The engineering of intermolecular interaction is challenging but critical for magnetically switchable molecules. Here, we prepared two cyanide‐bridged Fe4Co4 cube complexes via the alkynyl‐ and ...alcohol‐functionalized trispyrazoyl capping ligands. The alkynyl‐functionalized complex 1 exhibited a thermally‐induced incomplete metal‐to‐metal electron transfer (MMET) behaviour at around 220 K, while the mixed alkynyl/alcohol‐functionalized cube of 2 showed a complete and abrupt MMET behaviour at 232 K. Remarkably, both compounds showed a long‐lived photo‐induced metastable state up to 200 K. The crystallographic study demonstrated that the incomplete transition of 1 was likely due to the possible elastic frustration originating from the competition between the anion‐propagated elastic interactions and inter‐cluster alkynyl‐alkynyl & CH‐alkynyl interactions, whereas the latter are eliminated in 2 as a result of the partial substitution by the alcohol‐functionalized ligand. Additionally, the introduction of chemically distinguishable cobalt centers within the cube unit of 2 did not lead to a two‐step but a one‐step transition, possibly because of the strong ferroelastic intramolecular interaction through the cyanide bridges.
Two cyanide‐bridged Fe4Co4 cubes were prepared via a mixed‐ligand approach. The molecular origins of their distinct (incomplete vs. complete) metal‐to‐metal electron transfer (MMET) properties were identified as the presence and absence of the inter‐cluster alkynyl‐alkynyl and CH/π interactions. These compete with the cluster‐anion interactions, resulting in the underlying elastic frustration and stopping the complete spin transition in 1.
Promoting copper catalysts with C60Ethylene glycol, a commodity chemical used as a feedstock and antifreeze agent, is synthesized industrially from dimethyl oxalate (DMO) by hydrogenation over ...precious-metal palladium catalysts at high pressures (typically 20 bars). Copper-chromium catalysts supported on silica as an alternative have required even high pressures. Zheng et al. show the addition of fullerene (C60) onto copper-silica allows DMO hydrogenation to be performed at ambient pressures with high yield (98%) and without deactivation after 1000 hours (see the Perspective by Gravel and Doris). The use of C60 to stabilize electron-deficient copper species that enhance hydrogen adsorption could likely be applied to other hydrogenation reactions catalyzed by copper. —PDS
It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL ...expression in ovarian carcinoma are unclear.
In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.
Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.
The purpose of this study was to investigate the effects of secreted protein acidic and rich in cysteine (SPARC) on the maintenance of limbal epithelial stem cell (LESC) stemness and restoration of ...ocular surface. To determine the suitable concentration of SPARC for LESC culture, the marker expression, mitogenic effect, and holoclone‐forming capacity of LESCs treated with different concentrations of SPARC were analyzed. To investigate the mechanism of SPARC's action on the preservation of LESCs stemness, the phosphorylation of related signaling pathways was evaluated by Western blotting. A corneal wound model was established to verify the function of SPARC in ocular surface repair. Consecutive subculturing, colony‐forming efficiency, immunofluorescence, and 5‐ethynyl‐2‐deoxyuridine incorporation assays indicated that 1 μg/mL SPARC was a suitable concentration to stimulate LESC proliferation and preserve their proliferative potential. Compared with a control group, 1 μg/mL SPARC effectively increased the expression of ABCG‐2, Bmi‐1, and Ki67, while decreasing that of CK3/12. The mitogenic effect of SPARC on LESCs was found to be mediated by the phosphorylation of c‐Jun N‐terminal kinase (JNK) and p38‐MAPK signaling pathways, whereas the inhibitors of JNK and p38 MAPK reduced the marker expression and mitogenic capacity of LESCs. In a corneal injury model, SPARC facilitated corneal epithelial wound healing and promoted the proliferation of p63α‐positive cells both in the limbus and in the epithelial healing front. SPARC promotes proliferation while suppressing spontaneous differentiation of LESCs through JNK and p38‐MAPK signaling pathways, suggesting that SPARC is a promising factor for the improvement of LESCs culture in vitro and in vivo.
When cultured in medium containing1μg/mL secreted protein acidic and rich in cysteine (SPARC) in vitro, limbal epithelial stem cells (LESCs) showed a greater proliferative and clonogenic capacity and a higher expression of LESCs marker through c‐Jun N‐terminal kinase/p38 MAPK signal pathway. In corneal wounding model, exogenous SPARC accelerated corneal epithelial wound healing and promoted the proliferation of p63α‐positive cells both in limbus and in epithelial healing front.
