RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR ...activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.
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•Lactate inhibits RLR-mediated interferon production•This regulation occurs through direct sensing of lactate by MAVS•MAVS associates with hexokinase, but this association is disrupted by RIG-I•Targeting LDHA enhances type I IFN production and viral clearance
Lactate acts as a regulator of the adaptor MAVS, allowing a cross-regulation between antiviral signaling and energy metabolism
The interdiffusion of Ni
2+ and Na
+ can form p-doped NiO (i.e.
Na
x
Ni
1
-
2
x
2
+
Ni
x
3
+
O
) and n-doped NaTaO
3 (i.e. Ni
x
Na
1−
x
TaO
3) at the interface and facilitate charge transport for ...splitting water.
Perovskite-like NaTaO
3 photocatalysts, synthesized by sol–gel and solid-state methods, were loaded with NiO co-catalyst to enhance water splitting activity under UV illumination. Activity increased significantly with NiO loading and reached a maximum at 3 and 0.7
wt%, respectively, for the sol–gel and solid-state synthesized NaTaO
3. Beyond this point, photocatalytic activity decreased with further loading. Analysis using X-ray diffraction, high-resolution transmission electron microscopy, and diffuse reflectance spectroscopy shows that the interdiffusion of Na
+ and Ni
2+ cations created a solid–solution transition zone on the outer sphere of NaTaO
3. For NiO contents less than 3
wt%, no NiO clusters appeared on the NaTaO
3 surface, and the reduction/oxidation pretreatment did not enhance photocatalytic activity. The high activity resulting from a low NiO loading suggests that the interdiffusion of cations heavily doped the p-type NiO and n-type NaTaO
3, reducing the depletion widths and facilitating charge transfers through the interface barrier.
The serine/threonine kinase Akt plays a central role in cell proliferation, survival and metabolism, and its hyperactivation is linked to cancer progression. Here we report that Akt undergoes K64 ...methylation by SETDB1, which is crucial for cell membrane recruitment, phosphorylation and activation of Akt following growth factor stimulation. Furthermore, we reveal an adaptor function of histone demethylase JMJD2A, which is important for recognizing Akt K64 methylation and recruits E3 ligase TRAF6 and Skp2-SCF to the Akt complex, independently of its demethylase activity, thereby initiating K63-linked ubiquitination, cell membrane recruitment and activation of Akt. Notably, the cancer-associated Akt mutant E17K displays enhanced K64 methylation, leading to its hyper-phosphorylation and activation. SETDB1-mediated Akt K64 methylation is upregulated and correlated with Akt hyperactivation in non-small-cell lung carcinoma (NSCLC), promotes tumour development and predicts poor outcome. Collectively, these findings reveal complicated layers of Akt activation regulation coordinated by SETDB1-mediated Akt K64 methylation to drive tumorigenesis.
Perovskite-like NaTaO3 photocatalyst powders have generally been synthesized with a solid-state method, which formed the orthorhombic phase that has a direct band gap and a Ta-O-Ta bond angle of ca. ...163 deg . The present work reports a sol-gel synthesis, in which NaTaO3 nanoparticles were obtained at a temperature as low as 500 deg C by using sodium acetate and tantalum chloride as the starting materials and citric acid as the complexing agent. Because of the low-temperature condition used in the synthesis, the sol-gel NaTaO3 was of the monoclinic phase that has an indirect band gap, high densities of states near the band edges, and a Ta-O-Ta bond angle close to 180 deg . Thanks to the surface area as well as the electronic and crystalline structures, the sol-gel NaTaO3 was considered more favorable to photocatalytic reactions than the solid-state material. This interpretation was supported by the finding that the sol-gel NaTaO3 exhibited a remarkably higher photocatalytic activity in water splitting than the solid-state material.
Graphitic carbon nitride (g-C3N4) has been synthesized using a solvothermal method, revealing an excellent photocatalytic degradation activity under visible light illumination.
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...•g-C3N4 is solvothermally prepared with different conditions of the autoclave.•A phase transition of g-C3N4 is observed in the solvothermal synthesis.•Contraction of d100 spacing of g-C3N4 leads to the reduced PL emission.•High photocatalytic activity to degrade methylene orange dye is obtained.
