Inorganic PM2.5 reduction in Kanto, Japan: The role of ammonia and its emission sources control strategies.

Ammonia (NH3) is attracting attention as a carbon-free energy source and a significant precursor to inorganic PM2.5 (hereafter PM2.5), aside from NOx and SOx. Since the emission of NH3 has often been overlooked compared to NOx and SOx, this study aims to reveal the role of NH3 and its emission control on PM2.5 in Kanto, Japan. With the aid of gas ratio (GR) quantitatively defining the stoichiometry between the three precursors to PM2.5, and the aid of atmospheric modeling software ADMER-PRO, coupled with thermodynamics calculations, the spatiotemporal distribution along with PM2.5 reduction under different NH3 emission cutoff strategies in Kanto had been revealed for the first time. The cutoff of NH3 emission could effectively reduce the PM2.5 concentration, with sources originated from agriculture, human/pet activities, and vehicle sources, overall giving a 93.32% PM2.5 reduction. Different cutoff strategies lead to distinct reduction efficiencies of the overall and local PM2.5 concentrations, with GR as a crucial factor. The regions with GR ∼1, are sensitive to the NH3 concentration for forming PM2.5, at which the NH3 reduction strategies should be applied with high priority. On the other hand, installing a new NH3 emission source should be avoided in the region with GR < 1, suppressing the so-yielded PM2.5 pollution. The future PM2.5 pollution control related to the NH3 emission control strategies based on GR, which is stoichiometry-based and applicable to regions other than Kanto, has been discussed.

Dose Evaluation in 2-Phase Method for Advanced Esophageal Cancer by Hybrid Irradiation Techniques.

Purpose: In concurrent chemoradiotherapy for advanced esophageal cancer, a 2-phase method consisting of initial irradiation of a wide elective nodal region and boost irradiation of the primary lesion is commonly employed. Although dose escalation to the primary lesion may be required to achieve higher local control rates, the radiation dose to critical organs must not exceed dose constraints. To achieve an optimum balance of dose prescription and dose reduction to surrounding organs, such as the lungs and heart, we compared hybrid dose distributions and investigated the best combination of the following recent irradiation techniques: volumetric modulation arc therapy (VMAT), proton broad-beam irradiation, and intensity-modulated proton beam therapy (IMPT). Materials and Methods: Forty-five patients with advanced esophageal cancer whose primary lesions were located in the middle- or lower-thoracic region were studied. Radiotherapy plans for the initial and boost irradiation in the 2-phase method were calculated using VMAT, proton broad-beam irradiation, and IMPT calculation codes, and the dose-volume histogram indices of the lungs and heart for the accumulated plans were compared. Results: In plans using boost proton irradiation with a prescribed dose of 60 Gy(RBE), all dose-volume histogram indices were significantly below the tolerance limits. Initial and boost irradiation with VMAT resulted in the median dose of V30 Gy(RBE)(heart) of 27.4% and an achievement rate below the tolerance limit of 57.8% (26 cases). In simulations of dose escalation up to 70 Gy(RBE), initial and boost IMPT resulted in the highest achievement rate, satisfying all dose constraints in 95.6% (43 cases). Conclusion: Applying VMAT to both initial and boost irradiation is not recommended because of the increased risk of the cardiac dose exceeding the tolerance limit. IMPT may allow dose escalation of up to 70 Gy(RBE) without radiation risks to the lungs and heart in the treatment of advanced esophageal cancer.

FLASH Effect Is Not Always Induced by Ultra-high Dose-rate Proton Irradiation Under Hypoxic Conditions.

BACKGROUND/AIM: Pre-clinical studies have shown that irradiation with electrons at an ultra-high dose-rate (FLASH) spares normal tissue while maintaining tumor control. However, most in vitro experiments with protons have been conducted using a non-clinical irradiation system in normoxia alone. This study evaluated the biological response of non-tumor and tumor cells at different oxygen concentrations irradiated with ultra-high dose-rate protons using a clinical system and compared it with the conventional dose rate (CONV). MATERIALS AND METHODS: Non-tumor cells (V79) and tumor cells (U-251 and A549) were irradiated with 230 MeV protons at a dose rate of >50 Gy/s or 0.1 Gy/s under normoxic or hypoxic (<2%) conditions. The surviving fraction was analyzed using a clonogenic cell survival assay. RESULTS: No significant difference in the survival of non-tumor or tumor cells irradiated with FLASH was observed under normoxia or hypoxia compared to the CONV. CONCLUSION: Proton irradiation at a dose rate above 40 Gy/s, the FLASH dose rate, did not induce a sparing effect on either non-tumor or tumor cells under the conditions examined. Further studies are required on the influence of various factors on cell survival after FLASH irradiation.

Hepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture.

Hepatocytes play important roles in the liver, but in culture, they immediately lose function and dedifferentiate into progenitor-like cells. Although this unique feature is well-known, the dynamics and mechanisms of hepatocyte dedifferentiation and the differentiation potential of dedifferentiated hepatocytes (dediHeps) require further investigation. Here, we employ a culture system specifically established for hepatic progenitor cells to study hepatocyte dedifferentiation. We found that hepatocytes dedifferentiate with a hybrid epithelial/mesenchymal phenotype, which is required for the induction and maintenance of dediHeps, and exhibit Vimentin-dependent propagation, upon inhibition of the Hippo signaling pathway. The dediHeps re-differentiate into mature hepatocytes by forming aggregates, enabling reconstitution of hepatic tissues in vivo. Moreover, dediHeps have an unexpected differentiation potential into intestinal epithelial cells that can form organoids in three-dimensional culture and reconstitute colonic epithelia after transplantation. This remarkable plasticity will be useful in the study and treatment of intestinal metaplasia and related diseases in the liver.