One-Step Decoration of Subnanometer MoOx Clusters on Bi11VO19 Nanotubes for Visible-Light-Driven Water Oxidation.

For the sluggish reaction kinetics due to a four-electron transfer process, water oxidation is always a major obstacle to solar splitting of water to hydrogen. It remains a tough challenge to develop efficient nonnoble-metal photocatalysts for water oxidation. Herein, we decorate the host photocatalyst of Bi11VO19 nanotubes with the coatalyst of subnanometer MoOx clusters (denoted as Bi11VO19/MoOx hetero-nanotubes) via a one-step cation-exchange solvothermal reaction using Na2V6O16 nanowires as the hard template. It is observed that the morphology and microstructure of Bi11VO19/MoOx hetero-nanotubes vary with the dosage of Mo source and polyvinylpyrrolidone, as well as with the solvent composition. The optimized Bi11VO19/MoOx hetero-nanotubes significantly enhance the photooxidation of water to oxygen with visible light, delivering an oxygen production rate of 790 µmol g-1 h-1, which is 12 times that of bare Bi11VO19 nanotubes. In situ X-ray photoelectron spectroscopy and (photo)electrochemical characterization suggest that the enhanced photoactivity may be caused by the decorated cocatalyst of MoOx clusters, which extracts electrons from Bi11VO19 nanotubes, leaving an abundance of holes for water photooxidation. This work demonstrates a potential strategy to develop photocatalysts for energy conversion by constructing Bi11VO19-based nanostructures.

Dual-defect semiconductor photocatalysts for solar-to-chemical conversion: advances and challenges.

Among the renewable energy technologies to deal with increasing energy crisis and environmental concerns, solar-to-chemical conversion via photocatalysis holds great promise for sustainable energy supply. To date, a variety of modification strategies with different types of semiconducting materials have been proposed to boost photocatalytic efficiency. Recently, dual-defect semiconductor photocatalysts have emerged as an advantageous candidate with superior performance in improving photocatalytic activity compared to their defect-free or single-defect counterparts. In this review, focus is laid on the advances of dual-defect semiconductor photocatalysts for energy photocatalysis. Possible schemes for two different defects within a single semiconductor are firstly sorted based on the types of defects, and synthesis strategies to achieve various defect schemes as well as techniques to characterize different defects are then introduced. In particular, the effect of different defects on photocatalytic performance is emphasized, and the advances in dual-defect semiconductors for solar-to-chemical conversions are summarized based on different defect schemes. Finally, the future challenges and opportunities of dual-defect semiconductors for photocatalysis are discussed. This article is expected to provide an overall insight into existing dual-defect semiconductor photocatalysts and inspire the development of new defect-rich materials for photocatalytic energy production.

Performance of a non-irrigated bipolar radiofrequency ablation clamp on beating human hearts.

OBJECTIVE: This study is intended to examine the efficacy of a non-irrigated bipolar RF clamp and explore the factors that can influence its performance on beating human hearts using the electrophysiology mapping method. METHODS: A total of 83 atrial fibrillation (AF) patients were included in this study. Based on the Body mass index (BMI, kg/m2), the AF patients were divided into the normal group (18.5 ≤ BMI < 25) and the overweight or obese group (BMI ≥ 25). They all underwent a stand-alone surgical ablation through our off-pump biatrial mini-maze procedure. After we completed each time of ablation, the achievement of PV isolation was checked using the electrophysiology mapping method. The number of ablation times to achieve the PV isolation on the left and right PVs was recorded respectively. RESULTS: 86.7% (72/83) PV isolation on the LPV and 72.3% (60/83) PV isolation on the RPV could be achieved respectively after performing a single time of surgical ablation. Three times of ablations resulted in 100.0% PV isolation on the left and right PVs. In the normal BMI group, the ratio of patients who achieved a complete PV isolation after a single time of ablation was 83.7% (36/43), which was higher than the 60.0% (24/40) in the overweight or obese group. CONCLUSIONS: Performing three times of ablations resulted in 100% PV isolation on the left and right PVs. The bipolar RF clamp had a better performance on the LPV than on the RPV. The patients' BMI also influenced the Atricure clamp' s performance.

