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.

Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms.

Change in individual species phenology is often unsuitable for predicting change in community phenology because of different responses of different species to temperature change. However, few studies have observed community phenological sequences in the field. Here we explore the changes in timing and duration of the community phenological sequence (i.e. onset of leaf-out (OLO), first flower bud (FB), first flowering (FF), first fruiting-set (FFS), post-fruiting vegetation (OPFV), first leaf-coloring (FLC) and complete leaf-coloring (CLC)) along an elevation gradient from 3200 to 3800 m in an alpine meadow on the Tibetan plateau. Our results indicate that OLO and FFS significantly advanced and other timings of phenological events significantly delayed at 3200 m compared with higher elevations (3600 and 3800 m). The flowering duration of the community was shortest and other phenological durations (except budding stage and post-fruiting vegetation stage) were longest at 3200 m. The duration of the growing season decreased as elevation increased, and the ratio of the durations of the reproductive period and growing season was smallest at 3200 m. There were negative correlations between the proportion of early-spring flowering functional group plants and FB, and the durations of leafing and post-fruiting vegetation of the community. Positive correlations were found between the proportion of midsummer flowering functional group plants in the community and these variables. There were significant negative correlations between flowering duration of the community and annual mean air temperature and soil moisture. 4 Therefore, our results suggest that different community compositions might respond differently to climate change.