Study of Attenuation Correction Using a Cardiac Dynamic Phantom: Synchronized Time-Phase-Gated Attenuation Correction Method.

In cardiac nuclear medicine examinations, absorption in the body is the main factor in the degradation of the image quality. The Chang and external source methods were used to correct for absorption in the body. However, fundamental studies on attenuation correction for electrocardiogram (ECG)-synchronized CT imaging have not been performed. Therefore, we developed and improved an ECG-synchronized cardiac dynamic phantom and investigated the synchronized time-phase-gated attenuation correction (STPGAC) method using ECG-synchronized SPECT and CT images of the same time phase. Methods: As a basic study, SPECT was performed using synchronized time-phase-gated (STPG) SPECT and non-phase-gated (NPG) SPECT. The attenuation-corrected images were, first, CT images with the same time phase as the ECG waveform of the gated SPECT acquisition (with CT images with the ECG waveform of the CT acquisition as the reference); second, CT images with asynchronous ECG; third, CT images of the 75% region; and fourth, CT images of the 40% region. Results: In the analysis of cardiac function in the phantom experiment, left ventricle ejection fraction (heart rate, 11.5%-13.4%; myocardial wall, 49.8%-55.7%) in the CT images was compared with that in the STPGAC method (heart rate, 11.5%-13.3%; myocardial wall, 49.6%-55.5%), which was closer in value to that of the STPGAC method. In the phantom polar map segment analyses, none of the images showed variability (F (10,10) < 0.5, P = 0.05). All images were correlated (r = 0.824-1.00). Conclusion: In this study, we investigated the STPGAC method using a SPECT/CT system. The STPGAC method showed similar values of cardiac function analysis to the CT images, suggesting that the STPGAC method accurately reconstructed the distribution of blood flow in the myocardial region. However, the target area for attenuation correction of the heart region was smaller than that of the whole body, and changing the gated SPECT conditions and attenuation-corrected images did not affect myocardial blood flow analysis.

Correction: Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring.

Correction for 'Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring' by Tomoka Yoshii et al., Anal. Methods, 2023, 15, 1790-1796, https://doi.org/10.1039/D3AY00219E.

Mini-TCRs: Truncated T cell receptors to generate T cells from induced pluripotent stem cells.

Allogeneic T cell platforms utilizing induced pluripotent stem cell (iPSC) technology exhibit significant promise for the facilitation of adoptive immunotherapies. While mature T cell receptor (TCR) signaling plays a crucial role in generating T cells from iPSCs, the introduction of exogenous mature TCR genes carries a potential risk of causing graft-versus-host disease (GvHD). In this study, we present the development of truncated TCRα and TCRß chains, termed mini-TCRs, which lack variable domains responsible for recognizing human leukocyte antigen (HLA)-peptide complexes. We successfully induced cytotoxic T lymphocytes (CTLs) from iPSCs by employing mini-TCRs. Combinations of TCRα and TCRß fragments were screened from mini-TCR libraries based on the surface localization of CD3 proteins and their ability to transduce T cell signaling. Consequently, mini-TCR-expressing iPSCs underwent physiological T cell development, progressing from the CD4 and CD8 double-positive stage to the CD8 single-positive stage. The resulting iPSC-derived CTLs exhibited comparable cytokine production and cytotoxicity in comparison to that of full-length TCR-expressing T lymphocytes when chimeric antigen receptors (CARs) were expressed. These findings demonstrate the potential of mini-TCR-carrying iPSCs as a versatile platform for CAR T cell therapy, offering a promising avenue for advancing adoptive immunotherapies.

Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring.

