Background: Overweight and obese females demonstrate a significantly increased risk of anovulatory infertility. This study aims to investigate whether depression score could mediate the association between a body shape index (ABSI) and infertility, especially in overweight and obese population. Methods: We included 5431 adult female Americans from the National Health and Nutrition Examination Survey (NHANES, 2013–2018) database. ABSI manifested the body shape using waist circumference, weight, and height. Infertility or fertility status was defined by interviewing female participants aged ≥ 18 through the reproductive health questionnaires. Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) with total scores between 0 and 27. To investigate the association of infertility with ABSI and other individual components, survey-weighted multivariable logistic regression was performed. Mediation analysis of PHQ-9 score was conducted to disentangle the pathways that link ABSI to infertility among the NHANES participants. Results: 596 (10.97%) females were categorized with having infertility among 5431 participants. Participants with infertility showed higher ABSI and PHQ-9 score, appearing greater population proportion with depression symptoms. In the multivariable logistic regression model, ABSI (adjusted odds ratio = 0.14, 95% CI: 0.04 to 0.50) and PHQ-9 (adjusted odds ratio = 1.04, 95% CI: 1.01 to 1.07) were positively associated with infertility. PHQ-9 score was estimated to mediate 0.2% (P = 0.03) of the link between ABSI and infertility in all individuals, but to mediate 13.5% (P < 0.01) of the ABSI-infertility association in overweight and obese adult females. Conclusion: The association between ABSI and infertility seems to be mediated by depression symptoms scored by PHQ-9, especially in those adult females with overweigh and obesity. Future studies should be implemented to further explore this mediator in ABSI-infertility link.

Acute myeloid leukemia (AML) is a group of heterogeneous hematologic malignancies correlates with poor prognosis. It is important to identify biomarkers for effective treatment of AML. Kinases participate in many regulatory pathways and biological activities in AML. Previous studies demonstrated that MAP4K1, a serine/threonine kinase, was associated with immune regulation and cancer progression. However, its role and mechanism in acute myeloid leukemia (AML) have not been explored. RNA-seq profiling was performed for Homoharringtonine (HHT)-resistant and Homoharringtonine (HHT)-sensitive cell lines. Bioinformatic tools were used for differential analysis. Cell culture and transfection, Cell proliferation, apoptosis and Cell cycle assay, Quantitative RT-PCR, and Western blotting analysis were used to explore biological phenotypes in vitro. We found that MAP4K1 was highly expressed in HHT-induced resistant AML cell lines. In addition, overexpression of MAP4K1 in AML cells induced resistance of AML cells against HHT. Not only that, the findings of this study showed that overexpression of MAP4K1 was an independent risk factor that predicts poor prognosis of AML. Further, In vitro studies showed that MAP4K1 modulated cell cycle through MAPK and DNA damage/repair pathways. Therefore, MAP4K1 is a potential target for developing therapies for AML. This study demonstrates that MAP4K1 not only regulates HHT resistance but also independently predicts AML prognosis. In addition, understanding the regulatory mechanism of MAP4K1 reveals novel treatment strategies for resistant and refractory AML. Fundings: This work was supported by the National Natural Science Foundation of China (NSFC) (Grant No.81800199, 81670124, 82070118) and the Natural Science Foundation of Zhejiang Province (LY20H080008).

Key Points: C-terminal domain determines myosin II localization to the MK contractile ring and the specific role of NMII-B in MK polyploidization.

Background: Previous observational studies have associated infertility with fundamental physical parameters, including BMI, waist circumference, and excessive weight. Here, we introduced another convincing body shape parameter called A body shape index (ABSI), which can be calculated using waist circumference, weight, and height. To explore the association between ABSI and infertility in overweight and obese females, and the potential mediating factor in the association, we conducted this cross-sectional study. Methods: 5431 adult female participants from NHANES 2013-2018 were included in this study. The definition of infertility was based on the interviewees' answers to the reproductive health questionnaire, which asked if they had visited a doctor because they had been unable to conceive or had tried to get pregnant for at least a year without success. ABSI was calculated as a continuous variable using an acknowledged equation. PHQ-9 score was assessed when face-to-face interviews for all participants, reflecting their depression symptoms. Results: Among 5431 participants, 596 females (10.97% ) were diagnosed with infertility. Age, BMI, and ABSI were higher in infertile females. In multivariable logistic regression models, infertility status was positively related to increased ABSI (OR: 1.78e+15, 95% CI: 2.78e+5 to 1.15e+25), adjusted model by adjusting age, race/ethnicity, educational background, and family income. PHQ-9 score mediated 0.2% (p <0.05) of the link between ABSI and infertility in all individuals, but 13.5% (p <0.01) in overweight and obese adult females. Conclusion: Depression score might increase ABSI and induce infertility state among adult females with overweight and obesity.