Kv channels improve the temporal processing of auditory neurons in the cochlear nucleus.

Kv channels generate A-type current known to regulate neuronal excitability. Its role in processing timing information is understudied, especially in the auditory system where temporal information is crucial for hearing. In the cochlear nucleus, principal bushy neurons are specialized for temporal processing with distinct biophysical properties owing to their expression of various voltage-gated ion channels.

Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study.

Introduction: The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited.

Methods: We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled.

Global lysine succinylation analysis unveils post-translational regulation effect on phenylpropanoid metabolism remodeling during Lonicera japonica flower development.

Lonicera japonica plays a significant role in traditional Chinese medicine and as a food source, making it a focus of studies on protein succinylation and its potential role in regulating secondary metabolism during flower development. This study aimed to clarify the regulatory mechanism of protein succinylation on phenylpropanoid-related phenotypic changes by conducting a global lysine succinylation proteomic analysis across different flowering stages. A total of 586 lysine succinylated peptides in 303 proteins were identified during early and late floral stages.

Fish Physiologically Based Toxicokinetic Modeling Approach for In Vitro-In Vivo and Cross-Species Extrapolation of Endocrine-Disrupting Chemicals in Risk Assessment.

High-throughput in vitro assays combined with in vitro-in vivo extrapolation (IVIVE) leverage in vitro responses to predict the corresponding in vivo exposures and thresholds of concern. The integrated approach is also expected to offer the potential for efficient tools to provide estimates of chemical toxicity to various wildlife species instead of animal testing. However, developing fish physiologically based toxicokinetic (PBTK) models for IVIVE in ecological applications is challenging, especially for plausible estimation of an internal effective dose, such as fish equivalent concentration (FEC).

Potential uses of auditory nerve stimulation to modulate immune responses in the inner ear and auditory brainstem.

Bioelectronic medicine uses electrical stimulation of the nervous system to improve health outcomes throughout the body primarily by regulating immune responses. This concept, however, has yet to be applied systematically to the auditory system. There is growing interest in how cochlear damage and associated neuroinflammation may contribute to hearing loss.

Mechanisms of age-related hearing loss at the auditory nerve central synapses and postsynaptic neurons in the cochlear nucleus.

Sound information is transduced from mechanical vibration to electrical signals in the cochlea, conveyed to and further processed in the brain to form auditory perception. During the process, spiral ganglion neurons (SGNs) are the key cells that connect the peripheral and central auditory systems by receiving information from hair cells in the cochlea and transmitting it to neurons of the cochlear nucleus (CN). Decades of research in the cochlea greatly improved our understanding of SGN function under normal and pathological conditions, especially about the roles of different subtypes of SGNs and their peripheral synapses.

Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging.

Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and whether the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2-5 months (young), 17-19 months (middle-age), and 28-32 months (old).

Repression of ferroptotic cell death by mitochondrial calcium signaling.

The uptake of Ca into and extrusion of calcium from the mitochondrial matrix, regulated by the mitochondrial Ca uniporter (MCU), is a fundamental biological process that has crucial impacts on cellular metabolism, signaling, growth and survival. Herein, we report that the embryonic lethality of -deficient mice is fully rescued by orally supplementing ferroptosis inhibitor lipophilic antioxidant vitamin E and ubiquinol. Mechanistically, we found MCU promotes acetyl-CoA-mediated GPX4 acetylation at K90 residue, and K90R mutation impaired the GPX4 enzymatic activity, a step that is crucial for ferroptosis.

In vitro to in vivo extrapolation for predicting human equivalent dose of phenolic endocrine disrupting chemicals: PBTK model development, biological pathways, outcomes and performance.

In vitro to in vivo (IVIVE) leverages in vitro high-throughput biological responses to predict the corresponding in vivo exposures and further estimate the human safe dose. However, for phenolic endocrine disrupting chemicals (EDCs) linked with complicated biological pathways and adverse outcomes (AO), such as bisphenol A (BPA) and 4-nonylphenol (4-NP), plausible estimation of human equivalent doses (HED) by IVIVE approaches considering various biological pathways and endpoints is still challenging. To explore the capabilities and limitations of IVIVE, this study conducted physiologically based toxicokinetic (PBTK)-IVIVE approaches to derive pathway-specific HEDs using BPA and 4-NP as examples.

