Biophysical and biochemical aspects of immune cell-tumor microenvironment interactions.

The tumor microenvironment (TME), composed of and influenced by a heterogeneous set of cancer cells and an extracellular matrix, plays a crucial role in cancer progression. The biophysical aspects of the TME (namely, its architecture and mechanics) regulate interactions and spatial distributions of cancer cells and immune cells. In this review, we discuss the factors of the TME-notably, the extracellular matrix, as well as tumor and stromal cells-that contribute to a pro-tumor, immunosuppressive response. We then discuss the ways in which cells of the innate and adaptive immune systems respond to tumors from both biochemical and biophysical perspectives, with increased focus on CD8+ and CD4+ T cells. Building upon this information, we turn to immune-based antitumor interventions-specifically, recent biophysical breakthroughs aimed at improving CAR-T cell therapy.

Simultaneous Detection of Infectious Diseases Using Aptamer-Conjugated Gold Nanoparticles in the Lateral Flow Immunoassay-Based Signal Amplification Platform.

Various platforms for the accurate diagnosis of infectious diseases have been studied because of the emergence of coronavirus disease (COVID-19) in 2019. Recently, it has become difficult to distinguish viruses with similar symptoms due to the continuous mutation of viruses, and there is an increasing need for a diagnostic method to detect them simultaneously. Therefore, we developed a paper-based rapid antigen diagnostic test using DNA aptamers for the simultaneous detection of influenza A, influenza B, and COVID-19. Aptamers specific for each target viral antigen were selected and attached to AuNPs for application in a rapid antigen diagnosis kit using our company's heterogeneous sandwich-type aptamer screening method (H-SELEX). We confirmed that the three viruses could be detected on the same membrane without cross-reactivity based on the high stability, specificity, and binding affinity of the selected aptamers. Further, the limit of detection was 2.89 pg·mL-1 when applied to develop signal amplification technology; each virus antigen was detected successfully in diluted nasopharyngeal samples. We believe that the developed simultaneous diagnostic kit, based on such high accuracy, can distinguish various infectious diseases, thereby increasing the therapeutic effect and contributing to the clinical field.

High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq.

In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site.

Kinetics of martensitic transformations in magnetic field or under hydrostatic pressure.

We have recently constructed a phenomenological theory that provides a unified explanation for athermal and isothermal martensitic transformation processes. On the basis of this theory, we predict some properties of martensitic transformation and confirm them experimentally using some Fe-based alloys and a Ni-Co-Mn-In magnetic shape memory alloy.

Synthesis and topoisomerase II inhibitory and cytotoxic activity of oxiranylmethoxy- and thiiranylmethoxy-chalcone derivatives.

In order to find potential anticancer drug candidate targeting topoisomerases enzyme, we have designed and synthesized oxiranylmethoxy- and thiiranylmethoxy-retrochalcone derivatives and evaluated their pharmacological activity including topoisomerases inhibitory and cytotoxic activity. Of the compounds prepared compound 25 showed comparable or better cytotoxic activity against cancer cell lines tested. Compound 25 inhibited MCF7 (IC(50): 0.49 ± 0.21 µM) and HCT15 (IC(50): 0.23 ± 0.02 µM) carcinoma cell growth more efficiently than references. In the topoisomerases inhibition test, all the compounds were inactive to topoisomerase I but moderate inhibitors to topoisomerase II enzyme. Especially, compound 25 inhibited topoisomerase II activity with comparable extent to etoposide at 100 µM concentrations. Correlation between cytotoxicity and topoisomerase II inhibitory activity implies that compound 25 can be a possible lead compound for anticancer drug impeding the topoisomerase II function.

Abnormal motor function and the expression of striatal dopamine D2 receptors in manganese-treated mice.

Manganese (Mn) plays an important role in the etiology of several neurobehavioral disorders, but there is a lack of data regarding its specific effects on neurotransduction, especially dopaminergic neurotransduction. We investigated the relationship between motor deficits and alterations in the expression of tyrosine hydroxylase (TH) and dopamine D2-like receptors (DR), including the three dopaminergic subtypes, D2, D3, and D4, in low- and high-dose Mn-treated mice. After administration of Mn (intraperitoneal injections of 20 or 40 mg/kg MnCl(2).4H(2)O once per day for 5 d), motor activity and expression of TH and DR were examined in the striatum of the mouse brain. Mn treatment resulted in significant decrease in coordination and/or impaired motor learning after 5 d of treatment and this effect remained until 10 d after the end of Mn treatment. The expression of dopamine D2-like receptor D2 (DRD2), but not TH, DRD3, or DRD4, in the striatum was dose-dependent, and statistically significant increases were seen at the mRNA and protein levels. These findings indicate that Mn-induced motor deficits may be modulated in part by the expression of DRD2 in the striatum. In addition, our results suggest that the disturbance of dopaminergic neurotransmission mediated by DRD2 may be involved in the pathogenesis of Mn neurotoxicity.

Shape memory characteristics and superelasticity of Ti-Ni-Cu alloy ribbons with nano Ti2Ni particles.

Microstructures and deformation behaviour of Ti-45Ni-5Cu and Ti-46Ni-5Cu alloy ribbons prepared by melt spinning were investigated by transmission electron microscopy, thermal cycling tests under constant load and tensile tests. Spherical Ti2Ni particles coherent with the B2 parent phase were observed in the alloy ribbons when the melt spinning temperature was higher than 1773 K. Average size of Ti2Ni particles in the ribbons obtained at 1873 K was 8 nm, which was smaller than that (10 nm) in the ribbons obtained at 1773 K. Volume fraction of Ti2Ni phase in the ribbons obtained at 1873 K was 40%, which was larger than that (20%) in the ribbons obtained at 1773 K. The stress required at temperatures of Af + 10 K for the stress-induced martensitic transformation increased from 93 MPa to 229 MPa and apparent elastic modulus of the B2 parent phase increased from 56 GPa to 250 GPa with increasing the melt spinning temperature from 1673 K to 1873 K in Ti-45Ni-5Cu alloy ribbons. The critical stress for slip deformation of the ribbons increased by coherent Ti2Ni particles, and thus residual elongation did not occur even at 160 MPa, while considerable plastic deformation occurred at 60 MPa in the ribbons without Ti2Ni particles. Almost perfect superelastic recovery was found in the ribbons with coherent Ti2Ni particles, while only partial superelastic recovery was observed in the ribbons without coherent Ti2Ni particles.

Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain.

Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3.6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity.