IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome.

Cytokine release syndrome (CRS) is a life-threatening complication induced by systemic inflammatory responses to infections, including bacteria and chimeric antigen receptor T cell therapy. There are currently no immunotherapies with proven clinical efficacy and understanding of the molecular mechanisms of CRS pathogenesis is limited. Here, we found that patients diagnosed with CRS from sepsis, acute respiratory distress syndrome (ARDS), or burns showed common manifestations: strikingly elevated levels of the four proinflammatory cytokines interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and IL-10 and the coagulation cascade activator plasminogen activator inhibitor-1 (PAI-1). Our in vitro data indicate that endothelial IL-6 trans-signaling formed an inflammation circuit for robust IL-6, IL-8, and MCP-1 production and promoted PAI-1 production; additionally, an IL-6 signaling blockade by the human monoclonal antibody tocilizumab blunted endothelial cell activation. Plasma from severe COVID-19 patients similarly exhibited increased IL-6, IL-10, and MCP-1 levels, but these levels were not as high as those in patients with CRS from other causes. In contrast, the PAI-1 levels in COVID-19 patients were as highly elevated as those in patients with bacterial sepsis or ARDS. Tocilizumab treatment decreased the PAI-1 levels and alleviated critical illness in severe COVID-19 patients. Our findings suggest that distinct levels of cytokine production are associated with CRS induced by bacterial infection and COVID-19, but both CRS types are accompanied by endotheliopathy through IL-6 trans-signaling. Thus, the present study highlights the crucial role of IL-6 signaling in endothelial dysfunction during bacterial infection and COVID-19.

Strategic roadmap to assess forest vulnerability under air pollution and climate change.

Although it is an integral part of global change, most of the research addressing the effects of climate change on forests have overlooked the role of environmental pollution. Similarly, most studies investigating the effects of air pollutants on forests have generally neglected the impacts of climate change. We review the current knowledge on combined air pollution and climate change effects on global forest ecosystems and identify several key research priorities as a roadmap for the future. Specifically, we recommend (1) the establishment of much denser array of monitoring sites, particularly in the South Hemisphere; (2) further integration of ground and satellite monitoring; (3) generation of flux-based standards and critical levels taking into account the sensitivity of dominant forest tree species; (4) long-term monitoring of N, S, P cycles and base cations deposition together at global scale; (5) intensification of experimental studies, addressing the combined effects of different abiotic factors on forests by assuring a better representation of taxonomic and functional diversity across the ~73,000 tree species on Earth; (6) more experimental focus on phenomics and genomics; (7) improved knowledge on key processes regulating the dynamics of radionuclides in forest systems; and (8) development of models integrating air pollution and climate change data from long-term monitoring programs.

Pre- and post-accident environmental transfer of radionuclides in Japan: lessons learned in the IAEA MODARIA II programme.

An international review of radioecological data derived after the accident at the Fukushima Daiichi nuclear power plant was an important component of activities in working group 4 of the IAEA Models and data for radiological impact assessment, phase II (MODARIA II) programme. Japanese and international scientists reviewed radioecological data in the terrestrial and aquatic environments in Japan reported both before and after the accident. The environmental transfer processes considered included: (a) interception and retention radionuclides by plants, (b) loss of radionuclides from plant and systemic transport of radionuclides in plants (translocation), (c) behaviour of radiocaesium in soil, (d) uptake of radionuclides from soil by agricultural crops and wild plants, (e) transfer of radionuclides from feedstuffs to domestic and wild animals, (f) behaviour of radiocaesium in forest trees and forest systems, (g) behaviour of radiocaesium in freshwater systems, coastal areas and in the ocean, (h) transport of radiocaesium from catchments through rivers, streams and lakes to the ocean, (i) uptake of radiocaesium by aquatic organisms, and (j) modification of radionuclide concentrations in food products during food processing and culinary preparation. These data were compared with relevant global data within IAEA TECDOC-1927 'Environmental transfer of radionuclides in Japan following the accident at the Fukushima Daiichi Nuclear Power Plant'. This paper summarises the outcomes of the data collation and analysis within MODARIA II work group 4 and compares the Japan-specific data with existing radioecological knowledge acquired from past and contemporary radioecological studies. The key radioecological lessons learned are outlined and discussed.

Scoring system for identifying Japanese patients with COVID-19 at risk of requiring oxygen supply: A retrospective single-center study.

