ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective The finite element method was used to analyze the effect of height of bone graft on adjacent segment stress after anterior cervical decompression and fusion.Methods One healthy adult male was included in this study.A detailed,geometrically accurate three-dimensional cervical spine model had been successfully developed from computed tomography (CT) scanning of a healthy adult male.A pure moment of 1.0 N· m was applied in different directions on the upper endplate of C3 to simulate flexion,extension,left-right lateral bending,and left-right axial rotation.We did biomechanical experiment with goat cervical specimens in terms of the moment-rotation responses.The finite element (FE) model was compared and validated with the experimental data.The relevant data in the literature was also applied for comparison and validation.To construct the post-surgery model,we turned the property of disk annulus and disk nucleus into that of the cancellous bone at C4-5.The internal fixation systems were also implanted.We changed the height of bone graft in C4-5 to be 90％,150％,175％ and 200％ of the height between C4-5 pre-surgery.The finite element models were built to simulate the post-surgery scenarios with different bone graft height,respectively.A stress analysis was conducted on the bone graft and adjacent disks.Results Under different height of bone graft,the maximum yon Mises stress on C3-4 showed when the height of bone graft was 200％.The values were 0.99 MPa,0.85 MPa,0.91 MPa and 0.89 MPa in different loading condition.The values at 150％ of the height between C4-5 pre-surgery were only 81％,73％,80％ and 87％ of the values at 200％.For C5-6,the maximum yon Mises stress were 0.77 MPa,0.83 MPa,0.91 MPa and 0.81 MPa,observed at the height of bone graft was 175％ except extension.The values at 150％ of the height between C4-5 pre-surgery were only 76％,93％,86％ and 78％ of the biggest values.With regard to C4-5,the biggest yon Mises stress was 1.25 MPa,1.77 MPa,1.75 MPa and 1.81 MPa.It was observed when the height of bone graft was 200％ of the height between C4-5 pre-surgery.The values were smallest under height of 150％ of the height between C4-5 pre-surgery.The smallest values were 63％,63％,75％ and 52％ of the biggest values.The higher the bone graft was,the bigger the maximum von Mises stress on bone graft.In a word,it seems that the smallest stress was observed when the bone graft height was 150％.Concltusion The height of bone graft makes an important difference on the stress of adjacent segment after anterior cervical decompression and fusion.150％ of the height between C4-5 presurgery was proper bone graft height.In this case,the stress on the adjacent segments intervertebral disc is smaller.The probability of adjacent segments degeneration is smaller.