The first post-transcriptional step in mammalian mitochondrial gene expression, required for the synthesis of the 13 polypeptides encoded in mitochondrial DNA (mtDNA), is endonucleolytic cleavage of the primary polycistronic transcripts. Excision of the mtDNA-encoded transfer RNAs (tRNAs) releases most mature RNAs; however, processing of three noncanonical messenger RNAs (mRNAs) not flanked by tRNAs (CO1, CO3, and CYB) requires FASTKD5. To investigate the molecular mechanism involved, we created knockout human cell lines to use as assay systems. The absence of FASTKD5 produced a severe OXPHOS assembly defect due to the inability to translate two unprocessed noncanonical mRNAs and predicted altered folding patterns specifically at the 5'-end of the CO1 coding sequence. Structural features 13-15 nt upstream of the CO1 and CYB cleavage sites suggest FASTKD5 recognition mechanisms. Remarkably, a map of essential FASTKD5 amino acid residues revealed RNA substrate specificity; however, a key, putative active site residue was required for processing all three noncanonical pre-RNAs. Mutating this site did not significantly alter the binding of any client RNA substrate. A reconstituted in vitro system showed that wild-type, but not mutant, FASTKD5, was able to cleave client substrates correctly. These results establish FASTKD5 as the missing piece of biochemical machinery required to completely process the primary mitochondrial transcript.

The first post-transcriptional step in mammalian mitochondrial gene expression, required for the synthesis of the 13 polypeptides encoded in mitochondrial DNA (mtDNA), is endonucleolytic cleavage of the primary polycistronic transcripts. Excision of the mtDNA-encoded transfer RNAs (tRNAs) releases most mature RNAs; however, processing of three noncanonical messenger RNAs (mRNAs) not flanked by tRNAs (CO1, CO3, and CYB) requires FASTKD5. To investigate the molecular mechanism involved, we created knockout human cell lines to use as assay systems. The absence of FASTKD5 produced a severe OXPHOS assembly defect due to the inability to translate two unprocessed noncanonical mRNAs and predicted altered folding patterns specifically at the 5'-end of the CO1 coding sequence. Structural features 13-15 nt upstream of the CO1 and CYB cleavage sites suggest FASTKD5 recognition mechanisms. Remarkably, a map of essential FASTKD5 amino acid residues revealed RNA substrate specificity; however, a key, putative active site residue was required for processing all three noncanonical pre-RNAs. Mutating this site did not significantly alter the binding of any client RNA substrate. A reconstituted in vitro system showed that wild-type, but not mutant, FASTKD5, was able to cleave client substrates correctly. These results establish FASTKD5 as the missing piece of biochemical machinery required to completely process the primary mitochondrial transcript.

Superoxide dismutases (SODs) are essential antioxidant enzymes that prevent massive superoxide radical production and thus protect cells from damage induced by free radicals. However, this concept has rarely been applied to directly impede the function of driver oncogenes, thus far. Here, leveraging efforts from SOD model complexes, we report the novel finding of biomimetic copper complexes that efficiently scavenge intracellularly generated free radicals and, thereby, directly access the core consequence of colorectal cancer suppression. We conceived four structurally different SOD-mimicking copper complexes that showed distinct disproportionation reaction rates of intracellular superoxide radical anions. By replenishing SOD models, we observed a dramatic reduction of intracellular reactive oxygen species (ROS) and adenine 5'-triphosphate (ATP) concentrations that led to cell cycle arrest at the G2/M stage and induced apoptosis in vitro and in vivo. Our results showcase how nature-mimicking models can be designed and fine-tuned to serve as a viable chemotherapeutic strategy for cancer treatment.

This study presents a set of quantitative criteria for the definition of planar spatial resolution in scanning electrochemical microscopy (SECM) imaging using an effective diffusion ellipsoid (EDE) model. Experiments and simulations confirm that smaller electrodes improve imaging resolution, and the resolution-step-size equivalence holds across both feedback and generation-collection modes. The finding reported here enables the establishment of standardized conditions for surface activity mapping by SECM.

The global energy demand has driven the development of efficient and cost-effective visible-light-activated photocatalysts for the synthesis of fine chemicals. However, most high-performance photocatalysts possess bandgaps exceeding ∼3.0 eV, limiting their photocatalytic efficiency under visible light. In this study, Pd- and Pt-doped WO₃ nanoparticles were synthesized. Doping induced oxygen vacancies, which act as electron traps, reducing the bandgap and enhancing visible-light-driven photocatalytic activity. The photocatalytic performance was examined using hydroxymethylfurfural and benzyl alcohol as model substrates. The product yields for both substrates in the presence of Pd-doped WO₃ nanoparticles exceeded 95%. This work demonstrates a simple strategy for enhancing the solar-energy-driven photocatalytic efficiency of metal oxide nanoparticles, promoting sustainable fine chemical synthesis.

Carbon nanotube (CNT)-based therapies are emerging as powerful tools in oncology due to their ability to selectively target cancer cells while minimizing damage to healthy tissues. Leveraging the critical role of reactive oxygen species (ROS) in cancer progression, this study explores ROS-mediated photodynamic strategies to enhance therapeutic efficacy. We present a systematic design of five CNT derivatives-CNT-OH, Ti-doped CNT-OH, NaBH₄-treated Ti-doped CNT-OH, Cr-doped CNT-OH, and NaBH₄-treated Cr-doped CNT-OH-engineered to improve visible light absorption and photocatalytic activity. Our approach introduces two key innovations: transition metal doping to create oxygen vacancies that boost light responsiveness and NaBH₄ treatment to induce structural defects and elevate surface charge. These modifications not only fine-tune the physicochemical properties of CNTs but also modulate their biological interactions. Ti-doped CNTs exhibit efficient internalization into renal cancer cells and trigger apoptosis under visible light, offering a controlled and targeted therapeutic mechanism. In contrast, Cr-doped CNTs induce necrosis, likely due to inherent cytotoxicity, highlighting the importance of material composition in cell fate decisions. Furthermore, we demonstrate the dual applicability of these CNTs in sustainable photocatalysis. NaBH₄-treated Cr-doped CNT-OH shows superior photocatalytic conversion of furfuraldehyde, 5-hydroxymethylfurfural, and toluene, attributed to its optimized surface properties. This work underscores the potential of defect-engineered CNTs as multifunctional platforms for both advanced cancer therapy and sustainable chemical transformation.