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Endoscopy poses a high risk of severe acute respiratory syndrome coronavirus 2 infection for medical personnel due to the dispersal of aerosols from the patient. We investigated the location and size of droplets generated during esophagogastroduodenoscopy (EGD) and endoscopic submucosal dissection (ESD), the contamination of the surrounding area before and after the procedures, and the effectiveness of using an extraoral suction device (Free arm arteo; TOKYO GIKEN, Inc., Tokyo, Japan).Patients who consented to the study and underwent EGD or ESD between December 8, 2020, and April 15, 2021, at the National Cancer Center East Hospital were included. Adenosine triphosphate (ATP) hygiene monitoring tests and a particle counter were used for measurements.Assessments were performed on 22 EGD and 15 ESD cases. ATP hygiene monitoring tests showed significant elevations at three sites near the patient, and two sites 1.5 m away, for EGD, and at four sites near the patient and 1.5 m away for ESD. In both ESD and EGD, extraoral suction devices reduced the extent of the contamination. Particles5 μm in size were generated during endoscopic procedures and dispersed from both the forceps hole and the patient's mouth. The extraoral suction device did not reduce the number of particles generated.During endoscopic procedures, cleaning the surrounding environment is important in addition to standard precautions the endoscopist and caregivers take. The use of extraoral suction devices can also potentially reduce contamination of the surrounding environment.

Rapid and efficient isolation of intact lysosomes is necessary to study their functions and metabolites by proteomic analysis. We developed a swift and robust nanoparticle-based magnetic separation method in which magnetic-plasmonic hybrid nanoparticles (MPNPs) conjugated with amino dextran (aDxt) were targeted to the lumen of lysosomes

Matrin-3 is a multifunctional protein that binds to both DNA and RNA. Its DNA-binding activity is linked to the formation of the nuclear matrix and transcriptional regulation, while its RNA-binding activity is linked to mRNA metabolism including splicing, transport, stabilization, and degradation. Correspondingly, Matrin-3 has two zinc finger domains for DNA binding and two consecutive RNA recognition motif (RRM) domains for RNA binding. Matrin-3 has been reported to cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) when its disordered region contains pathogenic mutations. Simultaneously, it has been shown that the RNA-binding activity of Matrin-3 mediated by its RRM domains, affects the formation of insoluble cytoplasmic granules, which are related to the pathogenic mechanism of ALS/FTD. Thus, the effect of the RRM domains on the phase separation of condensed protein/RNA mixtures has to be clarified for a comprehensive understanding of ALS/FTD. Here, we report the 1H, 15N, and 13C resonance assignments of the two RNA binding domains and their solution structures. The resonance assignments and the solution structures obtained in this work will contribute to the elucidation of the molecular basis of Matrin-3 in the pathogenic mechanism of ALS and/or FTD.

Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a substrate for the modification. However, a limited number of enzymes responsible for this modification have been reported. Moreover, the biological role of histidine methylation has remained poorly understood. Here, we report that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traverse on tyrosine codons, allowing the proper folding of synthesized proteins. By performing an in vitro methylation assay with a methyl donor analog and quantitative mass spectrometry, we found that His245 of RPL3 is methylated at the τ-N position by METTL18. Structural comparison of the modified and unmodified ribosomes showed stoichiometric modification and suggested a role in translation tuning. Indeed, genome-wide ribosome profiling revealed suppressed ribosomal translocation at tyrosine codons by RPL3 methylation. Because the slower elongation provides enough time for nascent protein folding, RPL3 methylation protects cells from the cellular aggregation of Tyr-rich proteins. Our results reveal histidine methylation as an example of a “ribosome code” that ensures proteome integrity in cells.

Background: Glutamic acid, an amino acid that exhibits umami taste, is utilized in Japanese food and is abundant in human milk. We examined the influence of maternal habitual eating behavior on glutamic acid concentration in human milk. Research Aim: To determine the association between maternal dietary behaviors at the end of pregnancy and the 1st month postpartum and glutamic acid concentration in colostrum and mature milk. Method: This was a prospective, correlational, one-group longitudinal study. Women aged 20–30 years during the third trimester of pregnancy ( N = 30) consented to participate and completed the data collection. Dietary history questionnaires were used to measure food intake. Glutamic acid levels in whey from colostrum and mature milk and in plasma during late pregnancy and the first month postpartum were measured. Data were considered significant at p < .05. Basic statistics, correlation coefficients analysis, unpaired t test, and one-way analysis of variance were performed. Results: Glutamic acid concentrations in human milk and plasma were found to be significantly associated with the consumption of several different foods. There was no association between glutamic acid concentrations in human milk and plasma or between glutamic acid concentrations in colostrum and mature milk. The glutamic acid content of mature milk differed by physical activity level (mild and moderate) during the first month postpartum ( t [46] = 2.87, p < .01). Conclusion: There was no clear association between habitual dietary behavior and glutamic acid concentration in human milk. However, maternal factors other than diet may be important and require additional research.

