Inner ear hair cells (HCs) detect sound through the deflection of mechanosensory stereocilia. Stereocilia are inserted into the cuticular plate of HCs by parallel actin rootlets, where they convert sound-induced mechanical vibrations into electrical signals. The molecules that support these rootlets and enable them to withstand constant mechanical stresses underpin our ability to hear. However, the structures of these molecules have remained unknown. We hypothesized that αII- and βII-spectrin subunits fulfill this role, and investigated their structural organization in rodent HCs. Using super-resolution fluorescence imaging, we found that spectrin formed ring-like structures around the base of stereocilia rootlets. These spectrin rings were associated with the hearing ability of mice. Further, HC-specific, βII-spectrin knockout mice displayed profound deafness. Overall, our work has identified and characterized structures of spectrin that play a crucial role in mammalian hearing development.

A discrete model of cochlear mechanics is introduced that includes a full, three-dimensional, description of fluid coupling. This formulation allows the fluid coupling and basilar membrane dynamics to be analyzed separately and then coupled together with a simple piece of linear algebra. The fluid coupling is initially analyzed using a wavenumber formulation and is separated into one component due to one-dimensional fluid coupling and one comprising all the other contributions. Using the theory of acoustic waves in a duct, however, these two components of the pressure can also be associated with a far field, due to the plane wave, and a near field, due to the evanescent, higher order, modes. The near field components are then seen as one of a number of sources of additional longitudinal coupling in the cochlea. The effects of non-uniformity and asymmetry in the fluid chamber areas can also be taken into account, to predict both the pressure difference between the chambers and the mean pressure. This allows the calculation, for example, of the effect of a short cochlear implant on the coupled response of the cochlea.

The cochlear amplifier that provides our hearing with its extraordinary sensitivity and selectivity is thought to be the result of an active biomechanical process within the sensory auditory organ, the organ of Corti. Although imaging techniques are developing rapidly, it is not currently possible, in a fully active cochlea, to obtain detailed measurements of the motion of individual elements within a cross section of the organ of Corti. This motion is predicted using a two-dimensional finite-element model. The various solid components are modelled using elastic elements, the outer hair cells (OHCs) as piezoelectric elements and the perilymph and endolymph as viscous and nearly incompressible fluid elements. The model is validated by comparison with existing measurements of the motions within the passive organ of Corti, calculated when it is driven either acoustically, by the fluid pressure or electrically, by excitation of the OHCs. The transverse basilar membrane (BM) motion and the shearing motion between the tectorial membrane and the reticular lamina are calculated for these two excitation modes. The fully active response of the BM to acoustic excitation is predicted using a linear superposition of the calculated responses and an assumed frequency response for the OHC feedback.

Preservation of residual hearing after cochlear implantation is now considered an important goal of surgery. However, studies indicate an average post-operative hearing loss of around 20 dB at low frequencies. One factor which may contribute to post-operative hearing loss, but which has received little attention in the literature to date, is the increased stiffness of the round window, due to the physical presence of the cochlear implant, and to its subsequent thickening or to bone growth around it. A finite element model was used to estimate that there is approximately a 100-fold increase in the round window stiffness due to a cochlear implant passing through it. A lumped element model was then developed to study the effects of this change in stiffness on the acoustic response of the cochlea. As the round window stiffness increases, the effects of the cochlear and vestibular aqueducts become more important. An increase of round window stiffness by a factor of 10 is predicted to have little effect on residual hearing, but increasing this stiffness by a factor of 100 reduces the acoustic sensitivity of the cochlea by about 20 dB, below 1 kHz, in reasonable agreement with the observed loss in residual hearing after implantation. It is also shown that the effect of this stiffening could be reduced by incorporating a small gas bubble within the cochlear implant.

The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through “respiratory droplets”. Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 is used as a “spike”, so as to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses.

Current models of the cochlea can be characterized as being either based on the assumed propagation of a single slow wave, which provides good insight, or involve the solution of a numerical model, such as in the finite element method, which allows the incorporation of more detailed anatomical features. In this paper it is shown how the wave finite element method can be used to decompose the results of a finite element calculation in terms of wave components, which allows the insight of the wave approach to be brought to bear on more complicated numerical models. In order to illustrate the method, a simple box model is considered, of a passive, locally reacting, basilar membrane interacting via three-dimensional fluid coupling. An analytic formulation of the dispersion equation is used initially to illustrate the types of wave one would expect in such a model. The wave finite element is then used to calculate the wavenumbers of all the waves in the finite element model. It is shown that only a single wave type dominates the response until this peaks at the best place in the cochlea, where an evanescent, higher order fluid wave can make a significant contribution.

The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane (BM). Sounds enter the fluid-filled cochlea and cause deflection of the BM due to pressure differences between the cochlear fluid chambers. These deflections travel along the cochlea, increasing in amplitude, until a frequency-dependent characteristic position and then decay away rapidly. The hair cells can detect these deflections and encode them as neural signals. Modelling the mechanics of the cochlea is of help in interpreting experimental observations and also can provide predictions of the results of experiments that cannot currently be performed due to technical limitations. This paper focuses on reviewing the numerical modelling of the mechanical and electrical processes in the cochlea, which include fluid coupling, micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling.

We report a case series of ozonated autohemotherapy of four COVID-19 patients, classified as critically ill (1 patient), severe (1 patient), and moderate (2 patients). Each ozonated autohemotherapy treatment was performed at a concentration of 40 μg/ml of ozone per 100 ml of blood. The number of treatments varied from 1 to 9 depending on the disease severity. All 4 patients, including 1 critically ill patient with severe acute respiratory distress syndrome (ARDS) and life-threatening refractory hypoxemia, recovered uneventfully and were discharged from the hospital after viral clearance. The younger sibling of the critically ill patient was also diagnosed with COVID-19 and developed ARDS with hypoxemia, who received mechanical ventilation through an endotracheal tube and extracorporeal membrane oxygenation (ECMO) support. The overall medical cost for 18 days spent in the intensive care unit (ICU) and 56 days of hospitalization was $139,935 USD. On the other hand, our critically ill patient underwent 9 ozonated autohemotherapy treatments and spent 10 days in the ICU and was discharged on hospital day 30; his hospitalization cost amounted to $15,466.50 USD. This case series suggests that ozonated autohemotherapy may be an alternative noninvasive medical treatment for COVID-19 patients.