INTRODUCTION: Japan is facing the threat of medical system collapse due to the rapid spread of coronavirus disease 2019 (COVID-19). The present scoring system may help assess disease severity and oxygen supply requirements in COVID-19 patients. METHODS: Data on patient characteristics at baseline and throughout hospitalization for COVID-19 were extracted from medical records. Disease severity was dichotomized into two categories without or with oxygen supply as asymptomatic, mild, and moderate illness (AMMI), and severe and critical illness (CSI). The AMMI and CSI groups were compared. Predictors of disease severity, previously identified in the outpatient setting, were included in multivariable logistic regression analysis; the obtained coefficients were converted to integers and assigned a score. RESULTS: A total of 206 patients diagnosed with COVID-19 were included in this study. Correlation between COVID-19 severity and medical information was examined by comparing AMMI and CSI. Age, hemodialysis, and C-reactive protein (CRP) levels were candidate predictors of the need for oxygen supply in patients with COVID-19. Coefficients associated with age, hemodialysis, and CRP were as follows: 1 × age (in years, coded as 0 for values of <50, and as 1 for values of ≥50) + 1 × hemodialysis (coded as 0 for "no", and as 1 for "yes") + 1 × CRP (in mg/dL, coded as 0 for values of <1.0, and as 1 for values of ≥1.0). Patients with scores of ≥2 points required oxygen supply (sensitivity, 68.4%; specificity, 79.0%) CONCLUSION: The present model can help predict disease severity and oxygen requirements in COVID-19 patients in Japan.

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study.

INTRODUCTION: The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. METHODS: All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients' records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. RESULTS: Data from 61 patients (16 Pt-CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt-CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt-CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt-CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt-CSI than in Pt-MMI (P = 0.013). Among the 16 Pt-CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died. CONCLUSIONS: The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.

Inclusive Semileptonic Decays from Lattice QCD.

We develop a method to compute the inclusive semileptonic decay rate of hadrons fully nonperturbatively using lattice QCD simulations. The sum over all possible final states is achieved by a calculation of the forward-scattering matrix elements on the lattice, and the phase-space integral is evaluated using their dependence on the time separation between two inserted currents. We perform a pilot lattice computation for the B[over ¯]_{s}→X_{c}ℓν[over ¯] decay with an unphysical bottom quark mass and compare the results with the corresponding OPE calculation. The method to treat the inclusive processes on the lattice can be applied to other processes, such as the lepton-nucleon inelastic scattering.

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study.

BACKGROUND: In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies. METHODS: We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines. RESULTS: Patient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0-1/2/3-4: 24/4/2; Stage IIB-IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P < 0.005). Non-hematological adverse events of Grade ≥ 3 were observed in 5 (16.7%) of 30 patients. One CRC patient experienced Grade 3 hemoptysis and another 2 experienced Grade 3 anaphylaxis. One patient with cholangiocellular carcinoma and gastric cancer experienced Grade 3 pseudomembranous colitis as a result of a Clostridium difficile infection. One patient (3.3%) died of pemetrexed-induced pneumonitis. The success of the anti-MTB chemotherapy was 70.0%. There were no MTB-related treatment failures. The median overall survival (months, 95.0% confidence interval) was 10.5 (8.7-36.7), 8.7 (4.7-10.0), 36.7 (minimum 2.2), and 14.4 (minimum 9.6) for all patients combined, LC, CRC, and Other malignancies, respectively. LC patients experienced delayed MTB diagnosis and shorter overall survival. CONCLUSIONS: Concurrent chemotherapy is effective and safe for treating cancer patients with active MTB.

Available, Bed-sided, Comprehensive (ABC) score to a diagnosis of Methicillin-resistant Staphylococcus aureus infection: a derivation and validation study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. METHODS: This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable; this revision was validated by applying it to another patient population. RESULTS: A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI; 0.957-1). CONCLUSIONS: We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections; this system is applicable in a wide variety of situations.

Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter, open label clinical trial.

BACKGROUND: To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. METHODS: Japanese patients aged 5-65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). RESULTS: Between July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. CONCLUSIONS: Safety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU.

EXAMINATION OF THE EFFECTIVENESS OF SLOW AND DEEP INHALATION OF FP/FM-pMDI FOR THE SMALL-AIRWAYS DYSFUNCTION OF ADULT-ONSET ASTHMA.

