EGCG-NPs inhibition HO-1-mediated reprogram iron metabolism against ferroptosis after subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH), a devastating disease with a high mortality rate and poor outcomes, tightly associated with the dysregulation of iron metabolism and ferroptosis. (-)-Epigallocatechin-3-gallate (EGCG) is one of major bioactive compounds of tea catechin because of its well-known iron-chelating and antioxidative activities. However, the findings of iron-induced cell injuries after SAH remain controversial and the underlying therapeutic mechanisms of EGCG in ferroptosis is limited. Here, the ability of EGCG to inhibit iron-induced cell death following the alleviation of neurological function deficits was investigated by using in vivo SAH models. As expected, EGCG inhibited oxyhemoglobin (OxyHb)-induced the over-expression of HO-1, which mainly distributed in astrocytes and microglial cells. Subsequently, EGCG blocked ferrous iron accumulation through HO-1-mediated iron metabolic reprogramming. Therefore, oxidative stress and mitochondrial dysfunction was rescued by EGCG, which resulted in the downregulation of ferroptosis and ferritinophagy rather than apoptosis after SAH. As a result, EGCG exerted the superior therapeutic effects in the maintenance of iron homeostasis in glial cells, such as astrocytes and microglial cells, as well as in the improvement of functional outcomes after SAH. These findings highlighted that glial cells were not only the iron-rich cells in the brain but also susceptible to ferroptosis and ferritinophagy after SAH. The detrimental role of HO-1-mediated ferroptosis in glial cells can be regarded as an effective therapeutic target of EGCG in the prevention and treatment of SAH

Single‐Nucleotide Polymorphism C3435T in the ABCB1 Gene is Associated with Opioid Consumption in Postoperative Pain

Background ABCB1 is a major determinant of opioid bioavailability; however, no previous studies have provided positive evidence of an association between single‐nucleotide polymorphisms (SNPs) of ABCB1 and opioid usage in acute pain management. The aim of this study was to test the association between the functional SNP C3435T in ABCB1 and opioid consumption in postoperative pain in patients undergoing a nephrectomy. Additionally, we explored the association between C3435T and opioid side effect. Methods C3435T was genotyped in 152 patients undergoing a nephrectomy. Opioid consumption and pain scores were evaluated as well. The effect of genotype on opioid consumption was modeled using a general linear mixed model. Result Based on a mixed linear model, the ABCB1 three genotypes showed a statistically significant effect on opioid consumption (F = 4.20, P = 0.017). There was a statistically significant difference in opioid consumption among the ABCB1 three genotypes in the 0–6 hours (P = 0.031, 95% confidence interval [CI] CC 14.7–24.8 mg and TT 5.2–14.6 mg) and 6–12 hours (P = 0.009, 95% CI CC 5.6–13.8 mg and TT 1.2 mg–5.1 mg) postoperative period. There were no significant statistical differences in opioid consumption among the ABCB1 three genotypes in the 12–24 hours (P = 0.302) and 24–48 hours (P = 0.763) postoperative period. The TT genotype had significantly lower levels of cumulative opioid consumption compared with the CC genotype in first 24 hours after surgery (P = 0.029). No statistically significant differences among the three genotype groups were noted for postoperative pain scores or emesis medication use in the first 24 hours after surgery. Conclusion Our results demonstrate an association between the ABCB1 polymorphism (C3435T) and interindividual variations in opioid consumption in the acute postoperative period after nephrectomy. The ABCB1 polymorphism may serve as an important factor to guide acute pain therapy in postoperative patients

Flame-Retardant Thermoplastic Polyether Ester/Aluminum Butylmethylphosphinate/Phenolphthalein Composites with Enhanced Mechanical Properties and Antidripping

