No abstract

Heterotopic ossification (HO) occurs as a common complication after injury or in genetic disorders. The mechanisms underlying HO remain incompletely understood, and there are no approved prophylactic or secondary treatments available. Here, we identify a self-amplifying, self-propagating loop of Yes-associated protein (YAP)–Sonic hedgehog (SHH) as a core molecular mechanism underlying diverse forms of HO. In mouse models of progressive osseous heteroplasia (POH), a disease caused by null mutations in GNAS, we found that Gnas−/− mesenchymal cells secreted SHH, which induced osteoblast differentiation of the surrounding wild-type cells. We further showed that loss of Gnas led to activation of YAP transcription activity, which directly drove Shh expression. Secreted SHH further induced YAP activation, Shh expression, and osteoblast differentiation in surrounding wild-type cells. This self-propagating positive feedback loop was both necessary and sufficient for HO expansion and could act independently of Gnas in fibrodysplasia ossificans progressiva (FOP), another genetic HO, and nonhereditary HO mouse models. Genetic or pharmacological inhibition of YAP or SHH abolished HO in POH and FOP and acquired HO mouse models without affecting normal bone homeostasis, providing a previously unrecognized therapeutic rationale to prevent, reduce, and shrink HO.

Background Patients who had gone through orthodontic treatment experienced pain and discomfort which could be the highest-ranking reason for treatment disturbance or early termination. Thus, this review aimed to assess the efficacy of analgesics on the relief of pain in orthodontic treatment. Methods A computerized literature search was conducted in the databases of EMBASE (via OVID, 1974 to 2019 Week 50), MEDLINE (via OVID, 1946 to Dec 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (December 2019). The Cochrane Collaboration’s Review Manager 5.3 software was applied in the present study. And methodological quality was evaluated by the Cochrane Risk of Bias Tool. Results We identified twelve publications including 587 patients in 19 randomized controlled trials. The results showed that the mean difference of naproxen in visual analogue scale (VAS) were − 1.45 (95% CI -2.72, − 0.19; P = .02), − 2.11 (95% CI -3.96, − 0.26; P = .03) and − 1.90 (95% CI -3.33, − 0.47; P = .009) in 2 h, 6 h and 24 h respectively. As for ibuprofen, the standard mean differences were − 1.10 (95% CI -1.49, − 0.71), − 1.63(95% CI -2.32, − 0.95) and − 1.34 (95% CI -2.12, − 0.55) at 2 h, 6 h, and 24 h, with the overall P values all < 0.001. The mean difference of acetaminophen is − 0.68, − 1.34, − 1.91 at three time points and the overall P values all < 0.01. Conclusions This meta-analysis suggests that the use of analgesics is effective for patients in controlling orthodontic pain. Ibuprofen and naproxen are both of stable analgesic effects which could peak at 6 h, while the analgesic effect of acetaminophen increases steadily from 2 h through 24 h. Compared with ibuprofen and acetaminophen, naproxen shows a stronger analgesic effect either at 2 h or 6 h, and its effect lasts to 24 h.

The simpler, the better! A series of simple and highly fluorescent salicylaldehyde hydrazide molecules (41 samples) have been designed and prepared. Even though these soft materials contain a very small π‐conjugated system, they can go through multiple intramolecular and intermolecular hydrogen bonds promoted excited‐state intramolecular proton‐transfer (ESIPT) to display strong blue, green, yellow, and orange aggregation‐induced emission (AIE) with large Stokes shifts (up to 184 nm) and high fluorescence quantum yields (Ф up to 0.20). Unusual mechanochromic fluorescence enhancements are also found in some solid samples. Through coordination, hydrogen and halogen bonds, these flexible molecules can be used as Mg2+ (Ф up to 0.46) probes, universal anion (Ф up to 0.14) and unprotected amino acids (Ф up to 0.16) probes, and chiral diamine (enantiomeric selectivity and Ф up to 0.36 and 0.062, respectively) receptors. Combining their advantages of AIE and biocompatibility, these low cytotoxic dyes have potential application in living cell imaging. Furthermore, the effects of different functional groups on the molecule arrangement, ESIPT, AIE, probe, and chiral recognition properties are also examined, which provide a simple and bright paradigm for the design of multiple‐stimuli‐responsive smart materials.