http://hdl.handle.net/10453/30054 2026-04-10T16:08:59Z http://hdl.handle.net/10453/194642 Title: A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis. Authors: Qian, J; Ma, C; Waterbury, QT; Zhi, X; Moon, CS; Tu, R; Kobayashi, H; Wu, F; Zheng, B; Zeng, Y; Zheng, H; Ochiai, Y; White, RA; Harle, DW; LaBella, JS; Zamechek, LB; ZhongMing Hu, L; Moy, RH; Han, AS; Daugherty, BL; Lederman, S; Wang, TC Abstract: Pathologically activated immunosuppressive neutrophils impair cancer immunotherapy efficacy. The chemokine receptor CXCR4, a central regulator of hematopoiesis and neutrophil biology, represents an attractive target. Here, we fuse a secreted CXCR4 partial agonist, trefoil factor 2 (TFF2), to mouse serum albumin (MSA) and demonstrate that TFF2-MSA peptide synergizes with anti-PD-1 to inhibit primary tumor growth and distant metastases and prolongs survival in gastric cancer (GC) mouse models. Using histidine decarboxylase (Hdc)-GFP transgenic mice to track polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) in vivo, we find that TFF2-MSA selectively reduces the Hdc-GFP+CXCR4high immunosuppressive neutrophils, thereby boosting CD8+ T cell-mediated tumor killing with anti-PD-1. Importantly, TFF2-MSA reduces bone marrow granulopoiesis, contrasting with CXCR4 antagonism, which fails to confer therapeutic benefits. In GC patients, elevated CXCR4+LOX-1+ low-density neutrophils correlate with lower circulating TFF2 levels. Collectively, our studies introduce a strategy that utilizes CXCR4 partial agonism to restore anti-PD-1 sensitivity by targeting immunosuppressive neutrophils and granulopoiesis. 2025-08-11T00:00:00Z http://hdl.handle.net/10453/194641 Title: A comparative analysis of perceptions of insecurity in Milan and Beijing metro stations Authors: Liu, J; Yan, H; White, M; Huang, X Abstract: Metro stations, as essential public spaces, not only serve as vital transportation hubs but also form part of the broader built environment that shapes people's perceptions of insecurity. An important concern for passengers in these environments is safety, particularly in underground public space where the design and organization of the physical surroundings play a crucial role. Despite various modern renovations in older metro stations, newer stations are generally perceived as safer. To understand this discrepancy, this research compares how visual factors in the built environments of old and new metro stations influence people's perceptions of insecurity. By examining two cities—Milan and Beijing, which follow distinct urban development models—this research also explores how differences in urbanization processes affect the contrast between old and new stations. This research introduces a novel methodology for analyzing underground public space by integrating 360-degree image capture, an enhanced semantic segmentation process, and predictive modeling using XGBoost and SHAP to reveal the complex relationships between these visual factors and safety perceptions. The results indicate that while factors like artificial light, floor, and the presence of people are significant across all stations, certain factors are particularly influential in specific contexts—for example, exposed pipes are more negatively associated with safety perception in Beijing's old stations, and platform doors have a strongly positive effect in Milan's new stations. The findings provide valuable insights for guiding the modernization of metro stations in the future, and offering an innovative approach to studying underground public space. 2025-08-01T00:00:00Z http://hdl.handle.net/10453/194633 Title: OPINION: Twin shipping chokepoint crisis threatens Australian trade Authors: Chowdhury, P; Paul, S 2026-04-09T00:00:00Z http://hdl.handle.net/10453/194628 Title: Epigenetic Compound Library Screen Identifies Ibrutinib as an Inhibitor of Ovarian Clear Cell Carcinoma Viability. Authors: Ma, Y; Dickson, K-A; Sarker, FA; Alghalayini, A; Field, NR; Xie, T; Skipper, TS; Karafotias, A; Briscas, S; Yee, C; Ford, CE; Bowden, NA; Tran, N; Marsh, DJ Abstract: BACKGROUND: Ovarian clear cell carcinoma (OCCC) is an endometriosis-associated ovarian cancer subtype. Somatic mutations in OCCC are reported in ARID1A, PIK3CA, and the TERT promoter (TERTp), as well as less commonly in KRAS and TP53 among other genes. OCCC is typically resistant to standard-of-care chemotherapy, especially after relapse. While recent studies have seen favourable responses to immunotherapy, patients with OCCC face limited therapeutic options. METHODS: With the objective of discovering new drug treatments for OCCC, we screened OCCC (RMG-1, JHOC-5, OV207, OVISE, OVMANA, OVTOKO, and TOV-21G) and non-OCCC cell lines with a commercially available epigenetic drug compound library at two concentrations. Based on specified selection criteria, drugs were sought that preferentially inhibited viability of OCCC versus non-OCCC cells, with subsequent validation in 2D and 3D bioprinted models and exploration of a relevant signalling pathway. RESULTS: Taken together, OCCC cell lines were more sensitive to the Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib than non-OCCC cells, with some variation in response observed between cell lines in 2D and 3D bioprinted cultures. Furthermore, ibrutinib inhibited PI3K/AKT/mTOR cell survival signalling in some but not all OCCC cell lines, suggesting that this drug functions on additional pathways. CONCLUSIONS: Ibrutinib is used clinically to treat specific B cell disorders; however, it is not currently approved to treat solid tumours. Data presented in OCCC cell lines complements clinical observations of a therapeutic response to ibrutinib in low-grade serous ovarian cancer. Ibrutinib demonstrates potential for the treatment of certain rare subtypes of ovarian cancer and should be further investigated. 2026-04-01T00:00:00Z