The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity. In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates. However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2−/−) mice. In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects. Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5). Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.

Two narrow‐bandgap block conjugated polymers with a (D1–A1)–(D2–A2) backbone architecture, namely PBDB‐T‐b‐PIDIC2T and PBDB‐T‐b‐PTY6, are designed and synthesized for single‐component organic solar cells (SCOSCs). Both polymers contain same donor polymer, PBDB‐T, but different polymerized nonfullerene molecule acceptors. Compared to all previously reported materials for SCOSCs, PBDB‐T‐b‐PIDIC2T and PBDB‐T‐b‐PTY6 exhibit narrower bandgap for better light harvesting. When incorporated into SCOSCs, the short‐circuit current density (Jsc) is significantly improved to over 15 mA cm−2, together with a record‐high power conversion efficiency (PCE) of 8.64%. Moreover, these block copolymers exhibit low energy loss due to high charge transfer (CT) states (Ect) plus small non‐radiative loss (0.26 eV), and improved stability under both ambient condition and continuous 80 °C thermal stresses for over 1000 h. Determination of the charge carrier dynamics and film morphology in these SCOSCs reveals increased carrier recombination, relative to binary bulk‐heterojunction devices, which is mainly due to reduced ordering of both donor and acceptor fragments. The close structural relationship between block polymers and their binary counterparts also provides an excellent framework to explore further molecular features that impact the photovoltaic performance and boost the state‐of‐the‐art efficiency of SCOSCs.

Organic solar cells (OSCs) based on small molecular acceptors (SMAs) have made great development with a power conversion efficiency (PCE) over 16% due to the design of novel materials and advances in device preparation technology. This work fabricates two bulk‐heterojunction photovoltaic devices containing the same wide‐bandgap donor PM6, respectively, matched with popular Y6 and ITIC SMAs. The PM6:Y6‐based device achieves a much higher PCE of 15.21% than the PM6:ITIC‐based device of 9.02%. On the basis of comparisons of macroscopic performances in the quasistatic regime, transient absorption spectroscopy (TAS) is further performed to better understand the microscopic dynamics difference in charge separation processes between the two photovoltaic blends. According to the TAS results, the calculated hole transfer efficiency in PM6:Y6 is 71.4%, far greater than the efficiency of 13.1% in PM6:ITIC, demonstrating favorable charge separation at donor/acceptor interfaces via hole transfer channel in PM6:Y6. The favorable hole transfer in PM6:Y6 is accounted for by its better mutual miscibility between the donor and acceptor, and the formation of long‐lived delocalized intramoiety excimer state in the acceptor. These results highlight the important role of proper molecular design strategy with strong intermolecular coupling and beneficial film morphology on facilitating charge generation in OSCs adopting SMAs.

SIRT3 is a NAD-dependent mitochondrial protein deacetylase implicated in the regulation of central metabolism and mitochondrial proteostasis. SIRT3 is downregulated in clear cell renal cell carcinoma (ccRCC), which is the most common form of renal cancer. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction and elevated fat deposition, it is unknown whether SIRT3 plays a role in tumorigenesis and the development of this disease. In the present study, we found that SIRT3 overexpression and knockdown had opposing effects on the growth of ccRCC cells, decreasing and increasing the rate of cell proliferation, respectively. SIRT3 overexpression also increased mitochondrial mass in ccRCC cells. Unexpectedly, SIRT3 overexpression increased ROS levels, and sensitized cells to oxidative stress. Metabolomics and quantitative proteomics showed that SIRT3 overexpression alterd cellular metabolism and reversed the Warburg effect in ccRCC cells. Further studies demonstrated that SIRT3 promoted mitochondrial biogenesis by increasing both the expression and deacetylation of TFAM (transcription factor A, mitochondrial). Mutagenesis experiments revealed that acetylation of TFAM at K154 impaired TFAM interaction with mitochondrial DNA, thereby decreasing the activity of the protein and, consequently, mitochondrial biogenesis. Overall, our results suggest that SIRT3 regulates mitochondrial biogenesis and that its downregulation promotes a Warburg phenotype in ccRCC.