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The immunoproteasome (IP) is a stress-inducible specialization of the ubiquitin-proteasome system that integrates immune activation with cellular homeostasis in the central nervous system (CNS). Incorporation of the inducible β1i, β2i, and β5i subunits enhances proteolytic capacity under inflammatory, oxidative, and metabolic stress, thereby supporting redox balance, mitochondrial integrity, and proteostasis. IP expression is highly dynamic and cell type-specific, varying across astrocytes, microglia, endothelial cells, and neurons in response to local microenvironmental cues. Functionally, IP activation exhibits a dual nature: transient induction facilitates the clearance of damaged proteins and fine-tunes inflammatory signaling, whereas sustained or dysregulated activation reinforces NF-κB- and STAT-dependent inflammatory programs, disrupts proteostatic equilibrium, and increases neuronal and vascular vulnerability. Across neurological disorders, the IP acts as a context-dependent regulator, shaping post-ischemic inflammation and blood-brain barrier (BBB) integrity, contributing to maladaptive responses in Alzheimer’s and Parkinson’s disease, and amplifying immune-mediated injury in multiple sclerosis, neuromyelitis optica spectrum disorder, epilepsy, and infectious encephalitis. Elucidating the spatiotemporal regulation of the IP and its therapeutic selectivity may enable precision immunomodulatory strategies for CNS diseases.

Background Geese exhibit relatively low reproductive performance, and follicular atresia is an important factor that restricts the egg production of geese. Systematic analysis of the regulation of follicle atresia in geese through transcriptome and proteome levels could provide meaningful information on clarifying the mechanism of follicle atresia in poultry. Result The granulosa cell layer was loose, disintegrated and showed apoptosis in atretic follicles and remained intact in normal follicles. The hormone levels of FSH and LH were significantly decreased in the atresia follicles compared to the normal follicles ( P  < 0.05). A total of 954 differentially expressed genes (DEGs, 315 increased and 639 decreased) and 161 differentially expressed proteins (DEPs, 61 increased and 100 decreased) were obtained in atresia follicles compared to normal follicles, of which, 15 genes were differentially expressed in both transcriptome and proteome. The DEGs were mainly enriched in sodium transmembrane transport, plasma membrane, and transmembrane transporter activity based on the GO enrichment analysis and in the cell cycle pathway based on the KEGG enrichment analysis. The DEPs were mainly enriched in localization, lysosome, and phospholipid-binding based on the GO enrichment analysis. Candidate genes Smad2/3, Smad4, Annexin A1 ( ANXA1 ), Stromelysin-1 ( MMP3 ), Serine/threonine-protein kinase ( CHK1 ), DNA replication licensing factor ( MCM3 ), Cyclin-A2 ( CCNA2 ), mitotic spindle assembly checkpoint protein ( MAD2 ), Cyclin-dependent kinase 1 ( CDK1 ), fibroblast growth factor 12 ( FGF12 ), and G1/S-specific cyclin-D1 ( CCND1 ) were possibly responsible for the regulation of atresia. Conclusion The cell cycle is an important pathway for the regulation of follicular atresia. Sodium outflow and high expression of MMP3 and MMP9 could be responsible for structural destruction and apoptosis of follicular cells.

Regarding the antibacterial and antioxidant properties of Gallic acid (GA), it was used as feed additive to evaluate intestinal health and production performance of broilers. Yellow-feathered male broilers (375 birds at 21-day-old) with similar body weight were randomly divided into five groups, each with five replicates and 15 chickens per replicate. Chickens were fed basal diet with 0, 50, 100, 150, and 200 mg/kg GA for 42 days. Then, chickens were slaughtered for slaughter performance, intestinal function, gut microbiota measurement. Compared to the control group, supplementation with 150 mg/kg GA significantly increased body weight at 42, 56, and 63 days of age ( P  < 0.05), significantly increased average daily gain (ADG) and reduced feed conversion ratio (FCR) during the growth phase ( P  < 0.05), and increased abundances of Firmicutes and decreased abundances of Bacteroidetes ( P  < 0.05). Supplementation with both 100 and 150 mg/kg GA significantly decreased abdominal fat rate and increased breast muscle rate ( P  < 0.05), and enhanced expression of IL-1β , TNF-a , TLR4 , HSP70 , mucin2 and Nrf2 ( P  < 0.05). In conclusion, GA (150 mg/kg) was associated with improved growth and slaughter performance and with changes in intestinal gene expression and cecal microbiota compositions.

