Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-β (Aβ) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon–dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking. The current review aimed to explain the mechanisms of the PDK1/Akt/TACE signaling axis that exerts its modulatory effect on AD physiopathology. We provide an overview of the neuropathological features, genetics, Aβ aggregation, Tau protein hyperphosphorylation, neuroinflammation, and aging in the AD brain. Additionally, we summarized the phosphoinositide 3-kinase (PI3K)/PDK1/Akt pathway-related features and its molecular mechanism that is dependent on TACE in the pathogenesis of AD. This study reviewed the relationship between the PDK1/Akt signaling pathway and AD, and discussed the role of PDK1/Akt in resisting neuronal toxicity by suppressing TACE expression in the cell membrane. This work also provides a perspective for developing new therapeutics targeting PDK1/Akt and TACE for the treatment of AD.
Fermentation of paocai is a dynamic process of the microbial community structure, and the interaction between community structure and physicochemical factors endows paocai with unique taste and flavor. The study of bacterial and fungal community structure changes and the driving mechanism of physicochemical factors induced changes in community structure, showing that Pseudomonas belonging to Proteobacteria and Lactobacillus belonging to Firmicutes were the dominant bacteria in the process of paocai fermentation. The correlation analysis of physicochemical factors with bacterial community showed that titratable acid was significantly positively correlated with Lactobacillus and negatively correlated with Pseudomonas, while nitrite was the opposite. Redundancy analysis (RDA) showed that pH was positively correlated with the bacterial community in the early fermentation stage, amino acid nitrogen was positively correlated with the bacterial community in the middle fermentation stage, and titratable acid was positively correlated with the bacterial community in the late fermentation stage. Variance partitioning analysis (VPA) showed that environmental factors, pH and metabolites, were the main driving forces of bacterial community diversity, which jointly explained 32.02% of the bacterial community structure variation. To study the glucolysis and nitrogen metabolism in the process of paocai fermentation, we found that in the early stage of the fermentation, the nitrite reductase enzyme of Pseudomonas activity was high, with high nitrite content in the prophase, but by the end of fermentation, lactic acid bacteria rapidly increased, the content of L−lactic acid through the glycolysis pathway, making paocai fermentation environment become acidic, then Pseudomonas decreased. Ascomycota and Basidiomycota were the main phylum fungi in the fermentation process. RDA analysis showed that the fungal community was positively correlated with pH, nitrite, and soluble protein at the early fermentation stage, amino acid nitrogen was positively correlated with the fungal community at the middle fermentation stage, titratable acid and reducing sugar were positively correlated with the fungal community at the late fermentation stage. VPA analysis showed that metabolites were the main driving force of fungal community diversity and accounted for 45.58% of fungal community diversity. These results had a certain guiding significance for the production and preservation of naturally fermented paocai.
Social mating systems (e.g., monogamy, polygamy, or polyandry) are relatively stable behavioral strategies developed by environmental in animals, but the genetic imprint of a particular mating system is often incongruent with the social mating system due to extrapair matings. However, the genetics of mating systems remain little understood in rodents. In this study, we investigated the genetic signature of the mating system of 141 (63 females, 78 males) field-captured Midday Gerbils (Meriones meridianus) -a rodent species commonly found in the Minqin Desert in China-through microsatellite site analyses of genetic structure and relatedness. Seven pairs of highly polymorphic microsatellite loci were selected and were highly polymorphic, the combined exclusion probability was greater than 0.99. The parent pair paternity test by Cervus 3.0 software show that, eleven mother-offspring and nine father-offspring relationships were identified in 2018, involving 26 individuals from 10 families. Similarly, 19 mother-offspring and 19 father-offspring relationships were identified in 2019, involving 48 individuals from 18 families. All three types of genetic mating structure were identified: monogamy (19 families), polyandry (4 families), and polygyny (5 families), providing evidence that the genetics underlying mating systems in this species are variable, can be incongruent with behavioral evidence for social mating systems, and could vary based on environmental cues, including degree of perceived or actual predation.
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