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Nicole E De Long, Alison C Holloway Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada Abstract: The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity. Keywords: obesity, pesticides, polybrominated diphenyl ethers, heavy metals, acrylamide, endocrine-disrupting chemicals

To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg) three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

Abstract Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a. By combining with an inhibitor of non-homologous end joining (NHEJ) or the HDRobust strategy, these modular ssDNA donors achieve up to 90.03% (median 74.81%) HDR efficiency. The HDR-boosting modules targeting an endogenous protein enable a chemical modification-free strategy to improve the efficacy of ssDNA donors for precise gene editing.

Abstract Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature’s Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.

X-ray beams with orbital angular momentum (OAM) are a promising tool for x-ray characterization techniques. Beams with OAM have a helicity - an azimuthally varying phase - which leads to a gradient of the light field. New material properties can be probed by utilizing the helicity of an OAM beam. Here, we demonstrate a dichroic effect in resonant diffraction from an artificial antiferromagnet with a topological defect. We found that the scattered OAM beam has circular dichroism at the antiferromagnetic Bragg peak whose sign is coupled to its helicity, which reveals the real-space configuration of the antiferromagnetic ground state. Thermal cycling of the artificial antiferromagnet can change the ground state, as indicated by reversal of the sign of circular dichroism. This result is one of the first demonstrations of a soft x-ray spectroscopy characterization technique utilizing the OAM of x rays. This helicity-dependent circular dichroism exemplifies the potential to utilize OAM beams to probe matter in a way that is inaccessible using currently available x-ray techniques.

Abstract Background & aims The present study utilized extracted computed tomography radiomics features to classify the gross tumor volume and normal liver tissue in hepatocellular carcinoma by mainstream machine learning methods, aiming to establish an automatic classification model. Methods We recruited 104 pathologically confirmed hepatocellular carcinoma patients for this study. GTV and normal liver tissue samples were manually segmented into regions of interest and randomly divided into five-fold cross-validation groups. Dimensionality reduction using LASSO regression. Radiomics models were constructed via logistic regression, support vector machine (SVM), random forest, Xgboost, and Adaboost algorithms. The diagnostic efficacy, discrimination, and calibration of algorithms were verified using area under the receiver operating characteristic curve (AUC) analyses and calibration plot comparison. Results Seven screened radiomics features excelled at distinguishing the gross tumor area. The Xgboost machine learning algorithm had the best discrimination and comprehensive diagnostic performance with an AUC of 0.9975 [95% confidence interval (CI): 0.9973–0.9978] and mean MCC of 0.9369. SVM had the second best discrimination and diagnostic performance with an AUC of 0.9846 (95% CI: 0.9835– 0.9857), mean Matthews correlation coefficient (MCC)of 0.9105, and a better calibration. All other algorithms showed an excellent ability to distinguish between gross tumor area and normal liver tissue (mean AUC 0.9825, 0.9861,0.9727,0.9644 for Adaboost, random forest, logistic regression, naivem Bayes algorithm respectively). Conclusion CT radiomics based on machine learning algorithms can accurately classify GTV and normal liver tissue, while the Xgboost and SVM algorithms served as the best complementary algorithms.

The current study examined the role of family orientations on the achievement motivations (i.e., achievement goal orientations and intrinsic motivation) of high school youths of different generational status (i.e., from immigrant or non-immigrant families) when their perception of their parents' goals and classroom goal structures were tested simultaneously as predictors. A total of 331 high school students (ninth grade; ages 13-16, with 96% of the students in the ages of 14 or 15; 141 boys and 187 girls) from one high school in the United States participated in the study, completing a series of assessments with regard to their math classes. The findings show the complex role of the family contexts (parent goals and family orientations) on the adaptive mastery goals for children of immigrant families, going beyond previous studies that reported the relationships between family orientation and performance-approach or less adaptive performance-avoidance goals. This study still found that students' family orientations strongly predicted their desire to win over their peers with certain levels of internal pressure in order to meet their parents' expectations, aligned with previous literature. Through examining a context beyond the classroom context, studies should continue to examine the larger family and cultural context in understanding students with diverse backgrounds.

