Acid Catalysis over Low-Silica Faujasite Zeolites.

Low-silica faujasite (FAU) zeolites (with Si/Al ratio of ca. 1.2-1.8) sustain framework integrity and porosity upon moderate ion exchange (0.01 M NH4NO3 solution for 1 h at ambient temperature), which introduces two kinds of protons, distinctive in reactivity and coordination to the zeolite framework, within supercages (HSUP). Moderate ion exchange limited within supercages transpires while maintaining full occupancy of Na+ cations within associated sodalite cages; this in turn helps stabilize the framework of low-silica H-FAU zeolites. Protons located on site II (H3630) and site III (H3650) within supercages on low-silica FAU zeolites can be classified and enumerated by virtue of infrared spectroscopy, providing an opportunity to compare reactivities of these distinct protons for monomolecular protolytic reactions of propane. Protons on site II exhibit prominently higher reactivity for monomolecular propane dehydrogenation and cracking than protons on site III. Low-silica proton-form FAU zeolites (zeolite X) upon moderate ion exchange possess protons on site III that are unavailable on high-silica FAU zeolites (zeolite Y) and limit ion exchange within supercages, providing unprecedented high-temperature structural and chemical stability (>773 K) and enabling their application as solid-acid catalysts.

Cetrimonium bromide promotes the clearance of lipids by activating the TFEB-mediated autophagosome-lysosome pathway in hepatic cells.

Autophagy plays a key role in the metabolism of macromolecules via the degradative abilities of the lysosome. Transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Herein, we report that cetrimonium bromide (CTAB; a quaternary ammonium compound) promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. Knockdown of TFEB mediated by short hairpin RNA inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment significantly increases lipid metabolism in both palmitate- and oleate-treated HepG2 cells, and this increase was attenuated by knockdown of TFEB. Collectively, our results indicate that CTAB activates the autophagosome-lysosome pathway via inducing the nuclear translocation of TFEB by inhibiting the mTORC1 signaling pathway. These results add to the collective understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism.

Reexamining the Kuleshov effect: Behavioral and neural evidence from authentic film experiments.

Film cognition explores the influence of cinematic elements, such as editing and film color, on viewers' perception. The Kuleshov effect, a famous example of how editing influences viewers' emotional perception, was initially proposed to support montage theory through the Kuleshov experiment. This effect, which has since been recognized as a manifestation of point-of-view (POV) editing practices, posits that the emotional interpretation of neutral facial expressions is influenced by the accompanying emotional scene in a face-scene-face sequence. However, concerns persist regarding the validity of previous studies, often employing inauthentic film materials like static images, leaving the question of its existence in authentic films unanswered. This study addresses these concerns by utilizing authentic films in two experiments. In Experiment 1, multiple film clips were captured under the guidance of a professional film director and seamlessly integrated into authentic film sequences. 59 participants viewed these face-scene-face film sequences and were tasked with rating the valence and emotional intensity of neutral faces. The findings revealed that the accompanying fearful or happy scenes significantly influence the interpretation of emotion on neutral faces, eliciting perceptions of negative or positive emotions from the neutral face. These results affirm the existence of the Kuleshov effect within authentic films. In Experiment 2, 31 participants rated the valence and arousal of neutral faces while undergoing functional magnetic resonance imaging (fMRI). The behavioral results confirm the Kuleshov effect in the MRI scanner, while the neural data identify neural correlates that support its existence at the neural level. These correlates include the cuneus, precuneus, hippocampus, parahippocampal gyrus, post cingulate gyrus, orbitofrontal cortex, fusiform gyrus, and insula. These findings also underscore the contextual framing inherent in the Kuleshov effect. Overall, the study integrates film theory and cognitive neuroscience experiments, providing robust evidence supporting the existence of the Kuleshov effect through both subjective ratings and objective neuroimaging measurements. This research also contributes to a deeper understanding of the impact of film editing on viewers' emotional perception from the contemporary POV editing practices and neurocinematic perspective, advancing the knowledge of film cognition.

Clomiphene citrate induces nuclear translocation of the TFEB transcription factor and triggers apoptosis by enhancing lysosomal membrane permeabilization.

The autophagy-lysosome pathway plays a central role in cellular homeostasis by regulating the cellular degradative machinery. The transcription factor EB (TFEB) regulates the biogenesis and function of both lysosomes and autophagosomes, and enhancement of TFEB function has emerged as an attractive therapeutic strategy for lysosome-related disorders. However, little is known about the role of TFEB activation in regulating the cellular fate. Here, we describe that clomiphene citrate (CC), a selective estrogen receptor modulator, promotes nuclear translocation of TFEB and increases lysosomal biogenesis in HeLa and MDA-MB-231 cells. Treatment with CC inhibits cell viability and causes apoptosis by increasing the release of proteases cathepsin B (CatB) and cathepsin D (CatD) from lysosomes into the cytosol. In contrast, knockdown of TFEB rescues the cells from CC-induced cell death. Furthermore, CC-induced TFEB activation also enhances the autophagy flux in HeLa cells. Knockdown of autophagy-related gene 7 (ATG7) significantly decreases the CC-induced CatB and CatD release and cell death, suggesting that autophagy contributes to the lysosomal membrane permeabilization (LMP) caused by CC. Altogether, these findings have broad implications for our understanding of TFEB function and provide new insights into CC pharmacological therapy.

Piperlongumine-induced nuclear translocation of the FOXO3A transcription factor triggers BIM-mediated apoptosis in cancer cells.

The transcription factor forkhead box O 3A (FOXO3A) is a tumor suppressor that promotes cell cycle arrest and apoptosis. Piperlongumine (PL), a plant alkaloid, is known to selectively kill tumor cells while sparing normal cells. However, the mechanism of PL-induced cancer cell death is not fully understood. We report here that an association of FOXO3A with the pro-apoptotic protein BIM (also known as BCL2-like 11, BCL2L11) has a direct and specific function in PL-induced cancer cell death. Using HeLa cells stably expressing a FOXO3A-GFP fusion protein and several other cancer cell lines, we found that PL treatment induces FOXO3A dephosphorylation and nuclear translocation and promotes its binding to the BIM gene promoter, resulting in the up-regulation of BIM in the cancer cell lines. Accordingly, PL inhibited cell viability and caused intrinsic apoptosis in a FOXO3A-dependent manner. Of note, siRNA-mediated FOXO3A knockdown rescued the cells from PL-induced cell death. In vivo, the PL treatment markedly inhibited xenograft tumor growth, and this inhibition was accompanied by the activation of the FOXO3A-BIM axis. Moreover, PL promoted FOXO3A dephosphorylation by inhibiting phosphorylation and activation of Akt, a kinase that phosphorylates FOXO3A. In summary, our findings indicate that PL activates the FOXO3A-BIM apoptotic axis by promoting dephosphorylation and nuclear translocation of FOXO3A via Akt signaling inhibition. These findings uncover a critical mechanism underlying the effects of PL on cancer cells.