence of microtia is unclear. To obtain the characteristics of auricular deformity multiple case family (AD-MCF) and clarify the relationship between genetic similarity and auricle morphology similarity in AD-MCF. METHODS: This study included 463 AD patients who were diagnosed by Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from 2013 to 2019. Among these patients, 116 are from 43 MCF and the other 347 patients are sporadic. For the patients from families, the disease status of the four generations of immediate family members and the family tree map were collected to analyze the similarity of auricle shape in family members. A score evaluated the similarity of auricle shape according to the structure of the residual ear and the similarity in the morphology of each auricle. Moreover, the population distribution of AD and the gestational age of patients were further analyzed. RESULTS: From 2013 to 2019, a total of 463 patients were diagnosed as microtia in our hospital. There were 427 patients with unilateral disease and 36 patients with bilateral disease. Among them, 116 patients were from 34 families and 9 de novo families. The total scores of patients in different genetic difference levels were compared and were found significantly different (P<0.001). Moreover, 58.14% of families were consistent with the law of chromosomal recessive genetic diseases. Importantly, we found that the gestational age of father in microtia de novo families is 30.94±0.75, and mother in de novo is 28.39±0.73 that is significantly higher than the gestational ages of parents from microtia families with P value =0.0001. CONCLUSIONS: The auricle similarity between family members is positively related to the genetic distance between family members. The microtia patients are potentially associated with the gestational ages of parents.

Selected Blood Inflammatory and Metabolic Parameters Predicted Successive Bilateral Sudden Sensorineural Hearing Loss.

OBJECTIVES: To explore whether peripheral inflammatory, metabolic, and hemostatic parameters could predict the pathogenesis of successive bilateral sudden sensorineural hearing loss (SSNHL). METHODS: This study reviewed 33 patients with successive bilateral SSNHL and 215 patients with unilateral SSNHL. Clinical characteristics and hematological parameters were compared, including the inflammatory markers (like neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR)) and metabolic features (including hypertension, triglyceridemia, dyslipidemia, and hyperglycemia), as well as hemostatic indices (including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen). RESULTS: In the successive bilateral SSNHL group, older average onset age (48.67 ± 15.36 vs. 42.71 ± 13.58, p < 0.05), higher male to female ratio (18 : 15 vs. 112 : 103, p > 0.05), and poorer therapeutic efficacy (12% vs. 59%, p < 0.01) were observed than those in the unilateral SSNHL group. Compared to the unilateral SSNHL group, NLR, MLR, and PLR in the successive bilateral SSNHL group were significantly higher (NLR: 5.72 ± 2.23 vs. 4.45 ± 2.82, p = 0.01; MLR: 0.25 ± 0.15 vs. 0.17 ± 0.11, p < 0.01; PLR: 190.70 ± 69.79 vs. 148.18 ± 65.67; p < 0.01); the LDL level was significantly higher; yet, the HDL level was significantly lower (LDL: 3.79 ± 0.53 vs. 3.49 ± 0.74; HDL: 1.33 ± 0.32 vs. 1.44 ± 0.26; p < 0.05 for both); fibrinogen was significantly higher (4.03 ± 0.47 vs. 3.70 ± 0.65; p < 0.01). Logistic regression analysis demonstrated that the risk factors for successive bilateral SSNHL included age, NLR, MLR, PLR, LDL, HDL, diabetes, and fibrinogen. However, only NLR, MLR, PLR, diabetes, LDL, and HDL independently predicted successive bilateral SSNHL. CONCLUSION: Selected blood inflammatory markers combined with metabolic parameters were positively correlated with successive bilateral SSNHL.

SIRT1 protects cochlear hair cell and delays age-related hearing loss via autophagy.

Age-related hearing loss (AHL) is typically caused by the irreversible death of hair cells (HCs). Autophagy is a constitutive pathway to strengthen cell survival under normal or stress condition. Our previous work suggested that impaired autophagy played an important role in the development of AHL in C57BL/6 mice, although the underlying mechanism of autophagy in AHL still needs to be investigated. SIRT1 as an important regulator involves in AHL and is also a regulator of autophagy. Thus, we hypothesized that the modulation between SIRT1 and autophagy contribute to HC death and the progressive hearing dysfunction in aging. In the auditory cell line HEI-OC1, SIRT1 modulated autophagosome induction because of SIRT1 deacetylating a core autophagy protein ATG9A. The deacetylation of ATG9A not only affects the autophagosome membrane formation but also acts as a sensor of endoplasmic reticulum (ER) stress inducing autophagy. Moreover, the silencing of SIRT1 facilitated cell death via autophagy inhibition, whereas SIRT1 and autophagy activation reversed the SIRT1 inhibition media cell death. Notably, resveratrol, the first natural agonist of SIRT1, altered the organ of Corti autophagy impairment of the 12-month-old C57BL/6 mice and delayed AHL. The activation of SIRT1 modulates the deacetylation status of ATG9A, which acts as a sensor of ER stress, providing a novel perspective in elucidating the link between ER stress and autophagy in aging. Because SIRT1 activation restores autophagy with reduced HC death and hearing loss, it could be used as a strategy to delay AHL.

