Placenta-specific CYP11A1 overexpression lead to autism-like symptom in offspring with altered steroid hormone biosynthesis in the placenta-brain axis and rescued by vitamin D intervention.

Alterations in steroid hormone regulation have been implicated in the etiology and progression of autism spectrum disorders (ASD), with the enzyme cytochrome P450 family 11 subfamily A member 1 (CYP11A1)-a key catalyst in cholesterol side-chain cleavage, prominently expressed in the adrenal glands, ovaries, testes, and placenta-standing at the forefront of these investigations. The potential link between aberrations in placental Cyp11a1 expression and the resultant neurodevelopmental disorders, along with the mechanisms underpinning such associations, remains inadequately delineated. In this study, we employed a placental trophoblast-specific Cyp11a1 Hipp11 (H11) knock-in murine model to dissect the phenotypic manifestations within the placenta and progeny, thereby elucidating the underlying mechanistic pathways. Behavioral analyses revealed a diminution in social interaction capabilities alongside an augmented anxiety phenotype, as evidenced by open field and elevated plus maze assessments; both phenotypes were ameliorated after vitamin D3 supplementation. Electrophysiological assays underscored the augmented inhibition of paired-pulse facilitation, indicating impaired neuroplasticity in Cyp11a1 H11-modified mice. An elevation in progesterone concentrations was noted, alongside a significant upregulation of Th1-related cytokines (IL-6 and TNFα) across the plasma, placental, and frontal cortex-a pathological state mitigable through vitamin D3 intervention. Western blotting revealed a vitamin D-mediated rectification of vitamin D receptor and PGC-1α expression dysregulations. Immunofluorescence assays revealed microglial activation in the knock-in model, which was reversible upon vitamin D3 treatment. In conclusion, Cyp11a1 overexpression in the placenta recapitulated an autism-like phenotype in murine models, and vitamin D3 administration effectively ameliorated the resultant neurobehavioral and neuroinflammatory derangements. This study substantiates the application of Cyp11a1 as a biomarker in prenatal diagnostics and posits that prenatal vitamin D3 supplementation is a viable prophylactic measure against perturbations in steroid hormone metabolism associated with ASD pathogenesis.

Exploring the key deteriorative microorganisms on ancient ivories unearthed from the Sanxingdui Ruins site during temporary cold storage.

Introduction: The ancient ivories unearthed from the Sanxingdui Ruins site are valuable cultural relics, however, the microbial biodeterioration on ivories during temporary cold storage poses a great threat to their later long-term preservation. Methods: Here, the combination of high-throughput sequencing and biochemical assays was applied for the in-depth investigation of the key deteriorative microorganisms colonizing on the ivories and the tracing of their origin, as well as the assessment of the ethanol disinfection impact on the microbial communities on ivories. Results: It was observed that the surfaces of ivories were scattered by the fungal patches of white, dark grey, and hedge green colors during cold storage. The high-throughput sequencing results showed that the genera Mortierella (38.51%), Ilyonectria (14.43%), Penicillium (1.15%), and Aspergillus (1.09%) were the dominant fungi, while Pseudomonas (22.63%), Sphingopyxis (3.06%), and Perlucidibaca (2.92%) were the dominant bacteria on ivories. The isolated Aspergillus A-2 resulted in the highest amount of calcium releasing from the degradation of hydroxyapatite (HAP), the main component of ivory, by the organic acids produced, including oxalic acid and citric acid. The fast expectation-maximization for microbial source tracking (FEAST) analysis revealed that the majority of the fungi (57.45%) and bacteria (71.84%) colonizing on the ivories were derived from the soils surrounding ivories in the sacrifice pits, indicating soils as the primary source for the spoilage microbes growing on ivories. The dominant strains could degrade cellulose, the key components of wet cotton towels commonly applied on ivories for moisture maintenance, aiding the spoilage microbes colonizing on ivories. Notably, the ivory disinfection with 75% ethanol during the cleansing significantly decreased the relative abundance of the dominant genera of Ilyonectria, Aspergillus, and Pseudomonas, with Mortierella becoming the dominant one on ivories. Discussion: Together, the fungi, particularly Aspergillus and Penicillium, played a significant role in the microbial biodeterioration of unearthed ancient ivories by producing the organic acids. These results may improve the control of the microbial biodeterioration and develop more efficient strategies for the long-time conservation of unearthed ancient ivories and other cultural relics.

Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures.

Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells. A targeted transcriptomic approach was employed to understand the effects of differentiation protocols on these cell types. Pearson correlation and principal component analysis (PCA) separated most of the intended target cell types and undifferentiated iPSC models as distinct groups with a high correlation among replicates from the same model. Based on PCA, the intended target cell types could also be separated into the three germ layer groups (ectoderm, endoderm and mesoderm). Differential expression analysis (DESeq2) presented the upregulated genes in each intended target cell types that allowed the evaluation of the differentiation to certain degree and the selection of key differentiation markers. In conclusion, these data confirm the versatile use of iPSC differentiated cell types as standardizable and relevant model systems for in vitro toxicology.

Non-covalent binding of chlorogenic acid to myofibrillar protein improved its bio-functionality properties and metabolic fate.

As natural antioxidants added to meat products, polyphenols can interact with proteins, and the acid-base environment influenced the extent of non-covalent and covalent interactions between them. This study compared the bio-functional characteristics and metabolic outcomes of the myofibrillar protein-chlorogenic acid (MP-CGA) complexes binding in different environments (pH 6.0 and 8.5). The results showed that CGA bound with MP significantly enhanced its antioxidant activity and inhibitory effect on metabolism enzymes. CGA bound deeply into the MP structure hydrophobic cavity at pH 6.0, which reduced its degradation by digestive enzymes, thus increasing its bio-accessibility from 59.5% to 71.6%. The digestion products of the two complexes exhibited significant differences, with the non-covalent MP-CGA complexes formed at pH 6.0 showing significantly higher concentrations of rhetsinine and piplartine, two well-known compounds to modulate diabetes. This study demonstrated that non-covalent binding between protein and polyphenol in the acidic environment held greater promising prospects for improving health.