Enhanced Detection of Novel Low-Frequency Gene Fusions via High-Yield Ligation and Multiplexed Enrichment Sequencing.

Panel-based methods are commonly employed for the analysis of novel gene fusions in precision diagnostics and new drug development in cancer. However, these methods are constrained by limitations in ligation yield and the enrichment of novel gene fusions with low variant allele frequencies. In this study, we conducted a pioneering investigation into the stability of double-stranded adapter DNA, resulting in improved ligation yield and enhanced conversion efficiency. Additionally, we implemented blocker displacement amplification, achieving a remarkable 7-fold enrichment of novel gene fusions. Leveraging the pre-enrichment achieved with this approach, we successfully applied it to Nanopore sequencing, enabling ultra-fast analysis of novel gene fusions within one hour with high sensitivity. This method offers a robust and remarkably sensitive mean of analyzing novel gene fusions, promising the discovery of pivotal biomarkers that can significantly improve cancer diagnostics and the development of new therapeutic strategies.

Ultrasound-Driven Piezoelectrocatalytic Immunoactivation of Deep Tumor.

Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H2 ) and ultrasound (US) and the immunomodulation effects of H2 and lactic acid (LA), this work proposes a novel strategy of US-driven piezoelectrocatalytic tumor immunoactivation for high-efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US-responsive piezoelectric SnS nanosheets (SSN) is developed to realize US-triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H2 liberates effector CD8+ T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8+ T cells by inhibiting regulatory T cells, efficiently co-activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US-driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy.

Open-Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy.

Deleterious effects to normal tissues and short biological half-life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu2+ , and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu2+ contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu2+ to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half-life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.

Nano vanadium dioxide films deposited on biomedical titanium: a novel approach for simultaneously enhanced osteogenic and antibacterial effects.

Vanadium is a trace element in the human body, and vanadium compounds have a promising future in biological and medical applications due to their various biological activities and low toxicity. Herein, a novel pure vanadium dioxide (VO2) nanofilm was deposited on a substrate of biomedical titanium by magnetron sputtering. The antibacterial effect of VO2 against the methicillin-resistant Staphylococcus aureus (MRSA) was validated in vitro and in vivo. Moreover, the biocompatibility of VO2 and its osteogenic effects were systematically illustrated. A possible osteogenic mechanism involving the amelioration of highly reactive oxygen species (ROS) levels were investigated. According to the results of our present and previous studies, the simultaneous antibacterial and osteogenic effects of VO2 are attributed to its differential regulation of ROS levels in rat bone marrow mesenchymal stem cells (rBMSCs) and bacteria. This study is the first to report the simultaneous effects of VO2 on bactericidal and osteogenic activities through its differential modification of ROS activity in eukaryotic (rBMSCs) and prokaryotic (MRSA) cells. The findings in this work may yield a deeper understanding of the biological activities of vanadium compounds while also paving the way for the further investigation and application of VO2 in biological and medical materials.

The improvement of corrosion resistance, biocompatibility and osteogenesis of the novel porous Mg-Nd-Zn alloy.

A magnesium scaffold is a promising biodegradable bone repair material. However, its poor corrosion resistance limits its clinical application. In this study, we improved the corrosion resistance, biocompatibility and osteointergration ability of magnesium by alloying it with neodymium (Nd) and zinc (Zn), then fabricated a novel open-porous Mg-Nd-Zn (P-MNZ) alloy using a titanium wire space holder (TWSH) method. An in vitro corrosion experiment showed that corrosion resistance was enhanced. Both in vitro and in vivo experiments were performed to evaluate the biocompatibility and osteointergration ability of P-MNZ. The cell viability, cytoskeleton staining, ALP activity and osteogenic related gene expression confirm that the P-MNZ scaffold exhibits better biocompatibility and osteoblast differentiation properties in vitro. As for the in vivo experiment, the analysis of micro-CT scanning, Van Gieson staining and sequential polychrome labelling demonstrated that P-MNZ stimulates new bone formation and enhances the corrosion resistance of the P-MNZ scaffold. The results indicate that the P-MNZ alloy is a promising biodegradable bone repair material.