Buteyko breathing technique for obstructive Eustachian tube dysfunction: Preliminary results from a randomized controlled trial.

PURPOSE: To assess the effectiveness of Buteyko breathing technique in patients with obstructive Eustachian tube dysfunction (ETD). MATERIALS AND METHODS: Fifty-one patients (77 ears) aged between 21 and 62 years were randomized to Buteyko breathing in conjunction with medical management (nasal steroid) group or medical management alone group. The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) symptom scores, tympanogram, positive Valsalva maneuver were evaluated at baseline, 6-week and 12-week follow-up. RESULTS: Normalization of ETDQ-7 symptom scores at 6-week follow-up was observed in 30.0% (12/40) of the Buteyko breathing group versus 16.2% (6/37) of the controls (P > 0.05). At 12-week follow-up, the ratio rose to 50.0% (20/40) in the Buteyko breathing group and 24.3% (9/37) in the controls (P < 0.05). Tympanogram normalization at 12-week follow-up was observed in 53.6% (15/28) of the Buteyko breathing group versus 26.9% (7/26) of the controls (P < 0.05). The Buteyko breathing group showed slight improvement in positive Valsalva maneuver at 6- and 12-week follow-up (P > 0.05). CONCLUSIONS: Our study shows that Buteyko breathing technique might be an effective adjunctive intervention in treatment of obstructive ETD, especially for those patients who are refractory to medical treatment and cannot afford Eustachian tube balloon dilation surgery.

The diagnosis and treatment of a variant type of auricular sinus: postauricular sinus.

OBJECTIVES: To make otolaryngologists aware of the variant types of auricular sinus, we have performed a systematic review of patient diagnoses and presented our operative experiences. METHODS: From 2009 to 2013 in Sun Yat-Sen Memorial Hospital, there was a total of 20 children with the variant type of auricular sinuses including the comprehensive group. Postauricular sinuses have pits located posterior to the imaginary vertical line that is tangent to the external auditory canal. Sinuses that penetrate the cartilage and cause postauricular swelling or skin defects characterize type 1 of the variant type, while sinuses that adhere to the cartilage and cause preauricular or auricular swelling or skin defects characterize type 2. Patients with pits both anterior to and posterior to the imaginary vertical line comprise the comprehensive group. The patients who had infected underwent auricular sinusectomy using a dual approach, with accurate fistula tracing and proper cartilage removal. RESULTS: Sixteen children who had infected sinus underwent surgery, while the other four were asymptomatic. Ten children (62.5%) of 16 patients were diagnosed as type 1 of the variant type, 2 (12.5%) as type 2. Four children (25%) were diagnosis as the comprehensive group. The asymptomatic could not be defined as the sinuses location were unknown. Sixteen children (100%) of 16 patients who underwent surgery had a history of misdiagnosis and treatment. These patients did not experience recurrence over a 5-year follow-up period. CONCLUSION: The locations of pits and sinuses help to categorize the different types of auricular sinus. The effective method that we have described should be considered a viable way to reduce recurrence.

Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis.

Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and aging. Here we investigated the role of mitophagy and mitochondrial biogenesis in oxidative damage to the cochlear hair cells and age-related hearing loss. In cultured mouse House Ear Institute-Organ of Corti 1 hair cells, oxidative stress activated mitophagy but inhibited mitochondrial biogenesis and impaired mitochondrial function. Pharmacological inhibition of miR-34a/SIRT1 signaling enhanced mitophagy, mitochondrial biogenesis, and attenuated House Ear Institute-Organ of Corti 1 cell death induced by oxidative stress. In the cochlea of C57BL/6 mice, mitophagy and mitochondrial biogenesis were both upregulated during aging. Long-term supplementation with resveratrol, a SIRT1 activator, not only improved the balance between mitophagy and mitochondrial biogenesis but also significantly reduced age-related cochlear hair cell loss, spiral ganglion neuron loss, stria vascularis atrophy, and hearing threshold shifts in C57BL/6 mice. Moreover, SIRT1 overexpression or miR-34a deficiency both attenuated age-related cochlear hair cell loss and hearing loss in C57BL/6 mice. Our findings reveal that imbalance between mitophagy and mitochondrial biogenesis contributes to cochlea hair cell damage caused by oxidative stress and during aging. Coordinated regulation of these 2 processes by miR-34a/SIRT1 signaling might serve as a promising approach for the treatment of age-related cochlear degeneration and hearing loss.

