Comparative Effectiveness of Personal Sound Amplification Products Versus Hearing Aids for Unilateral Hearing Loss: A Prospective Randomized Crossover Trial.

BACKGROUND: This study compared hearing outcomes with use of personal sound amplification products (PSAPs) and hearing aids (HAs) in patients with moderate to moderately severe unilateral hearing loss. METHODS: Thirty-nine participants were prospectively enrolled, and randomly assigned to use either one HA (basic or premium type) or one PSAP (basic or high-end type) for the first 8 weeks and then the other device for the following 8 weeks. Participants underwent a battery of examinations at three visits, including sound-field audiometry, word recognition score (WRS), speech perception in quiet and in noise, real-ear measurement, and self-report questionnaires. RESULTS: Functional gain was significantly higher with HAs across all frequencies (P < 0.001). While both PSAPs and HAs improved WRS from the unaided condition, HAs were superior to PSAPs. The speech recognition threshold in quiet conditions and signal-to-noise ratio in noisy conditions were significantly lower in the HA-aided condition than in the PSAP-aided condition, and in the PSAP-aided condition than in the unaided condition. Subjective satisfaction also favored HAs than PSAPs in questionnaires, Abbreviated Profile of Hearing Aid Benefit, International Outcome Inventory for Hearing Aids, and Host Institutional Questionnaire. CONCLUSION: While PSAPs provide some benefit for moderate to moderately severe unilateral hearing loss, HAs are more effective. This underscores the potential role of PSAPs as an accessible, affordable first-line intervention in hearing rehabilitation, particularly for individuals facing challenges in accessing conventional HAs.

CORM­2 reduces cisplatin accumulation in the mouse inner ear and protects against cisplatin-induced ototoxicity.

INTRODUCTION: Cisplatin is a life-saving anticancer compound used to treat multiple solid malignant tumors, while it causes permanent hearing loss. There is no known cure, and the FDA has not approved any preventative treatment for cisplatin-based ototoxicity. OBJECTIVES: This study investigated whether the carbon monoxide (CO)-releasing tricarbonyldichlororuthenium (II) dimer, CORM-2, reverses cisplatin-induced hearing impairment and reduces cisplatin accumulation in the mouse inner ear. METHODS: Male 6-week-old BALB/c mice were randomly assigned to one of the following groups: control (saline-treated, i.p.), CORM-2 only (30 mg/kg, i.p., four doses), cisplatin only (20 mg/kg, i.p., one dose), and CORM-2 + cisplatin, to determine whether cisplatin-based hearing impairment was alleviated by CORM-2 treatment. RESULTS: Our results revealed CORM-2 significantly attenuated cisplatin-induced hearing loss in young adult mice. CORM-2 co-treatment significantly decreased platinum accumulation in the inner ear and activated the plasma membrane repair system of the stria vascularis. Moreover, CORM-2 co-treatment significantly decreased cisplatin-induced inflammation, apoptosis, and cochlear necroptosis. Because the stria vascularis is the likely cochlear entry point of cisplatin, we next focused on the microvasculature. Cisplatin induced increased extravasation of a chromatic tracer (fluorescein isothiocyanate [FITC]-dextran, MW 75 kDa) around the cochlear microvessels at 4 days post-treatment; this extravasation was completely inhibited by CORM-2 co-therapy. CORM-2 co-treatment effectively maintained the integrity of stria vascularis components including endothelial cells, pericytes, and perivascular-resident macrophage-type melanocytes. CONCLUSION: CORM-2 co-therapy substantially protects against cisplatin-induced ototoxicity by reducing platinum accumulation and toxic cellular stress responses. These data indicate that CORM-2 co-treatment may be translated into clinical strategy to reduce cisplatin-induced hearing loss.

A Novel Approach to Investigate the Superheating Grain Refinement Process of Aluminum-Bearing Magnesium Alloys Using Rapid Solidification Process.

