Mediating

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Neurodegeneration of the substantia nigra (SN) and diminished release of dopamine are prominent causes of this progressive disease. The current study aims to evaluate the protective potential of ethanolic extract of Mentha piperita (EthMP) against rotenone-mediated PD features, dopaminergic neuronal degeneration, oxidative stress and neuronal survival in a mouse model. Swiss albino male mice were assigned to five groups: control (2...

Most legumes are able to develop a root nodule symbiosis in association with proteobacteria collectively called rhizobia. Among them, the tropical species Aeschynomene evenia has the remarkable property of being nodulated by photosynthetic Rhizobia without the intervention of Nod Factors (NodF). Thereby, A. evenia has emerged as a working model for investigating the NodF-independent symbiosis. Despite the availability of numerous resources and tools to study the molecular basis of this atypical symbiosis, the lack of a transformation system based on Agrobacterium tumefaciens significantly limits the range of functional approaches...

System Thinking is an actual construct supported by several scientific evidence that offer a perspective on how phenomena relate. Rhythm methodology, teaching-learning, and enjoyment in physical education are the main system elements we hypothesize interacting closely to determine direct or mediated effects on motor creativity and rhythmic perceptive capacity. Seventy-six elementary and middle school students (8.9 ± 2.1 years) were randomly assigned to two groups: a) an intervention group that received a physical education lesson based on rhythmic methodology and b) a control group that received conventional lessons without specific rhythmic interventions...

More and more evidence shows that abnormal lipid metabolism leads to immune system dysfunction in AMD and promotes the occurrence of AMD by changing the homeostasis of ocular inflammation. However, the molecular mechanism underlying the effect of lipid metabolism on the phenotype and function of macrophages is still unclear, and the mechanism of association between AMD and cancer and COVID-19 has not been reported. The purpose of this study is to explore the interaction between lipid metabolism related genes, ferroptosis related genes and immunity in AMD, find out the key genes that affect the ferroptosis of AMD through lipid metabolism pathway and the molecular mechanism that mediates the action of macrophages, and find out the possible mechanism of lipid metabolism and potential co-therapeutic targets between AMD and cancer and COVID-19, so as to improve treatment decision-making and clinical results...

Serine phosphorylations on insulin receptor substrate 1 (IRS-1) by diverse kinases aoccur widely during obesity-, stress-, and inflammation-induced conditions in models of insulin resistance and type 2 diabetes. In this study, we define a region within the human IRS-1, which is directly C-terminal to the PTB domain encompassing numerous serine phosphorylation sites including Ser307 (mouse Ser302) and Ser312 (mouse 307) creating a phosphorylation insulin resistance (PIR) domain. We demonstrate that the IRS-1 PTB-PIR with its unphosphorylated serine residues interacts with the insulin receptor (IR) but loses the IR-binding when they are phosphorylated...

In gram-positive bacteria, phosphorylated arginine functions as a protein degradation signal in a similar manner as ubiquitin in eukaryotes. The protein-arginine phosphorylation is mediated by the McsAB complex, where McsB possesses kinase activity and McsA modulates McsB activity. Although mcsA and mcsB are regulated within the same operon, the role of McsA in kinase activity has not yet been clarified. In this study, we determined the molecular mechanism by which McsA regulates kinase activity. The crystal structure of the McsAB complex shows that McsA binds to the McsB kinase domain through a second zinc-coordination domain and the subsequent loop region...

A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon α/β receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 μg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine...

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells...

Oxidative damage to erythroid cells plays a key role in the pathogenesis of thalassemia. The oxidative stress in thalassemia is potentiated by heme, nonheme iron, and free iron produced by the Fenton reaction, due to degradation of the unstable hemoglobin and iron overload. In addition, the levels of antioxidant enzymes and molecules are significantly decreased in erythrocytes in α- and β-thalassemia. The control of oxidative stress in red blood cells (RBCs) is known to be mediated by microRNAs (miRNAs)...