Osteoradionecrosis of the Skull Base in Nasopharyngeal Carcinoma: Incidence and Risk Factors.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a type of malignancy with a high prevalence in southern China and Southeast Asia. The primary treatment modality is radiation therapy (RT). Osteoradionecrosis (ORN) of the skull base remains one of the most serious complications after RT, affecting survival time and quality of life. Thus far, skull base ORN has been seldom reported and can be difficult to distinguish and easy to misdiagnose. In this retrospective study, we report the incidence of skull base ORN and analyze its associated factors in an attempt to decrease the occurrence of ORN. METHODS AND MATERIALS: From January 2001 to December 2012, a total of 1348 patients who received diagnoses of NPC received 1 course of RT. Complete medical records were reviewed, and the patients were examined by magnetic resonance imaging and nasopharyngeal endoscopy during follow-up after primary treatment. Patients with other tumors of the head and neck, a history of RT, failure to complete RT, and those lost to follow-up were excluded. Treatment was delivered with external beam RT using standard linear accelerators. RESULTS: A total of 1348 patients with NPC were enrolled in this study after 1 course of RT; among these patients, 14 received diagnoses of skull base ORN. The incidence of skull base ORN was 1.04%. The average latency interval from the completion of RT to the diagnosis of skull base ORN was 45.57 months. Skull base ORN after 1 course of RT was associated with the T stage; total radiation dose to the nasopharynx, including the skull base in the radiation field; and anemia. CONCLUSIONS: The occurrence of skull base ORN was associated with primary tumors with advanced T stages, high doses of nasopharynx RT, and radiation fields that included the skull base. These factors may be used as predictors for the incidence of skull base ORN.

TGF-ß3 reduces apoptosis in ischemia-induced adipose-derived stem cells by enhancing DNA repair.

Adipose-derived stem cells (ADSCs) possess good proliferative and differentiative abilities, making then a promising candidate for the treatment of cartilage defects. However, local ischemia often causes apoptosis in ADSCs. Transforming growth factor-ß3 (TGF-ß3) is often used as a chondrogenic differentiation cytokine whose function in apoptosis is unclear. The aim of the present study was to investigate the role of TGF-ß3 in ischemia-induced ADSC apoptosis. In the present study, the phenotypes and multipotent differentiation properties of human ADSCs at passage 3 were analyzed using flow cytometry and cytochemical staining. ADSCs were cultured in a serum- and glucose-free medium under hypoxic conditions with or without exogenous TGF-ß3 treatment. The apoptosis rate was measured using a TUNEL array and Annexin V/propidium iodide staining. The expression of apoptosis-associated proteins was measured using western blotting. The results revealed ADSCs cultured in normal condition have multi-lineage differentiation potential and high levels of cluster of differentiation (CD)29, CD44 and CD105 expression. Furthermore, ADSCs weakly express CD14, CD34 and CD45, with strong clone formation and migration abilities. Serum deprivation under hypoxic conditions resulted in mitochondria-mediated apoptosis in ADSCs, which was attenuated by exogenous TGF-ß3 treatment via upregulation of poly ADP-ribose polymerase (PARP). The results of the present study indicate that TGF-ß3 is able to protect ADSCs from ischemia-induced apoptosis via PARP-associated DNA damage repair.

Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line.

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with in vitro results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity.

Resveratrol Promotes Recovery of Hearing following Intense Noise Exposure by Enhancing Cochlear SIRT1 Activity.

The sirtuin SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase known to have protective effects against a wide range of neurological disorders. In the present study, we discovered that C57BL/6 mice fed a long-term diet supplemented with high-dose resveratrol exhibited increased cochlear SIRT1 activity and presented a better recovery of hearing and less loss of hair cells after intense noise exposure compared with those fed a standard chew. Moreover, resveratrol attenuated cochlear SIRT1 decrease and reduced oxidative stress in the cochlea after noise exposure. These results suggest a considerable therapeutic potential of resveratrol for the treatment of noise-induced hearing loss.

Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells.

Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor. The effects of 7RH alone or in combination with dasatinib on cell viability were assessed using MTT assays and apoptosis was detected by flow cytometry. In addition, western blotting was performed to analyze the relative protein expression levels of cell cycle-associated genes in human NPC cell lines (CNE1, CNE2, HONE1 and SUNE1). Cell migration was also assessed using cell adhesion assays. Furthermore, tumor xenografts of CNE2 NPC cells were established in nude mice and the growth inhibitory effects of 7RH treatment alone or in combination with dasatinib were evaluated. Finally, knockdown of DDR1 protein expression was achieved by transfection of CNE2 cells with DDR1-specific small interfering RNA. Treatment with 7RH effectively suppressed the proliferation and induced the apoptosis of NPC cells. In addition, the Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT3) signaling pathway was downregulated by 7RH, whereas the activities of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways were upregulated in response to 7RH treatment. Furthermore, the expression levels of phosphorylated SRC were increased in NPC cells treated with 7RH; thus indicating that SRC exhibits a vital function in the resistance of NPC cells to 7RH via activation of the PI3K/AKT signaling pathway. The results of the present study indicate that DDR1 and SFK inhibition may present a potential therapeutic strategy for patients with NPC.