Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells.

The mammalian cochlea relies on outer and inner hair cells (OHCs/IHCs) for sound amplification and signal transmission. Rab3-interacting molecular binding protein 2 (RIMBP2), expressed in receptor cells and neurons at synaptic active zones, remains poorly characterized in hearing. We therefore generated a Rimbp2 knockout (KO) mouse model (Rimbp2), which exhibited severe hearing loss with elevated thresholds, prolonged latencies, and reduced amplitudes in auditory brainstem response Wave I.

Exploring the Potential and Advancements of Circular RNA Therapeutics.

Messenger RNA (mRNA) technology is revolutionizing the pharmaceutical industry owing to its superior safety profile, manufacturing capabilities, and potential applications in previously undruggable therapeutic targets. In addition to linear mRNA, such as conventional mRNA, self-amplifying mRNA, and trans-amplifying mRNA, circular mRNA has emerged as a promising candidate. Circular RNA (circRNA) is a class of single-stranded RNA with a covalently closed loop structure that offers enhanced stability compared to linear RNA by resisting degradation from RNases.

Viscoelastic and conductive nerve guidance conduits for peripheral nerve repair.

Peripheral nerve injury is challenging to self-repair and often leads to severe functional impairment. Utilizing neural tissue engineering scaffolds to promote nerve regeneration presents a promising strategy. However, current nerve scaffolds generally lack the ability to accurately replicate the viscoelastic properties of native neural tissues.

Single-Cell Dissection of the Serrated Pathway: Cellular Heterogeneity and Genetic Causality in Colorectal Cancer.

The serrated pathway represents a significant route to colorectal cancer (CRC), accounting for approximately 15-30% of cases, yet the specific epithelial cell subpopulations driving this pathway remain poorly understood. This study explores the causal relationship between serrated epithelial cells and CRC risk using single-cell transcriptomics and Mendelian randomization (MR). Publicly available single-cell RNA sequencing data were utilized to analyze epithelial cell subpopulations in CRC, focusing on specific serrated cells (SSCs).

Blood-labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus.

Hearing loss (HL) in patients with systemic lupus erythematosus (SLE) has been widely reported, though the underlying mechanisms remain unclear. In this study, we demonstrate significant HL in an imiquimod-induced mouse model of SLE, accompanied by blood-labyrinth barrier (BLB) damage in the stria vascularis (SV). We found that cytotoxic CD8 T lymphocytes and natural killer cells mediate BLB disruption, with granzyme b (Gzmb) acting as the primary factor inducing cell death of the cochlear capillary endothelial cells.

β-Hydroxybutyrate promotes cancer metastasis through β-hydroxybutyrylation-dependent stabilization of Snail.

β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completely unknown in cancer metastasis. Here, we report that β-hydroxybutyrate (BHB) is clinically associated with the progression of pancreatic cancer and functionally promotes pancreatic cancer cell metastasis.

Establishment of a Cochlear Organoid Platform for Remodeling the Extracellular Matrix.

Irreparable injury and depletion of inner ear hair cells lead to permanent hearing impairment. Cochlear organoids serve as a robust platform for investigating the pathogenesis of deafness and exploring therapeutic approaches. However, the widely used commercial Matrigel in cochlear organoid culture suffers from issues related to consistency and structural stability.

AAV gene therapy for autosomal recessive deafness 9: a single-arm trial.

Gene therapy for congenital deafness has shown promising results in children but lacks data in older populations. We conducted a single-arm trial of adeno-associated virus (AAV)-OTOF gene therapy using the Anc80L65 capsid in ten participants with autosomal recessive deafness 9 aged 1.5 to 23.

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.

Genomic profiling and prognostic factors of leptomeningeal metastasis in EGFR-mutant NSCLC after resistant to third-generation EGFR-tyrosine kinase inhibitors.

Background: Leptomeningeal metastasis (LM) is a devastating complication of advanced non-small cell lung cancer (NSCLC). Currently, there is no valid data and effective treatment for LM after resistance to third-generation EGFR-TKIs. This study aimed to analyze the genomic profiling and prognostic factors of EGFR-mutant NSCLC-LM after resistance to third-generation EGFR-TKIs.

