Single-Nucleus Transcriptomics Uncovers Xaf1-Driven PANoptosis as a Therapeutic Target in Aminoglycoside-Induced Hearing Loss.

Aminoglycoside antibiotics are essential in managing many life-threatening diseases. However, their derivatives, such as neomycin, are associated with severe side effects such as persistent sensorineural hearing loss. Therefore, it is essential to elucidate the molecular and biochemical mechanisms of aminoglycoside-induced ototoxicity and identify targets for alleviating ototoxic injury.

Sensitivity-Enhanced Pure Shift Spectroscopy Empowered by Deep Learning and PSYCHE.

Proton nuclear magnetic resonance (NMR) is the most used NMR technique. However, the limited range of chemical shifts and the complicated multiplet splitting often lead to severe spectral overlapping, making spectral analysis complex. Pure shift methods convert multiplets into singlets to greatly improve the spectral resolution but lead to severe sensitivity loss, aggravating the issue of low sensitivity of NMR compared to that of other spectroscopic techniques.

Small Extracellular Vesicles Orchestrate Cisplatin-Induced Ototoxicity: Potential Biomarker and Targets Discovery.

Cisplatin-induced ototoxicity remains a clinical dilemma with limited mechanistic understanding and no food and drug administration (FDA)-approved therapies. Despite emerging roles of small extracellular vesicles (sEV) in drug ototoxicity, their molecular cargo profiles and causal roles to cisplatin-induced ototoxicity are unexplored. This study systematically investigates sEV derived from cochlear explants treated with cisplatin (Cis-sEV) and controls (Ctrl-sEV) using multi-omics profiling.

Deep learning and its applications in nuclear magnetic resonance spectroscopy.

Nuclear Magnetic Resonance (NMR), as an advanced technology, has widespread applications in various fields like chemistry, biology, and medicine. However, issues such as long acquisition times for multidimensional spectra and low sensitivity limit the broader application of NMR. Traditional algorithms aim to address these issues but have limitations in speed and accuracy.

NMR Pure Shift Spectroscopy and Its Potential Applications in the Pharmaceutical Industry.

H nuclear magnetic resonance (NMR) spectroscopy plays an important role in the pharmaceutical industry, but for complex substances, spectral analysis is challenging due to the narrow chemical shift range and signal splitting caused by scalar coupling. Pure shift techniques can suppress scalar coupling, improving spectral resolution. This article provides a review of pure shift techniques, including the main homonuclear broadband decoupling experiments and the methods for obtaining optimal pure shift spectra with the assistance of deep learning.

Targeting Programmed Cell Death in Acquired Sensorineural Hearing Loss: Ferroptosis, Necroptosis, and Pyroptosis.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis.

In Situ Monitoring of Kefir Fermentation Process Using Signal-Separable NMR Techniques.

The fermentation time of fermented milk significantly influences its taste and nutritional value. Monitoring the fermentation process is crucial for ensuring the quality, flavor, and safety of fermented products. In this paper, the kefir fermentation process, as an example, was monitored in situ using advanced nuclear magnetic resonance (NMR) techniques.

Conditional Overexpression of Serpine2 Promotes Hair Cell Regeneration from Lgr5+ Progenitors in the Neonatal Mouse Cochlea.

Neonatal cochlear Lgr5+ progenitors retain limited hair cells (HCs) regenerative capacity, but the regulatory network remains incompletely defined. Serpin family E member 2 (Serpine2) is shown to participate in regulating proliferation and differentiation of cochlear Lgr5+ progenitors in the previous in vitro study. Here, the expression pattern and in vivo roles of Serpine2 in HC regeneration are explored by transgenic mice.

Deep learning network for NMR spectra reconstruction in time-frequency domain and quality assessment.

High-quality nuclear magnetic resonance (NMR) spectra can be rapidly acquired by combining non-uniform sampling techniques (NUS) with reconstruction algorithms. However, current deep learning (DL) based reconstruction methods focus only on single-domain reconstruction (time or frequency domain), leading to drawbacks like peak loss and artifact peaks and ultimately failing to achieve optimal performance. Moreover, the lack of fully sampled spectra makes it difficult, even impossible, to determine the quality of reconstructed spectra, presenting challenges in the practical applications of NUS.

Effectiveness and influencing factors of standardised training for nursing assistants: a cross-sectional study.

Objectives: To investigate the impact of standardised training on nursing assistants (NAs) and explore the factors influencing training effectiveness, specifically focusing on learning motivation and learning obstacles.

Design: A cross-sectional study was conducted from August 2022 to September 2022.

Setting: The study was conducted in Fujian Province, China.

Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.

Utricle is an important vestibular sensory organ for maintaining balance. 3,3'-iminodipropionitrile (IDPN), a prototype nitrile toxin, has been reported to be neurotoxic and vestibulotoxic, and can be used to establish an damage model of vestibular dysfunction. However, the mechanism of utricular HCs damage caused by IDPN is unclear.

Conditional Overexpression of Net1 Enhances the Trans-Differentiation of Lgr5 Progenitors into Hair Cells in the Neonatal Mouse Cochlea.

Sensorineural hearing loss is mainly caused by damage to hair cells (HC), which cannot be regenerated spontaneously in adult mammals once damaged. Cochlear Lgr5 progenitors are characterised by HC regeneration capacity in neonatal mice, and we previously screened several new genes that might induce HC regeneration from Lgr5 progenitors. Net1, a guanine nucleotide exchange factor, is one of the screened new genes and is particularly active in cancer cells and is involved in cell proliferation and differentiation.

Selective-excitation-based method for measurement of NMR relaxation time.