BACKGROUNDS: To date adult-onset asthmatic patients who lack a clear stridor and show prolonged coughs and chest discomfort caused by small-airways dysfunction have increased. We examined the small-airways function of these cases and the effectiveness of slow and deep inhalation of FP/FM-pMDI. METHODS: 62 adult-onset asthmatic patients who had prolonged coughs and chest discomfort with the middle or high dose of ICS/LABA combination agents under well technique (32 of BUD/FM-DPI group and 30 of FP/SM-pMDI group) were included into this study. ICS/LABAs were switched to FP/FM-pMDI and slow and deep inhalation for 2-3 seconds was carried out thoroughly. The dose of FP/FM-pMDI was reduced depending on the improvement of symptoms. ACT score, respiratory function tests and respiratory resistance were measured after approximately six months from switching (stable condition after switching) and were compared with the values of the same period of the last year (stable condition under the previous ICS/LABA). RESULTS: After switching to FP/FM-pMDI, asthmatic symptoms and plural values of small-airways function were improved in 93.7% (30/32 cases) of BUD/FM-DPI group and in 86.6% (26/30 cases) of FP/SM-pMDI group. Moreover, mean daily inhalation doses were decreased from 5.0 to 4.3 in BUD/FM-DPI group and decreased from 5.7 to 3.7 in FP/SM-pMDI group. CONCLUSIONS: Slow and deep inhalation of FP/FM-pMDI is effective in many asthmatic patients who have prolonged small-airways dysfunction. A prospective, multi-centered contrastive study is warranted to confirm the effectiveness of this inhalational method.

[STUDY OF DIRECT TB-LAMP USING NON-CENTRIFUGAL SPUTUMS ABOUT EFFICIENCY FOR RAPID DIAGNOSIS OF TUBERCULOSIS].

OBJECTIVE: To evaluate the efficiency of the direct tuberculosis-loop-mediated isothermal amplification (TB-LAMP) assay by using non-centrifuged sputum samples. STUDY PERIOD AND METHODS: The study was conducted between June 2013 and February 2014. We collected 111 sputum samples from patients who had been radiographically diagnosed with tuberculosis and had not received any treatments for longer than 5 days. In the direct TB-LAMP assay, a loop-mediated isothermal amplification kit and 60-µL sputum samples were used. A direct smear microscopy test was used as the smear test. Then, the same sputum samples were processed with a CCE pretreatment reagent, and 100 µL of the solution samples were cultured by using the mycobacterial growth indicator tube (MGIT) culture method. RESULTS: Forty-six of the 111 samples were positive in the smear microscopy tests. All the smear-positive samples were positive in both the MGIT and direct TB-LAMP assay (100%). The mean positive detection time with the direct TB-LAMP assay was 13 minutes 55 seconds. Of 56 smear-negative and MGIT positive samples, 44 (78.6%) were judged to be positive using the direct TB-LAMP assay, with a mean positive detection time of 15 minutes 59 seconds. DISCUSSION: The direct TB-LAMP assay using non-centrifuged sputum samples was demonstrated to have a high detection rate and thus may be considered useful for rapid and effective tuberculosis diagnosis.

Comparison of the clinical courses and chemotherapy outcomes in metastatic colorectal cancer patients with and without active Mycobacterium tuberculosis or Mycobacterium kansasii infection: a retrospective study.

BACKGROUND: Although active Mycobacterium tuberculosis (MTB) or Mycobacterium Kansasii (MK) infection could be present in patients with metastatic colorectal cancer (m-CRC), no study is available on the clinical courses and chemotherapy outcomes of these patients. The present study therefore aimed to retrospectively examine whether m-CRC patients with and without active MTB or MK infection could receive cancer chemotherapy similarly. METHODS: This study enrolled 30 m-CRC patients who received first-line chemotherapy between January 31, 2006 and January 31, 2013 at our institution, The clinical courses and tumor response of those with and without active MTB or MK infection were examined and compared. RESULTS: Of 30 m-CRC patients, 6 had active MTB infection, 1 with active MK and the other 23 had neither MTB nor MK. No significant demographic differences were observed between patients with MTB or MK and those without. Chemotherapy response rates of all patients, those with MTB or MK, and those without were 40.0%, 28.6% and 43.5%, respectively. Among patients with MTB or MK, 1 treated with bevacizumab experienced grade-3 hemoptysis while others did not report any severe toxicity. Median survival time of all studied patients, those with MTB or MK, and those without was 26.3, 36.7 and 22.6 months, respectively. No significant difference in overall survival was observed between patients with MTB or MK and those without. Multivariate analysis revealed that performance status and liver metastasis were significant prognostic factors of overall survival (P = 0.004 and 0.030, respectively), whereas other factors, including MTB or MK infection, were not. In our study, all 7 patients with MTB or MK did not experience infection relapse during or after cancer chemotherapy. CONCLUSIONS: Our results indicate that m-CRC patients with MTB or MK should be able to safely and effectively continue cancer chemotherapy to subsequently achieve comparable survival duration to those without the infection if they receive proper MTB or MK treatment.

