Effects of graded concentrations of supplemental selenium on selenium concentrations in tissues and prediction equations for estimating dietary selenium intake in pigs

The experiment was conducted to determine the effects of graded dietary selenium (Se) on organ weight and Se concentrations in tissues and to develop equations for estimating dietary Se intake in pigs. Sixteen barrows (initial body weight = 30.0 ± 2.6) were allotted to four dietary treatments including graded Se supplementations with 0, 1, 5, and 50 mg/kg of diet. The experimental diets fed to the pigs for 30 d, and then the pigs were euthanized, and the organs, muscle, and urine samples were collected. The hair and blood samples of pigs were collected on d 15 and 30. Equations were developed for predicting daily Se intake using the Se concentration in plasma, hair, liver, kidneys, muscle, or urine. For graded dietary Se concentrations, linear and quadratic effects on the final body weight, weight and relative weight of liver and kidneys were not observed. The Se concentration in plasma, hair, liver, kidneys, muscle, and urine were linearly and quadratically increased as dietary Se concentration increased (P  0.81, P < 0.001). The equations for estimating dietary Se intake using the Se concentration in the plasma, hair, or organ as an independent variable were significant (P < 0.05). In conclusion, the dietary Se concentration was well reflected in the Se concentration in the plasma, hair, liver, kidneys, and urine. The Se concentration in the plasma, hair, liver, and kidneys can be used as an independent variable for estimating the Se intake

Composition variations in Cu2ZnSnSe4 thin films analyzed by X-ray diffraction, energy dispersive X-ray spectroscopy, particle induced X-ray emission, photoluminescence, and Raman spectroscopy

Compositional and structural studies of Cu2ZnSnSe4 (CZTSe) thin films were carried out by X-ray diffraction, energy dispersive X-ray spectroscopy (EDS), particle induced X-ray emission (PIXE), photoluminescence, and Raman spectroscopy. CZTSe thin films with different compositions were deposited on sodalime glass by coevaporation. The composition of the filmsmeasured by two differentmethods, EDS and PIXE, showed significant differences. Generally, the Zn/Sn ratio measured by EDS is larger than that measured by PIXE. Both the micro- PIXE and the micro-Raman imaging results indicated the compositional and structural inhomogeneity of the sample. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/37033This researchwas supported by the International Research&Development Program of the National Research Foundation of Korea funded by theMinistry of Science, ICT and Future Planning of Korea (Grant number: 2011-0019204) and by the New & Renewable Energy of the Korea Institute of Energy Technology Evaluation and Planning grant funded by the Korea government’s Ministry of Trade, Industry and Energy (No. 20123010010130)

A differential risk assessment and decision model for Transarterial chemoembolization in hepatocellular carcinoma based on hepatic function

Background The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. Methods A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). Results Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system (ASAR). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570–0.871) in the derivation, 0.700 (95% CI = 0.445–0.905) in the internal validation, and 0.680 (95% CI = 0.652–0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., ASA(R), discriminated OS with a c-index of 0.788 (95% CI, 0.703–0.876) in the derivation, and 0.745 (95% CI, 0.646–0.862) in the internal validation, and 0.670 (95% CI, 0.605–0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001). Conclusions ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation

Dehydrogenation of homocyclic liquid organic hydrogen carriers (LOHCs) over Pt supported on an ordered pore structure of 3-D cubic mesoporous KIT-6 silica

Pt supported on ordered mesoporous silica (KIT-6) catalyst was examined for the dehydrogenation of homocyclic liquid organic hydrogen carriers (LOHCs, 1: MCH, 2: hydrogenated biphenyl-based eutectic mixture (H-BPDM)) conditions. The longer pore-residence time of the MCH molecules in the 3D bicontinuous pore structure of the Pt/KIT-6 catalyst strongly affected the catalytic activity because a higher MCH concentration was achieved in the vicinity of the Pt active sites. Pt/KIT-6 catalyst exhibited a higher surface area, pore volume, and Pt dispersion with narrower particle size distribution (average Pt particle size: ~1.3 nm). Therefore, higher LOHC conversion with faster hydrogen production occurred, with a higher hydrogen selectivity over Pt/KIT-6 compared with Pt/SiO2 and Pt/Al2O3. Long-term experiment results indicated that the Pt/KIT-6 catalytic activity was stable over the reaction time than that of the other catalysts. No significant structural collapse occurred in KIT-6 during the dehydrogenation. Carbon coking was observed for all three samples

Composition variations in Cu2ZnSnSe4 thin films analyzed by X-ray diffraction, energy dispersive X-ray spectroscopy, particle induced X-ray emission, photoluminescence, and Raman spectroscopy

