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Mutations in the BRCA2 tumor suppressor gene have been associated with an increased risk of developing prostate cancer. One of the paradoxes concerning BRCA2 is the fact that its inactivation affects genetic stability and is deleterious for cellular and organismal survival, while BRCA2-mutated cancer cells adapt to this detriment and malignantly proliferate. Therapeutic strategies for tumors arising from BRCA2 mutations may be discovered by understanding these adaptive mechanisms. In this study, we conducted forward genetic synthetic viability screenings in Caenorhabditis elegans brc-2 (Cebrc-2) mutants and found that Ceubxn-2 inactivation rescued the viability of Cebrc-2 mutants. Moreover, loss of NSFL1C, the mammalian ortholog of CeUBXN-2, suppressed the spindle assembly checkpoint (SAC) activation and promoted the survival of BRCA2- deficient cells. Mechanistically, NSFL1C recruited USP9X to inhibit the polyubiquitination of AURKB and reduce the removal of AURKB from the centromeres by VCP, which is essential for SAC activation. SAC inactivation is common in BRCA2-deficient prostate cancer patients, but PP2A inhibitors could reactivate the SAC and achieve BRCA2- deficient prostate tumor synthetic lethality. Our research reveals the survival adaptation mechanism of BRCA2-deficient prostate tumor cells and provides different angles for exploring synthetic lethal inhibitors in addition to targeting DNA damage repair pathways., Introduction Germline mutations of BRCA2 predispose humans to prostate, breast, ovarian, and pancreatic cancers (1, 2). As a tumor suppressor protein, BRCA2 is essential for stabilizing stalled replication forks (2, [...]

In the context of rapid urbanization, public spaces in traditional villages face challenges such as material ageing, loss of characteristics, and functional decline. The scientific and objective assessment of the quality of these public spaces is crucial for the sustainable development of traditional villages. Panoramic images, as an important source of spatial data, combined with deep learning technology, can objectively quantify the characteristics of public spaces in traditional villages. However, existing research has paid insufficient attention to the evaluation of the quality of public spaces in traditional villages at the micro-scale, often relying on questionnaires and interviews, which makes it difficult to meet the needs of planning and construction. This study constructs an evaluation system for the quality of public spaces in traditional villages, taking national-level traditional villages in the Fangshan District of Beijing as an example, based on traditional field research, using deep learning and panoramic images to automatically extract the features of public spaces in traditional villages, using a combination of the Analytic Hierarchy Process (AHP) and Criteria Importance Through Intercriteria Correlation (CRITIC) methods to determine the weights of the indicators and applying the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to evaluate the quality of public spaces in traditional villages. The study found that the quality of public spaces in Nanjiao Village is Grade I; Shuiyu Village and Liulinshui Village, Grade III; and Heilongguan Village, Grade IV and that there is still much room for improvement in general. The evaluation results match well with the public's subjective perceptions, with an R2 value of 0.832, proving that the constructed evaluation system has a high degree of accuracy. This study provides a scientific basis and an effective tool for the planning, design, and management of public spaces in traditional villages, which helps decision-makers better protect and utilize them. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). Methods: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. Results: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). Conclusion: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL. [ABSTRACT FROM AUTHOR]