Dendritic Degeneration and Altered Synaptic Innervation of a Central Auditory Neuron During Age-related Hearing Loss.

Cellular morphology and synaptic configuration are key determinants of neuronal function and are often modified under pathological conditions. In the first nucleus of the central auditory system, the cochlear nucleus (CN), principal bushy neurons specialize in processing temporal information of sound critical for hearing. These neurons alter their physiological properties during aging that contribute to age-related hearing loss (ARHL).

First metabolic profiling of 4-n-nonylphenol in human liver microsomes by integrated approaches to testing and assessment: Metabolites, pathways, and biological effects.

4-n-nonylphenol (4-n-NP), a typical endocrine disrupting chemical, has been so far frequently detected in various environmental mediums and editable food. However, the specific metabolic pathways in human and potential adverse effects of metabolites have not been elucidated yet. Here, metabolic profiling of 4-n-NP in human liver microsome (HLM) was comprehensively characterized by integrated approaches of testing and assessment.

Oxidative Damage in Roots of Rice (Oryza sativa L.) Seedlings Exposed to Microplastics or Combined with Cadmium.

This study aimed to investigate the effect of 10-40 mg L polystyrene microplastics (PS-MPs), 0.05 mg L cadmium (Cd) and their combination on the growth and related physiological and toxicological responses in Oryza sativa L. seedling roots.

An integrated screening strategy for novel AhR agonist candidate identification and toxicity confirmation in sediments.

Organic contaminants showing aryl hydrocarbon receptor (AhR) agonist activity are commonly detected in areas disturbed by intense human activities and they can initiate a variety of biochemical, physiological, and toxicological effects. A new integrated screening strategy for AhR agonist candidate identification and toxicity confirmation was developed to characterize the AhR-active pollutants in sediments of the contaminated Daqing River basin (DRB) in North China. The specific objectives were to (i) determine the concentrations of known AhR agonists, (ii) identify the novel AhR agonist candidates from nontarget screening (NTS) with structure alerts, computational toxicology (CompTox) Dashboard bioassays, and in silico predictions, and (iii) evaluate contributions of AhR agonists to the overall potencies and characterize the distribution and source of these pollutants.

Age-Related Hearing Loss Is Accompanied by Chronic Inflammation in the Cochlea and the Cochlear Nucleus.

Age-related hearing loss (ARHL) is a major hearing impairment characterized by pathological changes in both the peripheral and central auditory systems. Low-grade inflammation was observed in the cochlea of deceased human subjects with ARHL and animal models of early onset ARHL, which suggests that inflammation contributes to the development of ARHL. However, it remains elusive how chronic inflammation progresses during normal aging in the cochlea, and especially the accompanying changes of neuroinflammation in the central auditory system.

Calretinin-Expressing Synapses Show Improved Synaptic Efficacy with Reduced Asynchronous Release during High-Rate Activity.

Calretinin (CR) is a major calcium binding protein widely expressed in the CNS. However, its synaptic function remains largely elusive. At the auditory synapse of the endbulb of Held, CR is selectively expressed in different subtypes.

Neural Adaptation of the Electrically Stimulated Auditory Nerve Is Not Affected by Advanced Age in Postlingually Deafened, Middle-aged, and Elderly Adult Cochlear Implant Users.

Objective: This study aimed to investigate the associations between advanced age and the amount and the speed of neural adaptation of the electrically stimulated auditory nerve (AN) in postlingually deafened adult cochlear implant (CI) users.

Design: Study participants included 26 postlingually deafened adult CI users, ranging in age between 28.7 and 84.

Integrated passive sampling and fugacity model to characterize fate and removal of organophosphate flame retardants in an anaerobic-anoxic-oxic municipal wastewater treatment system.

