Soybean (Glycine max (L.) Merrill) oil is a complex mixture of five fatty acids (palmitic, stearic, oleic, linoleic, and linolenic). The high content of linoleic acid (LA) contributes to the oil having poor oxidative stability. Therefore, soybean seed with a lower LA content is desirable. To investigate the genetic architecture of LA, we performed a genome-wide association study (GWAS) using 510 soybean cultivars collected from China. The phenotypic identification results showed that the content of LA varied from 36.22% to 72.18%. The GWAS analysis showed that there were 37 genes related to oleic acid content, with a contribution rate of 7%. The candidate gene Glyma.04G116500.1 (GmWRI14) on chromosome 4 was detected in three consecutive years. The GmWRI14 showed a negative correlation with the LA content and the correlation coefficient was −0.912. To test whether GmWRI14 can lead to a lower LA content in soybean, we introduced GmWRI14 into the soybean genome. Matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF IMS) showed that the overexpression of GmWRI14 leads to a lower LA content in soybean seeds. Meanwhile, RNA-seq verified that GmWRI14-overexpressed soybean lines showed a lower accumulation of GmFAD2-1A and GmFAD2-1B than control lines. Our results indicate that the down-regulation of the FAD2 gene triggered by the transcription factor GmWRI14 is the underlying mechanism reducing the LA level of seed. Our results provide novel insights into the genetic architecture of LA and pinpoint potential candidate genes for further in-depth studies.

Background: Skin cancer represents a significant global public health concern. Comprehensive analysis of its global burden provides critical insights for evidence-based interventions. This study systematically evaluates the global disease burden of skin cancer and its subtypes.Methods: This study analyzed GBD 2021 data to assess ASIR and ASDR trends for total skin cancer and its subtypes (1990–2021), stratified by geography, age, and sex, using APC modeling, decomposition analysis, and inequality assessments, with projections through 2040.Results: First, skin cancer ASIR increased from 1990 to 2021, while ASDR significantly decreased. Second, geographical heterogeneity existed in distribution of histological subtypes. Third, skin cancer burden demonstrated age-dependent progression with compositional variance in subtypes across age groups. Fourth, sex disparities intensified beyond age 55, with increasing longitudinal divergence. Fifth, both the ASIR and ASDR of total skin cancer showed non‑linear associations with SDI. Sixth, international disparities in skin cancer burden demonstrated a decreasing trend. Finally, projections to 2040 indicate a continued increase in total skin cancer ASIR accompanied by a persistent decline in total skin cancer ASDR.Conclusion: ASIRs of total skin cancer and its subtypes showed increasing trends, while ASDRs demonstrated decreasing patterns, with significant heterogeneity across regions, age groups, and sex.

Objectives: This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs). Methods: The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes. Results: Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts. Conclusions: Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.

Major histocompatibility complex class I (MHC-I)-mediated antigen presentation plays a pivotal role in anti-tumor immunity by enabling CD8⁺ T cells to recognize and eliminate malignant cells. In melanoma, modulation of this pathway is critical for improving the efficacy of immunotherapies. Our study demonstrates that the natural compound Cepharanthine (CEP) exhibits notable antitumor activity by enhancing MHC-I-mediated antigen presentation. CEP treatment upregulated MHC-I expression (both membrane-bound and total levels) in melanoma cells in a concentration-dependent manner, thereby improving antigen-presenting capacity. Interestingly, when autophagy was pharmacologically blocked using Bafilomycin A1, co-treatment with CEP did not lead to further elevation of MHC-I expression, suggesting that CEP’s effect is mediated through disruption of the autophagic pathway. Mechanistically, CEP induced autophagosome accumulation, as evidenced by an increase in GFP-LC3 puncta. Fluorescence imaging further confirmed that CEP selectively impaired lysosomal acidification without affecting autophagosome–lysosome fusion, thereby inhibiting late-stage autophagic flux. Furthermore, CEP treatment promoted CD8⁺ T cell infiltration into tumor tissues and enhanced the antitumor efficacy of anti-PD-1 therapy, resulting in greater tumor suppression compared to either treatment alone. The study elucidates how CEP’s selective lysosomal inhibition creates a tumor microenvironment more susceptible to immune surveillance, primarily through preserved MHC-I surface expression and subsequent T cell recognition. This work highlights CEP as a promising immunomodulatory agent and provides a potential strategy for improving the outcomes of immune checkpoint blockade therapy.

Skin photoaging is a chronic inflammatory state induced by ultraviolet (UV) radiation. Ferroptosis has recently emerged as a critical mechanism implicated in the pathogenesis of photoaging. Ginsenosides, active compounds in ginseng, hold potential for treating skin photoaging, but their molecular mechanisms in regulating ferroptosis remain unclear. We utilized single-cell RNA sequencing (scRNA-seq) to analyze murine skin after UVB irradiation, focusing on keratinocyte subpopulations and ferroptosis-related genes. Molecular docking assessed ginsenoside binding to ferroptosis regulators. Embryotoxicity of ginsenosides was evaluated using zebrafish embryos. Ferroptosis gene expression in UVB-exposed keratinocytes with or without ginsenoside treatment was analyzed by Western blot and RT-qPCR. scRNA-seq revealed a significant increase in keratinocyte numbers and ferroptosis signals following UVB irradiation. We observed that UVB exposure reduced SLC7A11 and GPX4 expression while increasing HMGB1 in keratinocytes. Molecular docking experiments further indicated that ginsenosides C-K and C-Mc can target ferroptosis-related proteins, and are non-toxic in zebrafish embryos. Treatment with ginsenosides effectively attenuated skin photoaging by modulating the SLC7A11/GPX4 axis and suppressing HMGB1 expression, thereby reducing UVB-induced reactive oxygen species levels and restoring keratinocyte viability. Additionally, we also identified three differentiation trajectories of keratinocytes and found that bone marrow-derived cell Gas6 signaling may influence ferroptosis via the Axl/Tyro3 pathway. Our findings suggest that ginsenosides may represent promising therapeutic candidates for alleviating UVB-induced skin photoaging via modulation of the ferroptosis-associated SLC7A11/GPX4 axis and HMGB1 expression, providing novel mechanistic insights and therapeutic strategies against skin photoaging.

Fangji Huangqi Decoction (FJHQ), a traditional Chinese medicine formula derived from “Jin Gui Yao Lue,” has been reported to exhibit immunomodulatory and anti‐inflammatory effects. This study investigates its potential anti‐tumor mechanism via the enhancement of CD8 ⁺ T cell‐mediated immunity. In murine B16 melanoma and Lewis lung carcinoma models, FJHQ significantly suppressed tumor growth and enhanced CD8 ⁺ T cell infiltration and cytotoxicity. CD8 ⁺ T cell depletion abrogated these effects, confirming their necessity. In vitro, FJHQ treatment augmented antigen presentation by tumor cells through upregulation of MHC‐I expression, leading to improved CD8 ⁺ T cell recognition and killing. Mechanistically, FJHQ inhibited autophagic flux in tumor cells, as evidenced by mCherry‐GFP‐LC3 reporter assays and electron microscopy, resulting in impaired lysosomal function and elevated MHC‐I levels. Furthermore, combining FJHQ with anti–PD‐1 therapy synergistically promoted CD8 ⁺ T cell activity, increased granzyme B and IFN‐γ expression, and induced substantial tumor regression. These findings demonstrate that FJHQ enhances antitumor immunity by suppressing autophagy and elevating MHC‐I expression, thereby sensitizing tumors to PD‐1 blockade. FJHQ represents a promising immunoadjuvant for cancer therapy.