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The immunological implications of cuproptosis, a form of cell death highly sensitive to oxygen presence, remain largely unexplored in the context of tumor immunotherapy. Herein, we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis. Subsequently, an oxygen generator loaded with copper ions (Cu/APH‐M) has been constructed, which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment. Importantly, Cu/APH‐M‐mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA‐sequencing analysis, but also effectively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy, creating a robust immune memory effect. Our work reveals the beneficial effects of enhanced cuproptosis in radio‐immunotherapy and elucidates its underlying mechanisms, which provides a novel approach for the synergistic integration of cuproptosis with immunotherapy and radiotherapy, broadening the scope of cuproptosis‐mediated tumor therapy. We designed a copper‐ion‐loaded oxygen generator carrier to dual heighten cuproptosis and radiotherapy and further elucidated the antitumor immune response of augmented cuproptosis and its interaction with radiotherapy, which expands the application scope of cuproptosis in cancer treatment.

Abdominal aortic aneurysm (AAA), a life‐threatening cardiovascular disorder, necessitates the identification of novel molecular biomarkers to facilitate early diagnosis and precision therapeutic interventions. In this study, we employed an integrative bioinformatics strategy to systematically identify and characterise a potential biomarker for AAA. By reanalyzing GEO datasets and applying Lasso regression, we identified 10 candidate genes, whose intersection with known AAA‐associated genes pinpointed LEF1 as a pivotal regulator. Single‐cell transcriptomic analysis further demonstrated that LEF1 is predominantly expressed in aortic wall‐resident T cells, suggesting a spatially restricted regulatory role. Functional enrichment analysis highlighted significant associations with MHC class II protein complex binding and ribosomal structural integrity, implicating LEF1 in immune and translational regulation. Immunohistochemical analysis demonstrated significantly elevated expression of CD3, CD4 and CD8 markers in AAA tissues compared to controls. Flow cytometry and immunofluorescence analyses confirmed LEF1 co‐localisation with both CD8+ effector T cells and CD4+ memory T cells, with significantly enhanced LEF1 expression in AAA specimens versus controls. Overall, our study systematically discovered an important hub gene LEF1, which may serve as a biomarker for AAA.

Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression‐free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high‐risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1‐year, 3‐year, and 5‐year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single‐cell RNA sequencing to two castration‐related prostate cancer (CRPC) samples and two hormone‐related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression‐related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.

Transforming Growth Factor‐Beta (TGF‐β) signalling pathway is of paramount importance in the processes of wound healing, epidermal integrity maintenance and development of skin cancer. The objective of this research endeavour was to clarify the impact of gene mutations and variations in expression within TGF‐β family on mechanisms of tissue repair, as well as to identify potential targets for therapeutic purposes in non‐melanoma skin cancer (NMSC). The methods utilized in this study involved obtaining RNA‐seq data from 224 NMSC patients and paired normal skin tissues from the PRJNA320473 and PRJEB27606 databases. The purpose of the differential gene expression analysis was to identify genes whose expression had changed significantly. In order to evaluate the effects and interrelationships of identified gene variants, structural analysis with AlphaFold and PDB data and network analysis with the STRING database were both utilized. Critical gene expression was externally validated through the utilization of the GEPIA database. Tumour tissues exhibited a notable upregulation of genes associated with the TGF‐β pathway, specifically MMP1, MMP3, MMP9, EGF, COL3A1 and COL1A2, in comparison with normal tissues. As indicated by the central node status of these genes in the network analysis, they play a crucial role in the progression of NMSCs. The results of the structural analysis suggested that mutations might cause functional disruptions. External validation of the upregulation confirmed the expression trends and emphasized the biomarker potential of the upregulated genes. In conclusion, this research offered thorough examination of molecular modifications that occur in TGF‐β family genes, which are linked to cutaneous wound healing and NMSC. The modified expression of the identified hub genes may represent innovative targets for therapeutic intervention.

