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Effective delivery of engineered proteins into mitochondria is of great significance for developing efficient mitochondrial DNA editing tools and realizing accurate treatment of mitochondrial diseases. Here, the candidate genes, eGFP and Cas9 , were engineered with different mitochondrial localization signal (MLS) sequences introduced at their up- or/and down-streams. The corresponding expression vectors for the engineered proteins were constructed respectively, and HEK293T cells were transfected with these vectors. The fluorescence colocalization and Western blotting assays were used to analyze the mitochondrial targeting presentation effect of different engineered proteins. The results demonstrated that the daul-MLS modification of the eGFP and Cas9 proteins significantly improved the efficiency of mitochondrial targeted presentation, compared with the engineered proteins with single MLS added. Hence, it is speculated that dual MLS strategy can enhance the mitochondrial targeting of engineered proteins, which lays a theoretical foundation for the future development of efficient mitochondrial DNA editing tools.

Background: Liver disease caused by Fasciola is a significant zoonotic and parasitic disease with substantial economic impacts on humans and animals. Many studies have looked at the prevalence of fasciolis worldwide, yet the overall prevalence and risk factors in cattle, ruminants, and humans remains unknown., Methods: We conducted a systematic review and meta-analysis to estimate the global prevalence and risk factors of fascioliasis in humans and domestic ruminants. With this aim, we searched PubMed, ScienceDirect, Web of Science, and Scopus from inception to 8 December 2022 for studies reporting the prevalence of fascioliasis in humans or domestic ruminants post-2000. We then used random effects models to describe the prevalence of fascioliasis; trim-and-fill analysis and Egger's test to assess publication bias; and meta-regression and sensitivity analyses to examine the risk factors for prevalence and heterogeneity., Results: We retrieved 4422 articles, with 371 being included in the analysis, as they concerned fascioliasis in humans and ruminants globally. The pooled prevalence of bovine fasciolosis was 17%, while ovine fasciolosis and human fascioliasis had pooled prevalences of 13% and 5%, respectively. We also conducted subgroup analyses by continents, countries, Fasciola species, sampling years, altitude, rainfall, temperature, humidity, age, sex, feeding mode, and residence. Here, altitude and age emerged as risk factors associated with an increased prevalence of fascioliasis. Both the trim-and-fill analysis and Egger's test confirmed the presence of publication bias, while the sensitivity analysis showed that the omission of any single study did not significantly influence the combined pooled prevalence., Conclusions: Fascioliasis is a widely prevalent zoonosis among humans and livestock worldwide. Strategies targeting risk factors such as altitude and age are urgently needed for prevention and control of this disease, which will consequently reduce Fasciola infection. Additionally, given the inadequacy or absence of data in some countries, greater attention should be paid to Fasciola infection, with further epidemiological studies focussing on improving data quality., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background/aims: Animal models have shown that the absence of high-frequency visual information can precipitate the onset of myopia, but this relationship remains unclear in humans. This study aims to explore the association between the spatial frequency content of the visual environment and myopia in children., Methods: Images from the rooms of children and their frequently visited outdoor areas were taken by their parents and collected by the researcher through questionnaires. The spatial frequency was quantified using Matlab. Cycloplegic refraction was used to measure the spherical equivalent (SE), and IOL Master was used to measure axial length (AL) and corneal radius (CR). AL/CR ratio was calculated., Results: The study included 566 children with an average age of (8.04±1.47) years, of which 270 were girls (47.7%), and the average SE was (0.70±1.21) D. Image analysis revealed that indoor spatial frequency slope was lower than that of the outdoor environment (-1.43±0.18 vs -1.11±0.23, p<0.001). There were 79 myopic individuals (14.0%). Images from indoor content of myopic children had a lower spatial frequency slope than non-myopic children (-1.47±0.16 vs 1.43±0.18, p=0.03) while there was no significant difference in outdoor spatial frequency slope. Regression analysis indicated that the indoor spatial frequency slope was positively associated with SE value (β=0.60, p=0.02) and inversely related to myopia (OR=0.24, p<0.05)., Conclusion: The spatial frequency of the outdoor environment is significantly higher than that of the indoor environment. Indoor spatial frequency is related to children's refractive status, with lower indoor spatial frequency being associated with a higher degree of myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The molecular mechanisms underlying sensitivity and resistance to radiotherapy is an area of active investigation and discovery as its clinical applications have the potential to improve cancer patients' outcomes. In addition to the traditional pathways of radiation biology, our knowledge now includes molecular pathways of radiation sensitivity and resistance which have provided insights into potential targets for enhancing radiotherapy efficacy. Sensitivity to radiotherapy is influenced by the intricate interplay of various molecular mechanisms involved in DNA damage repair, apoptosis, cellular senescence, and epigenetics. Translationally, there have been several successful applications of this new knowledge into the clinic, such as biomarkers for improved response to chemo-radiation. New therapies to modify radiation response, such as the poly (ADP-ribose) polymerase (PARP) inhibitors, derived from research on DNA repair pathways leading to radiotherapy resistance, are being used clinically. In addition, p53-mediated pathways are critical for DNA damage related apoptosis, cellular senescence, and cell cycle arrest. As the understanding of genetic markers, molecular profiling, molecular imaging, and functional assays improve, these advances once translated clinically, will help propel modern radiation therapy towards more precise and individualized practices., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) for pulmonary metastases from pediatric sarcomas., Methods and Materials: This study was a single institutional retrospective chart review including patients younger than 21 years of age at diagnosis who had received SBRT for pulmonary metastasis from metastatic sarcoma. Our current electronic record system was queried for all eligible patients. Primary endpoint was tumor response as defined by Respone Evaluation Criteria in Solid Tumors 1.1 criteria. Secondarily, we analyzed factors that affected tumor response as well as toxicity of treatment. Median dose was 50 Gy ranging from 30 to 60 Gy in 5 fractions to the planning tumor volume., Results: There were 7 patients, ranging in age from 6 to 21 years with a total of 14 pulmonary lesions treated with SBRT. Median and mean follow-up times for the 7 patients were 10.6 months and 15.9 months, respectively. The complete response rate was 50%, partial response 21%, stable disease 21%, and progressive disease 7%. Four of the 7 patients were treated with concurrent systemic therapy, 3 of which were targeted oral therapies. Additionally, we observed that patients who were on targeted therapy such as regorafenib or pazopanib seemed to have better local control compared with patients without targeted therapy., Conclusions: With an overall response rate of 92%, SBRT provided a noninvasive effective palliative treatment option with few side effects in this small retrospective study of 7 patients. A larger prospective clinical trial is warranted to evaluate the role of SBRT in the treatment of unresectable metastatic pediatric sarcomas., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study examined the moderating role of outdoor time on the relationship between overweight and myopia., Methods: The data for this study was obtained from a prospective study in Shanghai, where non-myopic children wore wristwear and were followed up for 1 year. Eye examinations were performed at each visit. The modification effect was assessed on the additive scale using multivariable logistic regression, and relative excess risk due to interaction was used to calculate the modification effect., Results: A total of 4683 non-myopic children were included with 32.20% being overweight at baseline. Following a 1-year period, 17.42% of children had myopia. When compared to those who spent <90 minutes outdoors, children who spent >120 had a relative risk of myopia onset that was reduced to 0.61. As time spent outdoors decreased, more risks of myopia onset were identified among overweight children than among normal children, the modification effect on the additive scale was -0.007, with ~70% of this effect attributed to the modifying influence of outdoor time., Conclusions: Increasing outdoor time can reduce myopia more among overweight children than normal. Future interventions should focus on outdoor activities among overweight children to reduce myopia risks., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)