Molecular mechanism of potently neutralizing human monoclonal antibodies against severe fever with thrombocytopenia virus infection.

Unlabelled: Although severe fever with thrombocytopenia syndrome (SFTS) was first described in China in 2009, the case fatality rate remains >40% among patients with multi-organ failure. To date, no antivirals specifically targeting SFTSV have been approved. We obtained several monoclonal antibodies (mAbs) from SFTS survivors by single-cell RNA-seq.

Advances in Biocompatible Metal-Organic Frameworks for Biomedical Applications.

Metal-organic frameworks (MOFs) have many excellent properties, such as adjustable pore size and volume, clear active sites, high specific surface area and other inherent characteristics. It makes them suitable for various applications, including disease treatment, imaging, and sensing. The article reviews several types of biocompatible MOFs and their recent advances in biomedical applications, especially in disease therapy.

FuHsi maintains nucleolar integrity.

The nucleolus is a dynamic, membrane-less organelle that assembles around ribosomal DNA (rDNA) repeats and governs ribosome biogenesis. Its structural organization is tightly linked to its function. In our previous work, we identified FuHsi as a novel rDNA transcriptional regulator.

MMA-induced LOXL2 PSCs promote linear ECM alignment in the aging pancreas leading to pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is an age-associated malignancy closely linked to the extracellular matrix (ECM). However, the impact of age-related ECM changes in the normal pancreas on PDAC progression remains unclear. Here, we find that increased linear ECM alignment in normal pancreatic tissues from aged PDAC patients is associated with PDAC progression and worse outcomes.

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.

mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.

Age-related hearing loss (ARHL) is among the most prevalent and complex disorders in older adults. However, the pathogenesis of ARHL remains poorly understood. Using a single-cell transcriptomic landscape of mouse cochlea at five time points (1, 2, 5, 12 and 15 months), we found that the levels of human antigen R (HuR)-a classical RNA-binding protein-increase with age.

Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction.

Single nucleotide polymorphisms (SNPs) within 1p31.1 region have shown significant associations with depression, and our prior functional genomics pinpointed a regulatory variant rs3101339 among them. However, its precise role in depression pathogenesis remains elusive.

STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis.

Multicargo Porous Cochlear Electrode Coating for Antifibrosis After Cochlear Implantation.

Severe to profound sensorineural hearing loss seriously affects the communication and cognitive ability of the patients. Cochlear implantation (CI) is currently the most effective treatment, while it may damage the remaining inner ear function due to its poor biocompatibility and the resultant fibrosis. Herein, a porous methacrylated poly(dimethylsiloxane) (MA-PDMS)-coated cochlear electrode is presented for CI and hearing protection.

[mA modification regulates PLK1 expression and mitosis].

-methyladenosine (mA) modification plays a critical role in cell cycle regulation, while the mechanism of mA in regulating mitosis remains underexplored. Here, we found that the total mA modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and mA dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence.

Targeting prominin-2/BACH1/GLS pathway to inhibit oxidative stress-induced ferroptosis of bone mesenchymal stem cells.

Suppressing bone mesenchymal stem cell (BMSC) ferroptosis is expected to optimize BMSCs-based therapy for intervertebral disc degeneration (IVDD). Our previous study revealed that Prominin-2 could protect against ferroptosis by decreasing cellular Fe content and inhibiting transcription regulator protein BACH1 (BACH1) expression. In this study we probed the molecular mechanisms underlying the Prominin-2/BACH1 pathway in BMSC ferroptosis.

PLOD1 promotes the malignancy of hepatocellular carcinoma by facilitating the NF-κB/IL-6/STAT3-dependent TCA cycle.

Background & Aims: Procollagen lysyl hydroxylase 1 (PLOD1) is crucial in regulating collagen synthesis and cross-linking. However, its roles and underlying mechanisms in the progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we aimed to investigate the underlying biological functions and mechanisms of PLOD1 in HCC.