Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers.

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27-1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.

Polarized light sun position determination artificial neural network.

Our previous work has constructed a polarized light orientation determination (PLOD) artificial neural network. Although a PLOD network can determine the solar azimuth angle, it cannot determine the solar elevation angle. Therefore, this paper proposes an artificial neural network for polarized light solar position determination (PLSPD), which has two branches: the solar azimuth angle determination branch and the solar elevation angle determination branch. Since the solar elevation angle has no cyclic characteristics, and the angle range of the solar elevation angle is different from that of the solar azimuth angle, the solar elevation angle exponential function encoding is redesigned. In addition, compared with the PLOD, the PLSPD deletes a local full connection layer to simplify the network structure. The experimental results show that the PLSPD can determine not only the solar azimuth angle but also the solar elevation angle, and the solar azimuth angle determination accuracy of the PLSPD is higher than that of the PLOD.

Polarized light compass decoding.

The brains of some insects can encode and decode polarization information and obtain heading angle information. Referring to the encoding ability of insects, exponential function encoding is designed to improve the stability of the polarized light compass artificial neural network. However, in the decoding process, only neurons with the largest activation degree are used for decoding (maximum value decoding), so the heading information contained in other neurons is not used. Therefore, average value decoding (AVD) and weighted AVD are proposed to use the heading information contained in multiple neurons to determine the heading. In addition, concerning the phenomenon of threshold activation of insect neurons, threshold value decoding (TVD) and weighted TVD are proposed, which can effectively eliminate the interference of neurons with low activation. Moreover, this paper proposes to improve the heading determination accuracy of the artificial neural network through pre-training. The simulation and experimental results show that the new, to the best of our knowledge, decoding methods and pre-training can effectively improve the heading determination accuracy of the artificial neural network.

Polarized skylight compass based on a soft-margin support vector machine working in cloudy conditions.

The skylight polarization pattern, which is a result of the scattering of unpolarized sunlight by particles in the atmosphere, can be used by many insects for navigation. Inspired by insects, several polarization navigation sensors have been designed and combined with various heading determination methods in recent years. However, up until now, few of these studies have fully considered the influences of different meteorological conditions, which play key roles in navigation accuracy, especially in cloudy weather. Therefore, this study makes a major contribution to the study on bio-inspired heading determination by designing a skylight compass method to suppress cloud disturbances. The proposed method transforms the heading determination problem into a binary classification problem by segmentation, connected component detection, and inversion. Considering the influences of noise and meteorological conditions, the binary classification problem is solved by the soft-margin support vector machine. In addition, to verify this method, a pixelated polarization compass platform is constructed that can take polarization images at four different orientations simultaneously in real time. Finally, field experimental results show that the designed method can more effectively suppress the interference of clouds compared with other methods.

Exploration of (3-benzyl-5-hydroxyphenyl)carbamates as new antibacterial agents against Gram-positive bacteria.

A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4-Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4-8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.

Discovery of meta-Amido Bromophenols as New Antitubercular Agents.

A series of meta-amido bromophenol derivatives were designed and synthesized. The compounds were found to potently inhibit the growth of Mycobacterium tuberculosis H37Ra. They also exhibited moderate inhibitory activity against Mycobacterium tuberculosis H37Rv and multidrug-resistant strains. The compounds did not show inhibitory activity against normal Gram-positive and Gram-negative bacteria. Moderate cytotoxicities and good metabolic stability were observed for the selected compounds. The results demonstrated meta-amido bromophenols as a new class of antitubercular agents with good potentials.

Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as New Antitubercular Agents with Potent In Vitro and In Vivo Efficacy.

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 µg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.

Facile synthesis of substituted diaryl sulfones via a [3 + 3] benzannulation strategy.

A base-mediated [3 + 3] benzannulation strategy for the conversion of 1,3-bis(sulfonyl)propenes and ß,γ-unsaturated α-ketoesters to diaryl sulfones has been developed. This method provides facile, metal-free and efficient access to highly substituted diaryl sulfones in good to excellent yields. In addition, the sulfonyl group could be easily removed or converted to other functional groups via an organostannane intermediate.