Identification and verification of FN1, P4HA1 and CREBBP as potential biomarkers in human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that can lead to cardiac complications. The mechanisms involved in AF remain elusive. We aimed to explore the potential biomarkers and mechanisms underpinning AF. METHODS: An independent dataset, GSE2240, was obtained from the Gene Expression Omnibus database. The R package, "limma", was used to screen for differentially expressed genes (DEGs) in individuals with AF and normal sinus rhythm (SR). Weighted gene co-expression network analysis (WGCNA) was applied to cluster DEGs into different modules based on functional disparities. Enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed, and hub genes were identified using cytoHubba. Quantitative reverse-transcription PCR was used to validate mRNA expression in individuals with AF and SR. RESULTS: We identified 2, 589 DEGs clustered into 10 modules using WGCNA. Gene Ontology analysis showed specific clustered genes significantly enriched in pathways associated with the extracellular matrix and collagen organization. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched for proteoglycans in cancer, extracellular matrix-receptor interaction, focal adhesion, and the PI3K-Akt signaling pathway. Three hub genes, FN1, P4HA1 and CREBBP, were identified, which were highly correlated with AF endogenesis. mRNA expression of hub genes in patients with AF were higher than in individuals with normal SR, consistent with the results of bioinformatics analysis. CONCLUSIONS: FN1, P4HA1, and CREBBP may play critical roles in AF. Using bioinformatics, we found that expression of these genes was significantly elevated in patients with AF than in individuals with normal SR. Furthermore, these genes were elevated at core positions in the mRNA interaction network. These genes should be further explored as novel biomarkers and target candidates for AF therapy.

One-pot solvothermal synthesis of In-doped amino-functionalized UiO-66 Zr-MOFs with enhanced ligand-to-metal charge transfer for efficient visible-light-driven CO2 reduction.

Metal organic frameworks (MOFs) with high porosity and highly tunable physical/chemical properties can serve as heterogeneous catalysts for CO2 photoreduction, but the application is hindered by the large band gap (Eg) and insufficient ligand-to-metal charge transfer (LMCT). In this study, a simple one-pot solvothermal strategy is proposed to prepare an amino-functionalized MOF (aU(Zr/In)) featuring an amino-functionalizing ligand linker and In-doped Zr-oxo clusters, which enables efficient CO2 reduction driven with visible light. The amino functionalization leads to a significant reduction of Eg as well as a charge redistribution of the framework, allowing the absorption of visible light and the efficient separation of photogenerated carriers. Furthermore, the incorporation of In not only promotes the LMCT process by creating oxygen vacancies in Zr-oxo clusters, but also greatly lowers the energy barrier of the intermediates for CO2-to-CO conversion. With the synergistic effects of the amino groups and the In dopants, the optimized aU(Zr/In) exhibits a CO production rate of 37.58 ± 1.06 µmol g-1 h-1, outperforming the isostructural University of Oslo-66- and Material of Institute Lavoisier-125-based photocatalysts. Our work demonstrates the potential of modifying MOFs with ligands and heteroatom dopants in metal-oxo clusters for solar energy conversion.

Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients.

Background: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known. Objective: This study was aimed to explore the mitochondrial metabolism reprogrammed in AF patients by integrating metabolomics as well as proteomics of human atrium tissues. Methods and Results: Left atrial tissue samples were harvested from 10 non-valvular AF patients and 10 matched samples from healthy donors for transplantation. In metabolomics analysis, 113 metabolites were upregulated and 10 metabolites were downregulated in AF, where multiple pathways related to mitochondrial energy metabolism were enriched. Correlation analysis between the differentially expressed proteins and metabolites identified several hub proteins related to mitochondrial function including Glycerol-3-phosphate dehydrogenase 2 (GPD2), Synemin (SYNM), Plectin (PLEC), with MCC score of 27, 17, 16, respectively, which have the most interactions with the dysregulated metabolites and ranked at the top in network string interactions scored by MCC method. All 330 differentially expressed proteins including 225 upregulated and 105 downregulated molecules were revealed and analyzed, which identified the downregulation of GPD2 (p = 0.02 and FC = 0.77), PLEC (p < 0.001 and FC = 0.71) and SYNM (p = 0.04 and FC = 0.76) in AF patients. Gene Set Variation Analysis (GSEA) showed mitochondrial metabolism-associated pathways including oxidative phosphorylation (NES: -1.73) and ATP biosynthetic process (NES: -2.29), were dramatically diversified in human AF. In GSVA, the expression levels of GPD2, PLEC, and SYNM were demonstrated to be associated with multiple metabolic pathways related to mitochondrial function (e.g., lipid metabolism and AMP activated protein kinase signaling) and cardiac structural and electrical remodeling (e.g., contractile fiber, ion homeostasis), which were proven vital in the development and maintenance of AF. Conclusion: In all, this study provides new insights into understanding the mechanisms of AF progression, especially the reprogramming mitochondrial metabolism, and identifies several genes related to mitochondrial function as novel targets for AF, which may be involved in the occurrence and development of AF.