The superheating process is a unique grain refining method found only in aluminum-containing magnesium alloys. It is a relatively simple method of controlling the temperature of the melt without adding a nucleating agent or refining agent for grain refinement. Although previous studies have been conducted on this process, the precise mechanism underlying this phenomenon has yet to be elucidated. In this study, a new approach was used to investigate the grain refinement mechanism of aluminum-containing magnesium alloys by the melting superheating process. AZ91 alloy, a representative Mg-Al alloy, was used in the study, and a rapid solidification process was designed to enable precise temperature control. Temperature control was successfully conducted in a unique way by measuring the temperature of the ceramic tube during the rapid solidification process. The presence of Al8Mn5 and Al10Mn3 particles in non-superheated and superheated AZ91 ribbon samples, respectively, manufactured by the rapid solidification process, was revealed. The role of these Al-Mn particles as nucleants in non-superheated and superheated samples was examined by employing STEM equipment. The crystallographic coherence between Al8Mn5 particles and magnesium was very poor, while Al10Mn3 particles showed better coherence than Al8Mn5. We speculated that Al10Mn3 particles generated by the superheating process may act as nucleants for α-Mg grains; this was the main cause of the superheating grain refinement of the AZ91 alloy.

Antidepressant Use and Lung Cancer Risk and Survival: A Meta-analysis of Observational Studies.

Recent preclinical studies have linked antidepressants (AD) to their potential anticancer effects in multiple cancers, but the impact on lung cancer remains unclear. This meta-analysis examined the associations between ADs and lung cancer incidence and survival. The Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by June 2022. We conducted a meta-analysis using a random-effects model to compare the pooled risk ratio (RR) and 95% confidence interval (CI) in those treated with or without ADs. Heterogeneity was examined using Cochran Q test and inconsistency I2 statistics. The methodologic quality of the selected studies was assessed using the Newcastle-Ottawa Scale for observational studies. Our analysis, including 11 publications involving 1,200,885 participants, showed that AD use increased lung cancer risk by 11% (RR = 1.11; 95% CI = 1.02-1.20; I2 = 65.03%; n = 6) but was not associated with overall survival (RR = 1.04; 95% CI = 0.75-1.45; I2 = 83.40%; n = 4). One study examined cancer-specific survival. Subgroup analysis showed that serotonin and norepinephrine reuptake inhibitors (SNRIs) were associated with an increased lung cancer risk by 38% (RR = 1.38; 95% CI = 1.07-1.78; n = 2). The quality of selected studies was good (n = 5) to fair (n = 6). Our data analysis suggests that SNRIs were associated with an elevated risk of lung cancer, raising concerns regarding the use of AD treatment in patients vulnerable to lung cancer. The effects of ADs-particularly SNRIs-and their interplay with cigarette use and lung cancer risk in vulnerable patients merits further study. Significance: In this meta-analysis of 11 observational studies, we found evidence of a statistically significant association between the use of certain ADs and lung cancer risk. This effect merits further study, particularly as it relates to known environmental and behavioral drivers of lung cancer risk, such as air pollution and cigarette smoke.

Injectable Poloxamer Hydrogel Formulations for Intratympanic Delivery of Dexamethasone.

BACKGROUND: In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX). METHODS: DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements. RESULTS: The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation. CONCLUSION: P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release.

Degree of Impurity and Carbon Contents in the Grain Size of Mg-Al Magnesium Alloys.

In this study, the tendency of having different grain structures depending on the impurity levels in AZ91 alloys was investigated. Two types of AZ91 alloys were analyzed: commercial-purity AZ91 and high-purity AZ91. The average grain size of the commercial-purity AZ91 alloy and high-purity AZ91 is 320 µm and 90 µm, respectively. Thermal analysis revealed negligible undercooling in the high-purity AZ91 alloy, while undercooling of 1.3 °C was observed in the commercial-purity AZ91 alloy. A CS analyzer was employed to precisely analyze the carbon composition of both alloys. The carbon content of the high-purity AZ91 alloy was found to be 197 ppm, while the commercial-purity AZ91 alloy contained 104 ppm, indicating a difference of approximately 2 times. The higher carbon content in the high-purity AZ91 alloy is believed to be due to the use of high-purity pure Mg in its production (the carbon content of high-purity pure Mg is 251 ppm). To simulate the vacuum distillation process commonly used in the production of high-purity Mg ingots, experiments were conducted to investigate the reaction of carbon with oxygen to produce CO and CO2. XPS analysis and simulation results for activities confirmed the formation of CO and CO2 during the vacuum distillation process. It could be speculated that the carbon sources in the high-purity Mg ingot provide Al-C particles, which act as nucleants for Mg grains in the high-purity AZ91 alloy. Thus, it can be considered the main reason that high-purity AZ91 alloys have a finer grain structure than that of commercial-purity AZ91 alloys.