Background: Relaxation time provides invaluable insights into the molecular structure, interactions, and dynamics in nuclear magnetic resonance spectroscopy. However, conventional relaxation-time measurement techniques produce inaccurate relaxation times when the spectral peaks overlap because of the narrow chemical-shift range and J-coupled splitting. While the combination of pure-shift methods can solve this issue, they are not widely used due to their inherent drawbacks such as low sensitivity and long acquisition time.

Deep learning enabled ultra-high quality NMR chemical shift resolved spectra.

High quality chemical shift resolved spectra have long been pursued in nuclear magnetic resonance (NMR). In order to obtain chemical shift information with high resolution and sensitivity, a neural network named spin echo to obtain chemical shifts network (SE2CSNet) is developed to process the NMR data acquired by the spin echo pulse sequence. Through detecting the change of phase in the spin echo spectra, SE2CSNet can accurately detect the chemical shift position of spectral signals.

Isolation and Comprehensive Analysis of Cochlear Tissue-Derived Small Extracellular Vesicles.

Small extracellular vesicles (sEVs) act as a critical mediator in intercellular communication. Compared to sEVs derived from in vitro sources, tissue-derived sEVs can reflect the in vivo signals released from specific tissues more accurately. Currently, studies on the role of sEVs in the cochlea have relied on studying sEVs from in vitro sources.

Metabolic disorder and functional disturbance in the central executive network in minimal hepatic encephalopathy.

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach.

Arsenic trioxide-induced apoptosis contributes to suppression of viral reservoir in SIV-infected rhesus macaques.

Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (AsO) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of AsO independent of ART in chronically SIV-infected macaques.

Deep Learning Methodology for Obtaining Ultraclean Pure Shift Proton Nuclear Magnetic Resonance Spectra.

Nuclear magnetic resonance (NMR) is one of the most powerful analytical techniques. In order to obtain high-quality NMR spectra, a real-time Zangger-Sterk (ZS) pulse sequence is employed to collect low-quality pure shift NMR data with high efficiency. Then, a neural network named AC-ResNet and a loss function named SM-CDMANE are developed to train a network model.

Influenza Virus Infection Increases Host Susceptibility To Secondary Infection with Pseudomonas aeruginosa, and This Is Attributed To Neutrophil Dysfunction through Reduced Myeloperoxidase Activity.

Secondary bacterial infection greatly increased the morbidity and mortality of influenza virus infection. To investigate the underlying mechanism by which influenza impairs the pulmonary defense against secondary Pseudomonas aeruginosa (P. aeruginosa) infection, we established a lethal mouse model in which to study secondary P.

Simultaneous acquirement of pure shift 2D homonuclear correlation spectra.

Two dimensional homonuclear correlation spectra like COSY, TOCSY and NOESY are classic two-dimensional spectra for analyzing coupling networks and delivering structural information of molecules. Two main challenges of the homonuclear correlation spectra are resolution and efficiency. Because of the complexity of the molecular structure and the effect of scalar coupling, spectral resolution is still difficult to meet the demand, and a higher resolution is needed to improve the quality of the homonuclear correlation spectrum.

Fast Acquisition of High-Quality Nuclear Magnetic Resonance Pure Shift Spectroscopy via a Deep Neural Network.

Pure shift methods improve the resolution of proton nuclear magnetic resonance spectra at the cost of time. The pure shift yielded by chirp excitation (PSYCHE) method is a promising pure shift method. We propose a method of reconstructing the undersampled PSYCHE spectra based on deep learning to accelerate the spectra acquisition.

Evaluation of brown adipose tissue with intermolecular double-quantum coherence magnetic resonance spectroscopy at 3.0 T.

In the current study, we propose a single-voxel (SV) magnetic resonance spectroscopy (MRS) pulse sequence, based on intermolecular double-quantum coherence (iDQC), for in vivo specific assessment of brown adipose tissue (BAT) at 3 T. The multilocular adipocyte, present in BAT, typically contains a large number of small lipid droplets surrounded by abundant intracellular water, while the monolocular adipocyte, present in white adipose tissue (WAT), accommodates only a single large lipid droplet with much less water content. The SV-iDQC sequence probes the spatial correlation between water and fat spins at a distance of about the size of an adipocyte, thus can be used for assessment of BAT, even when mixed with WAT and/or muscle tissues.

Unambiguous and accurate measurement of scalar coupling constants through a selective refocusing NMR experiment.

Scalar coupling plays an important role in the analysis of molecular structure and dynamics. A great number of nuclear magnetic resonance (NMR) selective refocusing experiments, such as 2D G-SERF and PSYCHEDELIC, were developed to extract scalar coupling constants involving a selected proton from overlapped spectra. However, intense axial peaks occur in this type of experiments, leading to possible ambiguity in the assignment of spectral peaks and subsequent accurate measurement of H-H scalar coupling constants.

A simple data post-processing method for axial peaks free 2D PSYCHEDELIC NMR spectra.

Homonuclear scalar coupling plays an important role in the elucidation of molecular structure and dynamics. However, complex multiplets due to H-H scalar coupling splittings complicate the assignment of peaks in overcrowded spectral regions. Although many methods focusing on disentangling couplings have been proposed in recent years, some defects like intense axial peaks and dispersive components still exist.

Improvement in Signal-to-Noise Ratio of Liquid-State NMR Spectroscopy via a Deep Neural Network DN-Unet.

Nuclear magnetic resonance (NMR) is one of the most powerful analytical tools and is extensively applied in many fields. However, compared to other spectroscopic techniques, NMR has lower sensitivity, impeding its wider applications. Using data postprocessing techniques to increase the NMR spectral signal-to-noise ratio (SNR) is a relatively simple and cost-effective method.