Burden, Trends, and Inequalities of Heart Failure Globally, 1990 to 2019: A Secondary Analysis Based on the Global Burden of Disease 2019 Study.

Background Heart failure is a public health issue worldwide. However, no comprehensive study on the global burden of heart failure and its contributing causes has been reported. The present study aimed to quantify the burden, trends, and inequalities of heart failure globally. Methods and Results Heart failure data were extracted from the Global Burden of Diseases 2019 study. The number of cases, age-standardized prevalence, and years lived with disability in different locations from 1990 to 2019 were presented and compared. Joinpoint regression analysis was performed to assess trends in heart failure from 1990 to 2019. In 2019, the global age-standardized prevalence and years lived with disability rates for heart failure were 711.90 (95% uncertainty interval [UI], 591.15-858.29) and 63.92 (95% UI, 41.49-91.95) per 100 000 population, respectively. In general, the age-standardized rate decreased globally at an average annual percentage change of 0.3% (95% UI, 0.2-0.3). However, the rate increased at an average annual percentage change of 0.6% (95% UI, 0.4-0.8) from 2017 to 2019. Several nations and territories demonstrated an increased trend from 1990 to 2019, especially in less-developed countries. Ischemic heart disease and hypertensive heart disease accounted for the highest proportion of heart failure in 2019. Conclusions Heart failure remains a major health problem, with increased trends possible in the future. Efforts for prevention and control of heart failure should focus more on less-developed regions. It is essential to prevent and treat primary diseases such as ischemic heart disease and hypertensive heart disease for the control of heart failure.

One-pot solvothermal synthesis of flower-like Fe-doped In2S3/Fe3S4 S-scheme hetero-microspheres with enhanced interfacial electric field and boosted visible-light-driven CO2 reduction.

S-scheme heterojunctions hold great potential for CO2 photoreduction into solar fuels, but their activities are severely limited by the low efficiency of interfacial charge transfer. In this work, a facile one-pot solvothermal reaction has been developed to dope Fe into flower-like In2S3/Fe3S4 hetero-microspheres (Fe-In2S3/Fe3S4 HMSs), which are demonstrated as an efficient S-scheme photocatalyst for visible-light-driven CO2 photoreduction. The doping of Fe not only reduces the bandgap of In2S3 and thus extends the optical response to the visible-light region, but also increases the densities of donors and sulfur vacancies, which leads to an elevated Fermi level (Ef). The difference of Ef between In2S3 and Fe3S4 is enlarged and their band bending at the interface is therefore enhanced, which results in promoted carriers transfer in the S-scheme pathway due to the reinforced interfacial electric field. Moreover, Fe-doped In2S3 reduces the formation energy of the *CO intermediate, which thermodynamically favors the CO evolution at the surface. As a result, the Fe-In2S3/Fe3S4 HMSs exhibit a significantly boosted CO2 photoreduction activity in comparison with bare In2S3 and Fe-In2S3 samples. This work demonstrates the great potential of heteroatom-engineered S-scheme photocatalysts for CO2 photoreduction.

Comprehensive analysis of roles of atrial-fibrillation-related genes in lung adenocarcinoma using bioinformatic methods.

