Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzad002
The order Acipenseriformes, which includes sturgeons and paddlefishes, represents “living fossils” with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03943-6
Although liver transplantation (LT) is an effective strategy for end-stage liver diseases, the shortage of donor organs and the immune rejection hinder its widespread implementation in clinical practice. Mesenchymal stem cells (MSCs) transplantation offers a promising approach for patients undergoing liver transplantation due to their immune regulatory capabilities, hepatic protection properties, and multidirectional differentiation potential. In this review, we summarize the potential applications of MSCs transplantation in various LT scenarios. MSCs transplantation has demonstrated effectiveness in alleviating hepatic ischemia-reperfusion injury, enhancing the viability of liver grafts, preventing acute graft-versus-host disease, and promoting liver regeneration in split LT therapy. We also discuss the clinical progress, and explore the immunomodulatory functions of MSCs in response to both adaptive and innate immune responses. Furthermore, we emphasize the interactions between MSCs and different immune cells, including T cells, B cells, plasma cells, natural killer cells, dendritic cells, Kupffer cells, and neutrophils, to provide new insights into the immunomodulatory properties of MSCs in adoptive cell therapy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21416
BACKGROUND: Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation. However, its predictive indicators remain unclear. Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment, this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE: To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS: A retrospective analysis was conducted on medical records of 4,368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024. We screened 190 patients with a postoperative hospital stay of 15 days or longer. Based on postoperative wound healing and infection indicators, 41 patients with non-infectious poor healing were selected as the poor healing group. From the remaining 4,178 patients, 40 patients with good healing were selected as the good healing group. The poor healing group was further subdivided into osteoporosis and non-osteoporosis subgroups. Preoperative lumbar MRI images were collected, and Image J software was used to measure the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION: (1) There were no significant differences in gender, age, or diabetes between the poor healing and good healing groups (P > 0.05). (2) The functional cross-sectional area and fat infiltration percentage of the psoas major, erector spinae, and multifidus muscles were significantly different between the two groups (P < 0.05). (3) Logistic regression analysis showed that fat infiltration percentage was an independent risk factor for poor wound healing. (4) Receiver operating characteristic curve analysis showed that fat infiltration percentage had high predictive value for poor wound healing (area under the curve > 0.7). (5) One-way ANOVA indicated that osteoporosis was a risk factor for fat infiltration in the L4 multifidus muscle (P < 0.05). (6) The results indicate that paraspinal muscle fat infiltration percentage is an important predictor of non-infectious poor wound healing after traditional open posterior lumbar surgery, providing clinical reference. Osteoporosis was also confirmed as a risk factor for L4 multifidus fat infiltration, but due to the small subgroup sample size, whether osteoporosis affects non-infectious poor healing after lumbar surgery requires further clinical trials.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with late-stage 5-year survival rates below 50%. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) drive progression, yet the molecular mediators of CAF-tumor crosstalk are incompletely defined. This study identifies platelet-derived growth factor C (PDGFC) as a critical CAF-secreted factor that promotes epithelial-mesenchymal transition (EMT) and immunosuppression in LUAD. Analysis of patient specimens revealed elevated PDGFC expression in CAFs relative to nontumor tissue fibroblasts (NFs), and high PDGFC levels correlated with poor prognosis. Mechanistically, CAF-derived PDGFC activates the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in cancer cells, inducing EMT and matrix metalloproteinase 2 (MMP2) expression. PDGFC also stimulates PDGFRA expression in both tumor cells and fibroblasts, establishing a reciprocal positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. Immunologically, PDGFC promotes infiltration and polarization of immunosuppressive cell populations, including CD4+ Treg cells, M2 macrophages, and N2 neutrophils, while restraining immunocompetent NK cells. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC in modulating immunosuppression. These findings position PDGFC as a diagnostic indicator and potential immunotherapy target for LUAD, offering a novel TME-targeted therapeutic strategy.