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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a pandemic throughout 2020. Since the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry, increment of ACE2 would lead to an increased risk of SARS-CoV-2 infection. At the same time, an association of the ABO blood group system with COVID-19 has also been highlighted: there is increasing evidence to suggest that non-O individuals are at higher risk of severe COVID-19 than O individuals. These findings imply that simultaneous suppression of ACE2 and ABO would be a promising approach for prevention or treatment of COVID-19. Notably, we have previously clarified that histone deacetylase inhibitors (HDACIs) are able to suppress ABO expression in vitro. Against this background, we further evaluated the effect of HDACIs on cultured epithelial cell lines, and found that HDACIs suppress both ACE2 and ABO expression simultaneously. Furthermore, the amount of ACE2 protein was shown to be decreased by one of the clinically-used HDACIs, panobinostat, which has been reported to reduce B-antigens on cell surfaces. On the basis of these findings, we conclude that panobinostat could have the potential to serve as a preventive drug against COVID-19.

The human ABO blood group system is of great importance in blood transfusion and organ transplantation. ABO transcription is known to be regulated by a constitutive promoter in a CpG island and regions for regulation of cell-specific expression such as the downstream + 22.6-kb site for epithelial cells and a site in intron 1 for erythroid cells. Here we investigated whether the + 22.6-kb site might play a role in transcriptional regulation of the gene encoding odorant binding protein 2B (OBP2B), which is located on the centromere side 43.4 kb from the + 22.6-kb site. In the gastric cancer cell line KATOIII, quantitative PCR analysis demonstrated significantly reduced amounts of OBP2B and ABO transcripts in mutant cells with biallelic deletions of the site created using the CRISPR/Cas9 system, relative to those in the wild-type cells, and Western blotting demonstrated a corresponding reduction of OBP2B protein in the mutant cells. Moreover, single-molecule fluorescence in situ hybridization assays indicated that the amounts of both transcripts were correlated in individual cells. These findings suggest that OBP2B could be co-regulated by the + 22.6-kb site of ABO .

Three-dimensional (3D) reconstruction images using postmortem computed tomography (PMCT) are increasingly used to convey complex information to non-medical professionals, such as police and jurors. This case report demonstrates the effective use of 3D reconstruction images by integrating pre-autopsy, intra-autopsy, and knife CT data to achieve precise visualization of the wound path and associated injuries. The case involved a man in his 40s who was stabbed multiple times and pronounced dead approximately two hours after receiving emergency treatment. Initial PMCT revealed an intraperitoneal hemorrhage; however, no injuries to the abdominal organs or aorta were identified. During the autopsy, a critical abdominal aortic injury was discovered, prompting a further CT scan; however, the aorta remained in situ. By utilizing pre-autopsy, intra-autopsy, and knife CT data, the spatial relationships between the stab wound in the right hypochondriac area, aortic injury, and knife were effectively visualized. This novel approach highlights the potential of intra-autopsy CT for precise forensic visualization, offering a strategy for improvements in the accuracy and clarity of forensic evidence presentation.

Postmortem CT (PMCT) is widely used in forensic investigations to determine the causes of death and is particularly effective in trauma cases and for detecting foreign bodies such as gas or metallic fragments. However, PMCT utility in cases of advanced postmortem changes remains poorly explored. We present the case of a woman in her 60s with a history of schizophrenia who was found in an advanced state of decomposition. PMCT revealed a high-density foreign body in the pharynx, with a CT value of 154.4 HU. During autopsy, a white object, approximately 5 cm in size, was discovered in the pharynx, which was later identified as a mochi, a traditional Japanese rice cake. This led to the conclusion that the cause of death was asphyxiation due to airway obstruction caused by a mochi. This case highlights the diagnostic potential of PMCT in cases of advanced decomposition, particularly for detecting airway obstruction caused by food. Further research and accumulation of such cases are essential to completely evaluate the utility of PMCT in forensic investigations involving advanced decomposition.