Compositional and structural studies of Cu2ZnSnSe4 (CZTSe) thin films were carried out by X-ray diffraction, energy dispersive X-ray spectroscopy (EDS), particle induced X-ray emission (PIXE), photoluminescence, and Raman spectroscopy. CZTSe thin films with different compositions were deposited on sodalime glass by coevaporation. The composition of the filmsmeasured by two differentmethods, EDS and PIXE, showed significant differences. Generally, the Zn/Sn ratio measured by EDS is larger than that measured by PIXE. Both the micro- PIXE and the micro-Raman imaging results indicated the compositional and structural inhomogeneity of the sample. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/37033This researchwas supported by the International Research&Development Program of the National Research Foundation of Korea funded by theMinistry of Science, ICT and Future Planning of Korea (Grant number: 2011-0019204) and by the New & Renewable Energy of the Korea Institute of Energy Technology Evaluation and Planning grant funded by the Korea government’s Ministry of Trade, Industry and Energy (No. 20123010010130)

Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency

Background Targetable molecular drivers of gastric cancer (GC) metastasis remain largely unidentified, leading to limited targeted therapy options for advanced GC. We aimed to identify molecular drivers for metastasis and devise corresponding therapeutic strategies. Methods We performed an unbiased in vivo genome-wide CRISPR/Cas9 knockout (KO) screening in peritoneal dissemination using genetically engineered GC mouse models. Candidate genes were validated through in vivo transplantation assays using KO cells. We analyzed target expression patterns in GC clinical samples using immunohistochemistry. The functional contributions of target genes were studied through knockdown, KO, and overexpression approaches in tumorsphere and organoid assays. Small chemical inhibitors against Bcl-2 members and YAP were tested in vitro and in vivo. Results We identified Nf2 and Rasa1 as metastasis-suppressing genes through the screening. Clinically, RASA1 mutations along with low NF2 expression define a distinct molecular subtype of metastatic GC exhibiting aggressive traits. NF2 and RASA1 deficiency increased in vivo metastasis and in vitro tumorsphere formation by synergistically amplifying Wnt and YAP signaling in cancer stem cells (CSCs). NF2 deficiency enhanced Bcl-2-mediated Wnt signaling, conferring resistance to YAP inhibition in CSCs. This resistance was counteracted via synthetic lethality achieved by simultaneous inhibition of YAP and Bcl-2. RASA1 deficiency amplified the Wnt pathway via Bcl-xL, contributing to cancer stemness. RASA1 mutation created vulnerability to Bcl-xL inhibition, but the additional NF2 deletion conferred resistance to Bcl-xL inhibition due to YAP activation. The combined inhibition of Bcl-xL and YAP synergistically suppressed cancer stemness and in vivo metastasis in RASA1 and NF2 co-deficiency. Conclusion Our research unveils the intricate interplay between YAP and Bcl-2 family members, which can lead to synthetic lethality, offering a potential strategy to overcome drug resistance. Importantly, our findings support a personalized medicine approach where combined therapy targeting YAP and Bcl-2, tailored to NF2 and RASA1 status, could effectively manage metastatic GC.This research was supported by grants of the National Research Foundation (NRF) funded by the Korean government (NRF-RS-2023–00208984, NRF-2021M3H9A1030260, NRF-2021R1F1A1051220, NRF-2016M3A9D5A01952416)

Heterologous expression of tylosin polyketide synthase and production of a hybrid bioactive macrolide in Streptomyces venezuelae

Tylosin polyketide synthase (Tyl PKS) was heterologously expressed in an engineered strain of Streptomyces venezuelae bearing a deletion of pikromycin PKS gene cluster using two compatible low-copy plasmids, each under the control of a pikAI promoter. The mutant strain produced 0.5 mg/l of the 16-membered ring macrolactone, tylactone, after a 4-day culture, which is a considerably reduced culture period to reach the maximum production level compared to other Streptomyces hosts. To improve the production level of tylactone, several precursors for ethylmalonyl-CoA were fed to the growing medium, leading to a 2.8-fold improvement (1.4 mg/ml); however, switching the pikAI promoter to an actI promoter had no observable effect. In addition, a small amount of desosamine-glycosylated tylactone was detected from the extract of the mutant strain, revealing that the native glycosyltransferase DesVII displayed relaxed substrate specificity in accepting the 16-membered ring macrolactone to produce the glycosylated tylactone. These results demonstrate a successful attempt for a heterologous expression of Tyl PKS in S. venezuelae and introduce S. venezuelae as a rapid heterologous expression system for the production of secondary metabolites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45861/1/253_2006_Article_318.pd