Xiaoran Wu

This study aims to address gaps in understanding healthcare accessibility inequality in rural China, where traditional distance-based assessments and urban-centric biases are insufficient. By integrating real-time travel data from Amap and the two-step floating catchment area (2SFCA) method, we conducted a high-resolution (1 km grid) analysis across transportation modes, administrative scales, and time-sensitive populations. Results reveal that driving enables more stable, equitable access (characterized by higher supply–demand ratios and lower variability) than public transport, which distorts ratios due to limited coverage. Accessibility disparities are most pronounced at the county scale, with eastern rural counties (e.g., Yangtze River Delta) showing far higher accessibility (log₁₀(A-value) > 5.0) than remote western counties (log₁₀(A-value) < 1.5). High time-sensitive populations (urgent care) face extreme accessibility gaps, with only 15% of counties providing optimal access. In contrast, low time-sensitive groups benefit from extended travel time thresholds, achieving 62% coverage of optimal access. Targeted interventions—investing in rural high-tier hospitals, enhancing transit frequency, and county-specific policies—are needed to advance health equity. The findings of this study provide the first nationwide high-resolution healthcare accessibility map for rural China, improve assessment accuracy via real-time data, and identify county-level gaps—offering data-driven insights for targeted policies to advance health equity and support rural revitalization.

Satellite-based and reanalysis precipitation products have experienced increasing popularity in agricultural, hydrological and meteorological applications, but their accuracy is still uncertain in different areas. In this study, six frequently used high-resolution daily precipitation products, including Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS), Global Satellite Mapping of Precipitation (GSMaP), Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG), Multi-Source Weighted-Ensemble Precipitation (MSWEP), Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Cloud Classification System-Climate Data Record (PERSIANN-CCS-CDR) and European Center for Medium-Range Weather Forecasts Reanalysis V5-Land (ERA5-Land), were comprehensively evaluated and compared in nine regions of mainland China between 2015 and 2019. The results reveal that, in general, GSMaP is the best precipitation product in different agricultural regions, especially based on the Pearson correlation coefficient (CC) and critical success index (CSI). ERA5-Land and MSWEP tend to have the highest probability of detection (POD) values, and MSWEP tends to have the smallest relative root mean squared error (RRMSE) values. GSMaP performs better at almost all precipitation levels and in most agricultural regions in each season, while MSWEP has the best performance for capturing the time series of mean daily precipitation. In addition, all precipitation products perform better in summer and worse in winter, and they are more accurate in the eastern region. The findings of this study will contribute to understanding the uncertainties of precipitation products, improving product quality and guiding product selection.

4-1BB (CD137, TNFRSF9) is a potent co-stimulatory receptor found on T and NK cells. Activation of 4-1BB requires receptor clustering, which is naturally mediated by the endogenous trimeric 4-1BB ligand. Cross-linking via agnostic monoclonal antibodies can also activate 4-1BB but has generally resulted in unwanted side effects, mainly liver toxicity. To address the shortcomings of 4-1BB agonists, we have developed QL301, a PD-L1 x 4-1BB bispecific antibody that conditionally activates 4-1BB only when concurrently engaged to PD-L1, an immune checkpoint mediator elevated in the immuno-suppressive tumor microenvironment. The IgG1 backbone of QL301 was mutated to eliminate Fc gamma receptor-dependent functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), thereby preventing depletion of effector immune cells and non-specific activation of 4-1BB through Fc gamma receptor binding. In addition, QL301 blocks the suppressive interaction of PD-1 with PD-L1. Therefore, through a combination of 4-1BB agonism and PD-L1 blockade, QL301 provides both a co-stimulatory signal and the release of a suppressive signal to reinvigorate anti-tumor immune response. In vitro, QL301 induced robust cytokine release and expansion of CD8+ T cells conditional on the presence of tumor or antigen presenting cells expressing PD-L1. In xenograft and transgenic mice models, QL301 had potent anti-tumor effect that was superior to PD-L1 monoclonal antibodies. Tumor regression correlated with the expansion of CD8+ T cells. In addition, QL301 potentiated tumor cell killing mediated by an EGFR targeted CD3 bispecific antibody, providing a basis for combination therapy. In non-human primates, QL301 was well tolerated up to 30 mg/kg. There was no chronic elevation of serum AST and ALT levels, and histopathology analysis showed minimal inflammation of liver tissue. A phase 1 clinical trial to evaluate the safety, tolerability, and early efficacy of QL301 is currently ongoing. Citation Format: Shenda Gu, Irene Tang, Shirley Mihardja, Wei Wei Prior, Hieu V. Tran, Allan Chan, Anna McClain, Aaron Kurtzman, Shihao Chen, Youguang Luo, Xiaoyan Kang, Xiaoran Wu, Qingmei Zheng, Guodong Jia. QL301, a PD-L1 dependent 4-1BB agonist with enhanced preclinical anti-tumor efficacy and minimal liver toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4245.