For lateral flow immunoassay (LFIA), it is an important challenge to enhance the detection sensitivity to the same level as polymerase chain reaction or enzyme-linked immunosorbent assay to make LFIA pervasive in the field of on-site environmental analysis. We recently demonstrated that the LFIA sensitivity is dramatically enhanced by using Pt-nanoparticle-latex nanocomposite beads (Pt-P2VPs) as probes for the detection of the influenza A (H1N1) antigen compared with using conventional Au colloids as probes. Here, to further enhance the LFIA sensitivity using Pt-P2VPs, superparamagnetic iron oxide nanoparticles (SPIONs) were chemically conjugated to Pt-P2VPs (Pt-P2VP@SPION) to give them magnetic separation capability (enrichment and/or purification). To investigate the effect of magnetic enrichment on the LFIA sensitivity in a sandwich format, the C-reactive protein (CRP) was chosen as a model analyte and anti-CRP antibody (CRPAb)-conjugated Pt-P2VP@SPION (Pt-P2VP@SPION-CRPAb) beads were used as probes. The visual limit of detection (LOD) of LFIA was successfully lowered by increasing the magnetic enrichment factor φ. The minimum LOD under the present experimental conditions was 0.08 ng/mL for φ = 40, which is 26-fold lower than that of the standard Au-nanoparticle-based LFIA. In theory, the LOD can be unlimitedly decreased by just increasing φ. However, the times required for both the antigen-antibody binding reaction and magnetic separation dramatically increase with φ. We also propose solutions to overcome this drawback.

A 72-year-old man was treated with prednisolone and cyclosporine A for idiopathic pulmonary fibrosis. A nodule with a diameter of 19 mm was found in the right lung and diagnosed as lung squamous cell carcinoma. Anti-cancer treatments were not performed because of the presence of advanced interstitial pneumonia and chronic respiratory failure. Cyclosporine A was tapered to avoid suppression of anti-tumor immunity, and pirfenidone was initiated. Within 2 months, the tumor had shrunk to 10 mm in diameter and remained regressed for 9 months. This is the first report of a non-hematologic solid organ tumor responding to the discontinuation of immunosuppressants.

In humans, YTH (YT521-B homology) domain containing protein 2 (YTHDC2) plays a crucial role in the phase-shift from mitosis to meiosis. YTH domains bind to methylated adenosine nucleotides such as m6A. In a phylogenic tree, the YTH domain of YTHDC2 (YTH2) and that of the YTH containing protein YTHDC1 (YTH1) belong to the same sub-group. However, the binding affinity of m6A differs between these proteins. Here, we report 1H, 13C and 15N resonance assignment of YTH2 and its solution structure to examine the difference of the structural architecture and the dynamic properties of YTH1 and YTH2. YTH2 adopts a β1-α1-β2-α2-β3-β4-β5-α3-β6-α4 topology, which was also observed in YTH1. However, the β4-β5 loops of YTH1 and YTH2 are distinct in length and amino acid composition. Our data revealed that, unlike in YTH1, the structure of m6A-binding pocket of YTH2 formed by the β4-β5 loop is stabilized by electrostatic interaction. This assignment and the structural information for YTH2 will provide the insight on the further functional research of YTHDC2.

Spinel ferrite MFe2O4 (M = Mn, Fe, Co, Ni, and Zn) nanoparticles, coordinated with oleylamine, oleic acid, and trioctylphosphine oxide, were effectively synthesized by the microwave-assisted rapid ...

Thermoelectric (TE) materials have consistently gained momentum for use in waste heat utilization technology. Recently, we fabricated a Cu3AlSnS5 (CATS) nanobulk by pelletizing chemically synthesiz...

The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 106 iPSC within 7 weeks was 1.8‐4.0 × 109. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies., This translational study aimed to develop anti–GPC3 CAR‐expressing NK/ILC cells derived from HLA‐homozygous iPSC clone as an effective cell therapy against disseminated ovarian tumors and to assess the clinical cell manufacturing and pre–clinical aspects of the therapy, including safety and efficacy. Those aspects of the therapy clarified in the study provide perspective for the planned clinical trial.

The efficient removal of organic refractory pollutants such as dyes and antibiotics in wastewater is crucial for protecting the environment and human health. In this work, a NiCo-layered double hydroxide (NiCo-LDH) with a uniform microspherical, hierarchical structure and a high surface area was successfully synthesized as an effective peroxymonosulfate (PMS) activator for the degradation of various organic dyes and antibiotics. The influence of various parameters on the catalytic activity of the NiCo-LDH was determined. Radical scavenger studies unveiled the major reactive oxygen species (ROSs) generated in the NiCo-LDH/PSM system to be

Background Postoperative nausea and vomiting (PONV) delays postoperative recovery, prolongs hospital stays, and hinders patients’ return to society, thus making it a major cause of increased healthcare costs. It is also the most troubling postoperative complication in female patients undergoing surgery. However, in Japan, guidelines for the management of PONV have not been established, and the management protocol for PONV is left to each institution and anesthesiologist. Therefore, we developed criteria for intraoperative management of PONV. Methods In female surgical patients, the usefulness of the criteria was evaluated by comparing the implementation rate of intraoperative management and PONV incidence before and after the establishment of the criteria. An Apfel simplified score (Apfel score) ≥2 was set as an indication for intraoperative management of PONV. Results The implementation rate of intraoperative management increased from 91.2 to 96.0% after the introduction of the criteria. In patients with an Apfel score of 2, the intraoperative management implementation rate significantly increased from 81.1 to 94.7% (p = 0.016), while PONV incidence significantly decreased from 44.6 to 34.1% after the introduction of the criteria (p = 0.040). Conclusions The criteria for intraoperative management of PONV increased the implementation rate of intraoperative management and decreased PONV incidence, indicating the usefulness of the criteria.