Preparation and Preliminary Evaluation of a Promising 99mTc-Labeled Isonitrile-Containing 6-Thia-Fatty Acid Derivative for Myocardial Metabolism Imaging.

For over 40 years, none of the previous 99mTc-labeled fatty acids for myocardial imaging has potential clinical use. 99mTc-(C10-6-thia-CO2H)(MIBI)5 is the first 99mTc-labeled fatty acid to exhibit good myocardial uptake (2.06 ± 0.06%ID/g) at 60 min post injection, high heart-to-liver ratio (6.43 ± 1.85 and 9.68 ± 0.76), high heart-to-lung ratio (9.48 ± 1.39 and 11.02 ± 0.89), and high heart-to-blood ratio (164.01 ± 43.51 and 197.36 ± 32.29) at 60 and 120 min in Sprague-Dawley (SD) rats, respectively. It also demonstrated excellent myocardial imaging quality. The above target-to-nontarget ratios exceeded those of [123I]BMIPP and were higher than or close to those of 99mTc-MIBI at 60 and 120 min. Most of 99mTc-(C10-6-thia-CO2H)(MIBI)5 was partially ß-oxidized to protein-bound metabolites in myocardium. Administration of trimetazidine dihydrochloride (TMZ, a fatty acid ß-oxidation inhibitor) to rats caused 51% reduction in the myocardial uptake of 99mTc-(C10-6-thia-CO2H)(MIBI)5 and 61% reduction in the distribution of 99mTc-radioactivity in a residual tissue pellet at 60 min, indicating its considerable sensitivity to myocardial fatty acid ß-oxidation.

BIDL: a brain-inspired deep learning framework for spatiotemporal processing.

Brain-inspired deep spiking neural network (DSNN) which emulates the function of the biological brain provides an effective approach for event-stream spatiotemporal perception (STP), especially for dynamic vision sensor (DVS) signals. However, there is a lack of generalized learning frameworks that can handle various spatiotemporal modalities beyond event-stream, such as video clips and 3D imaging data. To provide a unified design flow for generalized spatiotemporal processing (STP) and to investigate the capability of lightweight STP processing via brain-inspired neural dynamics, this study introduces a training platform called brain-inspired deep learning (BIDL). This framework constructs deep neural networks, which leverage neural dynamics for processing temporal information and ensures high-accuracy spatial processing via artificial neural network layers. We conducted experiments involving various types of data, including video information processing, DVS information processing, 3D medical imaging classification, and natural language processing. These experiments demonstrate the efficiency of the proposed method. Moreover, as a research framework for researchers in the fields of neuroscience and machine learning, BIDL facilitates the exploration of different neural models and enables global-local co-learning. For easily fitting to neuromorphic chips and GPUs, the framework incorporates several optimizations, including iteration representation, state-aware computational graph, and built-in neural functions. This study presents a user-friendly and efficient DSNN builder for lightweight STP applications and has the potential to drive future advancements in bio-inspired research.

Limitation of Rayleigh sky model for bioinspired polarized skylight navigation in three-dimensional attitude determination.

Insects such as desert ants and drosophilae can sense polarized skylight for navigation. Inspired by insects, many researchers have begun to study how to use skylight polarization patterns for attitude determination. The Rayleigh sky model has become the most widely used skylight polarization model for bioinspired polarized skylight navigation due to its simplicity and practicality. However, this is an ideal model considering only single Rayleigh scatter events, and the limitation of this model in bio-inspired attitude determination has not been paid much attention and lacks strict inference proof. To address this problem, the rotational and plane symmetry of the Rayleigh sky model are analyzed in detail, and it is theoretically proved that this model contains only single solar vector information, which contains only two independent scalar pieces of attitude information, so it is impossible to determine three Euler angles simultaneously in real-time. To further verify this conclusion, based on a designed hypothetical polarization camera, we discuss what conditions different three-dimensional attitudes must satisfy so that the polarization images taken at different 3D attitudes are the same; this indicates that multiple solutions will appear when only using the Rayleigh sky model to determine 3D attitude. In conclusion, due to its single solar vector information and the existence of multiple solutions, it is fully proved that 3D attitude cannot be determined in real time based only upon the Rayleigh sky model. Code is available at: https://github.com/HuajuLiang/HypotheticalPolarizationCamera.