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Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi- scid /IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL. [ABSTRACT FROM AUTHOR]

Storkhead box 1 (STOX1) is a winged helix transcription factor structurally and functionally related to the forkhead family of transcription factors. Recent studies have highlighted its role in the central nervous system and revealed hints in the development of glioma. However, the expression profiles of STOX1, its association with clinicopathological characteristics, and potential functions in glioma remain unknown. In this study, we analyzed three publicly available datasets including CGGA, TCGA, and Rembrandt and revealed a grade-dependent reduction in STOX1 expression in glioma (P < 0.001). Chi-square test demonstrated that low STOX1 expression was significantly associated with older age at initial diagnosis (P < 0.001), less IDH1 mutation (P < 0.001), and advanced WHO grade (P < 0.001). Moreover, multivariate Cox regression analysis showed that STOX1 expression may serve as a novel independent prognostic biomarker in glioma patients. Bioinformatic functional analysis (GSEA) predicted that STOX1 was related to many key cancer pathways including P53 signaling pathway (P < 0.01), DNA replication (P < 0.05), homologous recombination (P < 0.05), and Wnt signaling pathway (P < 0.05). Taken together, these findings suggested that STOX1 may be used as a novel predictive molecular biomarker for glioma grading and overall patient survival. Further investigations on the functional roles and therapeutic value of STOX1 in glioma are warranted.

Coordinated uterine-embryonic axis formation and decidual remodeling are hallmarks of mammalian post-implantation embryo development. Embryonic-uterine orientation is determined at initial implantation and synchronized with decidual development. However, the molecular mechanisms controlling these events remain elusive despite its discovery a long time ago. In the present study, we found that uterine-specific deletion of Rbpj, the nuclear transducer of Notch signaling, resulted in abnormal embryonic-uterine orientation and decidual patterning at post-implantation stages, leading to substantial embryo loss. We further revealed that prior to embryo attachment, Rbpj confers on-time uterine lumen shape transformation via physically interacting with uterine estrogen receptor (ERα) in a Notch pathway-independent manner, which is essential for the initial establishment of embryo orientation in alignment with uterine axis. While at post-implantation stages, Rbpj directly regulates the expression of uterine matrix metalloproteinase in a Notch pathway-dependent manner, which is required for normal post-implantation decidual remodeling. These results demonstrate that uterine Rbpj is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner. Our data also substantiate the concept that normal mammalian embryonic-uterine orientation requires proper guidance from developmentally controlled uterine signaling.

The geomagnetically induced current (GIC) produced during extreme geomagnetic storms can easily lead to large‐scale blackouts in China due to the increase in the scale of its electric power grid. A power grid's resilience is its capability to resist various natural hazards, withstand primary failures, and quickly resume normal operation. To avoid power grid damages, this study developed a resilient power grid, incorporating failure, power flow calculation and recovery models under a uniform induced geoelectric field. We chose a system's performance loss as the resilience evaluation indicator, which intuitively reflected a system's loss under GIC. In addition, the recovery model was optimized using a genetic algorithm, and two resilience improvement measures were proposed. The IEEE‐RTS‐79 system, consisting of 10 generators, 24 buses and 5 transformers, was chosen as an example to verify the feasibility of this study. The results show that the genetic algorithm and optimization measures effectively enhanced the system's resilience indicator and provided a reference for preventing system damages under GIC and quick recovery after possible failures. Plain Language Summary: Extreme space weather produces large geomagnetic field disturbances; these disturbances propagate down to Earth, inducing secondary geomagnetically induced currents (GICs) in earthed electric power grids. GICs increase transformers' reactive power loss and raise their temperatures; this affects a power system's normal operation, and in extreme cases causes major blackouts. Therefore, it is vital to study power grids' resilience under GIC events. In this study, we calculated the GIC level using a uniform geoelectrical conductivity model. Based on this, we proposed a resilient power grid model consisting of the failure model, power flow calculation model and recovery model, and evaluated optimization strategies. Our results show that the proposed model can improve a power system's recovery performance after possible failure due to GICs and effectively avoid GIC‐related large‐scale blackouts. Key Points: We proposed a resilience assessment method for transmission systems under extreme space weatherWe calculated a resilience indicator and identified multiple effective methods to improve a system's resilienceWe chose the IEEE‐RTS‐79 system as an example to verify the effectiveness of a genetic algorithm and optimization measures [ABSTRACT FROM AUTHOR]

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre‐eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0) synthesis, reduced estradiol (E2), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE‐like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP‐treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2, but not T0, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1‐PKA‐CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β‐HSD3 and 3β‐HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE. [ABSTRACT FROM AUTHOR]