The effects of moderate-intensity aerobic exercise on cognitive function in individuals with stroke-induced mild cognitive impairment: a randomized controlled pilot study.

OBJECTIVE: To assess the impact of moderate-intensity aerobic exercise on working memory in stroke-induced mild cognitive impairment (MCI). DESIGN: Randomized, double-blind controlled study. SUBJECTS AND METHODS: Twenty MCI patients from the Fifth Affiliated Hospital of Guangzhou Medical University (December 2021 to February 2023), aged 34-79, 2-12 months post-stroke, were divided into an experimental group (EG) and a control group (CG), each with 10 participants. The EG underwent standard rehabilitation plus 40 minutes of aerobic exercise, while the CG received only standard therapy, 5 times weekly for 2 weeks. Working memory was tested using the n-back task, and overall cognitive function was measured with the MOCA and MMSE Scales before and after the intervention. RESULTS: The EG showed higher 3-back correctness (71.80 ± 14.53 vs 56.50 ± 13.66), MOCA scores (27.30 ± 1.57 vs 24.00 ± 3.13), and improved visuospatial/executive (4.60 ± 0.52 vs 3.30 ± 1.06) and delayed recall (4.30 ± 0.82 vs 3.00 ± 1.56) on the MOCA scale compared with the CG. CONCLUSION: Moderate-intensity aerobic exercise may enhance working memory, visuospatial/executive, and delayed recall functions in stroke-induced MCI patients.

The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I-Mediated Immune Response.

N6-Methyladenosine (m6A) is the most prevalent internal modification of mammalian mRNAs. Recent studies have shown that m6A methyltransferases METTL3 and METTL14 play important roles in urothelial bladder carcinoma (BLCA). To provide a more comprehensive understanding of the m6A regulatory landscape in bladder cancer, we investigated the role of YTHDF2, a crucial m6A reader, in BLCA. YTHDF2 was frequently upregulated at both the RNA and protein level in BLCA. Functionally, YTHDF2 promoted the proliferation and tumor growth of BLCA cells in vitro and in vivo, respectively. Integrative RNA sequencing and m6A sequencing analyses identified RIG-I as a downstream target of YTHDF2. Mechanistically, YTHDF2 bound to the coding sequence of DDX58 mRNA, which encodes RIG-I, and mediated its degradation in an m6A-dependent manner. Knockdown of RIG-I inhibited apoptosis and promoted the proliferation of BLCA cells. Depleting RIG-I was also able to reverse the effects of YTHDF2 deficiency. YTHDF2-deficient BLCA cells implanted orthotopically in recipient mice activated an innate immune response and promoted recruitment of CD8+ T lymphocytes into the tumor bed and the urothelium. Moreover, YTHDF2 deficiency enhanced the efficacy of Bacillus Calmette-Guérin immunotherapy treatment. This study reveals that YTHDF2 acts as an oncogene in BLCA. YTHDF2 inhibits RIG-I to facilitate immune evasion, supporting testing YTHDF2 inhibition in combination with immunotherapy. SIGNIFICANCE: YTHDF2 regulates RIG-I-mediated innate immune signaling to support bladder cancer progression, highlighting the functional importance of m6A modifications in bladder cancer and uncovering therapeutic opportunities to improve patient outcomes.