osteoarthritis (oa) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation. a previous study showed that microrna (mir)-671-3p is involved in the development of oa, however, its function and molecular target in chondrocytes during the pathogenesis of oa remain to be fully elucidated. in the present study, miR-671-3p was significantly downregulated in knee oa cartilage tissues compared with normal cartilage tissues. The expression levels of pro-inflammatory cytokines, including interleukin (il)-1β, il-6, il-8 and tumor necrosis factor (TnF)-α, in the knee oa cartilage tissues were significantly higher than those in the normal cartilage tissues. Through gain-of-function and loss-of-function experiments, miR-671-3p was shown to significantly affect matrix synthesis gene expression, cell proliferation, apoptosis and inflammation in chondrocytes from patients with oa. Subsequent bioinformatics analysis identified potential target sites of the miR-671-3p located in the 3'untranslated region of TnF receptor-associated factor (TraF3). The results of a dual-luciferase reporter assay showed that TraF3 is a target gene of mir-671-3p. Western blot analysis demonstrated that mir-671-3p inhibited the gene expression of TraF3. Furthermore, the restoration of TraF3 markedly abrogated the effect of mir-671-3p. Taken together, the present study suggests that mir-671-3p may be important in the pathogenesis of oa through targeting TraF3 and regulating chondrocyte apoptosis and inflammation, which may be a potential molecular target for oa treatment.

The treatment of a variety of recurrent or resistant hematologic malignancies with chimeric antigen receptor T cell (CAR- T) cell therapy has seen significant success in recent years. The current CAR- T cell therapy approach is not without flaws, nevertheless, and there are still several issues with clinical treatment, including antigen escape, significant toxicity, and sus-ceptibility to drug-resistant recurrence. This paper introduces the structural development and characteristics of CAR-T cells, reviews the limitations of CAR- T cell therapy, including an-tigen escape, toxicity, CAR-T cell depletion and drug-resistant relapse after treatment, and summarizes the related improvement and optimization strategies. The paper concludes that CAR-T cell immunotherapy has brought new hope to patients with hematologic malignancies, making a cure for refractory and recurrent hematologic malignancies possible. Although CAR-T cell therapy still has many challenges at present, such as immunogenicity, drug re-sistance, and toxicity.

The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress. We then demonstrate that increased Rap1 in the CA3 is sufficient in and of itself to produce stress-relevant dendritic spine and cognitive phenotypes. Further, using super-resolution imaging, we investigate how the pattern of Rap1 trafficking to synapses likely underlies its effects on the stability of select dendritic spine subtypes. These findings illuminate the involvement of aberrant Rap1 regulation in the hippocampus in contributing to the psychobiological effects of stress.