The demand for the development of metal-free, visible-light-active photocatalysts is increasing. This study reports the solvothermal synthesis of carbon nitride (C3N4) photocatalysts by using acetonitrile as a solvent and solvothermal temperatures of 150–220°C. The crystalline structures of the resulting C3N4 samples were obtained following a conversion from a mixed pseudocubic/beta phase to a graphitic phase by increasing the solvothermal temperature and the filling fraction of the autoclave. The interlayer spacing of tri-s-triazine units in the (100) direction within graphitic C3N4 (g-C3N4) was obtained from X-ray diffraction measurements and was observed to decrease because of pressurization, leading to improved interlayer stacking of the tri-s-triazine units and a high degree of overlap between the n states and antibonding π orbitals. The prepared catalysts had band gap energies of 1.5–2.5eV, and the g-C3N4 samples had high photocatalytic activity during the degradation of methyl orange solutions under visible light irradiation. The g-C3N4 samples obtained at high temperatures and filling fractions exhibited lower photoluminescence emission intensities than did the C3N4 specimens with mixed phases (i.e., pseudocubic- and beta-C3N4), suggesting that these active g-C3N4 catalysts with compact planar tri-s-triazine units had efficient charge separation. The present study demonstrated the influence of the experimental conditions used in the synthesis of C3N4 on the subsequent photocatalytic degradation activity of the specimens under visible light irradiation.
Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer ...potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.
Electrochemical deposition of p-type Cu2O films on transparent conducting glass from a Cu2SO4 solution was conducted at different temperatures. The films were examined for H2 evolution from ...photoelectrolysis of water under visible light illumination. Using Pt as the counter electrode, photocurrents with corresponding H2 evolution could be observed for the deposited Cu2O films in a Na2SO4 solution under a cathodic bias. The Cu2O films obtained at different deposition temperatures were in the cubic phase, but showed different out-of-plane crystalline orientations. An incident monochromatic photon-to-current conversion efficiency of 26% at 400nm was achieved for a Cu2O film with a 111 out-of-plane orientation, while an efficiency of only 17% was obtained for a film with a 110 orientation. The 111-oriented film exhibited a higher electronic conductivity, which might have led to a higher charge delocalization rate. By coupling with an n-type WO3 film to promote charge transport, the photocurrent for the Cu2O films was significantly improved.
Different p-type Cu2O powders were prepared from electrodeposition and subjected to analysis of their photocatalytic activity in water reduction. The electrodeposited Cu2O powders were obtained by ...scraping the deposited films off the substrate. Under illumination the Cu2O powders alone were not able to catalyze H2 generation from water reduction. However, these Cu2O powders exhibited photocatalytic activity in H2 generation when they were coupled with n-type WO3 in suspensions. The coupling was made to avoid back reactions of the photo-induced charges. The electrodeposited Cu2O powders showed higher photocatalytic activity than a commercially available Cu2O powder. The suspension containing electrodeposited Cu2O with a strong 1 1 1 orientation gave a larger amount of H2 evolution than that containing Cu2O with a 1 1 0 orientation. Appropriate crystalline-texture tuning, as well as charge delocalization promotion, is looked to as the key issue for efficient H2 generation from water reduction over p-type Cu2O photocatalysts.
We report the synthesis of wurtzite-like gallium oxynitride (GaON) photocatalysts by nitridation of Ga(OH)3 with NH3 at temperatures between 550 and 900 °C. Ga(OH)3 is a more suitable precursor for ...GaON synthesis than Ga2O3, because its crystal lattice contains unoccupied 12-coordinate sites that facilitate ionic transportation during nitridation. The prepared GaON catalysts had band gap energies from 2.2 to 2.8 eV and showed significant activities in the visible-light promoted evolution of H2 and O2 gases from methanol and AgNO3 solutions, respectively. The maximum H2 and O2 evolution rates occurred for catalysts synthesized at 625 and 700 °C, respectively. These active catalysts had an N/O atomic ratio close to unity, suggesting that extensive hybridization of N2p and O2p orbitals promotes charge mobility, and thus enhances photocatalytic activity. This study highlights the interesting possibility of synthesizing a large diversity of visible-light active, III-oxynitride catalysts using this Ga(OH)3 route.
Perovskite‐like NaTaO3 powders have potential applications in photoluminescence and photocatalysis. Sol–gel, hydrothermal and solid‐state methods were used to synthesize NaTaO3 powders of different ...crystalline structures, which were identified by Rietveld refinement simulation of X‐ray diffraction patterns and transmission electron microscopic diffraction. The refinement results show that the sol–gel specimen has a monoclinic phase with a Ta−O−Ta bond angle of 179° while the hydrothermal and solid‐state specimens have an orthorhombic phase with bond angles of 163° and 157°, respectively. By excitation with a 304 nm light source, these NaTaO3 specimens show photoluminescence emission at ca. 450 nm. The photoluminescence intensity of the specimens had an order solid state >hydrothermal >sol–gel, which is opposite to that of the Ta−O−Ta bond angle. On the other hand, the photocatalytic activity of the NaTaO3 specimens in water splitting showed the same order as that of the Ta−O−Ta bond angle. This paper directly evidenced that the Ta−O−Ta bond angle affects the separation rate of the photo‐induced charges, as well as that structure tuning of tantalates is achievable and crucial for applications in photoluminescence and photocatalysis.
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