Brucellosis is a zoonotic disease caused by Brucella spp. which seriously jeopardizes the health and safety of animals and human beings. Therefore, developing a live attenuated vaccine is a priority. In this study, a genetically stable Brucella rough RA343 strain was obtained by cross‐induction. The virulence and protective efficacy of RA343 were subsequently assessed, and RA343 showed reduction of survival ability in RAW264.7 cells and low pathogenicity in the murine model in vivo. Immunization with RA343 elevated expression levels of IFN‐γ and TNF‐α and a robust T‐cell immune response in mice. Guinea pigs were inoculated with RA343 at 1 × 109 CFU for single and booster immunization. After the single immunization of RA343, about 60% of guinea pigs could resist the attack of M28 or 2308 strain. The secondary immunization in guinea pigs confer 80% and 70% protection against M28 or 2308 challenges, respectively. Then, the gene expression profile of RAW264.7 cells infected with Brucella abortus A19 or RA343 was analyzed by RNA‐seq to investigate the cellular responses immediately after Brucella entry. The RNA‐seq analysis revealed that a total of 14,549 genes were significantly regulated by Brucella 1 h postinfection. The differential gene expression was predominantly associated with innate immune responses and many inflammatory pathways, such as MAPK, JAK‐STAT, and NF‐κB signaling ones. Our findings suggest that the RA343 strain is a promising novel vaccine candidate to protect animals from B. abortus and Brucella melitensis infection. Meanwhile, this study serves as a new reference for investigating the immune regulatory mechanisms of rough Brucella. Brucellosis is a zoonotic disease caused by Brucella spp. which seriously jeopardize the health and safety of animals and human beings. In this study, a genetically stable Brucella rough RA343 strain was obtained by cross‐induction. The virulence and protective efficacy of RA343 were subsequently assessed. Overall, the RA343 strain is a promising novel vaccine candidate to protect animals from Brucella abortus and Brucella melitensis infection.

Background Numerous diseases are associated with the interplay of mitochondrial and macrophage polarization. However, the correlation of mitochondria‐related genes (MRGs) and macrophage polarization‐related genes (MPRGs) with the prognosis of glioma remains unclear. This study aimed to examine this relationship based on bioinformatic analysis. Methods Glioma‐related datasets (TCGA‐GBMLGG, mRNA‐seq‐325, mRNA‐seq‐693, GSE16011, GSE4290, and GSE138794) were included in this study. The intersection genes were obtained by overlapping differentially expressed genes (DEGs) from differential expression analysis in GSE16011, key module genes from WGCNA, and MRGs. Subsequently, the intersection genes were further screened to obtain prognostic genes. Following this, a risk model was developed and verified. After that, independent prognostic factors were identified, followed by the construction of a nomogram and subsequent evaluation of its predictive ability. Furthermore, immune microenvironment analysis and expression validation were implemented. The GSE138794 dataset was utilized to evaluate the expression of prognostic genes at a cellular level, followed by conducting an analysis on cell‐to‐cell communication. Finally, the results were validated in different datasets and tissue samples from patients. Results ECI2, MCCC2, OXCT1, SUCLG2, and CPT2 were identified as prognostic genes for glioma. The risk model constructed based on these genes in TCGA‐GBMLGG demonstrated certain accuracy in predicting the occurrence of glioma. Additionally, the nomogram constructed based on risk score and grade exhibited strong performance in predicting patient survival. Significant differences were observed in the proportion of 27 immune cell types (e.g., activated B cells and macrophages) and the expression of 32 immune checkpoints (e.g., CD70, CD200, and CD48) between the two risk groups. Single‐cell RNA sequencing showed that CPT2, ECI2, and SUCLG2 were highly expressed in oligodendrocytes, neural progenitor cells, and BMDMs, respectively. The results of cell–cell communication analysis revealed that both oligodendrocytes and BMDMs exhibited a substantial number of interactions with high strength. Conclusion This study revealed five genes associated with the prognosis of glioma (ECI2, MCCC2, OXCT1, SUCLG2, and CPT2), providing novel insights into individualized treatment and prognosis. This study constructed a prognostic model for mitochondria and macrophage polarization correlation in glioma based on single‐cell and transcriptome sequencing. Five genes associated with the prognosis of glioma (ECI2, MCCC2, OXCT1, SUCLG2, and CPT2) were revealed and then, validated using glioma tissues, providing novel insights into individualized treatment and prognosis.

