Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab- CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)

ABSTRACT: BACKGROUND: The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS: Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. RESULTS: Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001). CONCLUSIONS: Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.     

SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages

Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers the activation of CASP1 (caspase 1) and secretion of proinflammatory cytokines. Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, suppresses prolonged NLRP3 inflammasome activation by clearance of damaged mitochondria through inducing mitophagy in macrophages. SESN2 plays a dual role in inducing mitophagy in response to inflammasome activation. First, SESN2 induces “mitochondrial priming” by marking mitochondria for recognition by the autophagic machinery. For mitochondrial preparing, SESN2 facilitates the perinuclear-clustering of mitochondria by mediating aggregation of SQSTM1 (sequestosome 1) and its binding to lysine 63 (Lys63)-linked ubiquitins on the mitochondrial surface. Second, SESN2 activates the specific autophagic machinery for degradation of primed mitochondria via an increase of ULK1 (unc-51 like kinase 1) protein levels. Moreover, increased SESN2 expression by extended LPS (lipopolysaccharide) stimulation is mediated by NOS2 (nitric oxide synthase 2, inducible)-mediated NO (nitric oxide) in macrophages. Thus, Sesn2-deficient mice displayed defective mitophagy, which resulted in hyperactivation of inflammasomes and increased mortality in 2 different sepsis models. Our findings define a unique regulatory mechanism of mitophagy activation for immunological homeostasis that protects the host from sepsis.     

Ginsenoside Re improves skin barrier function in HaCaT keratinocytes under normal growth conditions

Ginsenoside Re (Re), a major ginsenoside of ginseng, enhanced the cornified cell envelope (CE) formation in HaCaT keratinocytes under normal conditions. In HaCaT keratinocytes, Re was also able to upregulate filaggrin protein and caspase-14 activity in a concentration-dependent manner. These findings reasonably imply that Re possesses a desirable property of improving skin barrier function.     

Metabolomics investigation of flavonoid synthesis in soybean leaves depending on the growth stage

Soybean (Glycine max L.) leaves have unique nutraceutical and pharmacological benefits, and have been widely used as a source of healthy and functional food stuffs in Korea. In this study, we investigated the phytochemical metabolomic changes of soybean leaves depending on growth stages (maturation period) assessed based on UPLC–QTOF–MS analysis. Principal component analysis was carried out to trace the metabolite profiles of the phytochemicals from the vegetable stage (1D) through the seven reproductive stages (R1–R7). On the loading plot, significant changes in the contents of metabolites were found during the growth, and eight flavonoid kaempferol glycosides (2, 3, 6, 8, and 10), daidzein (14), genistein (17), and coumestrol (19) were evaluated as growth markers among the 19 isolated metabolites. The kaempferol glycosides were increasingly synthesized from the 1D to the R6 stage but decreased rapidly at stages R7–R8. The extensively synthesized daidzein and genistein were shown during seed growth in the pod (R5–R6), while coumestrol was increased significantly at stages R7–R8 (maturity period). The synthetic pathway of the flavonoids could be elucidated based on the concentration of the individual metabolites. These results demonstrate that the metabolite production changed depending on the growth stage; a possible pathway could be deduced using metabolomic analysis to provide information regarding physiological characterization and optimal harvesting time for crops.     

Optimized production of lignolytic manganese peroxidase in immobilized cultures of <Emphasis Type="Italic">Phanerochaete chrysosporium</Emphasis>

Manganese peroxidase (MnP) is a key enzyme involved in the lignolysis of white-rot fungi. The purpose of this study is to investigate the effect of immobilization and culture conditions on MnP production in cultures of Phanerochaete chrysosporium grown on polyurethane foam. Higher concentrations of foam and lower levels of spore inoculums resulted in the formation of scattered mycelial pellets, increased autolysis of chlamydospore-like cells (a reservoir of MnP), and a higher activity of MnP. Even though MnP was a secondary metabolite, the addition of 5 times more glucose and diammonium tartrate, as carbon and nitrogen sources, resulted in a 4 fold increase in the dry cell mass. However, MnP activity decreased under these conditions to less than half, due to the formation of increasingly dense pellets and the inhibited lysis of chlamydospore-like cells.     

Digital Twin‐Driven All‐Solid‐State Battery: Unraveling the Physical and Electrochemical Behaviors

The digital twin technique has been broadly utilized to efficiently and effectively predict the performance and problems associated with real objects via a virtual replica. However, the digitalization of twin electrochemical systems has not been achieved thus far, owing to the large amount of required calculations of numerous and complex differential equations in multiple dimensions. Nevertheless, with the help of continuous progress in hardware and software technologies, the fabrication of a digital twin‐driven electrochemical system and its effective utilization have become a possibility. Herein, a digital twin‐driven all‐solid‐state battery with a solid sulfide electrolyte is built based on a voxel‐based microstructure. Its validity is verified using experimental data, such as effective electronic/ionic conductivities and electrochemical performance, for LiNi_0.70Co_0.15Mn_0.15O₂ composite electrodes employing Li₆PS₅Cl. The fundamental performance of the all‐solid‐state battery is scrutinized by analyzing simulated physical and electrochemical behaviors in terms of mass transport and interfacial electrochemical reaction kinetics. The digital twin model herein reveals valuable but experimentally inaccessible time‐ and space‐resolved information including dead particles, specific contact area, and charge distribution in the 3D domain. Thus, this new computational model is bound to rapidly improve the all‐solid‐state battery technology by saving the research resources and providing valuable insights.