Aluminum butylmethylphosphinate AiBMP as a flame retardant and phenolphthalein as a synergistic agent were applied in a thermoplastic polyester elastomer (TPEE)) in the current study. The thermal properties, flame retardancy, crystallization and mechanical properties of TPEE/AiMBP with or without phenolphthalein were investigated using various characterizations, including the limiting oxygen index (LOI), vertical burning test (UL 94), thermogravimetric analysis TG, differential scanning calorimetry, microcombustion calorimeter (MCC), scanning electron microscopy (SEM), and mechanical tests. The results revealed that AiBMP alone is an efficient flame retardant of TPEE. Adding 15 wt.% AiBMP increases the LOI value of TPEE from 20% to 36%. The formula TPEE-15 AiBMP passed the UL 94 V-0 rating with no dripping occurring. The MCC test shows that AiBMP depresses the heat release of TPEE. In comparison with pure TPEE, the heat release rate at peak temperature and the heat release capacity of TPEE-15AiBMP are reduced by 46.1% and 55.5%, respectively. With the phenolphthalein added, the formula TPEE/13AiBMP/2Ph shows a higher char yield at high temperatures (>600 °C), and the char layer is stronger and more condensed than TPEE-15AiBMP.The tensile strength and elongation at break values of TPEE-13AiBMP-2Ph are increased by 29.63% and 4.8% in comparison with TPEE-15AiBMP. The SEM morphology of the fracture surface of the sample shows that phenolphthalein acts as a plasticizer to improve the dispersion of AiBMP within the matrix. The good char charming ability of phenolphthalein itself and improved dispersion of AiBMP make the TPEE composites achieve both satisfying flame retardancy and high mechanical properties

Genetic Mapping of Grain Shape Associated QTL Utilizing Recombinant Inbred Sister Lines in High Yielding Rice (Oryza sativa L.)

Grain shape is a key factor for yield and quality in rice. To investigate the genetic basis of grain shape in the high-yielding hybrid rice variety Nei2You No.6, a set of recombinant inbred sister lines (RISLs) were used to map quantitative trait loci (QTLs) determining grain length (GL), grain width (GW), and length-width ratio (LWR) in four environments. A total of 91 medium/minor-effect QTL were detected using a high-density genetic map consisting of 3203 Bin markers composed of single nucleotide polymorphisms, among which 64 QTL formed 15 clusters. Twelve of 15 clusters co-localized with QTL previously reported for grain shape/weight. Three new QTL were detected: qGL-7a, qGL-8, and qGL-11a. A QTL cluster, qLWR-12c/qGW-12, was detected across all four environments with phenotypic variation explained (PVE) ranging from 3.67% to 11.93%, which was subsequently validated in paired lines of F17 progeny and tightly linked marker assay in F10 generation. Subsequently, 17 candidate genes for qLWR-12c/qGW-12 were detected in the 431 Kb interval utilizing bulk segregant analysis (BSA). Among these, OsR498G1222170400, OsR498G1222171900, OsR498G1222185100, OsR498G1222173400, and OsR498G1222170500 were the best candidates, which lays the foundation for further cloning and will facilitate high-yield breeding in rice

Identification and Fine Mapping of <i>Osdsm3</i>, a Drought-Sensitive Gene in Rice (<i>Oryza sativa</i> L.)

Drought poses a significant constraint on rice production, and, in this study, we have discovered a novel drought-sensitive mutant, designated as dsm3, arising from the progenies of indica rice variety Zhonghui8015 treated with ethyl methane sulphonate (EMS). Under drought stress conditions, dsm3 exhibited characteristic withered leaf tips, accompanied by increased levels of malondialdehyde (MDA) and H2O2, a reduced net photosynthetic rate (Pn), and decreased activity of peroxidase (POD) and superoxide dismutase (SOD). Genetic analysis revealed that the withered leaf tip phenotype was governed by a single recessive gene, designated as Osdsm3. To begin with, Osdsm3 was initially mapped to the short arm of chromosome 1 through a cross involving dsm3 and 02428. Subsequently, utilizing a population of 2591 F2 individuals, we narrowed down the location of Osdsm3 to a 78 Kb interval, encompassing 13 open reading frames (ORFs). Sequencing analysis unveiled a mutation (1275G → A) in the exon of the candidate gene (LOC_Os01g10680), leading to premature translation termination. Moreover, a quantitative RT-PCR assay demonstrated a high expression of OsDSM3 in the panicle and sheath, with a significant upregulation of drought-stress-related genes under drought conditions. Phylogenetic analyses indicated that Osdsm3 shares evolutionary homology with UNE1, an intracellular transport protein found in Arabidopsis thaliana. Subcellular studies further confirmed that OsDSM3 resides in the cytoplasm. In conclusion, the forthcoming cloning of Osdsm3 holds promise for delving deeper into the molecular mechanisms governing rice drought resistance