Eukaryotic translation initiation factor (eIF) 4A — a DEAD-box RNA-binding protein — plays an essential role in translation initiation. Two mammalian eIF4A paralogs, eIF4A1 and eIF4A2, have been assumed to be redundant because of their high homology, and the difference in their functions has been poorly understood. Here, we show that eIF4A1, but not eIF4A2, enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. RNA-immunoprecipitation sequencing (RIP-Seq) of the two eIF4A paralogs revealed that eIF4A1 preferentially binds to mRNAs containing terminal oligopyrimidine (TOP) motifs, whose translation is rapidly repressed upon mTOR inhibition. This biased interaction depends on a La-related RNA-binding protein, LARP1. Ribosome profiling revealed that the deletion of EIF4A1, but not EIF4A2, rendered the translation of TOP mRNAs resistant to mTOR inactivation. Moreover, eIF4A1 enhances the affinity between TOP mRNAs and LARP1 and thus ensures stronger translation repression upon mTORC1 inhibition. Our data show that the distinct protein interactions of these highly homologous translation factor paralogs shape protein synthesis during mTORC1 inhibition and provide a unique example of the repressive role of a universal translation activator.

Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotide molecules on its substrate, unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. However, its precise mechanism has remained unclear. Here, our cryo-electron microscopy (cryo-EM) analysis reveals that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B retains nucleotide exchange activity even in the presence of eIF2(αP), in line with the cryo-EM structures of the eIF2B•SFSV NSs•unphosphorylated eIF2 complex. A genome-wide ribosome profiling analysis clarified that SFSV NSs expressed in cultured human cells attenuates the ISR triggered by thapsigargin, an endoplasmic reticulum stress inducer. Furthermore, SFSV NSs introduced in rat hippocampal neurons and human induced-pluripotent stem (iPS) cell-derived motor neurons exhibits neuroprotective effects against the ISR-inducing stress. Since ISR inhibition is beneficial in various neurological disease models, SFSV NSs may be a promising therapeutic ISR inhibitor., Here the authors show that a viral protein interferes with the binding of phosphorylated eIF2 to eIF2B, thereby suppressing the host integrated stress response (ISR). This suppression of the ISR abrogates translational changes of the host and ameliorates neurite degradation under stress.

Human lymphocyte antigen (HLA) class I molecules play a central role in cytotoxic T lymphocytes (CTL)‐based antitumor immunity. However, the expression rate of HLA class I in cancer cells remains a topic of discussion. We compared HLA class I expression levels between cancer cells and surrounding non–tumorous hepatocytes in 20 early‐stage hepatocellular carcinoma (HCC) patients by immunohistochemistry using EMR 8‐5. The expression levels of HLA class I were classified as negative, incomplete positive or complete positive. Similarly, for various types of solid cancers, HLA class I expression was examined. For the HLA class I expression in cancer cells, among 20 HCC patients, 13 were complete positive, 3 were incomplete positive, and 4 were negative. In addition, 15 (75.0%) had higher expression levels of HLA class I in cancer cells compared with that in surrounding non–tumorous hepatocytes. An interferon‐γ (IFN‐γ) enzyme‐linked immunospot (ELISPOT) assay indicated that cancer cells with positive expression of HLA class I had strong sensitivity to antigen‐specific CTL. We suggested that HLA class I expression in cancer cells could be involved in the clinical prognosis of HCC patients. Similarly, 66.7%, 100.0%, 66.7% and 62.5% of patients with early‐stage pancreatic, gallbladder, esophageal and breast cancers, respectively, had higher expression levels of HLA class I in cancer cells than in surrounding normal tissue cells. We suggest that in several early‐stage solid cancers, including HCC, HLA class I expression levels in cancer cells are higher than that in surrounding normal tissue cells, which could result in the anti–tumor effect of CTL‐based cancer immunotherapy.

To mitigate the damage caused by debris flows resulting from heavy precipitation and to aid in evacuation plan preparation, areas at risk should be mapped on a scale appropriate for affected individuals and communities. We tested the effectiveness of simply identifying debris-flow hazards through automated derivation of surface curvatures using LiDAR digital elevation models. We achieved useful correspondence between plan curvatures and areas of existing debris-flow damage in two localities in Japan using the analysis of digital elevation models (DEMs). We found that plan curvatures derived from 10m DEMs may be useful to indicate areas that are susceptible to debris flow in mountainous areas. In residential areas located on gentle sloping debris flow fans, the greatest damage to houses was found to be located in the elongated depressions that are connected to mountain stream valleys. Plan curvature derived from 5m DEM was the most sensitive indicators for susceptibility to debris flows.