Dynamic molecular crystals are of high interest due to their potential applications. Herein we report the reversible on–off switching of single-molecule magnet (SMM) behavior in a Mo(CN)74– based ...molecular compound. Upon dehydration and rehydration, the trinuclear Mn2Mo molecule Mn(L)(H2O)2Mo(CN)7·2H2O (1) undergoes reversible crystal-to-crystal transformation to a hexanuclear Mn4Mo2 compound Mn(L)(H2O)2Mn(L)2Mo(CN)72 (2). This structural transformation involves the breaking and reforming of coordination bonds which leads to significant changes in the color and magnetic properties. Compound 1 is an SMM with an energy barrier of 44.9 cm–1, whereas 2 behaves as a simple paramagnet despite its higher ground state spin value. The distortion of the pentagonal bipyramidal geometry of Mo(CN)74– in 2 disrupts the anisotropic exchange interactions that lead to SMM behavior in 1.
Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic ...metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy. The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. In a tissue microarray of human liver cancer, the combination of high HK2 expression and high SQSTM1 expression was shown to have biological and prognostic significance. Furthermore, 3-BrPA, a pyruvate analog targeting HK2, significantly decreased the growth of autophagy-impaired tumors in vitro and in vivo (p < 0.05). By demonstrating the regulation of glycolysis by autophagy through the TRAF6- and SQSTM1-mediated ubiquitination system, our study may open an avenue for developing a glycolysis-targeting therapeutic intervention for treatment of autophagy-impaired liver cancer.
This study aims to evaluate the effects of cold atmospheric plasma (CAP) treatment on the bonding of resin cement to high-translucency zirconia. Zirconia specimens were subjected to different ...treatments: no treatment (ZrT), 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer (ZrT-M), alumina particle air-abrasion with/without MDP-containing primer (ZrT-AM/ZrT-A), CAP with/without MDP-containing primer (ZrT-PM/ZrT-P). The surface topography, wettability, and chemical composition were evaluated. The shear bond strength (SBS) was tested before and after thermocycling. CAP did not alter the morphology, increased the wettability, and decreased the carbon/oxygen ratio of zirconia surface. The SBSs of ZrT-PM and ZrT-P were significantly higher than the other groups. After thermocycling, ZrT-A, ZrT-M, ZrT-AM, and ZrT-P showed comparable SBSs, all of which were lower than ZrT-PM. It was concluded that CAP improved the bonding performance of high-translucency zirconia without damaging its surface. The combination of CAP with MDP further enhanced the bond strength and may enable durable bonding.
Smooth muscle cell (SMC) loss is the characteristic feature in the pathogenesis of aortic dissection (AD), and ferroptosis is a novel iron-dependent regulated cell death driven by the excessive lipid ...peroxidation accumulation. However, whether targeting ferroptosis is an effective approach for SMC loss and AD treatment remains unclear. Here, we found that the iron level, ferroptosis-related molecules TFR, HOMX1, ferritin and the lipid peroxidation product 4-hydroxynonenal were increased in the aorta of AD. Then, we screened several inhibitors of histone methyltransferases and found that BRD4770 had a protective effect on cystine deprivation-, imidazole ketone erastin- or RSL3-induced ferroptosis of SMCs. The classic ferroptosis pathways, System Xc--GPX4, FSP1-CoQ10 and GCH1-BH4 pathways which were inhibited by ferroptosis inducers, were re-activated by BRD4770 via inhibiting mono-, di- and tri- methylated histone H3 at lysine 9 (H3K9me1/2/3). RNA-sequencing analysis revealed that there was a positive feedback regulation between ferroptosis and inflammatory response, and BRD4770 can reverse the effects of inflammation activation on ferroptosis. More importantly, treatment with BRD4770 attenuated aortic dilation and decreased morbidity and mortality in a β-Aminopropionitrile monofumarate-induced mouse AD model via inhibiting the inflammatory response, lipid peroxidation and ferroptosis. Taken together, our findings demonstrate that ferroptosis is a novel and critical pathological mechanism that is involved in SMC loss and AD development. BRD4770 is a novel ferroptosis inhibitor and has equivalent protective effect to Ferrostatin-1 at the optimal concentration. Translating insights into the anti-ferroptosis effects of BRD4770 may reveal a potential therapeutic approach for targeting SMC ferroptosis in AD.
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•Ferroptosis is a novel and critical pathological mechanism involved in SMC loss and AD development.•BRD4770 is a novel inhibitor of ferroptosis and protects against SMC ferroptosis via maintaining redox homeostasis.•BRD4770 relieves BAPN-induced AD by inhibiting ferroptosis and inflammatory cell infiltration.
Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial ...engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.
•Compartmentalizing the MVA pathway in yeast mitochondria can cause serious metabolic burden.•The phosphorylated metabolites of the MVA pathway are toxic within mitochondria.•Enhanced synthesis of mevalonate in cytosol can conquer the burden of mitochondrial engineering.•Cytoplasmic engineering is needed to take the full advantage of mitochondrial engineering.
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