Synthesis and Characterization of Al Chip-Based Syntactic Foam Containing Glass Hollow Spheres Fabricated by a Semi-Solid Process.

In this study, aluminum (Al) chip matrix-based synthetic foams were fabricated by hot pressing at a semi-solid (SS) temperature. The densities of the foams ranged from 2.3 to 2.63 g/cm3, confirming that the density decreased with increasing glass hollow sphere (GHS) content. These values were approximately 16% lower than the densities of Al chip alloys without GHS. The Al chip syntactic foam microstructure fabricated by the semi-solid process comprised GHS uniformly distributed around the Al chip matrix and a spherical microstructure surrounded by the Mg2Si phase in the interior. The resulting spherical microstructure contributed significantly to the improvement of mechanical properties. Mechanical characterization confirmed that the Al chip syntactic foam exhibited a compressive strength of approximately 225-288 MPa and an energy absorption capacity of 46-47 MJ/M3. These results indicate higher compressive properties than typical Al syntactic foam. The Al chip microstructure, consisting of the Mg2Si phase and GHS, acted as a load-bearing element during compression, significantly contributing to the compressive properties of the foam. An analysis was performed using an energy-dispersive spectrometer to validate the interfacial reaction between the GHS and the matrix. The results showed that MgAl2O4 was uniformly coated around GHS, which contributed not only to the strength of the matrix, but also to the mechanical properties via the appropriate interfacial reactive coating.

Sex differences in hearing impairment due to diet-induced obesity in CBA/Ca mice.

BACKGROUND: Obesity is an independent risk factor for hearing loss. Although attention has focused on major obesity comorbidities such as cardiovascular disease, stroke, and type 2 diabetes, the impact of obesity on sensorineural organs, including the auditory system, is unclear. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impact of diet-induced obesity on sexual dimorphism in metabolic alterations and hearing sensitivity. METHODS: Male and female CBA/Ca mice were randomly assigned to three diet groups and fed, from weaning (at 28 days) to 14 weeks of age, a sucrose-matched control diet (10 kcal% fat content diet), or one of two HFDs (45 or 60 kcal% fat content diets). Auditory sensitivity was evaluated based on the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and ABR wave 1 amplitude at 14 weeks of age, followed by biochemical analyses. RESULTS: We found significant sexual dimorphism in HFD-induced metabolic alterations and obesity-related hearing loss. Male mice exhibited greater weight gain, hyperglycemia, increased ABR thresholds at low frequencies, elevated DPOAE, and lower ABR wave 1 amplitude compared to female mice. The hair cell (HC) ribbon synapse (CtBP2) puncta showed significant sex differences. The serum concentration of adiponectin, an otoprotective adipokine, was significantly higher in female than in male mice; cochlear adiponectin levels were elevated by HFD in female but not male mice. Adiponectin receptor 1 (AdipoR1) was widely expressed in the inner ear, and cochlear AdipoR1 protein levels were increased by HFD, in female but not male mice. Stress granules (G3BP1) were significantly induced by the HFD in both sexes; conversely, inflammatory (IL-1ß) responses were observed only in the male liver and cochlea, consistent with phenotype HFD-induced obesity. CONCLUSIONS: Female mice are more resistant to the negative effects of an HFD on body weight, metabolism, and hearing. Females showed increased peripheral and intra-cochlear adiponectin and AdipoR1 levels, and HC ribbon synapses. These changes may mediate resistance to HFD-induced hearing loss seen in female mice.

Influence of Tempering Temperature and Time on Microstructure and Mechanical Properties of Additively Manufactured H13 Tool Steel.

Among various processes for manufacturing complex-shaped metal parts, additive manufacturing is highlighted as a process capable of reducing the wastage of materials without requiring a post-process, such as machining and finishing. In particular, it is a suitable new manufacturing technology for producing AISI H13 tool steel for hot-worked molds with complex cooling channels. In this study, we manufactured AISI H13 tool steel using the laser power bed fusion (LPBF) process and investigated the effects of tempering temperature and holding time on its microstructure and mechanical properties. The mechanical properties of the sub-grain cell microstructure of the AISI H13 tool steel manufactured using the LPBF process were superior to that of the H13 tool steel manufactured using the conventional method. These sub-grain cells decomposed and disappeared during the austenitizing process; however, the mechanical properties could be restored at a tempering temperature of 500 °C or higher owing to the secondary hardening and distribution of carbides. Furthermore, the mechanical properties deteriorated because of the decomposition of the martensite phase and the accumulation and coarsening of carbides when over-tempering occurred at 500 °C for 5 h and 550 °C for 3 h.