Atrial fibrillation (AF) is the most common tachyarrhythmia in the world. Lung cancer is the leading cause of cancer deaths in 93 countries. Previous studies demonstrated that the prevalence of AF was higher in patients with lung cancer. However, research on the associations between AF and lung cancer is still rare. In the present study, we first identified AF-related genes using weighted gene correlation network analysis. We then analyzed the expression profiles, prognosis, immune infiltration, and methylation characteristics of these genes in LUAD patients using bioinformatics analysis. We found several AF-related genes, including CBX3, BUB1, DSC2, P4HA1, and CYP4Z1, which differently expressed between tumor and normal tissues. Survival analysis demonstrated that CYP4Z1 was positively correlated with overall survival in LUAD patients, while CBX3, BUB1, DSC2, and P4HA1 were negatively correlated. Moreover, we found that the methylation level of DSC2 in normal lung tissues was significantly higher than that in tumor tissues, and six methylation sites in the DNA sequences of DSC2 were identified negatively correlated with its expression levels. Immune infiltration analysis suggested that levels of immune cell infiltration were related to gene expression levels in varying degrees. We identified AF-related genes and found these genes were correlated with prognosis, immune infiltration, and methylation levels in lung cancer patients. We also constructed a risk signature based on these genes in LUAD patients. We hoped that the current study could provide a novel insight into roles of AF-related genes in lung cancer patients.

Hypoxia Enhances Glioma Resistance to Sulfasalazine-Induced Ferroptosis by Upregulating SLC7A11 via PI3K/AKT/HIF-1α Axis.

Glioma is the most common primary brain tumor, with a high rate of recurrence and treatment resistance. Glioblastoma is highly invasive, infiltrating surrounding brain parenchyma, and is known to cause intracranial metastasis resulting in a dismal prognosis. Hypoxia contributes significantly to chemo- and radiotherapy resistance in cancer. Ferroptosis is a nonapoptotic oxidative cell death that has been identified as a potential anticancer mechanism. Sulfasalazine (SAS) activates ferroptosis and plays a potential role in tumor treatment. However, the relationship between hypoxia and SAS resistance has not been elucidated. This study is aimed at investigating the role of hypoxia in SAS-induced ferroptosis and the underlying mechanisms. Here, we found that hypoxia significantly suppressed SAS-induced ferroptosis by upregulating SLC7A11 expression in the U87 and U251 glioma cell lines. Hypoxia promotes SLC7A11 expression by enhancing the PI3K/AKT/HIF-1α pathway. The AKT inhibitor MK-2206 and HIF-1α inhibitor PX-478 significantly reversed this effect. In addition, under normoxia, PX-478 induced a higher lipid peroxidation level by decreasing SLC7A11 expression in the U87 and U251 cells but could not induce cell death directly; it could significantly enhance the tumor cell killing effect of SAS. In vivo, the combination of PX-478 and SAS had a coordinated synergistic effect on anticancer activity, as revealed by subcutaneous and orthotopic xenograft mouse models. In conclusion, hypoxia enhanced glioma resistance to SAS-induced ferroptosis by upregulating SLC7A11 via activating the PI3K/AKT/HIF-1α axis. Combination therapy with PX-478 and SAS may be a potential strategy against glioma.

An off-pump biatrial mini-maze procedure for long-standing persistent atrial fibrillation.

OBJECTIVES: The goal of the present study was to determine the safety and efficacy of a modified off-pump biatrial mini-maze procedure to treat long-standing persistent atrial fibrillation (AF). METHODS: Patients with long-standing persistent AF underwent our modified mini-maze procedure using bipolar radiofrequency ablation. Those patients first underwent a mini-maze procedure using the Dallas lesion set protocol. Second, a purse-string suture was performed on the right atrium, and then 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point by the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12 months and every year thereafter. RESULTS: A total of 102 patients were included in the study. There were no deaths, no surgical re-exploration for bleeding and no permanent pacemaker implants. The intraoperative cardioversion rate was 42.2% (43/102). A follow-up at intervals of 3, 6, 12, 24, 36 and 48 months showed that a success rate free from long-standing persistent AF was 95.1% (97/102), 94.4% (85/90), 94.8% (73/77), 91.5% (54/59), 90.3% (28/31) and 86.4% (19/22), whereas freedom from AF in patients off antiarrhythmic drugs was 88.2% (90/102), 85.6% (77/90), 81.8% (63/77), 78.0% (46/59), 74.2% (23/31) and 68.2% (15/22), respectively. CONCLUSIONS: The modified biatrial mini-maze procedure proved to be safe and feasible. Early follow-up demonstrated an acceptable success rate free from AF.

Hypothermia-Triggered Mesoporous Silica Particles for Controlled Release of Hydrogen Sulfide to Reduce the I/R Injury of the Myocardium.