Predictive biomarkers of COVID-19 prognosis identified in Bangladesh patients and validated in Japanese cohorts.

Despite high vaccination rates globally, countries are still grappling with new COVID infections, and patients diagnosed as mild dying at home during outpatient treatment. Hence, this study aim to identify, then validate, biomarkers that could predict if newly infected COVID-19 patients would subsequently require hospitalization or could recover safely with medication as outpatients. Serum cytokine/chemokine data from 129 COVID-19 patients within 7 days after the onset of symptoms in Bangladesh were used as training data. The majority of patients were infected with the Omicron variant and over 88% were vaccinated. Patients were divided into those with mild symptoms who recovered, and those who deteriorated to moderate or severe illness. Using the Lasso method, 15 predictive markers were identified and used to classify patients into these two groups. The biomarkers were then validated in a cohort of 194 Covid patients in Japan with a predictive accuracy that exceeded 80% for patients infected with Delta and Omicron variants, and 70% for Wuhan and Alpha variants. In an environment of widespread vaccination, these biomarkers could help medical practitioners determine if newly infected COVID-19 patients will improve and can be managed on an out-patient basis, or if they will deteriorate and require hospitalization.

[Comparative study of the efficacy of the COBAS TaqMan and LAMP assay for the rapid diagnosis of tuberculosis].

UNLABELLED: OBJECTIVE; The COBAS TaqMan real-time polymerase chain reaction (PCR) assay (TaqMan assay) is a well-accepted and widely distributed molecular-based diagnostic test for tuberculosis. In the present study, we evaluated the efficacy of the LAMP assay (loopamp MTBC detection kit) as an alternative molecular-based diagnostic kit for tuberculosis, through comparison with the TaqMan assay. STUDY PERIOD AND METHODS: This study was conducted over a period of approximately 2 months, between May and July 2012. We collected 48 samples (43 sputum, 2 gastric fluid, 2 pleural fluid, and 1 pus fluid samples) from patients who had been diagnosed with tuberculosis through the culture method, but had not received any treatment for more than one week. All samples were processed using the CC-E pre-treatment reagent (Japan BCG) prior to performing the TaqMan and LAMP assay. For the TaqMan assay, 100 microL of supernatant was used after centrifugation at 1,000 rpm for 1 minute, whereas 60 microL of the precipitate in the same sample was used for the LAMP assay. RESULTS: In total, 23 out of 48 samples were identified as positive for tuberculosis according to smear microscopy tests, among which 15, 4, and 4 samples had smear test scores or 1+, 2+, and 3+, respectively. All the samples that tested positive in the smear test, regardless of the score, also tested positive in both the TaqMan and TB-LAMP assays (100%). Of the 25 smear-negative samples, we noted that 16 tested positive by the TaqMan assay (64%), whereas 20 tested positive by the LAMP assay (80%). DISCUSSION: Compared with the TaqMan assay, the LAMP assay showed a higher positive rate among the smear-negative samples. We believe that this is because substances in the samples acted as co-precipitating agents, resulting in the presence of a larger number of bacteria in the precipitates than in the supernatants. Thus, the findings indicate that the application of the LAMP method to precipitates obtained following CC-E pre-treatments may lead to prompt diagnosis of tuberculosis, with a level of sensitivity comparable to that of culture tests.

Estimation of spatio-temporal distribution of 137Cs concentrations in litter layer of forest ecosystems in Fukushima using FoRothCs model.

The nuclear power plant accident in Fukushima had led to pollution of forest ecosystems with 137Cs in 2011. In this study, we simulated the spatiotemporal distribution of 137Cs concentrations of litter layer in the contaminated forest ecosystems in two decades from 2011, which is one of the key environmental components of 137Cs migration in the environment due to the high bioavailability of 137Cs in the litter. Our simulations showed that 137Cs deposition is the most important factor in the degree of contamination of the litter layer but vegetation type (evergreen coniferous/deciduous broadleaf) and mean annual temperature are also important for changes over time. Deciduous broadleaf trees had higher initial concentrations in the litter layer due to the direct initial deposition on the forest floor. However, the concentrations remained higher than those in evergreen conifers after 10 years due to redistribution of 137Cs by vegetation. Moreover, areas with lower average annual temperatures and lower litter decomposition activity retained higher 137Cs concentrations in the litter layer. The results of the spatiotemporal distribution estimation of the radioecological model suggest that, in addition to 137Cs deposition, elevation and vegetation distribution should also be considered in the long-term management of contaminated watersheds, which can be informative in identifying hotspots of 137Cs contamination on a long-term scale.

