👤 Yuhan Nong

Following spinal cord injury (SCI), neuroinflammation driven by lipid-laden macrophage foam cells is a key pathology, yet how these cells manage their lipid homeostasis is unclear. We delineate a neuroprotective axis in which macrophages deploy apolipoprotein E (APOE) to transfer intracellular lipids to neighboring cells, especially fibroblasts. Genetic ablation of The online version contains supplementary material available at 10.1186/s12974-026-03756-9. Show less

The accumulation of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease (AD). Central to AD pathology is the production of Aβ peptides through the amyloidogenic processing of amyloid-β protein precursor (AβPP) by β-secretase (BACE-1) and γ-secretase. Recent studies have shifted focus from Aβ plaque deposits to the more toxic soluble Aβ oligomers. One significant way in which Aβ peptides impair neuronal information processing is by influencing neurotransmitter receptor function. These receptors, including adrenergic, acetylcholine, dopamine, 5-HT, glutamate, and gamma-aminobutyric acid (GABA) receptors, play a crucial role in regulating synaptic transmission, which underlies perceptual and cognitive functions. This review explores how Aβ interacts with these key neurotransmitter receptors and how these interactions contribute to neural dysfunction in AD. Moreover, we examine how agonists and antagonists of these receptors influence Aβ pathology, offering new perspectives on potential therapeutic strategies to curb AD progression effectively and improve patients' quality of life. Show less

Growth traits are crucial for poultry breeding and production. Marker-assisted selection (MAS) and genomic selection (GS) of growth traits require a substantial number of accurate genetic markers. A genome-wide association study (GWAS) for body size traits was performed on 248 Luning chickens to identify significant single-nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs) related to the growth and development of chickens. A total of 30 significant SNPs and 13 INDELs were obtained for body size traits. Two notable regions, spanning from 43.072 to 43.219 Mb on chromosome 1 and from 4.751 to 4.800 Mb on chromosome 11, were found to be significantly associated with growth traits in the GWAS of both SNPs and INDELs. Some genes, including Show less

Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity. However, as an important source of lipids for ketogenic and daily diets, the function of fats extracted from different adipose tissue sites was largely unknown. In this study, we illustrated the function of fats extracted from adipose tissues with different "beigeing" properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure. We found that the anti-obesity effect of ketogenic diets was potentiated by using "beigeing" fat [porcine subcutaneous adipose tissue (SAT)] as a major energy-providing ingredient. Through lipidomic analyses, phosphatidylserine (PS) was identified as a functional lipid activating thermogenesis in adipose tissue. Moreover, in vivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice. In vitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes. Mechanistically, PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGC1α pathway. In addition, PS-PGC1a binding may affect the stability of the PGC1α protein, which further augments PS-induced thermogenesis. These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function. Thus, our findings suggest that as dietary fat, "beigeing" fat provides more beneficial lipids that contribute to the improvement of mitochondrial function, including PS, which may become a novel, nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases. Show less

Cyclic dipeptides (CDPs), known for their diverse biological activities, have potential therapeutic applications in mental and behavioral disorders (MBDs), particularly schizophrenia. This study explores the CDPs' therapeutic potential using bibliometric analysis, network pharmacology, molecular docking, and experimental verification, focusing on the interactions with the SIGMA1 receptor. A literature review over three decades utilizing the Web of Science Core Collection (WOSCC) was conducted to identify the emerging trends in CDPs research. A compound library was constructed from the PubChem database, and target prediction using SwissTargetPrediction revealed 800 potential protein targets. A compound-target network highlighted the key interactions with kinases, G protein-coupled receptors, and chromatin-modifying enzymes. Enrichment analysis revealed significant associations with schizophrenia and other MBDs. Schizophrenia-related targets among the potential protein targets were identified using the GEO database. Molecular docking results showed interactions of MC4R, OPRK1, SIGMA1, and CDK5R1 with various CDPs compounds, with SIGMA1 being especially noteworthy. Most CDPs exhibited lower binding energies than the control compounds NE-100 and duloxetine. Experimental validation demonstrated that CDPs such as Cyclo(Ala-Gln), Cyclo(Ala-His), and Cyclo(Val-Gly) exhibited IC Show less

High-fat diet (HFD) induced obesity (DIO) has been shown impacts on metabolism, hormonal profile, male fertility, and spermatogenesis. We employed genome-wide transcriptional analysis on the testis of diet induced obesity (DIO) and normal chow (NC) C57BL/6 J male mice to search genes regulated by obesity in testis. Both blood glucose and lipids contents significantly increased in DIO mice after 8 weeks fat-rich feeding. RNA-seq analysis revealed 371 down-regulated and 460 up-regulated transcripts in DIO group comparing to NC group. Chromosome 3, 4, 9, 16, and 18 were significantly more active, while chromosome 5, 10, and 19 were significantly more inactive after 8-week fat-diet feeding. Wilcoxon enrichment analysis discovered that the thermogenesis pathway (KEGG) was significantly enriched in the testis of DIO group (with 8 enriched up-regulated genes: Smarca2, Adcy3, Atp5pb, Creb1, Gnas, Rps6kb2, Upcrc1 and Dpf1). Real-time PCR further confirmed that Smarca2 and Atp5pb were upregulated in the testis of DIO mice. These finding implied that diet-induced thermogenesis pathways could be altered in the testis of DIO mice. Show less

Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis. Show less