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The methods of sampling, carrying and keeping, and the instruments for measuring atmospheric peroxyacetyl nitrate (PAN) and peroxypropionyl nitrate (PPN), were developed for field studies and had been used for the surveys on four remote islands and in the troposphere since 1991. PAN and PPN were detected in most of over 500 samples. Mean concentrations of PAN and PPN in the islands and in the lower troposphere(altitude; 400-4500 m) from the Yellow Sea to the Japan Sea are 0.1-0.4 ppb (10-9, v/v) and 0.01-0.03 ppb, respectively. Good correlation between PAN and PPN at each point was observed, and PPN was found to be 5-9% of PAN. In addition, PAN in the urban area had been monitored continuously at Ichihara close to metropolitan Tokyo since 1985. The yearly means of PAN there were constantly around 0.4 ppbfor ten years. The ratios of PANs to NOx* or NOx+ (which were detected by chemiluminescence type or Griess-Saltzman type of NOx analyzers) were found to be mostly, 1% in the urban air, 15-20% on the remote islands, and 15-60% in the lower troposphere (occasionally exceed 80% in the upper 2500 m altitude). PANs in the remote area were confirmed to be relatively more important, compared with in the urban area. The higher ratios in aircraft surveys were partly related to the atmospheric temperature in the sampling area. [ABSTRACT FROM AUTHOR]

Background: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial., Methods: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment., Results: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival., Conclusions: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clostridium perfringens type A causes gas gangrene characterized by myonecrosis and development of an effective therapy for treating affected patients is of clinical importance. It was recently reported that the expression of granulocyte colony-stimulating factor (G-CSF) is greatly up-regulated by C. perfringens infection. However, the role of G-CSF in C. perfringens -mediated myonecrosis is still unclear. Here, we assessed the destructive changes in C. perfringens -infected skeletal muscles and tested whether inhibition of G-CSF receptor (G-CSFR) signaling or administration of recombinant G-CSF affects the tissue injury. Severe edema, contraction of muscle fiber diameter, and increased plasma creatine kinase activity were observed in mice intramuscularly injected with C. perfringens type A, and the destructive changes were α-toxin-dependent, indicating that infection induces the destruction of skeletal muscle in an α-toxin-dependent manner. G-CSF plays important roles in the protection of tissue against damage and in the regeneration of injured tissue. However, administration of a neutralizing antibody against G-CSFR had no profound impact on the destructive changes to skeletal muscle. Moreover, administration of recombinant human G-CSF, filgrastim, imparted no inhibitory effect against the destructive changes caused by C. perfringens . Together, these results indicate that G-CSF is not beneficial for treating C. perfringens α-toxin-mediated myonecrosis, but highlight the importance of revealing the mechanism by which C. perfringens negates the protective effects of G-CSF in skeletal muscle.

During bacterial infection, granulocyte colony-stimulating factor (G-CSF) is produced and accelerates neutrophil production from their progenitors. This process, termed granulopoiesis, strengthens host defense, but Clostridium perfringens α-toxin impairs granulopoiesis via an unknown mechanism. Here, we tested whether G-CSF accounts for the α-toxin-mediated impairment of granulopoiesis. We find that α-toxin dramatically accelerates G-CSF production from endothelial cells in response to Toll-like receptor 2 (TLR2) agonists through activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Meanwhile, α-toxin inhibits G-CSF-mediated cell proliferation of Ly-6G + neutrophils by inducing degradation of G-CSF receptor (G-CSFR). During sepsis, administration of α-toxin promotes lethality and tissue injury accompanied by accelerated production of inflammatory cytokines in a TLR4-dependent manner. Together, our results illustrate that α-toxin disturbs G-CSF-mediated granulopoiesis by reducing the expression of G-CSFR on neutrophils while augmenting septic shock due to excess inflammatory cytokine release, which provides a new mechanism to explain how pathogenic bacteria modulate the host immune system., Competing Interests: The authors declare no competing interests.

Background: Factors associated with liver stiffness (LS) are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD) and non-alcoholic fatty (NAFLD) liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report., Methods: We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI), liver function (LF), alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls., Results: The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD) and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3%) of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results., Conclusions: Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.

Frequent chromosomal aberrations and/or losses of heterozygosity involving the short arm of chromosome 3 in carcinomas of the lung, kidney and other tissues imply that multiple putative tumor suppressor genes may be present on this chromosomal arm. To search for one of these genes, we determined DNA sequences in the genomic region at 3p22-21.3 where we had previously detected a homozygous deletion in a lung cancer cell line. The DNA sequence results of an about 685-kb region indicated that the size of the homozygously deleted segment was 638,489 bp, in which we identified only four genes including the integrin alpha RLC and the trans-Golgi p230 genes, both reported previously. The predicted amino acid sequences of one of the two novel genes showed high homology to villin, a human cytoskeleton protein; those of the other gene, termed HYA22, revealed significant homology to YA22, a hypothetical protein predicted from DNA sequences of Schizosaccharomyces pombe. The computer programs HEXON or GRAIL were able to predict three-fourths of the exons; the smallest exon predicted by either program was 46 base pairs. Repetitive sequences contained in the genomic region included 151 copies of the Alu sequence (1 copy/every 4.5 kb), 19 copies of the L1 sequence (1 copy/every 36 kb), and 10 copies of the THE sequence.