Nanoengineered mitochondria enable ocular mitochondrial disease therapy the replacement of dysfunctional mitochondria.

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

National validation of laparoscopic approach for locally advanced gastric cancer: Comparison of a randomized controlled trial and real-world practice results.

Objective: The laparoscopic approach for locally advanced gastric cancer has recently been adopted based on the results of several randomized controlled trials (RCTs). However, findings from RCTs have not been examined at the national level. This study aimed to investigate the external validity of the Korean Laparoscopic Gastrointestinal Surgery Study-02 (KLASS-02) trial involving 13 tertiary hospitals, using data from the Korean Gastric Cancer Association (KGCA)-led nationwide survey involving 68 tertiary or general hospitals.

CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis.

Background: House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although allergic sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, the molecular mechanisms driving this process remain incompletely elucidated.

Objective: This study aimed to elucidate the molecular mechanisms underlying HDM-induced AR.