Eggshell-based reversed-phase packing materials were applied to an analytical column for high-performance liquid chromatography. Commercially available eggshell powder was classified by a cyclone system to obtain three types of particles with different diameters (arithmetic mean ± standard deviation: 4.3 ± 3.8, 5.6 ± 3.3, and 9.5 ± 5.5 µm). Sedimentation separation removed tiny particles from each sample, resulting in particles with arithmetic means of 6.6 ± 5.5, 7.3 ± 4.5, and 10.2 ± 5.0 µm, respectively. The unclassified particles and three particle types treated with sedimentation separation were subsequently packed into analytical columns (150 mm × 4.6 mm I.D.), and their separation efficiencies were evaluated by comparing their height equivalent to a theoretical plate (HETP). The column without sedimentation separation exhibited the highest HETP, whereas the columns with sedimentation separation showed better separation efficiency and lower back pressure. The column with the best separation efficiency was applied for the separation of 10 alkylbenzenes and 5 steroids, and all peaks were observed with complete separation (peak resolution: RS > 1.5). Finally, the column was used for quantitative analysis of voriconazole, an azole antifungal agent, and imatinib, a first-generation molecularly targeted drug for cancer treatment, in spiked whole blood. Excellent accuracy (99.1-102.8%) and precision (0.6-1.9%) were observed for the spiked drugs and long-term stability (>3000 column volumes of mobile phase flow) indicated good applicability of the developed eggshell-based column as an analytical column for routine analyses of therapeutic drugs in blood.

Existence of circadian rhythm and its response behavior under different storage conditions of soybean sprouts.

The circadian system plays an essential role in plant cells, and numerous physiological events are generally modulated by circadian clock genes. To further improve postharvest handling of fresh produce, it is vital to understanding the behavior of clock gene expression and its underlying interactions with changes in quality. In this study, the effect of temperature and controlled atmosphere storage on the expression of clock genes (GmLCL1, GmPRR7, GmGI, GmTOC1, and GmLUX), postharvest quality characteristics and their related genes in soybean sprouts were investigated. By fitting the obtained gene expression level using the qPCR method with the cosine curve equation, it was successfully found that the circadian rhythm existed under constant dark storage conditions of soybean sprouts. A significant rhythm in clock gene expression was observed in control soybean sprouts. In contrast, low temperature storage diminished the cyclic expression of GmLCL1, GmPRR7, and GmTOC1, which also affected GmGI and GmLUX expression. Additionally, high CO2 concentrations during storage disturbed the circadian clock by affecting the phase and amplitude of each gene; for low O2 concentrations, it was only affected by amplitude. Interestingly, low temperature, low O2, and high CO2 maintained postharvest quality, including reduced respiration, weight loss and browning incidence. The expression behaviors of postharvest quality attribute-related genes (GmFUM1, GmCS, Gm2-OGDH, GmPPO1, GmPAL) were also influenced by the storage treatments. Overall, the findings first suggest a possible link between clock disruption and postharvest quality maintenance of soybean sprouts.

Anti-PD-1 antibodies recognizing the membrane-proximal region are PD-1 agonists that can down-regulate inflammatory diseases.

The PD-1 receptor triggers a negative immunoregulatory mechanism that prevents overactivation of immune cells and subsequent inflammatory diseases. Because of its biological significance, PD-1 has been a drug target for modulating immune responses. Immunoenhancing anti-PD-1 blocking antibodies have become a widely used cancer treatment; however, little is known about the required characteristics for anti-PD-1 antibodies to be capable of stimulating immunosuppressive activity. Here, we show that PD-1 agonists exist in the group of anti-PD-1 antibodies recognizing the membrane-proximal extracellular region in sharp contrast to the binding of the membrane-distal region by blocking antibodies. This trend was consistent in an analysis of 81 anti-human PD-1 monoclonal antibodies. Because PD-1 agonist antibodies trigger immunosuppressive signaling by cross-linking PD-1 molecules, Fc engineering to enhance FcγRIIB binding of PD-1 agonist antibodies notably improved human T cell inhibition. A PD-1 agonist antibody suppressed inflammation in murine disease models, indicating its clinical potential for treatment of various inflammatory disorders, including autoimmune diseases.

TOB is an effector of the hippocampus-mediated acute stress response.

Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior.