Two-photon decay of the neutral pion in lattice QCD.

We perform a nonperturbative calculation of the π(0) → γγ transition form factor and the associated decay width using lattice QCD. The amplitude for a two-photon final state, which is not an eigenstate of QCD, is extracted through a Euclidean time integral of the relevant three-point function. We utilize the all-to-all quark propagator technique to carry out this integration as well as to include the disconnected quark diagram contributions. The overlap fermion formulation is employed on the lattice to ensure exact chiral symmetry on the lattice. After examining various sources of systematic effects, except for a possible discretization effect, we obtain Γπ(0) → γγ = 7.83(31)(49) eV for the pion decay width, where the first error is statistical and the second is our estimate of the systematic error.

Ten-year trends in vertical distribution of radiocesium in Fukushima forest soils, Japan.

To elucidate interannual changes in the vertical distribution of 137Cs in forest ecosystems contaminated by the Fukushima Dai-ichi Nuclear Power Plant accident, we investigated 137Cs inventories in forest soils (both organic and mineral soil horizons) at 10 sampling plots with different 137Cs deposition levels and dominant species for up to 10 years after the accident. We examined the temporal variation of the 137Cs inventories by depth with exponential regression models (assuming that the transition and partitioning of 137Cs are still active) and exponential offset regression models (assuming a shift to a stable 137Cs distribution, defined as the "quasi-equilibrium steady-state" in the Chernobyl accident). In the organic horizon, the 137Cs inventories were exponentially decreasing, and it might take more time to converge in the quasi-equilibrium steady-state at most plots. In the mineral soil horizon, most of 137Cs was found in the surface layer of the mineral soil horizon (0-5 cm). In this layer, the inventories first increased and then become relatively constant, and the exponential offset model was selected at most plots, suggesting entry into the quasi-equilibrium steady-state over the observation period. Although we also observed exponentially increasing trends in a lower layer (5-10 cm) of the mineral soil horizon, there was no clear increasing or decreasing trend of 137Cs inventory in the deeper mineral soil layers (10-15 and 15-20 cm). Our calculation of the relaxation depth and migration center revealed that downward migration of 137Cs is not significant in terms of the overall 137Cs distribution in the mineral soil horizon over 10 years.

Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein.

A cytokine storm induces acute respiratory distress syndrome, the main cause of death in coronavirus disease 2019 (COVID-19) patients. However, the detailed mechanisms of cytokine induction due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To examine the cytokine production in COVID-19, we mimicked the disease in SARS-CoV-2-infected alveoli by adding the lysate of SARS-CoV-2-infected cells to cultured macrophages or induced pluripotent stem cell-derived myeloid cells. The cells secreted interleukin (IL)-6 after the addition of SARS-CoV-2-infected cell lysate. Screening of 25 SARS-CoV-2 protein-expressing plasmids revealed that the N protein-coding plasmid alone induced IL-6 production. The addition of anti-N antibody further enhanced IL-6 production, but the F(ab')2 fragment did not. Sera from COVID-19 patients also enhanced IL-6 production, and sera from patients with severer disease induced higher levels of IL-6. These results suggest that anti-N antibody promotes IL-6 production in SARS-CoV-2-infected alveoli, leading to the cytokine storm of COVID-19.

An ADP ribosylation factor-GTPase activating protein negatively regulates the production of proinflammatory mediators in response to lipopolysaccharide.

An ADP ribosylation factor-GTPase activating protein (ASAP1) is highly expressed in a variety of tumor cells and is involved in the cell motility, invasion, and metastasis. In order to elucidate the involvement of ASAP1 in lipopolysaccharide (LPS)-mediated inflammatory response, the effect of ASAP1 silencing on LPS-induced proinflammatory mediators production was examined by using RAW 264.7 macrophage-like cells. ASAP1 was constitutively expressed in the cells and the expression was augmented by LPS stimulation. Silencing of ASAP1 with small interfering RNA enhanced the production of tumor necrosis factor-α, interleukin 6, interferon-ß, and nitric oxide in response to LPS. ASAP1 silencing augmented the activation of nuclear factor (NF)-κB and several mitogen-activated protein kinases (MAPKs). On the other hand, ASAP1 silencing did not affect the expression of IRAK4, TRAF6, and Akt as the upstream molecules of NF-κB signaling. A series of toll-like receptor ligands as well as LPS augmented the ASAP1 expression. Taken together, ASAP1 was suggested to negatively regulate LPS-induced proinflammatory mediators production through down-regulating LPS signaling. The feedback function of ASAP1 in LPS-mediated inflammatory response is discussed.