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Poly (ADP‐ribose) Polymerase inhibitors (PARPi) have demonstrated remarkable clinical efficacy in treating ovarian cancer (OV) with BRCA1/2 mutations. However, drug resistance inevitably limits their clinical applications and there is an urgent need for improved therapeutic strategies to enhance the clinical utility of PARPi, such as Olaparib. Here, compelling evidence indicates that sensitivity of PARPi is associated with cell cycle dysfunction. Through high‐throughput drug screening with a cell cycle kinase inhibitor library, XL413, a potent cell division cycle 7 (CDC7) inhibitor, is identified which can synergistically enhance the anti‐tumor efficacy of Olaparib. Mechanistically, the combined administration of XL413 and Olaparib demonstrates considerable DNA damage and DNA replication stress, leading to increased sensitivity to Olaparib. Additionally, a robust type‐I interferon response is triggered through the induction of the cGAS/STING signaling pathway. Using murine syngeneic tumor models, the combination treatment further demonstrates enhanced antitumor immunity, resulting in tumor regression. Collectively, this study presents an effective treatment strategy for patients with advanced OV by combining CDC7 inhibitors (CDC7i) and PARPi, offering a promising therapeutic approach for patients with limited response to PARPi. [ABSTRACT FROM AUTHOR]

Many of the world's less developed regions may not be able to improve the well-being of rural residents through agricultural revitalization because of their remoteness from agricultural markets. Using the county-level data set of China's underdeveloped old revolutionary base areas from 2010 to 2021, this paper takes the policy planning of rural e-commerce as event intervention to investigate the driving role of the digital product market on agricultural economic development. Empirical results show that rural e-commerce planning policy has significantly promoted the agricultural added value of the pilot counties, and the digital market is the key driving factor of the agricultural economic growth in these underdeveloped areas. Both food production and livestock output have increased significantly as a result of e-commerce policies. Considering the potential bias of the bidirectional fixed effect estimators of staggered differences-in-differences (DID), this study uses heterogeneous robust estimators to verify the growth effect of the agricultural economy. Specifically, digital agricultural markets have significantly promoted agricultural mechanization and significantly improved agricultural total factor productivity. Moreover, empirical evidence does not support transmission mechanisms for off-farm employment and agricultural entrepreneurship. The findings can help less developed countries and regions develop policies to expand the agricultural markets with digital dividends, thereby promoting the development of the agricultural economy. [ABSTRACT FROM AUTHOR]

The rapid development of microfluidics has greatly facilitated the application of magnetic bead in biochemical analysis, where their mixing with reagents is a critical step to effectively capture the target substances and directly affect the accuracy of the results. This research delves into ultrasound-assisted mixing of magnetic beads based on acoustic streaming effect. We investigate the acoustic field and acoustic streaming generated in the reaction chambers made from three materials (PP, PC, PMMA) and four structures (spherical, cylindrical, square, EP tubular) and simulate the motion process of the magnetic beads. The findings of research suggests that cylindrical chambers and square chambers exhibit better mixing properties, especially the square chambers using PMMA materials, with about 14% of the magnetic beads able to reach the plane within 0.1 s. For current chambers with better mixing performance, PMMA material may be a more favourable material choice for magnetic beads mixing. This research enhances the understanding of ultrasound-assisted mixing mechanisms in biochemical reactions and provides possible recommendations for chamber structure design and material selection. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the application value of a degradable liquid fiducial marker (LFM) in image-guided radiotherapy. In vitro experiment: using a solid fiducial marker (SFM) as a reference, the visibility, artifact, and optimal injection volume of an LFM under different cone beam CT tube voltage conditions were evaluated. In vivo experiment: using the SFM as a reference, the stability and degradation status of the LFM in nude mice were evaluated. Nude mice implanted with tumor cells were randomly divided into four groups: single fraction radiotherapy group (16 Gy/fraction) without LFM injection, single fraction radiotherapy group (16 Gy/fraction) with LFM injection, 2 fractions radiotherapy group (8 Gy/fraction) with LFM injection, and 4 fractions radiotherapy group (4 Gy/fraction) with LFM injection. The impact of LFM on tumor growth was evaluated based on the irradiation results. Compared with SFM, the LFM artifacts were significantly smaller (all p

Objective: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients. Methods: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets. Results: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini‐Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini‐Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03–0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76–0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%. Interpretation: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74–86 [ABSTRACT FROM AUTHOR]