Postmortem computed tomography angiography (PMCTA) is a valuable tool for diagnosing vascular conditions, such as hemorrhages, in trauma cases. This case report demonstrates the use of the Voronoi algorithm to assess myocardial ischemia using coronary PMCTA. A male in his 70s was found unconscious in a car after colliding with a traffic light pole. Despite medical interventions, including pericardial drainage and cardiopulmonary resuscitation, the patient died two hours later. PMCTA revealed significant filling defects in the left anterior descending artery (LAD), consistent with plaque rupture and narrowing observed during autopsy. The cause of death in this case was likely cardiac tamponade due to cardiac rupture secondary to myocardial infarction resulting from LAD stenosis. Cardiac perfusion areas were analyzed using the Voronoi algorithm, demonstrating a total myocardial volume of 151.9 mL in the left ventricle. Perfusion volumes were calculated as 92.9 mL (61.2%) for the LAD, 34.2 mL (22.5%) for the left circumflex artery, and 24.9 mL (16.4%) for the right coronary artery. The predicted ischemic volume distal to the LAD stenosis was estimated to be 49.8 mL (32.8%). Furthermore, the ischemic areas observed during autopsy macroscopically corresponded well with the predicted ischemic regions. This case highlights that combining PMCTA with the Voronoi algorithm provides an accurate method for assessing myocardial ischemic areas, offering a non-invasive approach to visualize and quantify perfusion and ischemic regions.

Three-dimensional (3D) documentation is increasingly being utilized in forensic investigations to record injuries and reconstruct crime scenes accurately. Although photogrammetry offers a low-cost and accessible method for capturing surface details, its integration with postmortem CT (PMCT) data and virtual reality (VR) can further enhance spatial understanding. We report a fatal case of a stair-related fall of a man in his 70s, in which we visualized the injuries by combining PMCT data with surface models of the body and the staircase. A 3D model of the bones was created from the PMCT data, whereas surface models of the body and staircase were generated using photogrammetry. The reconstructed scene was visualized in VR using a MetaQuest 3 headset. The reconstructed scene clearly demonstrated the spatial relationship between the stair edges and injury sites, such as the occipital region, midthoracic spine, and sacrum. The vertical distances between the injuries closely matched the staircase step depth, supporting the interpretation of stair-related falls. This method provides an intuitive and immersive understanding of injury mechanisms. Our approach demonstrates the feasibility and utility of integrating CT, photogrammetry, and VR in forensic death investigations, offering enhanced documentation and visualization that can benefit not only forensic experts but also legal professionals and juries.

A- and B-antigens are present on red blood cells (RBCs) as well as other cells and secretions in Hominoidea including humans and apes such as chimpanzees and gibbons, whereas expression of these antigens on RBCs is subtle in monkeys such as Japanese macaques. Previous studies have indicated that H-antigen expression has not completely developed on RBCs in monkeys. Such antigen expression requires the presence of H-antigen and A- or B-transferase expression in cells of erythroid lineage, although whether or not ABO gene regulation is associated with the difference of A- or B-antigen expression between Hominoidea and monkeys has not been examined. Since it has been suggested that ABO expression on human erythrocytes is dependent upon an erythroid cell-specific regulatory region or the + 5.8-kb site in intron 1, we compared the sequences of ABO intron 1 among non-human primates, and demonstrated the presence of sites orthologous to the + 5.8-kb site in chimpanzees and gibbons, and their absence in Japanese macaques. In addition, luciferase assays revealed that the former orthologues enhanced promoter activity, whereas the corresponding site in the latter did not. These results suggested that the A- or B-antigens on RBCs might be ascribed to emergence of the + 5.8-kb site or the corresponding regions in ABO through genetic evolution.