This study was designed to isolate an anti-inflammatory activity oligopeptide from goose blood (GBP) for ameliorating LPS-mediated inflammation response and oxidative stress in RAW264.7 macrophages. In this study, GBP was isolated by tangential flow ultrafiltration system (TFUS) combined with size exclusion chromatography (SEC), ion exchange chromatography (IEC), and reversed-phase liquid chromatography (RP-LC), and then identified by liquid chromatography mass spectrometry (LC–MS/MS). The experiment results indicated that the amino acid sequence of oligopeptide with the best anti-inflammatory activity was IIe-Val-Tyr-Pro-Trp-Thr-Gln-Arg (IVYPWTQR), which had a molecular weight of 1062.5720 Da, and was derived from haemoglobin subunit beta OS in goose blood. In addition, IVYPWTQR was confirmed to have satisfactory stability and maintained high anti-inflammatory activity in a simulated gastrointestinal digestion. The mechanism by which the IVYPWTQR protected against LPS-mediated inflammation response was attributed to downregulating the TLR4/NF-kB/iNOS pathway. Moreover, IVYPWTQR ameliorated oxidative stress damage in inflammatory state was attributed to activating antioxidant defence system, which was regulated by Keap-1/NRF2/HO-1 signalling pathway for decreasing the accumulation of reactive oxide species (ROS). In summary, these results indicated GBP could serve as a potential functional factor for prevention and improvement of inflammation mediated by LPS and provided an affordable dietary intervention strategy to prevent inflammation.

Epilepsy is a neurological disorder involving mitochondrial dysfunction and neuroinflammation. This study examines the relationship between NLRP3 inflammasome activation and mitophagy in the temporal lobe epilepsy, which has not been reported before. A pilocarpine-induced epileptic rat model was used to assess seizure activity and neuronal loss. Pyroptosis markers (NLRP3, cleaved Gasdermin D, IL-1β/IL-18), and autophagy/mitophagy activity (LC3B-II/I, BNIP3, TOMM20/LC3B colocalization) were analyzed via immunofluorescence, Western blot, and transmission electron microscopy. NLRP3 inhibitors and anti-IL-1β antibodies were administered to evaluate therapeutic effects. Epileptic rats exhibited progressive neuronal loss and seizure aggravation, correlating with NLRP3 inflammasome activation and pyroptosis. While general autophagy was upregulated, mitophagy was selectively impaired in the hippocampus. NLRP3 activation promoted IL-1β release, which suppressed mitophagy via PPTC7 upregulation. NLRP3 activation inhibitor (MCC950) and anti-IL-1β treatment restored mitophagy and reduced seizures. NLRP3 inflammasome-driven pyroptosis exacerbates epilepsy by impairing mitophagy activity via IL-1β/PPTC7. Targeted NLRP3 inhibition mitigates this cascade, offering a promising strategy for refractory epilepsy.

Currently, the clinical benefits of tea polyphenols have contributed to the development of efficient systemic delivery systems with adequate bioavailability and stability. In this study, we aimed to establish a nanoparticle model to overcome the shortcomings of epigallocatechin gallate (EGCG) in the treatment of lung cancer. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with EGCG were prepared by the oil-in-water emulsion solvent evaporation technique. The characteristics of NPs, entrapment efficiency, and in vitro release were systematically evaluated. The cellular uptake, cytotoxic activity, and the effect of the formulation on cellular apoptosis of free-from EGCG and the NPs were compared. The interaction between protein-NF-κB and EGCG was detected by bio-layer interferometry (BLI). NF-κB signaling was evaluated by Western blotting and q-RT-PCR. The efficacy of the optimized nanoformulation was evaluated using a patient-derived tumor xenograft (PDX) model. EGCG-loaded NPs (175.8±3.8 nm in size) demonstrated its optimal efficacy, with approximately 86.0% of encapsulation efficiency and 14.2% of loading efficiency. Additionally, EGCG-encapsulated PLGA-NPs offered a 3-4-fold dose advantage compared to free EGCG in terms of exerting antiproliferative effects and inducing apoptosis at lower doses (12.5, 25 μM). Molecular interaction assays demonstrated that EGCG binds to NF-κB with high affnity (KD=4.8×10 M). EGCG-NPs were more effective at inhibiting NF-κB activation and suppressing the expression of NF-κB-regulated genes than free EGCG. Furthermore, EGCG-NPs showed superior anticancer activity in the PDX model than free EGCG. These findings indicated that the prepared EGCG-NPs were more effective than free EGCG in inhibiting lung cancer tumors in the PDX model.

