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Fruit ripening is accompanied by dramatic changes in color, texture, and flavor and is regulated by transcription factors (TFs) and epigenetic factors. However, the detailed regulatory mechanism remains unclear. Gene expression patterns suggest that PpNAC1 (NAM/ATAF1/2/CUC) TF plays a major role in peach (Prunus persica) fruit ripening. DNA affinity purification (DAP)-seq combined with transactivation tests demonstrated that PpNAC1 can directly activate the expression of multiple ripening-related genes, including ACC synthase1 (PpACS1) and ACC oxidase1 (PpACO1) involved in ethylene biosynthesis, pectinesterase1 (PpPME1), pectate lyase1 (PpPL1), and polygalacturonase1 (PpPG1) related to cell wall modification, and lipase1 (PpLIP1), fatty acid desaturase (PpFAD3-1), and alcohol acyltransferase1 (PpAAT1) involved in volatiles synthesis. Overexpression of PpNAC1 in the tomato (Solanum lycopersicum) nor (nonripening) mutant restored fruit ripening, and its transient overexpression in peach fruit induced target gene expression, supporting a positive role of PpNAC1 in fruit ripening. The enhanced transcript levels of PpNAC1 and its target genes were associated with decreases in their promoter mCG methylation during ripening. Declining DNA methylation was negatively associated with increased transcripts of DNA demethylase1 (PpDML1), whose promoter is recognized and activated by PpNAC1. We propose that decreased methylation of the promoter region of PpNAC1 leads to a subsequent decrease in DNA methylation levels and enhanced transcription of ripening-related genes. These results indicate that positive feedback between PpNAC1 and PpDML1 plays an important role in directly regulating expression of multiple genes required for peach ripening and quality formation. Transcription factor PpNAC1 and DNA demethylase PpDML1 form a feedback loop to synergistically regulate ethylene synthesis, softening, and flavor formation in peach fruit. [ABSTRACT FROM AUTHOR]

Objectives: The mechanisms of regional acceleratory phenomenon (RAP) induced by orthognathic osteotomy are unclear. It was not known if locally hypoxic microenvironment changes were involved in this phenomenon. Methods: Hypoxia‐induced factor‐1α knockout mice harboring Cathepsin K (CTSK) Cre were used to investigate the effect of hypoxia‐driven osteoclasts on alveolar bone remodeling. RAW264.7 cells were induced by CoCl2 to observe the effects of dendritic cell‐specific transmembrane protein (DC‐STAMP) on the fusion and differentiation of osteoclasts. Results: We found mandibular osteotomy of C57 mice induced active alveolar osteoclasts and increased hypoxia‐induced factor‐1α (HIF‐1α) positive staining areas. Alveolar bone density of the 10‐week‐old HIF‐1α conditional knockout (CKO) mouse was increased at 10 and 14 days after bilateral mandibular osteotomy. Moreover, decreased numbers of osteoclasts and matrix metalloproteinase 9 (MMP‐9)‐positive cells were observed on the surface of bone resorption lacunae in the CKO group. HIF‐1α could increase the expression level of DC‐STAMP to enhance osteoclastogenesis and cell fusion in active RAW264.7 cells. Conclusion: Our data considered hypoxia‐driven osteoclasts resorption to be an adaptive mechanism to permit alveolar bone loss after bilateral mandibular osteotomy of mice. [ABSTRACT FROM AUTHOR]

Objectives: Hypoxia is one of the characteristics of microenvironmental changes after orthognathic surgery for fractures. HIF‐1α is a main regulator of the hypoxic response and plays a crucial role in bone formation, remodelling, and homeostasis. Osteoclasts participate in bone absorption and affect osteogenesis, and osteoclasts differentiate in a path from the oxygen‐rich bone marrow to oxygen‐deficient bone lesions. Thus, we aimed to study the key functions of HIF‐1α in osteoclasts during mandibular healing after osteotomy. Materials and Methods: The function of HIF‐1α in osteoclasts during fracture healing in osteoclast‐specific HIF‐1α‐conditional‐knockout mice was investigated in mandibular osteotomy. Primary osteoclasts were used to explore the expression of HIF‐1α and cardiotrophin‐1 (CT‐1) at both the mRNA and protein levels. The ability of BMSCs co‐cultured with conditioned media from osteoclast‐specific HIF‐1α‐knockout primary osteoclasts was detected using osteoclast‐mediated osteogenesis experiments. Results: Hypoxia‐inducible factor‐1α increased osteoclastogenesis and bone resorption, and a delay in bone healing was found in osteoclast‐specific HIF‐1α‐conditional‐knockout mice compared with normal mice. HIF‐1α‐knockout primary osteoclasts inhibited bone resorption and CT‐1 expression, and HIF‐1α enhanced the osteoclast‐mediated stimulation of BMSC differentiation by secreting CT‐1. Conclusions: Hypoxia‐inducible factor‐1α can play a key role in the physiology and pathogenesis of bone resorption by promoting osteoclastogenesis during fracture and influencing osteogenesis through CT‐1 during bone healing. [ABSTRACT FROM AUTHOR]

To test whether targeting left and right posterior parietal cortex (PPC) with continuous theta-burst stimulation (cTBS) in healthy adults would strengthen associative memory (AM) performance. This study consisted of two experiments (a behavioral experiment and a formal experiment during each of the two experimental sessions). In Experiment 1, 18 adults (one male, age = 22.83 ± 3.92 years) were included in the behavioral phase and 18 adults (seven males, age = 40.11 ± 12.27 years) in the stimulation phase. There were 120 neutral facial images paired with 120 two-character nouns and then divided into six test versions (10 male faces and 10 female faces paired with 20 different nouns were considered as one version). In the behavioral experiment, participants were tested by six-version tests to assess memory materials, and in the formal experiment, participants' face-word AM performance was measured by certified tests based on a cued recall paradigm. Furthermore, 30 adults (seven males, age = 20.97 ± 1.85 years) and 15 adults (five males, age = 22.27 ± 1.29 years) participated in Experiment 2, respectively. Stimuli and procedure were the same as in Experiment 1, but the AM test was based on a forced-choice paradigm. Experiment 1 did not yield anticipated outcomes; Experiment 2 showed that cTBS of left and right PPC strengthened the AM performance compared with the control condition. In conclusion, cTBS to left and right PPC improved AM in healthy adults, which provided further experimental evidence for strengthening AM by cTBS., (© 2024 Massachusetts Institute of Technology.)