[Association of Geriatric Nutritional Risk Index with Adverse Events and Time to Treatment Failure in Malignant Lymphoma Patients Treated with(R-)EPOCH].

To date, there are no reports that examine the relationship between geriatric nutritional risk index(GNRI)at the start of chemotherapy for malignant lymphoma and adverse effects. In this study, we investigated the relationship between GNRI at the start of chemotherapy and the incidence of side effects and time to treatment failure(TTF)in(R-)EPOCH-treated patients with relapsed or refractory malignant lymphoma. A significant difference in the incidence of Grade 3 or higher thrombocytopenia was observed between high and low GNRI groups(p=0.043). The GNRI may be an indicator of hematologic toxicity in malignant lymphoma patients treated with(R-)EPOCH. There was a statistically significant difference in TTF between the high and low GNRI groups(p=0.025), suggesting that nutritional status at the start of(R-)EPOCH may affect treatment continuation.

Influence of Geriatric Nutritional Risk Index on Occurrence of Adverse Events and Duration of Treatment in Patients With Lymphoma Receiving R-CHOP Therapy.

BACKGROUND/AIM: No studies have examined the association between the Geriatric Nutritional Risk Index (GNRI) at the initiation of chemotherapy for malignant lymphoma and the occurrence of adverse events. Therefore, we investigated the impact of GNRI at treatment initiation on the occurrence of side effects and time to treatment failure (TTF) in patients with malignant lymphoma undergoing initial rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. PATIENTS AND METHODS: This study included 131 patients who underwent initial R-CHOP therapy between March 2016 and October 2021. Patients were stratified into those with high (GNRI ≥92; n=56) or low (GNRI <92; n=75) GNRI status. RESULTS: Comparing the High GNRI group and Low GNRI group, the incidence of febrile neutropenia (FN) and Grade ≥3 creatinine increase, alkaline phosphatase (ALP) increase, albumin decrease, hemoglobin decrease, neutropenia, and thrombocytopenia were significantly higher in the Low GNRI group. TTF in the High GNRI group was significantly longer than that in the Low GNRI group (p=0.045). Multivariate analysis showed that the factors influencing the duration of treatment were PS (≥2) at the start of treatment, serum albumin level, and GNRI. CONCLUSION: In patients undergoing R-CHOP therapy, GNRI <92 at regimen initiation increased the risks of developing FN and hematologic toxicity. Multivariate analysis revealed that performance status, albumin levels, and GNRI at regimen initiation were the factors influencing treatment duration. Nutritional status at treatment initiation may influence the development of hematologic toxicity and TTF.

Total syntheses of ent-hypocoprin A and ent-hypocoprin B.

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular SN2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.

The difference of chows affects mouse physiological conditions.

Acetaminophen-induced liver injury in mice is a model system of human acetaminophen overdose and oxidative stress in vivo. The system is technically established, and we usually obtain severe liver damage in the treated mice; however, it is possible that the degree of liver damage is affected by the type of chow fed to mice. Thus, in this experiment, we investigated the effect of different chows on mice by comparing acetaminophen-induced liver damage, liver antioxidant level, and serum amino-acid concentrations. The results showed that differences in chows, even standard ones, affected mouse physiological conditions, with the response to oxidative stress greatly affected.

DNase γ-dependent DNA fragmentation causes karyolysis in necrotic hepatocyte.

Karyolysis is the complete dissolution of nuclear components of a dying cell. However, the generation mechanism has not been clarified. We studied a necrotic DNA fragmentation factor DNase γ (also known as DNase1L3) and previously found that karyolysis was inhibited in DNase γ deficient (DNase γ-/-) mice. To confirm this, we transiently expressed DNase γ in the liver of DNase γ-/- mice and caused hepatocyte necrosis by acetaminophen overdose. As expected, karyolysis was induced in the necrotic hepatocytes. We also found that the depletion of Kupffer cells from wild type mice reduced the expression and activity of DNase γ in the liver. Thus, we concluded that DNase γ produced from Kupffer cells caused karyolysis of necrotic hepatocytes.

DNA Origami "Quick" Refolding Inside of a Micron-Sized Compartment.

Investigations into the refolding of DNA origami leads to the creation of reconstructable nanostructures and deepens our understanding of the sustainability of life. Here, we report the refolding of the DNA origami structure inside a micron-sized compartment. In our experiments, conventional DNA origami and truss-type DNA origami were annealed and purified to remove the excess staples in a test tube. The DNA origami was then encapsulated inside of a micron-sized compartment of water-in-oil droplets, composed of neutral surfactants. The re-annealing process was then performed to initiate refolding in the compartment. The resulting 100-nm-sized DNA nanostructures were observed using atomic force microscopy (AFM), and the qualities of their structures were evaluated based on their shape. We found that the refolding of the DNA origami structure was favored inside the droplets compared with refolding in bulk solution. The refolded structures were able to fold even under "quick" one-minute annealing conditions. In addition, the smaller droplets (average diameter: 1.2 µm) appeared to be more advantageous for the refolding of the origamis than larger droplets. These results are expected to contribute to understanding the principles of life phenomena based on multimolecular polymer self-assembly in a micron-sized compartment, and for the production and maintenance of artificially designed molecules.

Cell-free DNA in blood circulation is generated by DNase1L3 and caspase-activated DNase.

Cell-free DNA (cfDNA) (e.g. fetal- or tumor-derived DNA) is DNA found in the blood circulation. It is now widely investigated as a biomarker for prenatal screening, tumor diagnosis, and tumor monitoring as "liquid biopsies". However, the biological and biochemical aspects of cfDNA remain unclear. Although cfDNA is considered to be mainly derived from dead cells, information is scarce as to whether it is apoptotic or necrotic and what kinds of endonucleases or DNases are involved. We induced in vivo hepatocyte necrosis and apoptosis in mice deficient in DNase1L3 (also named DNase γ) and/or caspase-activated DNase (CAD) genes with acetaminophen overdose and anti-Fas antibody treatments. We found that (i) DNase1L3 was the endonuclease responsible for generating cfDNA in acetaminophen-induced hepatocyte necrosis and (ii) CAD and DNase1L3 cooperated in producing cfDNA for anti-Fas mediated hepatocyte apoptosis.

Unique Solid-State Emission Behavior of Aromatic Difluoroboronated ß-Diketones as an Emitter in Organic Light-Emitting Devices.

Aromatic difluoroboronated ß-diketone (BF2 DK) derivatives are a widely known class of luminescent organic materials that exhibit high photoluminescent quantum efficiency and unique aggregation-dependent fluorescence behavior. However, there have been only a few reports on their use in solid-state electronic devices, such as organic light-emitting devices (OLEDs). Herein, we investigated the solid-state properties and OLED performance of a series of π-extended BF2 DK derivatives that have previously been shown to exhibit intense fluorescence in the solution state. The BF2 DK derivatives formed exciplexes with a carbazole derivative and exhibited thermally activated delayed fluorescence (TADF) behavior to give orange electroluminescence with a peak external quantum efficiency of 10 % that apparently exceeds the theoretical efficiency limit of conventional fluorescent OLEDs (7.5 %), assuming a light out-coupling factor of 30 %.