Synthesis of Tantalum Carbide Using Purified Hexane by Titanium Powder.

Hexane is a safe, efficient, and cost-effective alternative to other commercial hydrocarbons for gaseous carburization; however, commercial hexane is not sufficiently pure. Titanium powder can remove oxygen-containing impurities from commercial hexane; however, research on the use of titanium powder remains limited. We investigated the purification of hexane using titanium, copper, and aluminum powders and used the purified hexane for the gaseous carburization of tantalum. Ti exhibited lower activation energy for oxidation (1.55 kJ/mol) than Cu (91.09 kJ/mol) and Al (150.25 kJ/mol) and a significantly higher oxidation rate (0.0269 g/h) in hexane at room temperature than Cu (0.0018 g/h) and Al (0.0001 g/h). The carbon content in tantalum carburized using the purified hexane was comparable to that carburized using unpurified hexane (approximately 6.22%); however, its oxygen content was significantly lower (1.39%), which indicates that the produced tantalum carbide has a higher purity. X-ray diffraction results revealed that the oxidation products of tantalum, such as Ta2O, TaO2, Ta0.8O2, and Ta2O5, were absent in the sample carburized using the purified hexane. Therefore, Ti powder can effectively remove oxygen-containing impurities from commercial hexane and facilitate its use as an effective carburizing medium for the synthesis of high-purity tantalum carbide.

Perception and expectations of personal sound amplification products in Korea: A hospital-based, multi-center, cross-sectional survey.

OBJECTIVES: The objective of this study was to investigate current perception and expected price of personal sound amplification products (PSAPs) and to analyze influencing factors through multi-center hospital-based surveys of outpatients, caregivers, and hearing experts. METHODS: A multi-center exploratory cross-sectional study was conducted in two groups of respondents with two separate surveys: 1) a perception survey of patients and caregivers who visited an otorhinolaryngology outpatient clinic in 5 general hospitals and 2) an opinion survey of hearing specialists about the expected price of PSAPs. A total of 197 outpatient visitors responded to the perception survey, and 42 hearing specialists responded to the opinion survey. RESULTS: Overall perception score (18 questions) was 3.04 (95% CI, 3.00-3.09). When 5 categories of perception (knowledge, needs, cost, expectation, and information categories) were analyzed, cost and expectation showed the highest scores of 3.33 (95% CI, 3.21-3.44) and 3.33 (95% CI, 3.27-3.40), respectively, and needs showed the lowest score of 2.23 (95% CI, 1.97-2.49). The ≥ 60-year-old group showed significantly higher perception of PSAPs (P = 0.002), and the individuals with greater severity of subjective hearing loss showed significantly higher perception of PSAPs (P = 0.002). The expected price of PSAPs of the outpatient visitors was 933.9 USD (95% CI, 811.9-1056.0) per ear. Mean expected price of PSAPs of hearing specialists was 291.3 USD (95% CI, 238.2-344.3) per ear. CONCLUSION: The perception rate of PSAPs was very low, and there was a discrepancy in the expected price of PSAPs between patients/caregivers and hearing experts. Hearing specialists should make effort to improve perception of PSAPs.

Knowledge and Expectations of Hearing Aid Apps Among Smartphone Users and Hearing Professionals: Cross-sectional Survey.

