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This paper utilizes the digital economy, regional spatial distribution digital mining technology, establishes the indicator system, assigns values to the indicators, and applies the indicator system to evaluate the development of industrial structure upgrading and transformation of the regional economy. According to the research results of the basic structure and algorithm of the self-organized neural network model, combined with the classification layer smoothing algorithm, the regional spatial clustering model is constructed. Using the constructed model, the regional economic spatial dynamic data is mined, and the path of industrial transformation and upgrading in the regional spatial area is dynamically studied. Furthermore, using the CA algorithm, the evolution law of land use structure in the region is predicted, and the development of the regional economy is inferred. At the same time, through the spatial autocorrelation regional prediction model, the relevant regional spatial expansion prediction method is proposed, the three research hypotheses of this paper are made, and the constructed model is utilized to innovate the exploration of industrial transformation and upgrading paths from the spatial dimension. Using empirical research methods, descriptive statistics, and mediating effect heterogeneity analysis are carried out to analyze the factors that influence regional economic variables in place A. The empirical analysis shows that the fluctuation range interval of industrial structure is between [0.811,10.2805], which brings a large positive impact on the regional economy.2017 national digital economic growth rate changed from -0.17446 to 0.17143 to realize a positive growth rate, and at the same time, there is a heterogeneity in the development of the east-west and central regions of A. The hypotheses presented in this paper are all valid.

Simple Summary: Despite major advances in treating non-small-cell lung cancer (NSCLC), the five-year survival rates for patients without specific genetic mutations remain low. This study aims to find better ways to treat these patients. We focused on a protein called Aurora kinase A (AURKA), which our prior study suggested may play a role in modulating resistance to the common cancer drug cisplatin. We looked at how AURKA affects the sensitivity of NSCLC cells to platinum-based chemotherapy and radiation. In lab tests, AURKA levels increased after cisplatin treatment. Blocking AURKA with a drug called alisertib or using a genetic method made cisplatin and radiation more effective, causing tumors to shrink in mouse models. The treated cancer cells showed more DNA damage and underwent cell death. Blocking AURKA also increased markers that help the immune system recognize cancer. Our study suggests that combining AURKA inhibitors with other treatments could improve outcomes for NSCLC patients. Despite major advances in non-small-cell lung cancer (NSCLC) treatment, the five-year survival rates for patients with non-oncogene-driven tumors remain low, necessitating combinatory approaches to improve outcomes. Our prior high-throughput RNAi screening identified Aurora kinase A (AURKA) as a potential key player in cisplatin resistance. In this study, we investigated AURKA's role in platinum and radiation sensitivity in multiple NSCLC cell lines and xenograft mouse models, as well as its effect on immune checkpoints, including PD-L1, B7x, B7-H3, and HHLA2. Of 94 NSCLC patient tumor specimens, 91.5% tested positive for AURKA expression, with 34% showing moderate-to-high levels. AURKA expression was upregulated following cisplatin treatment in NSCLC cell lines PC9 and A549. Both AURKA inhibition by alisertib and inducible AURKA knockdown potentiated the cytotoxic effects of cisplatin and radiation, leading to tumor regression in doxycycline-inducible xenograft mice. Co-treated cells exhibited increased DNA double-strand breaks, apoptosis, and senescence. Additionally, AURKA inhibition alone by alisertib increased PD-L1 and B7-H3 expression. In conclusion, our study demonstrates that AURKA inhibition enhances the efficacy of platinum-based chemotherapy in NSCLC cells and modulates the expression of multiple immune checkpoints. Therefore, combinatory regimens with AURKA inhibitors should be strategically designed and further studied within the evolving landscape of chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

By modifying the structures of targeted A 2A R antagonists and tracers, novel compounds 3 , 7a , 9 , 12c , and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3 , 12c , and BIBD-399 have high affinity for A 2A R. [ 18 F]3 and [ 18 F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [ 18 F]MNI-444 exhibits greater than that of [ 18 F]3 and [ 18 F]BIBD-399. PET imaging shows that [ 18 F]3 is off-target in the brain, while [ 18 F]BIBD-399 and [ 18 F]MNI-444 can be specifically imaged in regions with high A 2A R expression. Differently, [ 18 F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [ 18 F]MNI-444 shows a slowly increasing trend within 2 h of administration. [ 18 F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [ 18 F]BIBD-399 and [ 18 F]MNI-444 were inhibited by the A 2A R antagonist SCH442416 but not by the A 1 R antagonist DPCPX, demonstrating the high A 2A R binding specificity of [ 18 F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A 2A R. Further tMCAo imaging showed that [ 18 F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [ 18 F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [ 18 F]BIBD-399 has potential advantages in monitoring A 2A R changes, meriting further clinical investigation.

[ 18 F]Gln-OSO 2 F, [ 18 F]Arg-OSO 2 F, and [ 18 F]FSY-OSO 2 F were designed by introducing sulfonyl 18 F-fluoride onto glutamine, arginine, and tyrosine, respectively. [ 18 F]FSY-OSO 2 F can be prepared directly by sulfur 18 F-fluoride exchange, while [ 18 F]Gln-OSO 2 F and [ 18 F]Arg-OSO 2 F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [ 18 F]FSY-OSO 2 F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [ 18 F]FET. However, [ 18 F]Gln-OSO 2 F and [ 18 F]Arg-OSO 2 F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18 F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)