Despite the fact that heart transplantation (HTx) is a relatively mature procedure, heart ischemic and reperfusion (I/R) injury during HTx remains a challenge. Even after a successful operation, the heart will be at risk of primary graft failure and mortality during the first year. In this study, temperature-sensitive polymer poly(N-n-propylacrylamide-co-N-tert-butyl acrylamide) (PNNTBA) was coated on diallyl trisulfide (DATS)-loaded mesoporous silica nanoparticles (DATS-MSN) to synthesize hypothermia-triggered hydrogen sulfide (H2S) releasing particles (HT-MSN). Because the PNNTBA shell dissolves in phosphate-buffered saline at 4 °C, the loaded DATS could continuously release H2S within 6 h when activated by glutathione (GSH). Furthermore, after co-culturing biocompatible HT-MSN with cardiomyocytes, H2S released from HT-MSN at 4 °C was found to protect cardiomyocytes from ischemic and reperfusion (I/R) injury. In detail, the rate of cell apoptosis and lactate dehydrogenase activity was decreased, as manifested by increased BCL-2 expression and decreased BAX expression. More importantly, in an isolated heart preservation experiment, HT-MSN demonstrated potent protection against cardiac I/R injury and reduced expression of inflammatory factors TNF-α and IL-1ß. This study provided a new method for the controlled release of H2S by the donor and myocardial protection from I/R injury.

Perspective on Defective Semiconductor Heterojunctions for CO2 Photoreduction.

Photocatalytic CO2 reduction to value-added chemicals is a green solution to concurrently address CO2 emission and energy issues, and semiconductor heterojunctions hold great potential to achieve such conversion. However, the photocatalytic performance of the existing heterojunctions is limited by the low interfacial charge transfer efficiency and sluggish surface reaction kinetics. To overcome these obstacles, defect engineering has been applied to heterojunctions to boost CO2 photoreduction in the past 5 years. This perspective summaries the key roles and the related mechanism of various anion vacancies located at the surface, interface, and both surface and interface of heterojunctions in photocatalytic CO2 reduction. Challenges in constructing and characterizating defective heterojunctions as well as in promoting their CO2 photoreduction activity and hydrocarbon selectivity are then outlined. Finally, some solutions to the rational design of defective heterojunctions for efficient and stable CO2 photoreduction are also proposed.

Preparation of AIE Functional Single-Chain Polymer Nanoparticles and Their Application in H2 O2 Detection through Intermolecular Heavy-Atom Effect.

Single-chain polymer nanoparticles (SCNPs) are soft matter constructed by intrachain crosslinks, with promising prospects in detection and catalysis. Herein, a fluorescent core (SCNPs) with aggregation-induced emission (AIE) is prepared, applying for H2 O2 detection through intermolecular heavy-atom effect. In detail, the SCNPs precursors are synthesized by ring-opening copolymerization. Then the SCNPs are prepared by intramolecularly cross-linking via olefin metathesis. Imitating the structure of AIE dots, SCNPs are encapsulated by H2 O2 -responsive polymers. Probably due to the stable secondary structure of SCNPs, the obtained micelles show stable fluorescence performance. Furthermore, as the heavy-atom, tellurium is introduced into the carriers to construct the heavy-atom effect. In this micelle-based system, the SCNPs act as the fluorescent core, and the stimuli-responsive polymer acts as the carrier and the fluorescent switch. The hydrophilicity of the tellurium-containing segment is affected by the concentration of H2 O2 , resulting in a change in the distance from the SCNPs, which ultimately leads to a change in the fluorescence intensity. Furthermore, tellurium is particularly sensitive to H2 O2 , which can detect low concentrations of H2 O2 . The SCNPs are merged with AIE materials, with the hope of exploring new probe designs.

Coronary Artery Disease and Atrial Fibrillation: A Bidirectional Mendelian Randomization Study.

