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Purpose: Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [18F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy. Methods: [18F]d4-FET was synthesised by two automated radiochemistry modules. Biodistribution studies and imaging efficacy were evaluated in vivo and ex vivo in rodent models, while metabolic stability and radiation dosimetry were assessed in non-human primates. Additionally, preliminary imaging evaluations were carried out in five brain tumor patients: three glioma patients underwent imaging with both [18F]d4-FET and [18F]FET, and two patients with brain metastases were imaged using [18F]d4-FET and [18F]FDG. Results: [18F]d4-FET demonstrated high radiochemical purity and yield. PET/MRI in rodent models demonstrated superior TBR for [18F]d4-FET compared to [18F]FET, and autoradiography showed tumor margins that correlated well with pathological extents. Studies in cynomolgus monkeys indicated comparable in vivo stability and effective dose with [18F]FET. In glioma patients, [18F]d4-FET showed enhanced TBR, while in patients with brain metastases, [18F]d4-FET displayed superior lesion delineation compared to [18F]FDG, especially in smaller metastatic sites. Conclusion: We successfully synthesized the novel PET radiotracer [18F]d4-FET, which retains the advantageous properties of [18F]FET while potentially enhancing TBR for glioma imaging. Preliminary studies indicate excellent stability, efficacy, and sensitivity of [18F]d4-FET, suggesting its potential in clinical evaluations of brain tumors. Trial registration: ChiCTR2400081576, registration date: 2024–03-05, https://www.chictr.org.cn/bin/project/edit?pid=206162 [ABSTRACT FROM AUTHOR]

This study explores the onset of nonaggression pacts at the individual level, focusing on how leaders' perceived madness influences security agreements. While the Madman Theory suggests that perceived madness could be an asset in crisis bargaining, it also signals uncertainty and hostility to other states. Consequently, states seek security assurances through nonaggression pacts to manage the risks posed by such leaders. On the other hand, leaders adopting the Madman strategy may strategically pursue these pacts as signaling devices to alleviate diplomatic isolation and mitigate their overall reputation for madness for strategic purposes. By utilizing McManus's perception-based measures, my findings indicate that leaders with a strong reputation for madness significantly influence the formation of nonaggression pacts, whereas moderate levels of madness do not have the same effect. The impact of a strong reputation for madness diminishes when states are distant from the mad leader or are protected by more military alliances. This study sheds light on the role of leaders' reputations in security agreements and extends the scope of the Madman Theory beyond crisis bargaining to broader contexts of security cooperation. [ABSTRACT FROM AUTHOR]

N‐methyl‐D‐aspartate receptors (NMDAR), ionotropic glutamate receptors, mediate a slow component of excitatory synaptic transmission in the central nervous system and play a key role in normal brain function and development. Genetic variations in GRIN genes encoding NMDAR subunits that alter the receptor's functional characteristics are associated with a wide range of neurological and neuropsychiatric conditions. Pathological GRIN variants located in the M2 re‐entrant loop lining the channel pore cause significant functional changes, the most consequential alteration being a reduction in voltage‐dependent Mg2+ inhibition. Voltage‐dependent Mg2+ block is a unique feature of NMDAR biology whereby channel activation requires both ligand binding and postsynaptic membrane depolarization. Thus, loss of NMDAR Mg2+ block will have a profound impact on synaptic function and plasticity. Here, we choose 11 missense variants within the GRIN1, GRIN2A, and GRIN2B genes that alter residues located in the M2 loop and significantly reduce Mg2+ inhibition. Each variant was evaluated for tolerance to genetic variation using the 3‐dimensional structure and assessed for functional rescue pharmacology via electrophysiological recordings. Three FDA‐approved NMDAR drugs—memantine, dextromethorphan, and ketamine—were chosen based on their ability to bind near the M2 re‐entrant loop, potentially rectifying dysregulated NMDAR function by supplementing the reduced voltage‐dependent Mg2+ block. These results provide insight of structural determinants of FDA‐approved NMDAR drugs at their binding sites in the channel pore and may further define conditions necessary for the use of such agents as potential rescue pharmacology. [ABSTRACT FROM AUTHOR]

On the basis of centralized structure and distributed structure, the model based on peer-to-peer structure is established. Aimed in the problem of source optimal selection for passive location relative navigation under peer-to-peer structure, the Gauss-Newton method is used to set the initial value of relative navigation Kalman filter to make it converge quickly. With defining time, position, geometry and synthetic error factors, and setting different simulation environments, the influence of distance, speed, time deviation and geometric distribution position on relative navigation accuracy is studied. The simulation results show that the deviation is inversely proportional to the relative navigation accuracy, and the navigation accuracy is the highest when the connecting angle between the node to be located and the navigation source is 90°, the accuracy of the wide baseline scheme is significantly better than that of the narrow baseline scheme when the navigation source is configured linearly, and the accuracy of four-source positioning is better than that of two-source or three-source positioning. The algorithm model established in this paper is able to analyze the influence of different factors on positioning errors.

Achieving the "double carbon" goal and optimizing the energy structure necessitates strategic deployments such as low-carbon cities (LCCs) and new energy demonstration cities (NEDCs). Prior research has primarily examined the effectiveness of these two policies when implemented independently. Despite overlapping scopes, there remains a need for a definitive conclusion regarding whether the concurrent implementation of these policies will yield a synergistic effect, thereby further reducing carbon emissions. Employing panel data spanning 2007–2021 from 280 Chinese cities, this study investigates the carbon emission reduction (CER) effect of the dual pilot policy (DPP), focusing specifically on LCCs and NEDCs through a multi-period difference-in-differences (DID) analysis. The findings reveal a significant synergistic effect between LCCs and NEDCs on CER, with the sequence of policy implementation playing a crucial role in determining the effectiveness of CER. Notably, cities first become NEDCs and subsequently transition into LCCs, demonstrating a more pronounced CER effect. Further analysis of the impact mechanism underscores that the DPP fosters urban CER by elevating inventive and improved green technology innovation. Among these, the contribution of inventive green technology innovation is particularly prominent, accounting for as much as 24%, far surpassing the 20% contribution of improved green technology innovation. A heterogeneity analysis indicates that the DPP's impact is more significant in western and non-resource-based cities. Given China's status as one of the world's foremost carbon emitters, exploring China's CER pathways holds profound practical significance and offers invaluable empirical insights for advancing global CER efforts. [ABSTRACT FROM AUTHOR]