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Human-specific duplicated genes contributed to phenotypic innovations during the origin of our own species, such as an enlarged brain and highly developed cognitive abilities. While prior studies on transgenic mice carrying the human-specific SRGAP2C gene have shown enhanced brain connectivity, the relevance to humans remains unclear due to the significant evolutionary gap between humans and rodents. In this study, to investigate the phenotypic outcome and underlying genetic mechanism of SRGAP2C , we generated transgenic cynomolgus macaques (Macaca fascicularis) carrying the human-specific SRGAP2C gene. Longitudinal MRI imaging revealed delayed brain development with region-specific volume changes, accompanied by altered myelination levels in the temporal and occipital regions. On a cellular level, the transgenic monkeys exhibited increased deep-layer neurons during fetal neurogenesis and delayed synaptic maturation in adolescence. Moreover, transcriptome analysis detected neotenic expression in molecular pathways related to neuron ensheathment, synaptic connections, extracellular matrix and energy metabolism. Cognitively, the transgenic monkeys demonstrated improved motor planning and execution skills. Together, our findings provide new insights into the mechanisms by which the newly evolved gene shapes the unique development and circuitry of the human brain. [ABSTRACT FROM AUTHOR]

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions, and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may generate new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution. • Construction of a high-resolution Hi-C map of macaque fetal brain • Cross-species 3D genome analyses uncover human-specific chromatin structures • The subplate lamina shows human-specific regulatory changes during corticogenesis • The human-specific loop regulating EPHA7 affects neuron dendrite development High-resolution map of developing rhesus macaque brain genome architecture during corticogenesis reveals human-specific chromatin structure and regulatory changes that impact dendrite development. [ABSTRACT FROM AUTHOR]

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction., Competing Interests: TY, YG, XQ, WZ, HZ, BW, KL, BZ, XZ, O, YH, BS No competing interests declared, (© 2023, Yue, Guo, Qi et al.)

Due to its pharmacological activities, Paecilomyces tenuipes has previously been used as a folk medicine in Asia. The primary aim of the present study was to investigate the hypoglycemic, hypolipidemic and anti‑nephritic effects of P. tenuipes N45 aqueous extracts (PTNE) in a high fat diet/streptozotocin‑induced diabetic rat model. The rats were treated with 120 mg/kg of metformin or 0.04, 0.2 or 1.0 g/kg PTNE for 4 weeks. The hypoglycemic activity of PTNE was confirmed by the observation of reduced fasting blood glucose level and by partially normalized oral glucose tolerance. PTNE reduced total cholesterol and triglyceride content, and balanced the levels of low‑density and high‑density lipoproteins. The suppressive effects of PTNE on creatinine, blood urea nitrogen, interleukin (IL)‑2, IL‑6 and nuclear factor‑κB levels indicated its ability to provide protection against diabetic nephropathy. PTNE treatment increased superoxide dismutase, malondialdehyde and glutathione peroxidase levels, suggesting that its anti‑diabetic and anti‑nephropathic activities may be associated with the prevention of oxidative damage during type 2 diabetic mellitus. The findings of the present study provided experimental evidence for the application of Paecilomyces tenuipes N45 on the treatment of type 2 diabetic mellitus.