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The share of digital printing on flexible plastic packaging has been increasing rapidly in response to the market demand for agility in Japan. To meet all these challenges, our response is the aqueous inkjet ink “LUNAJET®”. By combining aqueous pigment nanodispersions with precise interfacial control technologies, “LUNAJET®” can contribute to the rapid digitization of flexible package printing while, at the same time, improving the environmental performance. Our analysis includes an evaluation of the environmental impact due to the conversion from gravure printing with an analog press to digital printing using an inkjet printer with water-based inks. In addition, inventory analyses and characterizations were carried out. It is shown that a 75% reduction in CO2 emissions and 33% reduction in VOC (volatile organic compounds) emissions can be expected, particularly in small-lot printing, where digital printing is most desirable. An environmental impact assessment was conducted in Japan, based upon the LIME3 (life cycle impact assessment method based on endpoint modeling version 3) approach. It was found that the waste reduction rate for aqueous inkjet printing, compared to analog printing, was as high as 57% for small-lot production, assuming a large variety of products; surprisingly, the reduction rate remained at 15%, even for long production runs. As the market rushes to embrace digital printing technologies for packaging, these results indicate that implementing inkjet printing using aqueous ink for flexible plastic substrates can reduce waste and decrease the environmental burden, both for short as well as long printing runs.

BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not been reported.METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions(>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of f T3, free thyroxine(f T4), and thyroidstimulating hormone(TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial f T3 levels in group M(1.95±0.37 pg/m L) were signifi cantly lower than those in group C(2.49±0.72 pg/m L; P<0.01) and remained low until 1 week after admission. Initial inter-group f T4 and TSH levels were not significantly different. TSH levels at 1 week(1.99±1.64 μIU/m L) were higher than at admission(1.48±0.5 μIU/m L) in group C(P<0.05).CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.

Natural decomposition of organic matter is essential in food systems, and compost is used worldwide as an organic fermented fertilizer. However, as a feature of the ecosystem, its effects on the animals are poorly understood. Here we show that oral administration of compost and/or its derived thermophilic Bacillaceae, i.e., Caldibacillus hisashii and Weizmannia coagulans, can modulate the prophylactic activities of various industrial animals. The fecal omics analyses in the modulatory process showed an improving trend dependent upon animal species, environmental conditions, and administration. However, structural equation modeling (SEM) estimated the grouping candidates of bacteria and metabolites as standard key components beyond the animal species. In particular, the SEM model implied a strong relationship among partly digesting fecal amino acids, increasing genus Lactobacillus as inhabitant beneficial bacteria and 2-aminoisobutyric acid involved in lantibiotics. These results highlight the potential role of compost for sustainable protective control in agriculture, fishery, and livestock industries.

Hydrogen boride nanosheets (HB sheets) are facilely synthesized via ion-exchange treatment on magnesium diboride (MgB 2 ) in an acetonitrile solution. Optical absorption and fluorescence spectra of HB sheets indicate that their bandgap energy is 2.8 eV. According to first-principles calculations, optical absorption seen at 2.8 eV is assigned to the electron transition between the σ-bonding states of B and H orbitals. In addition, density functional theory (DFT) calculations suggest the other allowed transition from the σ-bonding state of B and H orbitals to the antibonding state with the gap of 3.8 eV. Significant gaseous H 2 release is found to occur only under photoirradiation, which causes the electron transition from the σ-bonding state to the antibonding state even under mild ambient conditions. The amount of H 2 released from the irradiated HB sheets is estimated to be 8 wt%, indicating that the sheets have a high H 2 -storage capacity compared with previously reported metal H 2 -storage materials. The development of lightweight and safe hydrogen carrier materials is desirable for hydrogen energy storage and release. Here, authors prepare hydrogen boride nanosheets and observe hydrogen gas production induced by light irradiation.

BackgroundAs non-ampullary duodenal cancer is relatively rare, the optimal treatment strategy, including the appropriate surgical procedure and efficacy of adjuvant chemotherapy, remains unclear. This nationwide survey aimed to clarify the actual lymph node spread pattern and determine the optimal treatment strategy for this disease, using a large-scale database.MethodsWe used a questionnaire and a retrospective registry of 1083 patients with non-ampullary duodenal cancer who had undergone surgery during 2008–2017 in 114 high-volume Japanese Society of Hepatobiliary and Pancreatic Surgery-certified training institutions. Propensity score-matched analyses were conducted to minimise background bias. Cox regression was performed to identify covariates associated with recurrence-free survival. There were distinct disparities in the nodal dissection rate according to the predominant tumor location and tumor invasion depth. Metastases were frequently observed in the peripancreatic nodes and those along the superior mesenteric artery, irrespective of tumor location. Their dissection seemed to be beneficial for improved survival. In the overall cohort, no survival benefit was observed in patients who received adjuvant chemotherapy when compared with that in patients who underwent surgery alone. Nevertheless, in the matched cohort, adjuvant chemotherapy for > 6 months was associated with a significant improvement in recurrence-free survival (median: 43.5 vs. 22.5 months, p = 0.016), particularly in patients with tumor invasion of the subserosa or deeper tumor invasion, lymph node metastasis, or elevated serum carbohydrate antigen 19-9 levels.ConclusionPancreatoduodenectomy should be the standard procedure for advanced non-ampullary duodenal cancer. Adjuvant chemotherapy for > 6 months, especially for advanced tumors, significantly improves survival.