It is evident how corrosion flaws affect the tension and strain of pipelines that pass oblique-slip faults. The pipeline is very risky and is more likely to experience tensile and buckling damage when corrosion develops in the major deformation region of the pipeline. This will also significantly diminish the pipeline's failure slippage. This research uses a three-dimensional finite element modeling of trans-fault pipes to study the mechanical reaction and influencing factors of corroded pipelines under the action of oblique-slip faults. It is determined that the distribution of stress and strain as well as the pipeline's extension trend are changed when corrosion faults are present. The concentration of tensile and compressive strain along the corroded circular cross-section at the time of damage, followed by a gradual expansion through the entire corroded circumferential cross-section, and the pipeline's extrusion, folding, and bulging, are the manifestations of the influence of corrosion defects on the pipeline at damage. Tensile and compressive strains in the pipeline increase, failure slippage is reduced, and the pipeline experiences tensile damage and corrosion. The length of the pipeline corroded in the circumferential direction, the length of the corroded length in the direction of corrosion along the pipeline axis, and the corrosion depth increase all contribute to these outcomes. The location of corrosion defects has the greatest influence on the dynamics of the pipeline and is most dangerous in the large deformation section from -10 m to 10 m; the corrosion effect is very small when the corrosion is located on the right side of the fracture surface at 25 m. The risk of buckling damage is higher in this scenario, where the corrosion depth has the greatest effect. The conclusions of this paper can be used as a reference for the seismic and corrosion-resistant design of cross-fault pipelines.

Abstract Lactobacillus rhamnosus GG (LGG), the well‐characterized human‐derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase‐3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)‐producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase‐3−GSDMEa pyroptosis is initiated by the species‐specific recognition of SpaC by TLR4ba, which accounts for the species‐specificity of the SpaC‐inducing intestinal pyroptosis in zebrafish. The observed pyroptosis‐driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host‐specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

Introduction:Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism’s pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets.Methods:Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed.Results:MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol’s binding to IRF3, indicating a stable interaction.Conclusion:This study comprehensively elucidates inflammation, immune response, and metabolism’s intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo’s etiology, informing future research and drug development endeavors.

IntroductionMany studies have shown that the functional adaptation of immigrants to high-altitude is closely related to oxygen transport, inflammatory response and autonomic nervous system. However, it remains unclear how human attention changes in response to hypoxia-induced neurophysiological activity during high-altitude exposure.MethodsIn the present study, we analyzed the relationship between hypoxic-induced neurophysiological responses and attention networks in 116 immigrants (3,680 m) using an attention network test to simultaneously record electroencephalogram and electrocardiogram in combination with specific routine blood markers.ResultsOur analysis revealed that red blood cells exert an indirect influence on the three attention networks, mediated through inflammatory processes and heart rate variability.DiscussionThe present study provides experimental evidence for the role of a neuroimmune pathway in determining human attention performance at high- altitude. Our findings have implications for understanding the complex interactions between physiological and neurocognitive processes in immigrants adapting to hypoxic environments.

The current study investigated whether semantic (meaning) knowledge benefits learning orthography (spelling). Adult readers read 14 novel non-words embedded in sentences with informative or uninformative context. Orthographic and semantic posttests assessed learning. In E1, results indicated that the relationship between context and orthographic accuracy was moderated by spelling frequency. In E2, all novel words had low-frequency spelling bodies. The results did not show a main effect of access to meaning on learning spelling, but they did reveal a strong association between learning spelling and meaning. In E3, participants received fewer exposures to increase the task difficulty. There was no main effect of access to words' meaning on learning spellings, but there were strong associations between orthographic and semantic posttest accuracy. These findings indicate that teaching words' spellings and meanings independently of one another may not be the most beneficial means of learning new words.