BACKGROUND: Despite the increasing prevalence of hearing loss, the cost and psychological barriers to the use of hearing aids may prevent their use in individuals with hearing loss. Patients with hearing loss can benefit from smartphone-based hearing aid apps (SHAAs), which are smartphone apps that use a mobile device as a sound amplifier. OBJECTIVE: The aim of this study is to determine how ear, nose, and throat outpatients perceive SHAAs, analyze the factors that affect their perceptions, and estimate the costs of an annual subscription to an app through a self-administered questionnaire survey of smartphone users and hearing specialists. METHODS: This study used a cross-sectional, multicenter survey of both ear, nose, and throat outpatients and hearing specialists. The questionnaire was designed to collect personal information about the respondents and their responses to 18 questions concerning SHAAs in five domains: knowledge, needs, cost, expectations, and information. Perception questions were rated on a scale of 1 (strongly disagree) to 5 (strongly agree). Questions about the expected cost of SHAAs were included in the questionnaire distributed to hearing experts. RESULTS: Among the 219 smartphone users and 42 hearing specialists, only 8 (3.7%) respondents recognized SHAAs, whereas 18% (47/261) of respondents reported considering the use of an assistive device to improve their hearing capacity. The average perception score was 2.81 (SD 1.22). Among the factors that shaped perceptions of SHAAs, the needs category received the lowest scores (2.02, SD 1.42), whereas the cost category received the highest scores (3.29, SD 1.14). Age was correlated with the information domain (P<.001), and an increased level of hearing impairment resulted in significantly higher points in the needs category (P<.001). Patients expected the cost of an annual app subscription to an SHAA to be approximately US $86, and the predicted cost was associated with economic status (P=.02) and was higher than the prices expected by hearing specialists (P<.001). CONCLUSIONS: Outpatients expected SHAAs to cost more than hearing specialists. However, the perception of the SHAA was relatively low. In this regard, enhanced awareness is required to popularize SHAAs.

Injectable glycol chitosan thermogel formulation for efficient inner ear drug delivery.

We prepared a new injectable thermogel to enhance the efficiency of inner ear delivery of dexamethasone (DEX). Hexanoyl glycol chitosan (HGC) was synthesized and evaluated as an amphiphilic thermogel (Tgel ~ 32 °C) for use as a solubilizing agent as well as an injectable carrier for intratympanic delivery of the hydrophilic and hydrophobic forms of DEX. Various thermogel formulations with different drug types and concentrations were prepared, and their physicochemical and thermogelling properties were characterized by 1H NMR, ATR-FTIR, and rheometer. They exhibited versatile release kinetics from several hours to more than 2 weeks, depending on drug type and concentration. Our formulations further showed good residual stability for more than 21 days without any cytotoxicity or inflammation in the middle and inner ear and could deliver a considerably high drug concentration into the inner ear. Therefore, HGC thermogel has great potential as an effective and safe formulation for inner ear drug delivery.

Molecular-based detection, genetic characterization and phylogenetic analysis of porcine circovirus 4 from Korean domestic swine farms.

Porcine circovirus 4 (PCV4), a novel and unclassified member of the genus Circovirus, was first reported in China in 2019. Aiming to provide more evidence about the active circulation of PCV4, this study screened 335 pooled internal organs and detected the virus (i) at a rate of 3.28%, (ii) from both clinically healthy and clinically sick pigs of various age groups, and (iii) in six out of nine provinces of Korea. The complete genomic sequence of the Korean PCV4 strain (E115) was 1,770 nucleotides in length and had 98.5%-98.9% identity to three PCV4 strains currently available at GenBank. Utilizing a set of bioinformatic programs, it was revealed that the Korean PCV4 strain contained several genomic features of (i) a palindrome stem-loop structure with a conserved nonanucleotide, (ii) packed overlapping ORFs oriented in different directions and (iii) two intergenic regions in between genes encoding the putative replication-associated protein (Rep) and capsid (Cap) proteins. This study also predicted the presence of essential elements for the replication of circoviruses in all PCV4 strains, for example the origin of DNA replication, endonuclease and helicase domains of Rep, and the nuclear localization signal on the putative Cap protein. Finally, based on the phylogeny inferred from sequences of the putative Rep protein, this study further clarified the genetic relationships between PCV4 and other CRESS DNA viruses in general and circoviruses in particular.

Genomic Characterization of a Novel Alphacoronavirus Isolated from Bats, Korea, 2020.

Coronavirus, an important zoonotic disease, raises concerns of future pandemics. The bat is considered a source of noticeable viruses resulting in human and livestock infections, especially the coronavirus. Therefore, surveillance and genetic analysis of coronaviruses in bats are essential in order to prevent the risk of future diseases. In this study, the genome of HCQD-2020, a novel alphacoronavirus detected in a bat (Eptesicus serotinus), was assembled and described using next-generation sequencing and bioinformatics analysis. The comparison of the whole-genome sequence and the conserved amino acid sequence of replicated proteins revealed that the new strain was distantly related with other known species in the Alphacoronavirus genus. Phylogenetic construction indicated that this strain formed a separated branch with other species, suggesting a new species of Alphacoronavirus. Additionally, in silico prediction also revealed the risk of cross-species infection of this strain, especially in the order Artiodactyla. In summary, this study provided the genetic characteristics of a possible new species belonging to Alphacoronavirus.

