TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction 38% vs. 56%, p less then 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.A genome-wide association study (GWAS) was performed to identify new single nucleotide polymorphisms (SNPs) and genes associated with mastitis resistance in Assaf sheep by using the Illumina Ovine Infinium® HD SNP BeadChip (680K). In total, 6173 records from 1894 multiparous Assaf ewes with at least three test day records and aged between 2 and 7 years old were used to estimate a corrected phenotype for somatic cell score (SCS). Then, 192 ewes were selected from the top (n = 96) and bottom (n = 96) tails of the corrected SCS phenotype distribution to be used in a GWAS. Although no significant SNPs were found at the genome level, four SNPs (rs419096188, rs415580501, rs410336647, and rs424642424) were significant at the chromosome level (FDR 10%) in two different regions of OAR19. The SNP rs419096188 was located in intron 1 of the NUP210 and close to the HDAC11 genes (61 kb apart), while the other three SNPs were totally linked and located 171 kb apart from the ARPP21 gene. These three genes were related to the immune system response. These results were validated in two SNPs (rs419096188 and rs424642424) in the total population (n = 1894) by Kompetitive Allele-Specific PCR (KASP) genotyping. Furthermore, rs419096188 was also associated with lactose content.Rugby players need muscular strength and power to meet the demands of the sport; therefore, a proper assessment of the performance in rugby players should include both variables. The purpose of this study was to examine the strength and power characteristics (SPC) during the squat (SQ) and bench press (BP) in national amateur rugby players and to analyze gender- and position-related differences. A total of 47 players (30 males and 17 females; age 25.56 ± 1.14 and 23.16 ± 1.38 years, respectively) participated in the study. The one repetition-maximum (1-RM) and SPC in SQ and BP were obtained using a Smith Machine. Then, subjects performed one set of five repetitions on the SQ and BP against six relative loads (30-40-50-60-70-80% 1-RM) using a linear transducer. Differences between genders were found in 1-RM for maximal power, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in BP (p less then 0.00) and 1-RM, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in SQ (p less then 0.00). Comparisons between variables in SQ and BP present a significant relationship (p less then 0.01) in SQ and BP 1-RM with kilograms lifted at maximal power (r = 0.86 and r = 0.84), maximal strength (r = 0.53 and r = 0.92) and maximal power (r = 0.76 and r = 0.93). This study confirms the importance of the SPC assessment for training prescription in rugby amateur players.With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs).  https://www.selleckchem.com/  NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes. This review aims to highlight the recent epigenetic findings related to the NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to attenuate or delay the age-related decline in the neuromuscular system.Divisive faultlines caused by the uneven distribution of relationship strength play an essential role in knowledge search in the technological innovation network, which serves as an important requirement for the technological innovation network's macro level to expand to the meso-subgroup level and promote its healthy development. Given that the biopharmaceutical industry, as a high-tech industry, plays a vital role in promoting healthy development, this paper uses the joint patent applications of global biopharmaceutical firms from 2003 to 2018 as a sample to construct a technological innovation network, to explore the relationship between divisive faultlines and knowledge search in the technological innovation network. We also study the moderating effect of structural holes in this relationship. The empirical results show that divisive faultlines significantly affect the depth of knowledge search in the technological innovation network. Divisive faultlines have an inverted U-shaped effect on the breadth of knowledge search in the technological innovation network.