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Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally antiproliferative and when the cell is damaged beyond repair or intensely stressed the p53 protein contributes to apoptosis. Given its key role in preventing cancer it is no wonder that it is the most frequently mutated gene in human cancer. Surprisingly, a subset of missense mutations occurring in p53 (gain-of-function) cause it to lose its suppressor activity and acquire new functionalities that turn the tumor suppressor protein into an oncoprotein. A solid body of evidence exists demonstrating increased malignancy of cancers with mutated p53 in all aspects considered "hallmarks of cancer". In this review, we summarize current findings concerning the cellular processes altered by gain-of-function mutations in p53 and their influence on cancer invasiveness and metastasis. We also present the variety of molecular mechanisms regulating these processes, including microRNA, direct transcriptional regulation, protein-protein interactions, and more.To assess changes of metabolite content and regulation mechanism of the phenolic acid biosynthesis pathway at different developmental stages of leaves, this study performed a combined metabolome and transcriptome analysis of Cyclocarya paliurus leaves at different developmental stages. Metabolite and transcript profiling were conducted by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer and high-throughput RNA sequencing, respectively. Transcriptome identification showed that 58 genes were involved in the biosynthesis of phenolic acid. Among them, 10 differentially expressed genes were detected between every two developmental stages. Identification and quantification of metabolites indicated that 14 metabolites were located in the phenolic acid biosynthetic pathway. Among them, eight differentially accumulated metabolites were detected between every two developmental stages. Association analysis between metabolome and transcriptome showed that six differentially expressed structural genes were significantly positively correlated with metabolite accumulation and showed similar expression trends. A total of 128 transcription factors were identified that may be involved in the regulation of phenolic acid biosynthesis; these include 12 MYBs and 10 basic helix-loop-helix (bHLH) transcription factors. A regulatory network of the phenolic acid biosynthesis was established to visualize differentially expressed candidate genes that are involved in the accumulation of metabolites with significant differences. The results of this study contribute to the further understanding of phenolic acid biosynthesis during the development of leaves of C. paliurus.Armed conflict and internal displacement of persons create new health challenges for women in Africa. To outline the research literature on this population, we conducted a review of studies exploring the health of internally displaced persons (IDP) women in Africa. In collaboration with a health research librarian and a review team, a search strategy was designed that identified 31 primary research studies with relevant evidence. Studies on the health of displaced women have been conducted in South- Central Africa, including Democratic Republic of Congo (DRC); and in Eastern, East central Africa, and Western Africa, including Eritrea, Uganda, and Sudan, Côte d'Ivoire, and Nigeria. We identified violence, mental health, sexual and reproductive health, and malaria and as key health areas to explore, and observed that socioeconomic power shifts play a crucial role in predisposing women to challenges in all four categories. Access to reproductive health services was influenced by knowledge, geographical proximity to health services, spousal consent, and affordability of care. As well, numerous factors affect the mental health of internally displaced women in Africa excessive care-giving responsibilities, lack of financial and family support to help them cope, sustained experiences of violence, psychological distress, family dysfunction, and men's chronic alcoholism. National and regional governments must recommit to institutional restructuring and improved funding allocation to culturally appropriate health interventions for displaced women.Cherry fruit has a high content in flavonoids. These are important diet components protecting against oxidative stress, inflammation, and endothelial dysfunction, which are all involved in the pathogenesis of atherosclerosis, which is the major cause of cardiovascular diseases (CVD). Since the seasonal availability of fresh fruit is limited, research has been focused on cherry extract (CE), which also possesses a high nutraceutical potential. Many clinical studies have demonstrated the nutraceutical efficacy of fresh cherries, but only a few studies on CE antioxidant and anti-inflammatory activities have been carried out. Here, the results concerning the antioxidant and anti-inflammatory activities of CE are reviewed. These were obtained by an in vitro model based on Human Umbilical Vein Endothelial Cells (HUVEC). To clarify the CE mechanism of action, cells were stressed to induce inflammation and endothelial dysfunction. Considering that antioxidants' polyphenol compounds are easily degraded in the gastrointestinal tract, recent strategies to