An efficient formylation of pyrrolo[2,1- a ]isoquinoline derivatives has been reached by the use of TBHP ( t BuOOH) and Et3 N as the mediator. In this strategy, CHO and CDO can be readily incorporated into heteroarenes by the utilization of CHCl3 and CDCl3 as the carbonyl sources. Interestingly, a solvent-controlled chemoselectivity was observed. The use of PhCl as a solvent resulted in dearomatization and peroxidation of pyrrolo[2,1- a ]isoquinolines, delivering functionalized peroxides in 53-64% yields.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown...

Power can increase overconfidence and illusory thinking. We investigated whether power is also related to the illusion of explanatory depth (IOED), people's tendency to think they understand the world in more detail, coherence, and depth than they actually do. Abstract thinking was reported as a reason for the IOED, and according to the social distance theory of power, power increases abstract thinking. We linked these literatures and tested construal style as a mediator. Further, predispositions can moderate effects of power and we considered narcissism as a candidate because narcissism leads to overconfidence and may thus increase the IOED especially in combination with high power...

OBJECTIVE: We sought to examine the relationship of unfavorable psychosocial working conditions with slips and lapses and poor patient interaction as well as potential intermediate factors among medical assistants (MAs) in Germany based on prospective data. METHODS: We used data from 408 MAs from a 4-year cohort study (follow-up: 2021). At baseline, psychosocial working conditions were assessed by the established effort-reward-imbalance questionnaire and a MA-specific questionnaire with 7 subscales...

In the setting of an Ebstein's anomaly, a right-to-left shunt via a patent foramen ovale (PFO) may be the cause of a significant cyanosis. In these patients, the PFO closure is able to improve the arterial saturation. Furthermore, a partial closure is often recommended to obtain a reduction in the PFO right-left shunt without a significant impact on the right chamber hemodynamics. However, in some cases, a complex PFO anatomy may prevent an effective device closure. We describe the case of a patient with Ebstein's anomaly and a significant cyanosis due to a right-to-left shunt via the PFO wherein an effective partial PFO closure with a suture-mediated NobleStitch EL system was achieved in a setting of a complex PFO anatomy (large aneurismatic septum, long stiff tunnel, and hypertrophic septum secundum) after a failed device-closure attempt...

Precise integration of DNA constructs greater than 3 kb into mouse zygotes is difficult. Here, we present a protocol for large DNA transgenesis in mice using the Cas9+Bxb1 toolbox. We describe steps for choosing mouse strains with preplaced attachment sites. We then detail procedures for microinjecting mouse zygotes with the plasmid donor DNA construct to generate transgenic mice by recombination-mediated cassette exchange. This protocol has the potential for application in exploring the functional implications of large structural variations in cancer...

Post-transcriptional mRNA regulation shapes gene expression, yet how cis-elements and mRNA translation interface to regulate mRNA stability is poorly understood. We find that the strength of translation initiation, upstream open reading frame (uORF) content, codon optimality, AU-rich elements, microRNA binding sites, and open reading frame (ORF) length function combinatorially to regulate mRNA stability. Machine-learning analysis identifies ORF length as the most important conserved feature regulating mRNA decay...

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion...

This study aims to elucidate associations among self-compassion, depression, and suicidal ideation, particularly with respect to gender differences. Using a multigroup cross-lagged panel model, we conducted a longitudinal evaluation of 424 Chinese adolescents (55.85% boys; Mage = 18.02, SD = 0.73 at baseline). Our findings indicated that suicidal ideation at T1 positively predicted depression 6 months later, while negatively predicted self-compassion. However, self-compassion negatively predicted depression 6 months later, specifically in boys, but not in girls...

The protein-repairing enzyme (PRE) PROTEIN L-ISOASPARTYL METHYLTRANSFERASE (PIMT) influences seed vigor by repairing isoaspartyl-mediated protein damage in seeds. However, PIMTs function in other seed traits, and the mechanisms by which PIMT affects such seed traits are still poorly understood. Herein, through molecular, biochemical, and genetic studies using overexpression and RNAi lines in Oryza sativa and Arabidopsis thaliana, we demonstrate that PIMT not only affects seed vigor but also affects seed size and weight by modulating enolase (ENO) activity...

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2 H -thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2 H -thiopyrans are novel precursors for unstudied 2 H -thiopyran-2-ones and 4 H -thiopyran-4-ones. The 4 H -thiopyran-4-ones were obtained via a novel O2 /Et3 N-mediated oxidative deformylation...