Background: Several works of observational clinical research indicate that coronary artery disease (CAD) and atrial fibrillation (AF) aggravate each other. However, it is unknown whether these associations reveal independent causal processes. Objective: The present study aimed to evaluate causal associations between CAD and AF using two-sample Mendelian randomization (TSMR) analysis. Methods: Summary-level Genome-wide association study (GWAS) data for CAD were obtained from the CARDIoGRAMplusC4D consortium, including 60,801 patients and 123,504 controls. General data for AF were acquired from the largest meta-analysis, comprising of 60,620 patients with AF and 970,216 non-cases. After data harmonization, three different methods­inverse-variance weighted (IVW), MR-Egger, and weighted-median­were applied for TSMR analysis. Results: The calculated ORs (95% CIs) for AF using IVW, MR-Egger, and weighted-median analysis were 1.11 (1.05, 1.17; p-value < 0.001), 1.14 (1.00, 1.29; p-value = 0.049), and 1.13 (1.08, 1.19; p-value < 0.001), respectively; for CAD, the results were 1.01 (0.97, 1.04; p-value = 0.76), 0.95 (0.89, 1.02; p-value = 0.15), and 1.00 (0.95, 1.05; p-value = 0.97). Conclusion: This comprehensive TSMR analysis provides evidence that patients with CAD are associated with an increased risk of AF. However, no causal association was found between patients with AF and the risk of CAD. These findings benefit clinical decision-making. Early heart-rhythm monitoring should be performed in patients with CAD. The prevention and treatment of AF complications such as thrombosis may be essential to reduce the incidence of CAD in AF patients.

Dissecting the Association of Genetically Predicted Neuroticism with Coronary Artery Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Observational studies on the association between neuroticism and coronary artery disease (CAD) are still rare, and the results of existing studies are not consistent. The present study aimed to explore causal associations of neuroticism with CAD. METHODS: The summary-level data of GWAS for neuroticism and 12 items used to assess neuroticism were extracted from the UK Biobank, and included up to 380,506 participants. The general data for CAD were obtained from the CARDIoGRAMplusC4D consortium, which assembled 60,801 CAD patients and 123,504 non-cases. Single-nucleotide polymorphisms associated with neuroticism and 12 items at genome-wide significance were explored as instrumental variables. Two-sample Mendelian randomization (TSMR) analyses were performed to evaluate causal associations amongst the genetically predicted neuroticism and 12 items with CAD. RESULTS: The present TSMR study did not reveal the genetic association of neuroticism with CAD. The calculated ORs for CAD using inverse-variance weighted, weighted median, and MR-Egger analysis were 1.12 (p-value = 0.187), 0.99 (p-value = 0.943), and 0.82 (p-value = 0.683), respectively. Further TSMR analysis of 12 dichotomous items for assessing neuroticism suggested that mood swings genetically increased the risk of CAD (OR = 1.67, p-value < 0.001). CONCLUSIONS: This study reported no genetically causal association of neuroticism with CAD. The present study also found that mood swings may genetically increase the risk of CAD. These findings may highlight the potential of mood control as a preventive measure for CAD.

RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m6A-dependent manner.

Ferroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout of NF-κB activating protein (NKAP), an RNA-binding protein, increased lipid peroxidation level in naive T cells and induced cell death in colon cancer cells. However, there was no literature reported the relationship between NKAP and ferroptosis in glioblastoma cells. Notably, the mechanism of NKAP modulating ferroptosis is still unknown. Here, we found NKAP knockdown induced cell death in glioblastoma cells. Silencing NKAP increased the cell sensitivity to ferroptosis inducers both in vitro and in vivo. Exogenous overexpression of NKAP promoted cell resistance to ferroptosis inducers by positively regulating a ferroptosis defense protein, namely cystine/glutamate antiporter (SLC7A11). The regulation of SLC7A11 by NKAP can be weakened by the m6A methylation inhibitor cycloleucine and knockdown of the m6A writer METTL3. NKAP combined the "RGAC" motif which was exactly in line with the m6A motif "RGACH" (R = A/G, H = A/U/C) uncovered by the m6A-sequence. RNA Immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) proved the interaction between NKAP and m6A on SLC7A11 transcript. Following its binding to m6A, NKAP recruited the splicing factor proline and glutamine-rich (SFPQ) to recognize the splice site and then conducted transcription termination site (TTS) splicing event on SLC7A11 transcript and the retention of the last exon, screened by RNA-sequence and Mass Spectrometry (MS). In conclusion, NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting SLC7A11 mRNA splicing and maturation.

In-situ photodeposition of cadmium sulfide nanocrystals on manganese dioxidenanorods with rich oxygen vacancies for boosting water-to-oxygen photooxidation.

