Design, synthesis and biological evaluation of novel podophyllotoxin derivatives as tubulin-targeting anticancer agents

Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity. This study synthesizes PPT derivatives to assess their anticancer activities. Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound E5 on A549 cell growth were evaluated through molecular docking, in vitro assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and in vivo tests in female BALB/c nude mice treated with E5 (2 and 4 mg/kg). E5 (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group. Among the 16 PPT derivatives tested for cytotoxicity, E5 exhibited potent effects against A549 cells (IC50: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. E5-induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of E5 to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins. This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with E5 call for extended research and clinical validation, leading to novel and more effective cancer therapies.</p

Fully Printable Mesoscopic Perovskite Solar Cells with Organic Silane Self-Assembled Monolayer

By the introduction of an organic silane self-assembled monolayer, an interface-engineering approach is demonstrated for hole-conductor-free, fully printable mesoscopic perovskite solar cells based on a carbon counter electrode. The self-assembled silane monolayer is incorporated between the TiO₂ and CH₃NH₃PbI₃, resulting in optimized interface band alignments and enhanced charge lifetime. The average power conversion efficiency is improved from 9.6% to 11.7%, with a highest efficiency of 12.7%, for this low-cost perovskite solar cell

m6A reader YTHDC2 mediates NCOA4 mRNA stability affecting ferritinophagy to alleviate secondary injury after intracerebral haemorrhage

Oxidative stress and neuronal dysfunction caused by intracerebral haemorrhage (ICH) can lead to secondary injury. The m6A modification has been implicated in the progression of ICH. This study aimed to investigate the role of the m6A reader YTHDC2 in ICH-induced secondary injury. ICH models were established in rats using autologous blood injection, and neuronal cell models were induced with Hemin. Experiments were conducted to overexpress YTH domain containing 2 (YTHDC2) and examine its effects on neuronal dysfunction, brain injury, and neuronal ferritinophagy. RIP-qPCR and METTL3 silencing were performed to investigate the regulation of YTHDC2 on nuclear receptor coactivator 4 (NCOA4). Finally, NCOA4 overexpression was used to validate the regulatory mechanism of YTHDC2 in ICH. The study found that YTHDC2 expression was significantly downregulated in the brain tissues of ICH rats. However, YTHDC2 overexpression improved neuronal dysfunction and reduced brain water content and neuronal death after ICH. Additionally, it reduced levels of ROS, NCOA4, PTGS2, and ATG5 in the brain tissues of ICH rats, while increasing levels of FTH and FTL. YTHDC2 overexpression also decreased levels of MDA and Fe2+ in the serum, while promoting GSH synthesis. In neuronal cells, YTHDC2 overexpression alleviated Hemin-induced injury, which was reversed by Erastin. Mechanistically, YTHDC2-mediated m6A modification destabilized NCOA4 mRNA, thereby reducing ferritinophagy and alleviating secondary injury after ICH. However, the effects of YTHDC2 were counteracted by NCOA4 overexpression. Overall, YTHDC2 plays a protective role in ICH-induced secondary injury by regulating NCOA4-mediated ferritinophagy.</p

Hu Li_figures_ESM.pdf from Mitochondrial phylogenomics of Hemiptera reveals adaptive innovations driving the diversification of true bugs

Figures S1-S1

134_taxa_PCG12RNA

134_taxa_PCGRNA dataset for PhyloBayes analysi

Thieno[3,2‑<i>b</i>]thiophene-Bridged D−π–A Polymer Semiconductor Based on Benzo[1,2‑<i>b</i>:4,5‑<i>b</i>′]dithiophene and Benzoxadiazole

Thieno­[3,2-<i>b</i>]­thiophene-bridged polymer semiconductor, <b>P­(BDT-TT-BO)</b>, featuring benzoxadiazole (<b>BO</b>) acceptor unit was designed and synthesized. <b>P­(BDT-TT-BO)</b> showed broad absorption, in the wavelength range of 350–700 nm, and low highest occupied molecular orbital (HOMO) energy level (−5.31 eV). The benzoxadiazole-based polymer semiconductor exhibited very promising optoelectronic performance. Power conversion efficiency of the polymer solar cell with <b>P­(BDT-TT-BO)</b> as donor reached 7.05%, which is the champion efficiency in benzoxadiazole containing conjugated polymers and comparable to that of the most efficient benzothiadiazole-based donor polymers. The sensitive dependence of carrier mobility on the annealing temperature of the polymer semiconductors was systematic studied. After annealing at 200 °C, <b>P­(BDT-TT-BO)</b>-based polymer field effect transistor showed a mobility of more than 12 times that of unannealed devices, reached 0.023 cm² V^–1 s^–1, with a high on/off current ratio of 2.7 × 10⁵

134_taxa_AA

134_taxa_AA dataset for PhyloBayes analysi

134_taxa_PCGRNA

134_taxa_PCGRNA dataset for PhyloBayes analysi

Solution-Processable Organic Molecule Photovoltaic Materials with Bithienyl-benzodithiophene Central Unit and Indenedione End Groups

Two solution-processable acceptor–donor–acceptor (A-D-A) structured organic molecules with bithienyl-substituted benzodithiophene (BDTT) as central and donor unit, indenedione (ID) as acceptor unit and end groups, and thiophene (T) or bithiophene (bT) as π-bridges, D1 and D2, are designed and synthesized for the application as donor materials in organic solar cells (OSCs). Two corresponding molecules with alkoxy side chains on BDT, DO1, and DO2 are also synthesized for comparison. The four compounds possess broad absorption covering the wavelength range 450–740 nm and relatively lower HOMO energy levels from −5.16 to about −5.19 eV. D2 and DO2 with bithiophene π-bridges demonstrate stronger absorbance and higher hole mobilities than the compounds with thiophene π-bridges. The power conversion efficiency (PCE) values of the OSCs based on the organic compounds/PC₇₀BM (1.5:1, w/w) are 6.75% for D2, 5.67% for D1, 5.11% for DO2, and 4.15% for DO1. The results indicate that the molecules with thienyl conjugated side chains and bithiophene π-bridges show better photovoltaic performance. The PCE of the D2-based OSC are among the highest values in the OSCs based on the solution-processed organic small molecules

117_taxa_PCGRNA

PCGRNA dataset with the removal of 17 species according to the branch length and the heterogeneity in sequence divergenc