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Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number, morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites, restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety- and depression-like behaviors in mice. Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament (F-actin) organization. Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3 (Ser3). Inhibition of ROCK2 activity with belumosudil (KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders. [ABSTRACT FROM AUTHOR]

Aims: To study the relationship of soy foods and nuts consumption during early pregnancy with the risk of gestational diabetes mellitus (GDM). Methods: This was a prospective observational study conducted in Southwest China. Dietary information was assessed through 3-day 24-h dietary recalls at 6–14 gestational weeks. For soy foods and nuts, non-consumers were used as the reference category and the consumers were categorized into tertiles. GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to assess the effects of soy foods and nuts on GDM. Results: Of the 1495 pregnant women, 529 were diagnosed with GDM. Median (IQRs) intakes of soy foods and nuts were 2.9 (0.0, 10.3) and 5.0 (0.0, 15.0) g/d, respectively. Our study found that, compared with the non-consumers, the highest tertile of soy foods intake was associated with a decrease in risk of GDM (RR = 0.73, 95%CI: 0.54–0.99, p = .049). Similarly, compared with the non-consumers, a negative relationship between the highest tertile of nuts intake and GDM risk was identified (RR = 0.65, 95%CI: 0.48–0.89, p = .007). Conclusions: Consumption of soy foods and nuts are independently inversely associated with the risk of GDM during early pregnancy. [ABSTRACT FROM AUTHOR]