RESUMEN
Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.
Asunto(s)
Modelos Químicos , Péptidos/química , Secuencia de Aminoácidos , Interacciones Hidrofóbicas e Hidrofílicas , Simulación de Dinámica Molecular , Método de Montecarlo , Agregado de Proteínas , Estructura Secundaria de Proteína , Relación Estructura-ActividadRESUMEN
A novel facile combination of precipitation and plasma discharge reaction is successfully employed for one-step synthesis of an α-Fe2O3-Fe3O4 graphene nanocomposite (GFs). The co-existence and anchoring of hematite (α-Fe2O3) and magnetite (Fe3O4) nanoparticles onto a graphene sheet in the as synthesized GFs were verified by results of XRD, Raman, SEM, TEM, and XPS. HRTEM characterization was used for confirming the bonding between α-Fe2O3/Fe3O4 nanoparticles and the graphene sheet. Consequently, GFs shows superior photodegrading performance towards methylene blue (MB), compared to individual α-Fe2O3/Fe3O4 nanoparticles, as a result of band gap narrowing and the electron-hole pair recombination rate reducing. Moreover, GFs allows a good possibility of separating and recycling under an external-magnetic field, suggesting potential in visible-light-promoted photocatalytic applications.
RESUMEN
BACKGROUND: In this study, we evaluated MHH patients who wished to preserve fertility, assessing the efficacy of a short course (12 months) of a combined hCG +clomiphene citrate. MATERIALS AND METHODS: The cross-sectional study included 19 patients with hypogonadotropic hypogonadism who were admitted to the Andrology and Fertility Hospital of Hanoi between March 2016 and March 2018. Using hCG every three days in combination with clomiphene citrate 25mg per day until normal testosterone levels are reached, maintain the dose until spermatozoa are present. RESULTS: The mean age was 30.2 ± 5.6. Differences in penis length between the time before and after treatment were significant (p=0.005). The average dose of hCG using in our study was 5579 ± 1773.7 IU. After treatment 6 months and 12 months, the changes in clinical features in all patients and the total hypogonadotropic hypogonadism group were statistically significant (p<0.001). In particular, the differences in testosterone hormone levels in the partial hypogonadotropic hypogonadism group were also statistically significant (p=0.03). No adverse event was observed in our study. The number of patients appearing sperm in the semen is 9 patients (47.4%) after 12 months, but most of the sperm were completely deformed (<1%), and the average motility in the progressive motility group was below 8%. CONCLUSION: In conclusion, a combination of hCG and clomiphene citrate may be an option for MHH patients who desired fertility. After 12 months, 47.4% of patients have sperm in semen but almost all of them were deformity. Hormone profile and secondary sexual characteristics improved significantly. There was no adverse event in our study that considered it as safe therapy.