reduce the degradation and improve the bioavailability of CE are also presented and discussed. In particular, we report on results obtained with nanoparticles (NP) based on chitosan derivatives (Ch-der), which improved the mucoadhesive properties of the chitosan polymers, as well as their positive charge, to favor high cellular interaction and polyphenols intestinal absorption, compared with a non-mucoadhesive negative surface charged poly(lactic-co-glycolic) acid NP. The advantages and safety of different nanosystems loaded with natural CE or other nutraceuticals are also discussed.The Editorial Office of Plants wants to make the following corrections to the paper by Tobias, L.M., et al. (2020)[...].A new pleuromutilin derivative, 22-(2-amino-phenylsulfanyl)-22-deoxypleuromutilin (amphenmulin), has been synthesized and proved excellent in vitro and in vivo efficacy than that of tiamulin against methicillin-resistant Staphylococcus aureus (MRSA), suggesting this compound may lead to a promising antibacterial agent to treat MRSA infections. In this study, the effectiveness and safety of amphenmulin were further investigated. Amphenmulin showed excellent antibacterial activity against MRSA (minimal inhibitory concentration = 0.0156~8 µg/mL) and performed time-dependent growth inhibition and a concentration-dependent postantibiotic effect (PAE). Acute oral toxicity test in mice showed that amphenmulin was a practical non-toxic drug and possessed high security as a new drug with the 50% lethal dose (LD50) above 5000 mg/kg. The pharmacokinetic properties of amphenmulin were then measured. After intravenous administration, the elimination half-life (T1/2), total body clearance (Clβ), and area under curve to infinite time (AUC0→∞) were 1.92 ± 0.28 h, 0.82 ± 0.09 L/h/kg, and 12.23 ± 1.35 μg·h/mL, respectively. After intraperitoneal administration, the T1/2, Clβ/F and AUC0→∞ were 2.64 ± 0.72 h, 4.08 ± 1.14 L/h/kg, and 2.52 ± 0.81 μg·h/mL, respectively, while for the oral route were 2.91 ± 0.81 h, 6.31 ± 2.26 L/h/kg, 1.67 ± 0.66 μg·h/mL, respectively. Furthermore, we evaluated the antimicrobial activity of amphenmulin in an experimental model of MRSA wound infection. Amphenmulin enhanced wound closure and promoted the healing of wound, which inhibited MRSA bacterial counts in the wound and decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1.This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Smoothened Agonist purchase Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.Laser flash photolysis and high-resolution mass spectrometry were used to investigate the mechanism of one-electron oxidation of two S-alkylglutathiones using 3-carboxybenzophenone (3CB) as a photosensitizer. This report indicates an unexpected reaction pathway of the α-aminoalkyl radical cation (αN+) derived from the oxidation of S-alkylglutathiones. Instead of a common hydrolysis reaction of αN+ reported earlier for methionine and other sulfur-containing aminoacids and peptides, an intramolecular ring-closure reaction was found for S-alkylglutathiones.CDKL5 deficiency disorder (CDD) is a complex of clinical symptoms resulting from the presence of non-functional CDKL5 protein, i.e., serine-threonine kinase (previously referred to as STK9), or its complete absence. The clinical picture is characterized by epileptic seizures (that start within the first three months of life and most often do not respond to pharmacological treatment), epileptic encephalopathy secondary to seizures, and retardation of psychomotor development, which are often observed already in the first months of life. Due to the fact that CDKL5 is located on the X chromosome, the prevalence of CDD among women is four times higher than in men. However, the course is usually more severe among male patients. Recently, many clinical centers have analyzed this condition and provided knowledge on the function of CDKL5 protein, the natural history of the disease, therapeutic options, and their effectiveness and prognosis. The International CDKL5 Disorder Database was established in 2012, which focuses its activity on expanding knowledge related to this condition and disseminating such knowledge to the families of patients.Introducing leadership and mobility is known to benefit wireless sensor networks in terms of consensus-building and collective decision-making. However, these benefits are neither analytically proven nor quantified in the literature. This paper fills this gap by investigating the mobility dynamics in wireless sensor networks analytically. The results of the analytical investigation are presented as a set of theorems and their proofs. This paper also establishes a natural synergy between the leader-follower model and its bipartite graph representation. It demonstrates the advantages of the leader-follower model for consensus-building over others in terms of improved convergence rate. It presents a strategy for choosing leaders from among the agents participating in the consensus-building process using the well-known graph-coloring solution. Then, it shows how the leader-follower model helps improve the convergence rate of consensus-building. Finally, it shows that the convergence rate of the consensus-building process can be further improved by making the leaders mobile.
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