Osteoclast cells (OCs) are differentiated from bone marrow-derived macrophages (BMMs) by activation of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Activation of NADPH oxidase (Nox) isozymes is involved in RANKL-dependent OC differentiation, implicating Nox isozymes as therapeutic targets for treatment of osteoporosis. Here, we show that a novel pyrazole derivative, Ewha-18278 has high inhibitory potency on Nox isozymes. Blocking the activity of Nox with Ewha-18278 inhibited the responses of BMMs to RANKL, including reactive oxygen species (ROS) generation, activation of mitogen-activated protein (MAP) kinases and NF-κB, and OC differentiation. To evaluate the anti-osteoporotic function of Ewha-18278, the derivative was applied to estrogen-deficient ovariectomized (OVX) ddY mice. Oral administration of Ewha-18278 (10 mg/kg/daily, 4 weeks) into the mice recovered bone mineral density, trabecular bone volume, trabecular bone length, number and thickness, compared to control OVX ddY mice. Moreover, treatment of OVX ddY mice with Ewha-18278 increased bone strength by increasing cortical bone thickness. We provide that Ewha-18278 displayed Nox inhibition and blocked the RANKL-dependent cell signaling cascade leading to reduced differentiation of OCs. Our results implicate Ewha-18278 as a novel therapeutic agent for the treatment of osteoporosis.

The evaluation of over- or under-weighted infants warrants considering both of maternal age and BMI.

Various maternal-infantile factors were found to affect HM composition. Interestingly, delivery mode, gender of infant, and birth height were associated with changes in HM macronutrient as well as postpartum age.

This article argues that some denialists of Japan's military sexual slavery are responsible for past epistemic injustices. In the literature on epistemic responsibility, backward-and forward-looking justifications of responsibility are rarely distinguished. Moreover, notions of epistemic responsibility are mostly forward-looking. To fill the gap in the literature, this article offers a notion of backward-looking epistemic responsibility by arguing that some morally responsible agents who committed epistemic injustices are liable to make epistemic amends for past epistemic injustices. The article proceeds as follows. I introduce Japan's military sexual slavery and how it is denied in two ways (state-led denial and individual-led denial). Both types of denial may involve epistemic injustices. Based on moral responsibility, I argue that some agents are liable to make epistemic amends for past epistemic injustices. I then offer three conditions to discern who is liable, which are conditions of causality, autonomy and epistemic competence. I apply my notion of backward-looking epistemic responsibility to Japan's military sexual slavery and highlight its limits. Finally, I provide a concept of acknowledgment as a process of making epistemic amends.

HMO patterns were found not to be affected by pasteurization and freeze-drying of donor milks. We hope that introducing freeze-drying to the human milk banks would be encouraged by the present study. However, the storage length without composition changes of HMOs after freeze-drying needs to be evaluated in the further studies.