Cation/anion-doping induced electronic structure modulation of CoMoO4 for enhanced hydrogen evolution.

The design and fabrication of high-performance, inexpensive and durable electrocatalyst toward hydrogen evolution reaction (HER) is supremely significant for alleviating energy crisis and environmental concerns, but still remaining challenging. Herein, we develop an experimental work based on etching and reduction strategy to reveal the remarkable effect of cation/anion co-doping in CoMoO4 on its intrinsic HER activity. The CoMoO4 with Fe and B incorporation (Fe/B-CoMoO4) exhibits a current density of 10 mA cm-2 with strikingly low potential of 38 mV coupling with Tafel slope of 51 mV dec-1, and manifesting a robust durability for 100 h with no attenuation, which is comparable to the state-of-the-art commercial Pt/C catalyst. The collective experimental and theoretical findings concomitantly illustrate that the enhanced performances are due to the strong synergistic effect resulting from the co-doping of Fe and B, which plays a pivotal role in finely tuning the electronic structure of CoMoO4, further optimizing the adsorption free energy of H intermediates and shifting the center of the d-band of Fe/B-CoMoO4 away from the Fermi level. This fantastic work highlights the critical role of foreign element incorporating for optimizing electronic structure of transition metal oxides toward HER, and offers valuable guiding principles for rational design of more efficient energy conversion devices.

Double-layered microneedle patch loaded with bioinspired nano-vaccine for melanoma treatment and wound healing.

Malignant melanoma is a challenging problem worldwide, because the remaining tumor cells and extensive skin defects following surgical resection are difficult to treat. Biomaterial-mediated immunotherapy has emerged as a superior strategy for anti-tumor applications in recent years. Herein, a unique double-layer MNP was developed to address the problem of malignant melanoma. Hydroxyapatite (HAP) and short-chain peptides from tumor cells were self-assembled to prepare the bioinspired nano-vaccine, and then they were loaded onto the microneedle tips of methacrylated gelatin (GelMA)-based MNP. The products (dubbed HVMN) demonstrated relatively good biocompatibility and immune activity, inhibiting the proliferation and inducing apoptosis of malignant melanoma in a B16 cell-bearing model of C57BL/6 mice, and promoting skin tissue regeneration in a full thickness skin defect model of SD rats in 15 days. The putative molecular pathways were examined preliminarily. In conclusion, this research will develop a competitive microneedle patch with dual anti-tumor and pro-regenerative properties for the postoperative treatment of malignant melanoma.

Discovering and Validating Cuproptosis-Associated Marker Genes for Accurate Keloid Diagnosis Through Multiple Machine Learning Models.

Background: Keloid is a common condition characterized by abnormal scarring of the skin, affecting a significant number of individuals worldwide. Objective: The occurrence of keloids may be related to the reduction of cell death. Recently, a new cell death mode that relies on copper ions has been discovered. This study aimed to identify novel cuproptosis-related genes that are associated with keloid diagnosis. Methods: We utilized several gene expression datasets, including GSE44270 and GSE145725 as the training group, and GSE7890, GSE92566, and GSE121618 as the testing group. We integrated machine learning models (SVM, RF, GLM, and XGB) to identify 10 cuproptosis-related genes (CRGs) for keloid diagnosis in the training group. The diagnostic capability of the identified CRGs was validated using independent datasets, RT-qPCR, Western blotting, and IHC analysis. Results: Our study successfully categorized keloid samples into two clusters based on the expression of cuproptosis-related genes. Utilizing WGCNA analysis, we identified 110 candidate genes associated with cuproptosis. Subsequent functional enrichment analysis results revealed that these genes may play a regulatory role in cell growth within keloid tissue through the MAPK pathway. By integrating machine learning models, we identified CRGs that can be used for diagnosing keloid. The diagnostic efficacy of CRGs was confirmed using independent datasets, RT-qPCR, Western blotting, and IHC analysis. GSVA analysis indicated that high expression of CRGs influenced the gene set related to ECM receptor interaction. Conclusion: This study identified 10 cuproptosis-related genes that provide insights into the molecular mechanisms underlying keloid development and may have implications for the development of targeted therapies.

Immunogenic cell death-related classification reveals prognosis and effectiveness of immunotherapy in breast cancer.

Lack of specific biomarkers and effective drug targets constrains therapeutic research in breast cancer (BC). In this regard, therapeutic modulation of damage-associated molecular patterns (DAMPs)-induced immunogenic cell death (ICD) may help improve the effect of immunotherapy in individuals with BC. The aim of this investigation was to develop biomarkers for ICD and to construct ICD-related risk estimation models to predict prognosis and immunotherapy outcomes of BC. RNA-seq transcriptome information and medical data from individuals with BC (n = 943) were obtained from TCGA. Expression data from a separate BC cohort (GEO: GSE20685) were used for validation. We identified subtypes of high and low ICD gene expression by consensus clustering and assessed the connection between ICD subtypes and tumor microenvironment (TME). In addition, different algorithms were used to construct ICD-based prognostic models of BC. BC samples were categorized into subtypes of high and low ICD expression depending on the expression of genes correlated with ICD. The subtype of ICD high-expression subtypes are correlated with poor prognosis in breast cancer, while ICD low-expression subtypes may predict better clinical outcomes. We also created and verified a predictive signature model depending on four ICD-related genes (ATG5, CD8A, CD8B, and HSP90AA1), which correlates with TME status and predicts clinical outcomes of BC patients. We highlight the connection of ICD subtypes with the dynamic evolution of TME in BC and present a novel ICD-based prognostic model of BC. In clinical practice, distinction of ICD subtype and assessment of ICD-related biomarkers should help guide treatment planning and improve the effectiveness of tumor immunotherapy.

circ_0001429 targets miR-139-5p/TGIF1 molecular axis to regulate biological behaviors of bladder cancerT24 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1（TGIF1）axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24, 5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_ 0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assayconfirmedthatthereisatargetingrelationshipbetweencirc_0001429andmiR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.