Junctional Modulation of Round Window Membrane Enhances Dexamethasone Uptake into the Inner Ear and Recovery after NIHL.

Delivery of substances into the inner ear via local routes is increasingly being used in clinical treatment. Studies have focused on methods to increase permeability through the round window membrane (RWM) and enhance drug diffusion into the inner ear. However, the clinical applications of those methods have been unclear and few studies have investigated the efficacy of methods in an inner ear injury model. Here, we employed the medium chain fatty acid caprate, a biologically safe, clinically applicable substance, to modulate tight junctions of the RWM. Intratympanic treatment of sodium caprate (SC) induced transient, but wider, gaps in intercellular spaces of the RWM epithelial layer and enhanced the perilymph and cochlear concentrations/uptake of dexamethasone. Importantly, dexamethasone co-administered with SC led to significantly more rapid recovery from noise-induced hearing loss at 4 and 8 kHz, compared with the dexamethasone-only group. Taken together, our data indicate that junctional modulation of the RWM by SC enhances dexamethasone uptake into the inner ear, thereby hastening the recovery of hearing sensitivity after noise trauma.

Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation.

Employed for over half a century to study protein synthesis, cycloheximide (CHX, 1) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been applied to ribosome profiling, a method for mapping ribosome positions on mRNA genome-wide. Despite CHX's extensive use, CHX treatment often results in incomplete translation inhibition due to its rapid reversibility, prompting the need for improved reagents. Here, we report the concise synthesis of C13-amide-functionalized CHX derivatives with increased potencies toward protein synthesis inhibition. Cryogenic electron microscopy (cryo-EM) revealed that C13-aminobenzoyl CHX (8) occupies the same site as CHX, competing with the 3' end of E-site tRNA. We demonstrate that 8 is superior to CHX for ribosome profiling experiments, enabling more effective capture of ribosome conformations through sustained stabilization of polysomes. Our studies identify powerful chemical reagents to study protein synthesis and reveal the molecular basis of their enhanced potency.

Hearing Impairment in a Mouse Model of Diabetes Is Associated with Mitochondrial Dysfunction, Synaptopathy, and Activation of the Intrinsic Apoptosis Pathway.

Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Leprdb/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria.

Microstructural Improvement of Eutectic Al + Mg2Si Phases on Al-Zn-Si-Mg Cast Alloy with TiB2 Particles Additions.

In this study, the effects of adding TiB2 particles to eutectic Al + Mg2Si phases in aluminum alloys were analyzed. The eutectic Al + Mg2Si phases were modified effectively when a large amount of TiB2 was added, and changes in the shape, size, and distribution of the eutectic Al + Mg2Si phases were confirmed using a polarizing microscope and FE-SEM. The crystal structure of the TiB2 particles and Mg2Si phases were analyzed using HR-TEM, and the analysis confirmed that the TiB2 particles can act as heterogeneous nucleation sites. This paper intends to clarify the principle of phase modification of the eutectic Al + Mg2Si phases by TiB2 particles and proposes a new mechanism to improve Mg2Si phase modification when TiB2 particles are added.

Wear Behavior of Conventionally and Directly Aged Maraging 18Ni-300 Steel Produced by Laser Powder Bed Fusion.

This study aims to explore the wear performance of maraging 18Ni-300 steel, fabricated via laser powder bed fusion (LPBF). The building direction dependence of wear resistance was investigated with various wear loads and in terms of ball-on-disk wear tests. The effect of direct aging heat treatment, i.e., aging without solution heat treatment, on the wear performance was investigated by comparing the wear rates of directly aged samples, followed by solution heat treatment. The effect of counterpart material on the wear performance of the maraging steel was studied using two counterpart materials of bearing steel and ZrO2 balls. When the bearing steel ball was used as the counterpart material, both the as-built and heat-treated maraging steel produced by the LPBF showed pronounced building direction dependence on their wear performance when the applied wear load was sufficiently high. However, when the ZrO2 ball was used as the counterpart material, isotropic wear resistance was reported. The maraging steel produced by the LPBF demonstrated excellent wear resistance, particularly when it was aging heat-treated and the counterpart material was ZrO2. The directly aged sample showed wear performance almost the same as the sample solution heat-treated and then aged, indicating that direct aging can be used as an alternative post heat treatment for tribological applications of the maraging steels produced by LPBF.