Organic-inorganic hybrid halide perovskites are emerging as promising materials for next-generation light-emitting diodes (LEDs). However, the poor stability of these materials has been the main obstacle challenging their application. Here, we performed first-principles calculations, revealing that the molecule dissociation energy of Dion-Jacobson (DJ) structure using 1,4-bis(aminomethyl)benzene molecules as bridging ligands is two times higher than the typical Ruddlesden-Popper (RP) structure based on phenylethylammonium ligands. Accordingly, LEDs based on the DJ structure show a half-lifetime over 100 hours, which is almost two orders of magnitude longer compared with those based on RP structural quasi–two-dimensional perovskite. To the best of our knowledge, this is the longest lifetime reported for all organic-inorganic hybrid perovskites operating at the current density, giving the highest external quantum efficiency (EQE) value. In situ tracking of the film composition in operation indicates that the DJ structure was maintained well after continuous operation under an electric field.
Kaposiform hemangioendothelioma (KHE) is an aggressive disease with high morbidity and mortality. The aim of this study was to retrospectively evaluate the efficacy and safety of sirolimus for the treatment of progressive KHE. A multicenter, retrospective cohort study was conducted in patients with progressive KHE treated with sirolimus. A total of 52 patients were analyzed. Thirty-seven (71%) patients exhibited Kasabach-Merritt phenomenon (KMP) and were significantly younger than the patients without KMP [95% confidence interval (CI), 14.39-41.61; p < 0.001]. Patients without KMP were all treated with sirolimus alone, whereas 21 KMP patients with severe symptoms received short-term combination therapy with prednisolone. Overall, 96% and 98% of patients showed improved relief of notable symptoms and/or improved complications at 6 and 12 months after treatment, respectively. After sirolimus treatment, significant decreases in mean severity scores occurred at 6 months (95% CI, 2.23-2.54, p < 0.001) and 12 months (95% CI, 1.53-1.90, p < 0.001). Compared to KMP patients, patients without KMP showed a response that was similar to but less pronounced during the 12 months of treatment (95% CI, 40.87-53.80; p < 0.001). For subgroup analysis of KMP patients, there were no significant differences in tumor shrinkage between those treated with combination therapy and those receiving sirolimus alone (95% CI, 18.11-25.02; p > 0.05). No patients permanently discontinued treatment due to toxicity-related events, and no drug-related deaths occurred. Sirolimus was effective and safe for the treatment of progressive KHE. Sirolimus may be considered as a first-line therapy or as part of a multidisciplinary approach for the treatment of KHE.
Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP.
Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision- or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, β-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-α-mediated and PDGF/PDGF-R-β pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways.
Currently, propranolol is the preferred treatment for problematic proliferating infantile haemangiomas (IHs). The rapid action of propranolol has been shown to be especially dramatic in IHs involving dyspnoea, haemodynamic compromise, palpebral occlusion or ulceration. Another remarkable aspect of propranolol treatment revealed that the growth of the IHs was not only stabilized, but also that the improvement continued until complete involution was achieved, leading to a considerable shortening of the natural course of IH. However, the mechanisms underlying the effects of propranolol have not been fully elucidated. Recent studies have offered evidence of a variety of mechanisms. These include the promotion of pericyte-mediated vasoconstriction, the inhibition of vasculogenesis and catecholamine-induced angiogenesis, the disruption of haemodynamic force-induced cell survival, and the inactivation of the renin-angiotensin system. This review summarizes these mechanisms and the new concepts that are emerging in this area of research. Moreover, several molecular mechanisms by which propranolol may modify neovascularization in IH have also been proposed. The antihaemangioma effect of propranolol may not be attributable to a single mechanism, but rather to a combination of events that have not yet been elucidated or understood. Further studies are needed to evaluate and verify these mechanisms to gain a greater understanding of the effects of the intake of propranolol on haemangioma involution.
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