Background Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight. Methods This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring. Results Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m 2 ; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P  < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability. Conclusions Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes. Trial registration Trial number, UMIN000028014; registered on June 30, 2017

Dimethylated histone H3 Lys36 (H3K36me2) regulates gene expression, and aberrant H3K36me2 upregulation, resulting from either the overexpression or point mutation of the dimethyltransferase NSD2, is found in various cancers. Here we report the cryo-electron microscopy structure of NSD2 bound to the nucleosome. Nucleosomal DNA is partially unwrapped, facilitating NSD2 access to H3K36. NSD2 interacts with DNA and H2A along with H3. The NSD2 autoinhibitory loop changes its conformation upon nucleosome binding to accommodate H3 in its substrate-binding cleft. Kinetic analysis revealed that two oncogenic mutations, E1099K and T1150A, increase NSD2 catalytic turnover. Molecular dynamics simulations suggested that in both mutants, the autoinhibitory loop adopts an open state that can accommodate H3 more often than the wild-type. We propose that E1099K and T1150A destabilize the interactions that keep the autoinhibitory loop closed, thereby enhancing catalytic turnover. Our analyses guide the development of specific inhibitors of NSD2. An upregulation of NSD2, a histone H3 lysine 36 (H3K36) methyltransferase is linked to multiple myeloma and other types of cancer. Here, the authors provide insights into the regulatory mechanism of NSD2 by determining the 2.8 Å cryo-EM structure of the NSD2 bound nucleosome complex, and based on MD simulations they discuss how two oncogenic mutations enhance NSD2 activity.

Cancer therapy is often hampered by the disease’s development of resistance to anticancer drugs. We previously showed that the autonomously upregulated product of fibroblast growth factor 13 gene ( FGF13 ; also known as FGF homologous factor 2 ( FHF2 )) is responsible for the cisplatin resistance of HeLa cisR cells and that it is likely responsible for the poor prognosis of cervical cancer patients treated with cisplatin. Here we show that cloperastine and two other histamine H1 receptor antagonists selectively kill HeLa cisR cells at concentrations that little affect parental HeLa S cells. The sensitivity of HeLa cisR cells to cloperastine was abolished by knocking down FGF13 expression. Cisplatin-resistant A549 cisR cells were similarly susceptible to cloperastine. H2, H3, and H4 receptor antagonists showed less or no cytotoxicity toward HeLa cisR or A549 cisR cells. These results indicate that histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells and suggest that this effect is exerted through a molecular mechanism involving autocrine histamine activity and high-level expression of FGF13 . We think this represents a potential opportunity to utilize H1 receptor antagonists in combination with anticancer agents to treat cancers in which emergent drug-resistance is preventing effective treatment.

BackgroundAlthough indocyanine green (ICG) fluorescence imaging has been reported to be useful for assessing colorectal perfusion, unstable quantification remains an issue. We performed ICG fluorescence observation from the luminal side and examined the usefulness of the transanal approach.MethodsA total of 69 patients who underwent left-side colon surgery were enrolled in this cohort study. After the anastomosis had been constructed, ICG 0.2 mg/kg was injected intravenously. The anastomotic site was then observed by a scope inserted transanally. The following items were examined in the areas of the anastomotic site with the highest- and lowest-fluorescence intensity: maximum fluorescence (Fmax), time from ICG injection to Fmax (Tmax), time from start of dyeing to Fmax (ΔT), and the contrast pattern of the mucosa.ResultsAnastomotic leakage (AL) occurred in nine cases. Tmax and ΔT values of the lowest-fluorescence area in the distal intestine showed significant differences in the cases with AL (P = 0.015 and P = 0.040, respectively). Regarding the contrast pattern of the mucosa of the lowest-fluorescence area in the proximal and distal intestine, the patients in whom the vessels were not depicted in the area had a significantly higher incidence of AL than those in whom vessels were depicted in the area (P = 0.031 and P = 0.030, respectively). Some of the areas in which vessels were not depicted by ICG fluorescence observation from the luminal side corresponded to the points of leakage. There were heterogeneous changes that might not be grasped by observation from the serosal side.ConclusionTransanal ICG fluorescence imaging can evaluate perfusion over the entire circumference of the anastomosis in detail and aid in assessing the risk of AL. Therefore, the examination of the detailed low-perfusion area enables us to take measures for AL and to search for safer operative managements.