Curcumin doped functionalized cellulose nanofibers based edible chitosan coating on kiwifruits.

The developed edible coating with curcumin facilitated iron functionalized cellulose nanofiber (f-CNF) reinforced chitosan (CS) were applied on kiwifruits for maintaining the quality during storage life. The f-CNF was fabricated via anchoring iron particles onto the surface of CNF as evident by FESEM, FETEM, and XRD analysis. The inclusion of f-CNF and curcumin as a component of edible coating can provide a synergistic effect in maintaining the quality of kiwifruits. The f-CNF (1.5 wt%) dispersed CS edible coating assisted by curcumin provided a lamellar and heterogonous surface morphology with a hazy appearance. The used edible coating materials were effective in reducing mass loss, firmness loss, respiration rate, and microbial count of the kiwifruits during storage life (10 days at 10 °C). Additionally, color, and physiological properties of kiwifruits can be modified by using the addressed edible coating materials.

Identification of a freshness marker metabolite in stored soybean sprouts by comprehensive mass-spectrometric analysis of carbonyl compounds.

The objective of this study was to identify metabolites that quantitatively indicate degrees of freshness of soybean sprouts. Self-cultivated soybean sprouts were stored at 5 °C, 10 °C or 20 °C, and respiratory CO2 production rates were monitored using gas chromatography during storage. Carbonyl compounds (CCs) were analyzed comprehensively using mass-spectroscopic metabolomics analyses. CCs were derivatized using dansyl hydrazine (DH) and were then analyzed using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-MS/MS) with multiplexed multiple reaction monitoring (MRM). In the MRM chromatogram, 171 to 358 peaks were observed from stored soybean sprouts. Principle component analysis and discriminant analysis (PCA-DA) selected the CC-DH derivative ion with a m/z 512 at a retention time of 9.34 min as the most significant metabolite. Searching online metabolomics databases and matching fragment patterns of product ion mass spectra of an authentic standard revealed abscisic acid is a freshness marker of soybean sprouts.

Investigation of color-deepening phenomenon in catechin-(4→8)-dimer as a proanthocyanidin model and structural determination of its derivatives by oxidation.

To elucidate the mechanism of the color-deepening phenomenon in aged red rice samples, a partial structure of proanthocyanidin, (+)-catechin-(4→8)-dimer (1), was synthesized as a model compound and subjected to chemical oxidation. HPLC analysis of oxidized 1 revealed new peaks which were isolated; among these, four compounds (2-5) having formed intramolecular bonds between the D and B rings were determined. These compounds and their derivatives in red rice extracts were identified by multiple reaction monitoring mass spectrometry. The UV-Vis spectra of 1-5 were recorded to clarify the correlation between the color-deepening effect and their chemical structures. Hence, the spectral absorption maxima between 300 and 500nm, corresponding to the oxidation products, increase. Therefore, the color-deepening phenomenon of red rice is thought to proceed via the formation of intramolecular bonds in proanthocyanidin by oxidation.

CO2 processing and hydration of fruit and vegetable tissues by clathrate hydrate formation.

CO2 hydrate can be used to preserve fresh fruits and vegetables, and its application could contribute to the processing of carbonated frozen food. We investigated water transformation in the frozen tissue of fresh grape samples upon CO2 treatment at 2-3 MPa and 3°C for up to 46 h. Frozen fresh bean, radish, eggplant and cucumber samples were also investigated for comparison. X-ray diffraction indicated that after undergoing CO2 treatment for several hours, structure I CO2 hydrate formed within the grape tissue. Phase-contrast X-ray imaging using the diffraction-enhanced imaging technique revealed the presence of CO2 hydrate within the intercellular spaces of these tissues. The carbonated produce became effervescent because of the dissociation of CO2 hydrate through the intercellular space, especially above the melting point of ice. In addition, suppressed metabolic activity resulting from CO2 hydrate formation, which inhibits water and nutrient transport through intercellular space, can be expected.