In land plants, heteroblasty broadly refers to a drastic change in morphology during growth through ontogeny. Juniperus flaccida and Pinus cembroides are conifers of independent lineages known to exhibit leaf heteroblasty between the juvenile and adult life stage of development. Juvenile leaves of P. cembroides develop spirally on the main stem and appear decurrent, flattened, and needle‐like; whereas adult photosynthetic leaves are triangular or semi‐circular needle‐like, and grow in whorls on secondary or tertiary compact dwarf shoots. By comparison, J. flaccida juvenile leaves are decurrent and needle‐like, and adult leaves are compact, short, and scale‐like. Comparative analyses were performed to evaluate differences in anatomy and gene expression patterns between developmental phases in both species. RNA from 12 samples was sequenced and analyzed with available software. They were assembled de novo from the RNA‐Seq reads. Following assembly, 63,741 high‐quality transcripts were functionally annotated in P. cembroides and 69,448 in J. flaccida. Evaluation of the orthologous groups yielded 4140 shared gene families among the four references (adult and juvenile from each species). Activities related to cell division and development were more abundant in juveniles than adults in P. cembroides, and more abundant in adults than juveniles in J. flaccida. Overall, there were 509 up‐regulated and 81 down‐regulated genes in the juvenile condition of P. cembroides and 14 up‐regulated and 22 down‐regulated genes in J. flaccida. Gene interaction network analysis showed evidence of co‐expression and co‐localization of up‐regulated genes involved in cell wall and cuticle formation, development, and phenylpropanoid pathway, in juvenile P. cembroides leaves. Whereas in J. flaccida, differential expression and gene interaction patterns were detected in genes involved in photosynthesis and chloroplast biogenesis. Although J. flaccida and P. cembroides both exhibit leaf heteroblastic development, little overlap was detected, and unique genes and pathways were highlighted in this study. Juniperus flaccida and Pinus cembroides exhibit leaf heteroblasty between the juvenile and adult life stage of development. Comparative analyses were performed to evaluate differences in anatomy and gene expression patterns between developmental phases in both species.

The increasing incidence of hyperlipidemia is a serious threat to public health. The development of effective and safe lipid‐lowering drugs with few side effects is necessary. The purpose of this study was to assess the lipid‐lowering activity of Sanghuangporus vaninii extract (SVE) in rat experiments and reveal the molecular mechanism by transcriptome analysis. Hyperlipidemia was induced in the animals using a high‐fat diet for 4 weeks. At the end of the 4th week, hyperlipidemic rats were assigned into two control groups (model and positive simvastatin control) and three treatment groups that received SVE at 200, 400, or 800 mg kg−1 day−1 for another 4 weeks. A last control group comprised normal chow‐fed rats. At the end of the 8th week, rats were sacrificed and lipid serum levels, histopathology, and liver transcriptome profiles were determined. SVE was demonstrated to relieve the lipid disorder and improve histopathological liver changes in a dose‐dependent manner. The transcriptomic analysis identified changes in hepatocyte gene activity for major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone signaling, and glucagon signaling. The changed expression of crucial genes in the different groups was confirmed by qPCR. Collectively, this study revealed that SVE could relieve hyperlipidemia in rats, the molecular mechanism might be to promote the metabolism of lipids and the excretion of cholesterol, inhibit the biosynthesis of cholesterol by activating the AMPK signaling pathway, the thyroid hormone signaling pathway, and the glucagon signaling pathway. Extracts of Sanghuangporus vaninii can relieve hyperlipidemia in rats. The results of transcriptomic analysis indicated that S. vaninii extract can activate the AMPK signaling pathway, which subsequently promotes the metabolism of lipids and inhibits the biosynthesis of cholesterol, meanwhile facilitating the excretion of cholesterol, exciting the glucagon signaling pathway and affecting the thyroid hormone signaling pathway, which all contribute to the observed anti‐hyperlipidemic effect.

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.

Background Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1 H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. Methods We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton’s tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1 H MRS. Results Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. Conclusions Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.