Sudden death, or unexpected natural death of a healthy individual, is a serious problem in all nations. Sudden cardiac death (SCD) mainly due to ischemic heart diseases is the top cause of sudden death. However, there are pathophysiological conditions, referred to as sudden arrhythmic death syndrome, in which no apparent lesion can be identified even after complete conventional or ordinary autopsy. While postmortem genetic analyses have accumulated evidence about underlying genetic abnormality in such cases, the precise relationships between genetic background and the phenotype have been largely elusive. In this study, a retrospective investigation of 17 autopsy cases in which lethal arrhythmia was suspected to be the cause of death was carried out. Genetic analysis focusing on 72 genes reported to be associated with cardiac dysfunctions was performed, in combination with detailed histopathological and postmortem imaging examination, and a family study. As a result, in two cases of suspected arrhythmogenic cardiomyopathy (ACM), we found a nonsense variant in PKP2 and frameshift variant in TRPM4 gene. In contrast, the other 15 cases showed no morphological changes in the heart despite the presence of a frameshift variant and several missense variants, leaving the clinical significance of these variants obscure. The findings of the present study suggest that nonsense and frameshift variants could be involved in the morphological abnormality in cases of SCD due to ACM, while missense variants alone rarely contribute to massive structural changes in the heart.

Forensic pathologists often encounter cases of acute subdural hematoma (SDH) due to trauma, whereas those attributable to endogenous causes are rare. Here, we report a case of the latter type in a 42-year-old man who was found dead at home after several months of fever and malaise. Postmortem computed tomography (PMCT) and autopsy were undertaken to clarify the cause of death. PMCT images revealed a fatal SDH and a localized hyper-density area in the right parietal lobe; macroscopic and microscopic examinations revealed SDH due to rupture of a mycotic aneurysm (MA) associated with meningitis. The PMCT images also indicated thickening and calcification of the mitral valve, while autopsy demonstrated infective endocarditis (IE). In addition, PMCT demonstrated a low-density area in the spleen, which was shown to be a splenic abscess at autopsy. PMCT also demonstrated tooth cavities. Based on the findings of autopsy, the cause of death was considered to be SDH due to rupture of the MA resulting from meningitis with IE and splenic abscess. Although PMCT was unable to clarify the significance of any individual feature, a retrospective review of the PMCT images might have suggested IE, bacteremia, or ruptured MA leading to SDH. This case suggests that, instead of interpreting individual features demonstrated on PMCT images, integrated interpretation of overall PMCT findings might provide clues for identifying causes of death, despite the fact that PMCT lacks diagnostic accuracy for infectious diseases such as IE and meningitis.

The dynamic cross correlation (DCC) analysis is a popular method for analyzing the trajectories of molecular dynamics (MD) simulations. However, it is difficult to detect correlative motions that appear transiently in only a part of the trajectory, such as atomic contacts between the side-chains of amino acids, which may rapidly flip. In order to capture these multi-modal behaviors of atoms, which often play essential roles, particularly at the interfaces of macromolecules, we have developed the \"multi-modal DCC (mDCC)\" analysis. The mDCC is an extension of the DCC and it takes advantage of a Bayesian-based pattern recognition technique. We performed MD simulations for molecular systems modeled from the (Ets1)2-DNA complex and analyzed their results with the mDCC method. Ets1 is an essential transcription factor for a variety of physiological processes, such as immunity and cancer development. Although many structural and biochemical studies have so far been performed, its DNA binding properties are still not well characterized. In particular, it is not straightforward to understand the molecular mechanisms how the cooperative binding of two Ets1 molecules facilitates their recognition of Stromelysin-1 gene regulatory elements. A correlation network was constructed among the essential atomic contacts, and the two major pathways by which the two Ets1 molecules communicate were identified. One is a pathway via direct protein-protein interactions and the other is that via the bound DNA intervening two recognition helices. These two pathways intersected at the particular cytosine bases (C110/C11), interacting with the H1, H2, and H3 helices. Furthermore, the mDCC analysis showed that both pathways included the transient interactions at their intermolecular interfaces of Tyr396-C11 and Ala327-Asn380 in multi-modal motions of the amino acid side chains and the nucleotide backbone. Thus, the current mDCC approach is a powerful tool to reveal these complicated behaviors and scrutinize intermolecular communications in a molecular system.