Inflammation is a key contributor to ovarian cancer cell seeding.

The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer

EVE: Efficient Vision-Language Pre-training with Masked Prediction and Modality-Aware MoE

Building scalable vision-language models to learn from diverse, multimodal data remains an open challenge. In this paper, we introduce an Efficient Vision-languagE foundation model, namely EVE, which is one unified multimodal Transformer pre-trained solely by one unified pre-training task. Specifically, EVE encodes both vision and language within a shared Transformer network integrated with modality-aware sparse Mixture-of-Experts (MoE) modules, which capture modality-specific information by selectively switching to different experts. To unify pre-training tasks of vision and language, EVE performs masked signal modeling on image-text pairs to reconstruct masked signals, i.e., image pixels and text tokens, given visible signals. This simple yet effective pre-training objective accelerates training by 3.5x compared to the model pre-trained with Image-Text Contrastive and Image-Text Matching losses. Owing to the combination of the unified architecture and pre-training task, EVE is easy to scale up, enabling better downstream performance with fewer resources and faster training speed. Despite its simplicity, EVE achieves state-of-the-art performance on various vision-language downstream tasks, including visual question answering, visual reasoning, and image-text retrieval.Comment: Accepted by AAAI 202

Effects of Simulated Microgravity on Vascular Development in Zebrafish

Research in microgravity is of utmost importance for disclosing the impact of gravity on biological processes and organisms. With the development of space technology, scientists pay more attention to cardiovascular diseases associated with microgravity. However, up to date only sparse data exist on microgravity and cardiovascular development mechanisms. In this study, zebrafish was chosen as the model organism. Zebrafish embryos were exposed to microgravity using a ground-based simulation microgravity (SM) bioreactor. The effects of SM on the development of early embryonic vascular system were studied in vivo in real-time. Zebrafish embryos were selected and divided into two groups at 12 hpf. One group was cultured in the MG-IIA bioreactor whereas the control group was cultured under normal gravity conditions. SM did not affect the number of live zebrafish and there were nonspecific developmental phenotypes in two groups. The heart rate in SM zebrafish embryos was significantly decreased. Then the vascular development differences between two groups were analyzed by qPCR and whole mount in situ hybridization. The effect of SM on zebrafish vascular development was not evident at 12 hpf - 24 hpf stage, but it had significant influences at 24 hpf-36 hpf stage.We also found that nos2b expression was up-regulated in the SM group both at 24 hpf and 36 hpf, interesting, all nos2b expression was observed in the hypothalamus at 24 hpf, it was no difference in the hypothalamus but significantly increased in the dorsal near the vascular at 36 hpf. These data suggested that the effect of SM on vasculogenesis stage is not obvious, but it has significant influences on angiogenesis, which maybe has relationship with the expression of nos2b

Shear Stress-mediated Angiogenesis Through Id1 Relevant to Atherosclerosis

Abnormal shear stress in the blood vessel is an important stimulating factor for the formation of angiogenesis and vulnerable plaques. This paper intended to explore the role of shear stress-regulated Id1 in angiogenesis. First, we applied a carotid artery ring ligation to create local stenosis in ApoE-/- mice. Then, 3D geometry of the vessel network was reconstructed based on MRI, and our analysis of computational fluid dynamics revealed that wall shear stress of the proximal region was much higher than that of the distal region. In addition, results from histological staining of the proximal region found more vulnerable-probe plaques with new capillary formation, the presence of macrophages and collagen fibers degradation. Our in vitro and in vivo experiments further indicated high shear stress can induce endothelial cell-mediated angiogenesis and high expression of Id1. Id1-overexpression promoted endothelial cells migration and angiogenesis through collagen degradation mediated by MT-MMPs. Together, our results support a biomechanical role for Id1 in angiogenesis, suggesting manipulation of the Id1 activity may offer a novel anti-angiogenic therapeutic strategy in vulnerable plaques

Creating a Humanized Tumor Model in Drosophila melanogaster

Drosophila melanogaster (common fruit fly), and humans share many genetic similarities such as the main genes related to ovarian cancer in humans: PTEN, BRCA2, P53, NF1, and RB1. These are present in the form of homologous genes with important roles in cell cycle regulation, DNA repair, and cell polarity. Previous research indicates that loss of function of these genes results in High Grade Serous Ovarian Cancer (HGSOC). After silencing different combinations of those target genes using the GAL4/UAS GAL80ts in our lab, epithelial deformation was observed within Drosophila ovaries, successfully creating a tumor model. We achieved a stronger tumor-like phenotype by effective silencing of the genes through prolonging silencing time and increasing working temperature. My objective is to use DAPI and immunohistochemistry as markers to determine morphological and polarity changes in ovarian follicle cells and quantify abnormalities in samples where the target genes were silenced. In addition, we applied the RNA-seq technique to detect any changes at the expression level of genes associated with the 5 gene alterations