The N6-methyladenosine (m⁶A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death.

Alpha-fetoprotein (AFP) is an important clinical tumor marker of hepatoblastoma, and the concentration of AFP in serum is closely related to the staging of hepatoblastoma. We report a magnetic bead separation platform based on a switching aptamer triggered hybridization chain reaction (SAT-HCR) and the CRISPR-Cas12a sensor for the in vitro detection of AFP. AFP aptamer, as an easily regulated nucleic acid strand, is responsible for binding to AFP into nucleic acid detection, while HCR-CRISPR-Cas12a, regulated by functionalized magnetic nanoparticles, is responsible for highly specific nucleic acid signal amplification. Under the optimal conditions, the fluorescence intensity was proportional to the concentration of AFP in the range of 0.5–10⁴ ng mL⁻¹ and the limit of detection was 0.170 ng mL⁻¹. In addition, we have successfully applied this biosensor to detect AFP in clinical samples from patients with hepatoblastoma, with greater sensitivity relative to ELISA. Our proposed method showed great potential application in clinical diagnosis and pharmaceutical-related fields with the properties of high sensitivity, low cost and high selectivity.

The healing of bacterial biofilm‐infected wounds is a complex process, and the construction of emerging therapeutic modalities that regulate the microenvironment to magnify therapeutic effects and reduce biotoxicity is still highly challenging. Herein, an engineered microneedle (MN) patch is reported to mediate the efficient delivery of black phosphorus nanosheets (BP NSs) and copper peroxide nanodots (CP NDs) for dual nanodynamic sterilization and methicillin‐resistant staphylococcus aureus (MRSA)‐infected wound healing. Results demonstrate that the system can eliminate biofilm, reduce cytotoxicity, promote angiogenesis and tissue regeneration by the multiple advantages of chemodynamic therapy (CDT), enhanced photodynamic therapy (PDT), and improved degradation process from BP NSs to phosphate for promoting cell proliferation. Notably, the balance between excellent photodynamic stability and rapid degradability of BP NSs is maintained, and the improved degradation mechanism of BP NSs is vividly elucidated by density functional theory (DFT)‐based molecular dynamics (MD) calculations. Furthermore, the transcriptional changes of treated MRSA‐infected skin are studied using RNA‐seq technology to reveal the potential therapeutic mechanism. As envisaged, the proposed MN patch provides a safe, easy, also highly effective approach to achieve the temporal regulation of sterilization and tissue regeneration for bacterial biofilm‐infected wounds.

Programmed cell death (PCD) plays an important role in the onset and progression of various cancers. The molecular events surrounding the occurrence of abnormally expressed long noncoding RNAs (lncRNAs) leading to colon cancer (CC) have become a focus. We comprehensively evaluated the roles of PCD-related lncRNAs in the clinical management of CC and their immune responses. Therefore, we screened 41 prognostic PCD-related lncRNAs in The Cancer Genome Atlas database using co-expression analysis and assigned patients to groups according to the results of cluster analysis. The immune response and functions of cluster 2 were substantially suppressed, which might explain the poor prognosis in this group. A prognostic model comprising eight PCD-related lncRNAs was developed, and its effectiveness was verified using an external database. High-and low-risk groups had different epigenetic modifications and changes in immune cell infiltration. Patients in the high-risk group were resistant to immunotherapy and various chemotherapeutic drugs. Studies in vitro and in vivo further confirmed a carcinogenic role of the lncRNA U62317.4. Our findings of the prognostic value of PCD-related lncRNAs revealed their important roles in immune response disorders, thus providing valuable insights into the clinical management and molecular mechanisms of CC.

Original Article CRISPR/Cas9 ribonucleoprotein (RNP) complex enables higher viability of transfected cells in genome editing of acute myeloid cells Qinquan Cheng, Jing Xia, Kaimin Wang, Yue Zhang, Yan Chen, Qi Zhong, Xue Wang, Qi Wu