Background Egg quality directly determines embryo development in meat-type poultry. However, it is difficult to directly select the egg quality of Muscovy duck. The genes and SNPs associated with egg quality screened by GWAS can be used for molecular breeding and accelerate the progress of selection in Muscovy duck. Result 295 Muscovy ducks were used for whole genome sequencing, and a total of 6,131,623 SNPs were obtained for further analysis. The heritability of egg quality ranged from 0.01 to 0.41, in which egg weight (EW) was 0.19, albumen weight (AW) was 0.16 and the yolk weight (YW) was 0.27. The genetic correlation of EW and AW, EW and YW, and eggshell thickness (EST) and eggshell strength (ESS) were 0.65, 0.51, and 0.74, respectively. Phenotypic correlations between egg quality ranged from − 0.13 to 0.17. A total of 68 SNPs significantly associated with EW were located within the genes PSMG4 , SLC22A23 , DNAH5 , FABP6 , ADAMST17 , IGF1R , NTRK3 , and SCAI . The linkage disequilibrium (LD) analysis identified 2_75684453_C > G, 2_76305509_A > G, 2_76350118_T > A, 11_3834664_C > T, 11_4339778_C > T, and 11_8079686_C > T as tagSNPs to represent the significant SNPs. Fifty SNPs significantly associated with YW were located within the genes XKR6 , DNAJC24 , SNCB , UNC5A , MAD1L1 , NOTCH1 , and WDR7 . The SNPs 14_9186714_C > T, 14_9199818_A > G, 15_5452098_C > T, and 18_9038052_C > T were selected as tagSNPs. Fifty-four SNPs significantly associated with albumen height were located within the genes LIN9 and NID1 . The SNP 3_17718980_A > G was selected as the tagSNP. The significant SNPs associated with eggshell strength were located within the genes CLPX , EPHA5 , ZBTB44 , NOL6 , and UBAP1 . The SNPs 25_1996726_A > C and 25_2078328_A > G were selected as tagSNPs. Genes associated with egg quality were significantly enriched in the positive regulation of the BMP signaling pathway in the GO enrichment analysis of biological processes. The KEGG enrichment analysis suggested that the SNPs located genes were significantly enriched in Axon guidance, Endocrine resistance, and Progesterone-mediated oocyte maturation. Conclusion Some tagSNPs were identified that may be useful for molecular breeding of egg quality. RNF423 , RNF220 , IGF1R , SLC22A23 , WDR7 , and NTRK3 may be candidate genes for egg quality traits in Muscovy duck.

