Generation and phenotypic characterization of S100A9 gene knockout mice by CRISPR/Cas9-mediated gene targeting / 生理学报

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F

Integrated 3D bioprinting-based geometry-control strategy for fabricating corneal substitutes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#The shortage of donor corneas is a severe global issue, and hence the development of corneal alternatives is imperative and urgent. Although attempts to produce artificial cornea substitutes by tissue engineering have made some positive progress, many problems remain that hamper their clinical application worldwide. For example, the curvature of tissue-engineered cornea substitutes cannot be designed to fit the bulbus oculi of patients.@*OBJECTIVE@#To overcome these limitations, in this paper, we present a novel integrated three-dimensional (3D) bioprinting-based cornea substitute fabrication strategy to realize design, customized fabrication, and evaluation of multi-layer hollow structures with complicated surfaces.@*METHODS@#The key rationale for this method is to combine digital light processing (DLP) and extrusion bioprinting into an integrated 3D cornea bioprinting system. A designable and personalized corneal substitute was designed based on mathematical modelling and a computer tomography scan of a natural cornea. The printed corneal substitute was evaluated based on biomechanical analysis, weight, structural integrity, and fit.@*RESULTS@#The results revealed that the fabrication of high water content and highly transparent curved films with geometric features designed according to the natural human cornea can be achieved using a rapid, simple, and low-cost manufacturing process with a high repetition rate and quality.@*CONCLUSIONS@#This study demonstrated the feasibility of customized design, analysis, and fabrication of a corneal substitute. The programmability of this method opens up the possibility of producing substitutes for other cornea-like shell structures with different scale and geometry features, such as the glomerulus, atrium, and oophoron.

Practice and exploration of the tuition-free medical students' in rural areas of Sichuan province / 中国卫生政策研究

Objective:This paper summarizes the practical problems encountered in the implementation of the tuition-free medical students' policyin rural areas of Sichuan Province, and provides a reference for the implementation of this policy across the province. Methods :Semi-structured interviews were conducted with the principals of the orientation management policies of the health administrative departments and county level and primary health care in-stitutionsin Sichuan, and the focus group interviews were used to understand the dynamics of directed students. Results :The survey results showed that there were limited channels for students to understand the policy ; students' barren understanding of the work of grass-roots doctors ; credit and integrity files played a relatively low role in retaining medical talent students;the willingness of orientation students is higher, but there is a contradiction between applying for graduate students and retaining grassroots in rural areas ; and the relevant departments lacked a rational and efficient management mode for students. Conclusions :In order to ameliorate the construction of rural health human resources,policy administrators should place their emphasis on cultivating the sense of honor and responsibility in the rural-oriented tuition-free medical students'policy, improve the reward and punishment mechanism in policies, optimize the management and assessment process, and promote the orientation of the work among the various policy-participating departments in a more harmonious and orderly manner.

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways (AU)

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Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1ß, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.