Murphyhyde5660

Marfan syndrome is one of the most common dominantly inherited connective tissue disorders, affecting 2-3 in 10,000 individuals, and is caused by one of over 2800 unique FBN1 mutations. Mutations in FBN1 result in reduced fibrillin-1 expression, or the production of two different fibrillin-1 monomers unable to interact to form functional microfibrils. Darapladib Here, we describe in vitro evaluation of antisense oligonucleotides designed to mediate exclusion of FBN1 exon 52 during pre-mRNA splicing to restore monomer homology. Antisense oligonucleotide sequences were screened in healthy control fibroblasts. The most effective sequence was synthesised as a phosphorodiamidate morpholino oligomer, a chemistry shown to be safe and effective clinically. We show that exon 52 can be excluded in up to 100% of FBN1 transcripts in healthy control fibroblasts transfected with PMO52. Immunofluorescent staining revealed the loss of fibrillin 1 fibres with ~50% skipping and the subsequent re-appearance of fibres with >80% skipping. However, the effect of exon skipping on the function of the induced fibrillin-1 isoform remains to be explored. Therefore, these findings demonstrate proof-of-concept that exclusion of an exon from FBN1 pre-mRNA can result in internally truncated but identical monomers capable of forming fibres and lay a foundation for further investigation to determine the effect of exon skipping on fibrillin-1 function.Metastasis is the main cause of cancer-related death. Despite its high fatality, a comprehensive study that covers anti-metastasis of herbal medicines has not yet been conducted. The aim of this study is to investigate and assess the anti-metastatic efficacies of herbal medicines in the five major cancers, including lung, colorectal, gastric, liver, and breast cancers. We collected articles published within five years using PubMed, Google Scholar, and Web of Science with "cancer metastasis" and "herbal medicine" as keywords. Correspondingly, 16 lung cancer, 23 colorectal cancer, 10 gastric cancer, 10 liver cancer, and 18 breast cancer studies were systematically reviewed. The herbal medicines attenuated metastatic potential targeting various mechanisms such as epithelial mesenchymal transition (EMT), reactive oxygen species (ROS), and angiogenesis. Specifically, the drugs regulated metastasis related factors such as matrix metalloproteinase (MMP), serine-threonine protein kinase/extracellular regulated protein kinase (AKT/ERK), angiogenic factors, and chemokines. Overall, the present study is the first review, comprehensively investigating the anti-metastasis effect of herbal medicines on five major cancers, providing the experimental models, doses and durations, and mechanisms. Herbal medicines could be a potent candidate for anti-metastatic drugs.The COVID-19 pandemic has contributed to mental health problems worldwide. Nurses are particularly prone to stress because they directly care for individuals with suspected or confirmed cases of COVID-19. The aims of this study were (a) to explore the association between the mental health promotion strategies used by nurses during the COVID-19 outbreak and their symptoms of depression, anxiety, and stress; (b) to compare the symptoms of depression, anxiety, and stress of mental health nurses to those of non-mental health nurses; and (c) to compare the frequency of use of mental health strategies of mental health nurses to those of non-mental health nurses. A cross-sectional study was conducted with a sample of 821 nurses. Univariate and multivariate regression models were developed to identify potential protective factors of depression, anxiety, and stress. The chi-square test was also used to compare the use of strategies among mental health and non-mental health nurses. Portuguese nurses demonstrated high symptoms of depressive symptoms, stress, and anxiety. Healthy eating, physical activity, rest between shifts, maintaining social contacts, verbalizing feelings/emotions, and spending less time searching for information about COVID-19 were associated with better mental health. Mental health nurses had less depression, anxiety, and stress, and used more strategies to promote mental health than other nurses. We consider it important to promote nurses' mental health literacy by encouraging them to develop skills and strategies aimed at improving their resilience and ability to deal with difficult situations while caring for the population.Emotion recognition plays an important role in human-computer interactions. Recent studies have focused on video emotion recognition in the wild and have run into difficulties related to occlusion, illumination, complex behavior over time, and auditory cues. State-of-the-art methods use multiple modalities, such as frame-level, spatiotemporal, and audio approaches. However, such methods have difficulties in exploiting long-term dependencies in temporal information, capturing contextual information, and integrating multi-modal information. In this paper, we introduce a multi-modal flexible system for video-based emotion recognition in the wild. Our system tracks and votes on significant faces corresponding to persons of interest in a video to classify seven basic emotions. The key contribution of this study is that it proposes the use of face feature extraction with context-aware and statistical information for emotion recognition. We also build two model architectures to effectively exploit long-term dependencies in temporal information with a temporal-pyramid model and a spatiotemporal model with "Conv2D+LSTM+3DCNN+Classify" architecture. Finally, we propose the best selection ensemble to improve the accuracy of multi-modal fusion. The best selection ensemble selects the best combination from spatiotemporal and temporal-pyramid models to achieve the best accuracy for classifying the seven basic emotions. In our experiment, we take benchmark measurement on the AFEW dataset with high accuracy.In the attempt to improve the purification yield of native toxin A (TcdA) and toxin B (TcdB) from Clostridioides difficile (C. difficile), we systematically evaluated culture parameters for their influence on toxin production. In this study, we showed that culturing C. difficile in a tryptone-yeast extract medium buffered in PBS (pH 7.5) that contained 5 mM ZnCl2 and 10 mM glucose supported the highest TcdB production, measured by the sandwich ELISA. These culture conditions were scalable into 5 L and 15 L dialysis tube cultures, and we were able to reach a TcdB concentration of 29.5 µg/mL of culture. Furthermore, we established a purification protocol for TcdA and TcdB using FPLC column chromatography, reaching purities of >99% for both toxins with a yield around 25% relative to the starting material. Finally, by screening the melting temperatures of TcdA and TcdB in various buffer conditions using differential scanning fluorimetry, we found optimal conditions for improving the protein stability during storage.