It is crucial to deeply understand the fate and removal mechanism of various organophosphate flame retardants (PFRs) in specified wastewater treatment processes. However, concentration fluctuation and matrix effect in wastewater challenge quantification of PFR flux for both field observation and model validation. We present measured seasonal distribution profiles of time-weighted average (TWA) concentrations by in situ hydrophobic and polar passive samplers and modeled mass transport and transformation by means of fugacity for 11 PFRs with varied structures in an anaerobic-anoxic-oxic (A-A-O) municipal wastewater treatment system, and provided a systematic approach to characterize fate and removal mechanism of PFRs in major compartments via various treatment processes.

eDNA metabarcoding revealed differential structures of aquatic communities in a dynamic freshwater ecosystem shaped by habitat heterogeneity.

Freshwater ecosystems have been threatened by complicated disturbances from both natural and anthropogenic variables, especially in dynamic and complex river basins. The environmental DNA (eDNA)-based approach provides a broader spectrum and higher throughput way of biomonitoring for biodiversity assessment compared with traditional morphological survey. Most eDNA metabarcoding studies have been limited to a few specific taxa/groups and habitat scopes.

Biased auditory nerve central synaptopathy is associated with age-related hearing loss.

Key Points: Sound information is transmitted by different subtypes of spiral ganglion neurons (SGN) from the ear to the brain. Selective damage of SGN peripheral synapses (cochlear synaptopathy) is widely recognized as one of the primary mechanisms of hearing loss, whereas the mechanisms at the SGN central synapses remain unclear. We report that different subtypes of SGN central synapses converge at different ratios onto individual target cochlear nucleus neurons with distinct physiological properties, and show biased morphological and physiological changes during age-related hearing loss (ARHL).

The Differential Metabolic Profiles Between Deltamethrin-Resistant and -Susceptible Strains of Aedes albopictus (Diptera: Culicidae) by 1H-NMR.

Metabolomics can indicate the physiological and biochemical responses of mosquitoes to different stimulants, including insecticides, which allow them to adapt to different inhospitable environments. Though metabolic differences between insecticide-resistant and -susceptible strains have been established for other mosquito species, such as Anopheles and Culex, it is yet to be done for Aedes albopictus (Skuse). In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis performed on Ae.

A neuronal wiring platform through microridges for rationally engineered neural circuits.

Precisely engineered neuronal circuits are promising for both fundamental research and clinical applications. However, randomly plating thousands of cells during neural network fabrication remains a major technical obstacle, which often results in a loss of tracking in neurons' identities. In this work, we demonstrated an accurate and unique neural wiring technique, mimicking neurons' natural affinity to microfibers.

D-Stellate Neurons of the Ventral Cochlear Nucleus Decrease in Auditory Nerve-Evoked Activity during Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is associated with weakened inhibition in the central auditory nervous system including the cochlear nucleus. One of the main inhibitory neurons of the cochlear nucleus is the D-stellate neuron, which provides extensive glycinergic inhibition within the local neural network. It remains unclear how physiological activities of D-stellate neurons change during ARHL and what are the underlying mechanisms.

Classification of neurons in the adult mouse cochlear nucleus: Linear discriminant analysis.

The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their morphology, neurotransmitter receptors, ion channel expression and intrinsic excitability.

Principal Neurons in the Anteroventral Cochlear Nucleus Express Cell-Type Specific Glycine Receptor α Subunits.

Signal processing in the principal neurons of the anteroventral cochlear nucleus (AVCN) is modulated by glycinergic inhibition. The kinetics of IPSCs are specific to the target neurons. It remains unclear what glycine receptor subunits are involved in generating such target-specific IPSC kinetics in AVCN principal neurons.

Radiate and Planar Multipolar Neurons of the Mouse Anteroventral Cochlear Nucleus: Intrinsic Excitability and Characterization of their Auditory Nerve Input.

Radiate and planar neurons are the two major types of multipolar neurons in the ventral cochlear nucleus (VCN). Both cell types receive monosynaptic excitatory synaptic inputs from the auditory nerve, but have different responses to sound and project to different target regions and cells. Although the intrinsic physiology and synaptic inputs to planar neurons have been previously characterized, the radiate neurons are less common and have not been as well studied.