Variation in body weight, glucose/insulin tolerances, blood lipids and liver enzymes in mice in response to a high-fat-diet from lard.

It raises questions about the impact of lard on the health and the differences in individual responses. Therefore, we developed a model of mice fed with high fat (HF) from lard in 130 days. The weight of the mice was measured every two days. Glucose tolerance test and insulin tolerance tests were performed at 70 days and 130 days of experiment. At the end of the study, the fat tissue was collected to check the weight, and a blood sample was collected to check the blood lipids and liver enzymes. Surprisingly, mice responded variously to the HF by being classified into two groups, one group had significantly high gained weight (HG_HF) versus the mice fed a standard diet (STD) (p < 0.001), and another group (LG_HF) has not difference in body weight compared to the STD groups. This phenomenon in body weight is directly reflected by the white fat accumulation, but not by brown fat. Eating HF from lard for a long time can disrupt glucose tolerance and cause dyslipidemia in mice, even in the LG_HF group, but can not disrupt insulin tolerance and cause liver enzyme disorders. In summary, our findings are a wake-up call for many cases where eating HF from lard does not gain weight and not increase the white fat storage, but still has the potential to cause adverse health effects. Further studies are encouraged to understand the molecular mechanisms that causes the body to regulate its weight and responses when eating HF from lard, especially in the LG_HF group.

Drug repurposing for metabolic disorders: Scientific, technological and economic issues.

Obesity, diabetes, and other metabolic disorders place a huge burden on both the physical health and financial well-being of the community. While the need for effective treatment of metabolic disorders remains urgent and the reality is that traditional drug development involves high costs and a very long time with many pre-clinical and clinical trials, the need for drug repurposing has emerged as a potential alternative. Scientific evidence has shown the anti-diabetic and anti-obesity effects of old drugs, which were initially utilized for the treatment of inflammation, depression, infections, and even cancers. The drug library used modern technological methods to conduct drug screening. Computational molecular docking, genome-wide association studies, or omics data mining are advantageous and unavoidable methods for drug repurposing. Drug repurposing offers a promising avenue for economic efficiency in healthcare, especially for less common metabolic diseases, despite the need for rigorous research and validation. In this chapter, we aim to explore the scientific, technological, and economic issues surrounding drug repurposing for metabolic disorders. We hope to shed light on the potential of this approach and the challenges that need to be addressed to make it a viable option in the treatment of metabolic disorders, especially in the future fight against metabolic disorders.

Rationally engineered Staphylococcus aureus Cas9 nucleases with high genome-wide specificity.

RNA-guided CRISPR-Cas9 proteins have been widely used for genome editing, but their off-target activities limit broad application. The minimal Cas9 ortholog from Staphylococcus aureus (SaCas9) is commonly used for in vivo genome editing; however, no variant conferring high genome-wide specificity is available. Here, we report rationally engineered SaCas9 variants with highly specific genome-wide activity in human cells without compromising on-target efficiency. One engineered variant, referred to as SaCas9-HF, dramatically improved genome-wide targeting accuracy based on the genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) method and targeted deep sequencing analyses. Among 15 tested human endogenous sites with the canonical NNGRRT protospacer adjacent motif (PAM), SaCas9-HF rendered no detectable off-target activities at 9 sites, minimal off-target activities at 6 sites, and comparable on-target efficiencies to those of wild-type SaCas9. Furthermore, among 4 known promiscuous targeting sites, SaCas9-HF profoundly reduced off-target activities compared with wild type. When delivered by an adeno-associated virus vector, SaCas9-HF also showed reduced off-target effects when targeting VEGFA in a human retinal pigmented epithelium cell line compared with wild type. Then, we further altered a previously described variant named KKH-SaCas9 that has a wider PAM recognition range. Similarly, the resulting KKH-HF remarkably reduced off-target activities and increased on- to off-target editing ratios. Our finding provides an alternative to wild-type SaCas9 for genome editing applications requiring exceptional genome-wide precision.

Author Correction: Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors.

In the initial published version of this article, we inadvertently stated that "all procedures were conducted with the approval and under the supervision of the Institutional Animal Care and Use Committee (IACUC) at the University of California, San Diego". Given that all animal work that was conducted for this project was performed at the City University of Hong Kong and Guangzhou Women and Children's Medical Center, we would like to instead, acknowledge these programs for their oversight of the animal studies. This correction does not affect the description of the results or the conclusions of this work.

Acceptability of and willingness to pay for using a smartphone-based vaccination application in a Vietnamese cohort.

BACKGROUND: The increasing accessibility of smartphone in Vietnam shows potential in using smartphone applications for vaccination management to improve compliance. However, the acceptability and financial feasibility of using this application in Vietnam have not yet been understood. This study measured the general perception of and willingness to pay (WTP) for using smartphone-based vaccination management applications and their associated factors in Vietnam. SUBJECTS AND METHODS: A cross-sectional study was conducted between March and April 2016 in an urban vaccination clinic at the Hanoi Medical University in Vietnam. Convenience sampling was used to recruit 429 adult participants who had received vaccinations or whose children were vaccinated. Sociodemographic characteristics and the acceptability of and WTP for using smartphone-based vaccination management applications were evaluated. RESULTS: Among participants who used smartphone applications, 5% were aware of existing vaccination management applications, of whom 57.9% had previously used the applications. About 69.6% of participants believed that the applications were necessary, 93.7% of them were also willing to use the applications, and 79.1% were willing to pay 92.7 thousand Vietnamese dong (VND) for the applications on average. Participants who were older, unemployed, earned more household income, and having knowledge about functions and benefits of vaccination were less likely to use the vaccination applications. Participants who brought their children to get vaccinated at younger age and with higher level of education were willing to pay more for vaccination applications. CONCLUSION: High levels of acceptability of, willingness to use, and WTP for smartphone-based vaccination management applications among Vietnamese participants are reported. Increased education and awareness about the benefits of vaccination and vaccination management applications through community health workers might increase the feasibility of implementing such applications and perception toward their usage among young adult smartphone users. In addition, building a stronger relationship with health care providers at hospitals might improve the application's visibility and adoption.