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Abstract Purpose This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. Methods CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133−) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). Results The performance of CD133+OVCAR4 cells was much better than that of CD133−OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133−OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. Conclusion The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway.

The Central Asian Orogenic Belt (CAOB) was formed by the aggregation and collage of numerous Paleozoic subduction‐accretion assemblages and Precambrian microcontinental blocks. However, the tectonic nature of the southeastern CAOB remains controversial, which complicates the reconstruction of the Paleo‐Asian Ocean. To address this issue, a deep seismic reflection survey was initiated across the southeastern CAOB and reveals broad gentle sub‐horizontal reflectors in the middle‐lower crust and a relatively transparent zone in the upper crust. Combining with the Precambrian geological outcrops and other geophysical features, we support a microcontinental block, the Xilinhot Block, existed in the Paleo‐Asian domain. Thus, the Paleo‐Asian Ocean was separated into two branches that underwent north‐dipping and double‐dipping oceanic plate subduction, respectively, to form the Hegenshan‐Heihe and Solonker sutures. Multiple relics beneath Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Plain Language Summary: During the consumption of the Paleo‐Asian Ocean, a great number of Paleozoic subduction‐related accretionary complexes were developed and combined with pre‐existing Precambrian continental fragments to form the Central Asian Orogenic Belt (CAOB). However, research on the tectonic evolution of this area has been limited, and the tectonic nature of the southeastern CAOB remains controversial. A deep seismic reflection survey along the southeastern CAOB shows the crustal architecture in detail. The broad gentle sub‐horizontal reflectors and a relatively transparent zone in the profile reveal a Precambrian continental fragment existed in the North Orogenic Belt of CAOB. The Paleo‐Asian Ocean was further separated into two parts, the fossil subduction zones of which show northward and bidirectional dipping characteristics beneath the Hegenshan‐Heihe and Solonker sutures, respectively. Several relics of the unidirectional subduction beneath the Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Key Points: A preserved microcontinental block has been revealed in the North Orogenic Belt of Central Asian Orogenic BeltThe Paleo‐Asian Ocean was separated into two branches, which were closed respectively by north‐dipping and double‐dipping subductionMultiple unidirectional subduction‐accretion and oceanic magmatism may contribute to continental growth [ABSTRACT FROM AUTHOR]

Background: Alternative and complementary therapies play an imperative role in the clinical management of Type 2 diabetes mellitus (T2DM), and exploring and utilizing natural products from a genetic perspective may yield novel insights into the mechanisms and interventions of the disorder., Methods: To identify the therapeutic target of baicalin for T2DM, we conducted a Mendelian randomization study. Druggable targets of baicalin were obtained by integrating multiple databases, and target-associated cis-expression quantitative trait loci (cis-eQTL) originated from the eQTLGen consortium. Summary statistics for T2DM were derived from two independent genome-wide association studies available through the DIAGRAM Consortium (74,124 cases vs. 824,006 controls) and the FinnGen R9 repository (9,978 cases vs. 12,348 controls). Network construction and enrichment analysis were applied to the therapeutic targets of baicalin. Colocalization analysis was utilized to assess the potential for the therapeutic targets and T2DM to share causative genetic variations. Molecular docking was performed to validate the potency of baicalin. Single-cell RNA sequencing was employed to seek evidence of therapeutic targets' involvement in islet function., Results: Eight baicalin-related targets proved to be significant in the discovery and validation cohorts. Genetic evidence indicated the expression of ANPEP, BECN1, HNF1A, and ST6GAL1 increased the risk of T2DM, and the expression of PGF, RXRA, SREBF1, and USP7 decreased the risk of T2DM. In particular, SREBF1 has significant interaction properties with other therapeutic targets and is supported by strong colocalization. Baicalin had favorable combination activity with eight therapeutic targets. The expression patterns of the therapeutic targets were characterized in cellular clusters of pancreatic tissues that exhibited a pseudo-temporal dependence on islet cell formation and development., Conclusion: This study identified eight potential targets of baicalin for treating T2DM from a genetic perspective, contributing an innovative analytical framework for the development of natural products. We have offered fresh insights into the connections between therapeutic targets and islet cells. Further, fundamental experiments and clinical research are warranted to delve deeper into the molecular mechanisms of T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Li, Liang, Liu, Chu and Li.)