Development of a mugineic acid family phytosiderophore analog as an iron fertilizer

Iron (Fe) is an essential nutrient, but is poorly bioavailable because of its low solubility in alkaline soils; this leads to reduced agricultural productivity. To overcome this problem, we first showed that the soil application of synthetic 2′-deoxymugineic acid, a natural phytosiderophore from the Poaceae, can recover Fe deficiency in rice grown in calcareous soil. However, the high cost and poor stability of synthetic 2′-deoxymugineic acid preclude its agricultural use. In this work, we develop a more stable and less expensive analog, proline-2′-deoxymugineic acid, and demonstrate its practical synthesis and transport of its Fe-chelated form across the plasma membrane by Fe(III)•2’-deoxymugineic acid transporters. Possibility of its use as an iron fertilizer on alkaline soils is supported by promotion of rice growth in a calcareous soil by soil application of metal free proline-2’-deoxymugineic acid

Editorial for the Special Issue: Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections

In Japan, there is a proverb that the common cold is associated with all diseases [...

Factors associated with serious psychological distress during the COVID-19 pandemic in Japan: a nationwide cross-sectional internet-based study.

ObjectiveTo investigate the factors associated with serious psychological distress (SPD) during the COVID-19 pandemic in Japan.DesignNationwide cross-sectional study using survey data.SettingInternet survey using sampling weights for national estimates conducted between 25 August and 30 September 2020 in Japan.ExposuresDemographics (age, gender), socioeconomic status (income level, employment type, educational attainment, marital status, family composition and caregiving burden); the experience of domestic violence (DV), the state of emergency and fear of and stigma related to COVID-19.Main outcome measuresPrevalence of SPD, defined as Kessler 6 Scale score ≥13.ResultsAmong 25 482 respondents, 10.0% met the criteria of SPD. Overall, women (adjusted OR (aOR) 1.59; 95% CI 1.17 to 2.16; p=0.003), ages 15-29 (aOR 2.35 compared with ages 45-59 years; 95% CI 1.64 to 3.38; p<0.001), low-income level (aOR 1.70 compared with intermediate income; 95% CI 1.16 to 2.49; p=0.007), providing caregiving to family members (aOR 5.48; 95% CI 3.51 to 8.56; p<0.001), experiencing DV (aOR 5.72; 95% CI 3.81 to 8.59; p<0.001) and fear of COVID-19 (aOR 1.96; 95% CI 1.55 to 2.48; p<0.001) were associated with SPD. Among women aged 15-29 years, who have a higher risk of suicide during the COVID-19 pandemic in Japan, caregiving, DV, fear of COVID-19 and COVID-19-related stigma were associated with SPD.ConclusionsEconomic situation, caregiving burden, DV and fear of COVID-19 were independently associated with SPD during the COVID-19 pandemic. Among young women, similar factors, except economic situation, were associated with SPD. Targeted interventions based on age and gender may be more effective in mitigating the negative impact of the COVID-19 pandemic on the population's mental health

Prevalence and changes of low-value care at acute care hospitals: a multicentre observational study in Japan.

ObjectivesWe aimed to examine the use and factors associated with the provision of low-value care in Japan.DesignA multicentre observational study.SettingRoutinely collected claims data that include all inpatient and outpatient visits in 242 large acute care hospitals (accounting for approximately 11% of all acute hospitalisations in Japan).Participants345 564 patients (median age (IQR): 62 (40-75) years; 182 938 (52.9%) women) seeking care at least once in the hospitals in the fiscal year 2019.Primary and secondary outcome measuresWe identified 33 low-value services, as defined by clinical evidence, and developed two versions of claims-based measures of low-value services with different sensitivity and specificity (broader and narrower definitions). We examined the number of low-value services, the proportion of patients receiving these services and the proportion of total healthcare spending incurred by these services in 2019. We also evaluated the 2015-2019 trends in the number of low-value services.ResultsServices identified by broader low-value care definition occurred in 7.5% of patients and accounted for 0.5% of overall annual healthcare spending. Services identified by narrower low-value care definition occurred in 4.9% of patients and constituted 0.2% of overall annual healthcare spending. Overall, there was no clear trend in the prevalence of low-value services between 2015 and 2019. When focusing on each of the 17 services accounting for more than 99% of all low-value services identified (narrower definition), 6 showed decreasing trends from 2015 to 2019, while 4 showed increasing trends. Hospital size and patients' age, sex and comorbidities were associated with the probability of receiving low-value service.ConclusionsA substantial number of patients received low-value care in Japan. Several low-value services with high frequency, especially with increasing trends, require further investigation and policy interventions for better resource allocation