Background Substantial evidence suggests that immunoproteasome is implicated in the various neurological diseases such as stroke, multiple sclerosis and neurodegenerative diseases. However, whether the immunoproteasome itself deficiency causes brain disease is still unclear. Therefore, the aim of this study was to explore the contribution of the immunoproteasome subunit low molecular weight protein 2 (LMP2) in neurobehavioral functions. Methods Male LMP2 gene completed knockout (LMP2-KO) and littermate wild type (WT) Sprague–Dawley (SD) rats aged 12-month-old were used for neurobehavioral testing and detection of proteins expression by western blotting and immunofluorescence. A battery of neurobehavioral test tools including Morris water maze (MWM), open field maze, elevated plus maze were used to evaluate the neurobehavioral changes in rats. Evans blue (EB) assay, Luxol fast blue (LFB) and Dihydroethidium (DHE) staining were applied to explore the blood–brain barrier (BBB) integrity, brain myelin damage and brain intracellular reactive oxygen species (ROS) levels, respectively. Results We firstly found that LMP2 gene deletion did not cause significantly difference in rats’ daily feeding activity, growth and development as well as blood routine, but it led to metabolic abnormalities including higher levels of low-density lipoprotein cholesterol, uric acid and blood glucose in the LMP2-KO rats. Compared with the WT rats, LMP2-KO rats displayed obviously cognitive impairment and decreased exploratory activities, increased anxiety-like behavior and without strong effects on gross locomotor abilities. Furthermore, multiple myelin loss, increased BBB leakage, downregulation of tight junction proteins ZO-1, claudin-5 and occluding, and enhanced amyloid-β protein deposition were observed in brain regions of LMP2-KO rats. In addition, LMP2 deficiency significantly enhanced oxidative stress with elevated levels of ROS, caused the reactivation of astrocytes and microglials and markedly upregulated protein expression levels of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), IL-6 and tumor necrosis factor-α (TNF-α) compared to the WT rats, respectively. Conclusion These findings highlight LMP2 gene global deletion causes significant neurobehavioral dysfunctions. All these factors including metabolic abnormalities, multiple myelin loss, elevated levels of ROS, increased BBB leakage and enhanced amyloid-β protein deposition maybe work together and eventually led to chronic oxidative stress and neuroinflammation response in the brain regions of LMP2-KO rats, which contributed to the initial and progress of cognitive impairment.

The mechanism which regulates differential fat deposition in egg yolk from the indigenous breeds and commercial laying hens is still unclear. In this research, Chinese indigenous Huainan Partridge chickens and Nongda III commercial laying hens were used for egg collection and liver sampling. The weight of eggs and yolk were recorded. Yolk fatty acids were determined by gas chromatography-mass spectrometry. Lipid metabolites in the liver were detected by liquid chromatography-mass spectrometry. Yolk weight, yolk ratio and yolk fat ratio exhibited higher in the Huainan Partridge chicken than that of the Nongda III. Compared to the Nongda III, the content of total saturated fatty acid was lower, while the unsaturated fatty acid was higher in the yolk of the Huainan Partridge chicken. Metabolites of phosphatidylinositol and phosphatidylserine from glycerolphospholipids, and metabolites of diacylglycerol from glycerolipids showed higher enrichment in the Huainan Partridge chicken than that of the Nongda III, which promoted the activation of the adipocytokine signaling pathway. However, metabolites of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine from glycerol phospholipids, and metabolites of triacylglycerol from glycerolipids showed lower enrichment in the Huainan Partridge chicken than that of the Nongda III. The high level of yolk fat deposition in the Huainan Partridge chicken is regulated by the activation of the adipocytokine signaling pathway which can promote the accumulation of diacylglycerol and ceramide in the liver.

Broodiness, one of the maternal behaviors and instincts for natural breeding in birds, is an interesting topic in reproductive biology. Broodiness in poultry is characterized by persistent nesting, usually associated with cessation of egg laying. The study of avian broodiness is essential for bird conservation breeding and commercial poultry industry. In this study, we examined the hypothalamus transcriptome of Muscovy duck in three reproductive stages, including egg-laying anaphase (LA), brooding prophase (BP) and brooding metaphase (BM). Differences in gene expression during the transition from egg-laying to broodiness were examined, and 155, 379, 292 differently expressed genes (DEGs) were obtained by pairwise comparisons of LA-vs-BP, LA-vs-BM and BP-vs-BM, respectively (fold change≥1.5, P < 0.05). Gene Ontology Term (GO) enrichment analysis suggested a possible role of oxidative stress in the hypothalamus might invoke reproductive costs that potentially change genes expression. KEGG analysis revealed glutamatergic synapse, dopaminergic synapse, serotonergic synapse and GABAergic synapse pathway were significantly enriched, and regulator genes were identified. Eight gene expression patterns were illustrated by trend analysis and further clustered into three clusters. Additional six hub genes were identified through combining trend analysis and protein-protein interaction (PPI) analysis. Our results suggested that the cyclical mechanisms of reproductive function conversion include effects of oxidative stress, biosynthesis of neurotransmitters or their receptors, and interactions between glucocorticoids and thyroid hormones and regulatory genes. These candidate genes and biological pathways may be used as targets for artificial manipulation and marker-assisted breeding in the reproductive behavior.