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Fulltext Nuanced contribution of gut microbiome in the early brain development of mice

Yeo XY, Chae WR, Lee HU, Bae HG, Pettersson S, Grandjean J, et al.

Gut Microbes, 2023 Dec;15(2):2283911.
PMID: 38010368 DOI: 10.1080/19490976.2023.2283911

The complex symbiotic relationship between the mammalian body and gut microbiome plays a critical role in the health outcomes of offspring later in life. The gut microbiome modulates virtually all physiological functions through direct or indirect interactions to maintain physiological homeostasis. Previous studies indicate a link between maternal/early-life gut microbiome, brain development, and behavioral outcomes relating to social cognition. Here we present direct evidence of the role of the gut microbiome in brain development. Through magnetic resonance imaging (MRI), we investigated the impact of the gut microbiome on brain organization and structure using germ-free (GF) mice and conventionalized mice, with the gut microbiome reintroduced after weaning. We found broad changes in brain volume in GF mice that persist despite the reintroduction of gut microbes at weaning. These data suggest a direct link between the maternal gut or early-postnatal microbe and their impact on brain developmental programming.
Incidence of fragility hip fracture across the Asia-pacific region: A systematic review

Chan LL, Ho YY, Taylor ME, Mcveigh C, Jung S, Armstrong E, et al.

Arch Gerontol Geriatr, 2024 Mar 21;123:105422.
PMID: 38579379 DOI: 10.1016/j.archger.2024.105422

PURPOSE: This systematic review aimed to update fragility hip fracture incidences in the Asia Pacific, and compare rates between countries/regions.
METHOD: A systematic search was conducted in four electronic databases. Studies reporting data between 2010 and 2023 on the geographical incidences of hip fractures in individuals aged ≥50 were included. Exclusion criteria were studies reporting solely on high-trauma, atypical, or periprosthetic fractures. We calculated the crude incidence, age- and sex-standardised incidence, and the female-to-male ratio. The systematic review was registered with PROSPERO (CRD42020162518).
RESULTS: Thirty-eight studies were included across nine countries/regions (out of 41 countries/regions). The crude hip fracture incidence ranged from 89 to 341 per 100,000 people aged ≥50, with the highest observed in Australia, Taiwan, and Japan. Age- and sex-standardised rates ranged between 90 and 318 per 100,000 population and were highest in Korea and Japan. Temporal decreases in standardised rates were observed in Korea, China, and Japan. The female-to-male ratio was highest in Japan and lowest in China.
CONCLUSION: Fragility hip fracture incidence varied substantially within the Asia-Pacific region. This observation may reflect actual incidence differences or stem from varying research methods and healthcare recording systems. Future research should use consistent measurement approaches to enhance international comparisons and service planning.
Rapid quantitative high-throughput mouse embryoid body model for embryotoxicity assessment

Quah Y, Jung S, Ham O, Jeong JS, Kim S, Kim W, et al.

Arch Toxicol, 2024 Sep 05.
PMID: 39235594 DOI: 10.1007/s00204-024-03845-9

Individuals are exposed to a wide arrays of hazardous chemicals on a daily basis through various routes, many of which have not undergone comprehensive toxicity assessments. While traditional developmental toxicity tests involving pregnant animals are known for their reliability, they are also associated with high costs and time requirements. Consequently, there is an urgent demand for alternative, cost-efficient, and rapid in vitro testing methods. This study aims to address the challenges related to automating and streamlining the screening of early developmental toxicity of chemicals by introducing a mouse embryoid body test (EBT) model in a 384-ultra low attachment well format. Embryoid bodies (EBs) generated in this format were characterized by a spontaneous differentiation trajectory into cardiac mesoderm by as analyzed by RNA-seq. Assessing prediction accuracy using reference compounds suggested in the ICH S5(R3) guideline and prior studies resulted in the establishment of the acceptance criteria and applicability domain of the EBT model. The results indicated an 84.38% accuracy in predicting the developmental toxicity of 23 positive and 9 negative reference compounds, with an optimized cutoff threshold of 750 µM. Overall, the developed EBT model presents a promising approach for more rapid, high-throughput chemical screening, thereby facilitating well-informed decision-making in environmental management and safety assessments.
Predictive biomarkers for embryotoxicity: a machine learning approach to mitigating multicollinearity in RNA-Seq

Quah Y, Jung S, Chan JY, Ham O, Jeong JS, Kim S, et al.

Arch Toxicol, 2024 Sep 06.
PMID: 39242367 DOI: 10.1007/s00204-024-03852-w

Multicollinearity, characterized by significant co-expression patterns among genes, often occurs in high-throughput expression data, potentially impacting the predictive model's reliability. This study examined multicollinearity among closely related genes, particularly in RNA-Seq data obtained from embryoid bodies (EB) exposed to 5-fluorouracil perturbation to identify genes associated with embryotoxicity. Six genes-Dppa5a, Gdf3, Zfp42, Meis1, Hoxa2, and Hoxb1-emerged as candidates based on domain knowledge and were validated using qPCR in EBs perturbed by 39 test substances. We conducted correlation studies and utilized the variance inflation factor (VIF) to examine the existence of multicollinearity among the genes. Recursive feature elimination with cross-validation (RFECV) ranked Zfp42 and Hoxb1 as the top two among the seven features considered, identifying them as potential early embryotoxicity assessment biomarkers. As a result, a t test assessing the statistical significance of this two-feature prediction model yielded a p value of 0.0044, confirming the successful reduction of redundancies and multicollinearity through RFECV. Our study presents a systematic methodology for using machine learning techniques in transcriptomics data analysis, enhancing the discovery of potential reporter gene candidates for embryotoxicity screening research, and improving the predictive model's predictive accuracy and feasibility while reducing financial and time constraints.
Fulltext Enhancing operational stability of OLEDs based on subatomic modified thermally activated delayed fluorescence compounds

Jung S, Cheung WL, Li SJ, Wang M, Li W, Wang C, et al.

Nat Commun, 2023 Oct 14;14(1):6481.
PMID: 37838720 DOI: 10.1038/s41467-023-42019-6

The realization of operationally stable blue organic light-emitting diodes is a challenging issue across the field. While device optimization has been a focus to effectively prolong device lifetime, strategies based on molecular engineering of chemical structures, particularly at the subatomic level, remains little. Herein, we explore the effect of targeted deuteration on donor and/or acceptor units of thermally activated delayed fluorescence emitters and investigate the structure-property relationship between intrinsic molecular stability, based on isotopic effect, and device operational stability. We show that the deuteration of the acceptor unit is critical to enhance the photostability of thermally activated delayed fluorescence compounds and hence device lifetime in addition to that of the donor units, which is commonly neglected due to the limited availability and synthetic complexity of deuterated acceptors. Based on these isotopic analogues, we observe a gradual increase in the device operational stability and achieve the long-lifetime time to 90% of the initial luminance of 23.4 h at the luminance of 1000 cd m-2 for thermally activated delayed fluorescence-sensitized organic light-emitting diodes. We anticipate our strategic deuteration approach provides insights and demonstrates the importance on structural modification materials at a subatomic level towards prolonging the device operational stability.
Author Correction: Enhancing operational stability of OLEDs based on subatomic modified thermally activated delayed fluorescence compounds

Jung S, Cheung WL, Li SJ, Wang M, Li W, Wang C, et al.

Nat Commun, 2023 Oct 26;14(1):6821.
PMID: 37884574 DOI: 10.1038/s41467-023-42698-1