Rhinovirus Infection and Virus-Induced Asthma

While the aetiology of asthma is unclear, the onset and/or exacerbation of asthma may be associated with respiratory infections. Virus-induced asthma is also known as virus-associated/triggered asthma, and the reported main causative agent is rhinovirus (RV). Understanding the relationship between viral infections and asthma may overcome the gaps in deferential immunity between viral infections and allergies. Moreover, understanding the complicated cytokine networks involved in RV infection may be necessary. Therefore, the complexity of RV-induced asthma is not only owing to the response of airway and immune cells against viral infection, but also to allergic immune responses caused by the wide variety of cytokines produced by these cells. To better understand RV-induced asthma, it is necessary to elucidate the nature RV infections and the corresponding host defence mechanisms. In this review, we attempt to organise the complexity of RV-induced asthma to make it easily understandable for readers

Interferon (IFN)-Induced Protein 35 (IFI35), a Type I Interferon-Dependent Transcript, Upregulates Inflammatory Signaling Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells

Background/Aims: Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antiviral and “pseudoviral” immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs. Methods: We treated human MCs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, then analysed the IFI35 expression by reverse transcription-polymerase chain reaction and western blotting. To examine the regulation of IFI35 expression, we subjected MCs to RNA interference (siRNA) against IFN-β, RIG-I, and MDA5. Results: Activation of TLR3 by poly IC induces the IFI35 expression in MCs. siRNA against IFN-β inhibited poly IC-induced IFI35 expression. Knockdown of IFI35 resulted in a decrease of poly IC-induced RIG-I and MDA5 protein as well as decreased CCL5 and CXCL10 mRNA and protein expression. However, it did not affect the expression of none of phosphorylated signal transducers or activator of transcription (STAT) 1 protein, or RIG-I and MDA5 in mRNA levels. Conclusion: Regional expression of IFI35 and its dysregulation may be involved in the pathogenesis of glomerular inflammation in CKD

Hydrogen Rearrangement Rules: Computational MS/MS Fragmentation and Structure Elucidation Using MS-FINDER Software

Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: “resolved” (regular HR behavior following HR rules), “semiresolved” (irregular HR behavior), and “formula-assigned” (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases, and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages, and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5063 MassBank MS/MS records and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http://prime.psc.riken.jp/

Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A

We performed evolution, phylodynamics, and reinfection-related antigenicity analyses of respiratory syncytial virus subgroup A (RSV-A) fusion (F) gene in globally collected strains (1465 strains) using authentic bioinformatics methods. The time-scaled evolutionary tree using the Bayesian Markov chain Monte Carlo method estimated that a common ancestor of the RSV-A, RSV-B, and bovine-RSV diverged at around 450 years ago, and RSV-A and RSV-B diverged around 250 years ago. Finally, the RSV-A F gene formed eight genotypes (GA1-GA7 and NA1) over the last 80 years. Phylodynamics of RSV-A F gene, including all genotype strains, increased twice in the 1990s and 2010s, while patterns of each RSV-A genotype were different. Phylogenetic distance analysis suggested that the genetic distances of the strains were relatively short (less than 0.05). No positive selection sites were estimated, while many negative selection sites were found. Moreover, the F protein 3D structure mapping and conformational epitope analysis implied that the conformational epitopes did not correspond to the neutralizing antibody binding sites of the F protein. These results suggested that the RSV-A F gene is relatively conserved, and mismatches between conformational epitopes and neutralizing antibody binding sites of the F protein are responsible for the virus reinfection