Age and wounding are two major determinants for regeneration. In plants, the root regeneration is triggered by woundinduced auxin biosynthesis. As plants age, the root regenerative capacity gradually decreases. How wounding leads to the auxin burst and how age and wound signals collaboratively regulate root regenerative capacity are poorly understood. Here, we show that the increased levels of three closely-related miR156-targeted Arabidopsis (Arabidopsis thaliana) SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL2, SPL10, and SPL11, suppress root regeneration with age by inhibiting wound-induced auxin biosynthesis. Mechanistically, we find that a subset of APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors including ABSCISIC ACID REPRESSOR1 and ERF109 is rapidly induced by wounding and serves as a proxy for wound signal to induce auxin biosynthesis. In older plants, SPL2/10/11 directly bind to the promoters of AP2/ERFs and attenuates their induction, thereby dampening auxin accumulation at the wound. Our results thus identify AP2/ERFs as a hub for integration of age and wound signal for root regeneration.
Timolol has been demonstrated to be efficacious in the topical treatment of superficial infantile hemangiomas (IHs). We conducted a prospective study to evaluate the short-term efficacy and safety of timolol in the treatment of superficial IH in Chinese infants. From March to November 2012, 124 patients with superficial IHs were included in the prospective study. The patients were divided into two groups: treatment (101 patients, the timolol drops were administered on the surface of the lesions three times daily, and erythromycin ointment was applied around the lesions) and observation (23 patients, without treatment). The results were categorized into three grades: class 1 (ineffective), class 2 (controlled growth) and class 3 (promoted regression). Within one week of the initiation of timolol treatment, a number of the lesions became softer and lighter in color. Four months following the initiation of timolol treatment, the overall response was class 1 in eight patients (7.9%), class 2 in 36 patients (35.6%) and class 3 in 57 patients (56.4%). Complete tumor regression was observed in 12 patients. No adverse effects were recorded during the treatment period. Among the patients in the observation group, there were 15 class 1 patients (65.2%), seven class 2 patients (30.4%) and only one class 3 patient (4.3%). In conclusion, timolol is an effective and safe treatment for superficial IH. In addition, it may be used in the treatment of proliferative superficial IH, particularly in infants within 6 months of age.
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