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Oriented continua play an important role in micropolar elasticity modelling. All realizations of micropolar theories are conceptually possible only within the framework of the pseudotensor formalism and the orientable manifold notion. This particularly concerns the theory of micropolar hemitropic elastic media. In this paper, a pseudotensor description is used in contrast to Kartan's formalism. The pseudotensor formulation of Stokes' integral theorem is almost unknown in the current scientific literature. Here we consider various formulations of Stokes' integral theorem for an arbitrary asymmetric covariant pseudotensor field of a given weight and valency. This extends the theorem to the case of pseudotensors. This fact makes it possible to use the mentioned generalization for micropolar continua. The study mostly relies on the class of special coordinate systems often employed in classical physical field theories. A procedure for orientations consistency inside and on the boundary of a manifold is discussed for various formulations of Stokes' integral theorem.

Several disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to identify compounds that can modulate M-cell regeneration by causing neuro-protection and -toxicity. Here, we developed a simple and efficient in vivo assay using Tg (hsp: Gal4FF62A; UAS: nfsB-mCherry) transgenic zebrafish larvae. Interestingly, via the phenotype-based drug screening approach, we rapidly investigated 1,260 compounds from the United States drug collection and validated these in large numbers, including 14 compounds, that were obstructing this regeneration process. Next, 4 FDA-approved drugs out of 14 compounds were selected as the lead hits for in silico analysis to clarify their binding patterns with PTEN and SOCS3 signaling due to their significant potential in the inhibition of axon regeneration. Molecular docking studies indicated good binding affinity of all 4 drugs with the respective signaling molecules. This may point to PTEN and SOCS3 as the signaling molecules responsible for reducing axon regeneration. Moreover, the acute effect of compounds in reducing M-cell regeneration delineated their toxic effect. In conclusion, our in vivo along with in silico screening strategy will promote the rapid translation of new therapeutics to improve knowledge of the toxicity profile of approved/non-approved drugs efficiently.

The paper deals with the problems of the tensor element of volume (area) of an M-cell for a manifold immersed in a "plane" multidimensional space. The corresponding considerations imply the choice of the reper orientation, which determines the volume (area) element. The latter circumstance is of exceptional importance in micropolar theories of elasticity. The indicated theories can be correctly developed only within the framework of the pseudotensor formalism. This is especially true for the theory of hemitropic elastic continua. The governing information from the algebra of pseudotensors is presented. Manifolds given by Gaussian parametrization are considered. The concept of an M-cell on a manifold and its orientation is introduced. An algorithm for comparing the orientations of M-dimensional cells is described. The concept of the tensor element of volume (area) for the M- cell is determined. The formula for transformation a natural volume element to an invariant volume element is shown. Important applications for the mechanics of the micropolar continuum are noted and discussed. [ABSTRACT FROM AUTHOR]

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Several disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to identify compounds that can modulate M-cell regeneration by causing neuro-protection and -toxicity. Here, we developed a simple and efficient in vivo assay using Tg (hsp: Gal4FF62A; UAS: nfsB-mCherry) transgenic zebrafish larvae. Interestingly, via the phenotype-based drug screening approach, we rapidly investigated 1,260 compounds from the United States drug collection and validated these in large numbers, including 14 compounds, that were obstructing this regeneration process. Next, 4 FDA-approved drugs out of 14 compounds were selected as the lead hits for in silico analysis to clarify their binding patterns with PTEN and SOCS3 signaling due to their significant potential in the inhibition of axon regeneration. Molecular docking studies indicated good binding affinity of all 4 drugs with the respective signaling molecules. This may point to PTEN and SOCS3 as the signaling molecules responsible for reducing axon regeneration. Moreover, the acute effect of compounds in reducing M-cell regeneration delineated their toxic effect. In conclusion, our in vivo along with in silico screening strategy will promote the rapid translation of new therapeutics to improve knowledge of the toxicity profile of approved/non-approved drugs efficiently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumari, Zeng, Rahaman, Farooq, Huang, Alee, Yao, Ali, Khalifa and Badr.)