Hunan First Normal University

Targeted protein degradation (TPD) technology has emerged as a transformative therapeutic strategy for selectively eliminating aberrant proteins across diverse pathological conditions. This comprehensive review systematically examines recent advances in DNA-based proteolysis-targeting chimeras (DNA-PROTACs), which harness the exceptional specificity and binding affinity of DNA to substantially expand the targetable protein repertoire beyond conventional small molecule PROTACs. Through extensive literature analysis encompassing mechanistic studies, preclinical evaluations, and clinical investigations, we demonstrate that DNA-PROTACs effectively target previously undruggable proteins, including transcription factors, cell membrane proteins, and DNA damage response mediators. These innovative chimeric constructs exhibit superior catalytic efficiency through E3 ubiquitin ligase recruitment via the proteasomal degradation pathway, with unique advantages in linker optimization enabled by precise nucleotide-level control during DNA synthesis. Cell-based assays consistently reveal enhanced selectivity profiles and expanded therapeutic windows compared to traditional PROTAC modalities and alternative RNA-based approaches. Despite promising preclinical outcomes and advancing clinical development timelines, challenges in delivery optimization, molecular stability enhancement, and clinical translation persist. The integration of artificial intelligence-assisted drug design platforms and in vivo aptamer evolution technologies presents unprecedented opportunities for accelerating DNA-PROTACs development toward sub-nanomolar potency targets, positioning this technology as a paradigm-shifting approach in precision medicine across oncology, immunotherapy, and neurodegeneration therapeutics.

The characteristics of a Q-switched erbium-doped all-fiber laser incorporating a bismuth-doped fiber (BDF) as a saturable absorber (SA) are explored for the first time, to the best of our knowledge, using various BDF lengths. The nonlinear optical absorption of the BDF-SA results from excited-state absorption (ESA) and concentration-dependent effects, wherein bismuth ions in higher energy levels absorb photons, causing up-conversion losses. These effects are characterized by modulation depths of 4.2% and 5.6% for 15 and 30 cm BDF lengths, respectively. By integrating 15 cm of BDF into the Er-doped laser cavity, stable, self-starting Q-switched pulses are generated, achieving a maximum pulse energy of 160 µJ, a minimum pulse duration of 2.28 µs, and a repetition rate of up to 99.6 kHz. These performance metrics are constrained by the available pump power of 142 mW from a 980 nm laser diode. The findings provide valuable insights into the design and optimization of Q-switched fiber lasers working in the 1.56 µm wavelength region using BDF as the SA.

Empathy plays a crucial role in determining how one understands others' emotional experiences and behavioral decisions. This study aimed to explore whether empathic concern affects the processing of self-related and charity-related outcome evaluations. In this study, participants performed gambling tasks for themselves and low- and high-empathy charities. The behavioral results showed that low-empathy charities had a significantly higher risk rate than the self, whereas there was no significant difference between low-and high-empathy charities. The event-related potential (ERP) results showed that the P300 valence difference (d-P300) of the self was significantly higher for high-empathy charitable activities than for low-empathy charitable activities, and the d-P300 of high-empathy charitable activities was significantly higher than that of low-empathy charitable activities. The P300 valence differences primarily originated from activation difference in the posterior mid-cingulate cortex (pMCC) and medial prefrontal cortex (mPFC). The time-frequency analysis showed that positive outcomes induced greater β2 event-related desynchronization (ERD) amplitudes for high-empathy charitable activities compared to negative outcomes. These findings suggest that empathic concern increased the distinction between good and bad outcomes for charities and promoted greater cognitive effort allocation toward prosocial rewards. The d-P300 is closely linked to activations in the pMCC and mPFC.