Carrier separation and surface reaction kinetic are two main bottlenecks limiting photocatalytic efficiency of photocatalysts towards an industrial level. In this regard, heterostructures and defects engineering have been proven to be effective strategies for addressing the two issues. However, the integrated construction of heterostructures and defects has been reported rarely. Herein, a facile in-situ photodeposition strategy has been developed to grow CdS nanocrystals on MnO2-x nanorods with rich oxygen vacancies (VO) as a direct Z-scheme photocatalyst for boosting water oxidation. It has been found that the Cd2+ ions accept photoelectrons from MnO2-xunder irradiation for the in-situ growth of CdS nanocrystals, which enables a close contact between the two components, providing high-speed electron-transport channels for photocatalysis. Meanwhile, the photooxidation half reactions extract surface lattice oxygen, leading to the increase of VO content in MnO2-x, which supplies abundant active sites for oxygen evolution. Owing to the synergistic effects of VO and Z-scheme systems, the optimized MnO2-x/CdS photocatalyst displays a dramatically enhanced photocatalytic activity with an O2 production rate of 779 µmol g-1h-1 under visible-light irradiation without any cocatalysts, which is 2.33 times higher than the bare MnO2-x. This work reveals the cooperative manipulation of VO and CdS nanocrystals on MnO2-x for achieving efficient photocatalysis, providing new insights into the construction of high-performance photocatalysts via a combined strategy of Z-scheme heterostructures and surface defects.

NOX4-derived ROS-induced overexpression of FOXM1 regulates aerobic glycolysis in glioblastoma.

BACKGROUND: Increased expression of the transcription factor Forkhead box M1 (FOXM1) has been reported to play an important role in the progression and development of multiple tumors, but the molecular mechanisms that regulate FOXM1 expression remain unknown, and the role of FOXM1 in aerobic glycolysis is still not clear. METHODS: The expression of FOXM1 and NADPH oxidase 4 (NOX4) in normal brain tissues and glioma was detected in data from the TCGA database and in our specimens. The effect of NOX4 on the expression of FOXM1 was determined by Western blot, qPCR, reactive oxygen species (ROS) production assays, and luciferase assays. The functions of NOX4 and FOXM1 in aerobic glycolysis in glioblastoma cells were determined by a series of experiments, such as Western blot, extracellular acidification rate (ECAR), lactate production, and intracellular ATP level assays. A xenograft mouse model was established to test our findings in vivo. RESULTS: The expression of FOXM1 and NOX4 was increased in glioma specimens compared with normal brain tissues and correlated with poor clinical outcomes. Aberrant mitochondrial reactive oxygen species (ROS) generation of NOX4 induced FOXM1 expression. Mechanistic studies demonstrated that NOX4-derived MitoROS exert their regulatory role on FOXM1 by mediating hypoxia-inducible factor 1α (HIF-1α) stabilization. Further research showed that NOX4-derived MitoROS-induced HIF-1α directly activates the transcription of FOXM1 and results in increased FOXM1 expression. Overexpression of NOX4 or FOXM1 promoted aerobic glycolysis, whereas knockdown of NOX4 or FOXM1 significantly suppressed aerobic glycolysis, in glioblastoma cells. NOX4-induced aerobic glycolysis was dependent on elevated FOXM1 expression, as FOXM1 knockdown abolished NOX4-induced aerobic glycolysis in glioblastoma cells both in vitro and in vivo. CONCLUSION: Increased expression of FOXM1 induced by NOX4-derived MitoROS plays a pivotal role in aerobic glycolysis, and our findings suggest that inhibition of NOX4-FOXM1 signaling may present a potential therapeutic target for glioblastoma treatment.

Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes.

BACKGROUND: The AMP-activated protein kinase alpha (AMPKα) pathway has widely been considered a key factor in energy metabolism. Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate (TMPA) is a novel AMPK agonist, which influences the stability of Nuclear Receptor Subfamily 4, Group A, Member 1 (Nur77)-serine-threonine kinase 11 (LKB1) in the nucleus. A recent study has determined that TMPA can ameliorate the reduction of insulin resistance in type II db/db mice. However, the role of TMPA in hepatocyte lipid metabolism has not been elucidated. OBJECTIVE: To investigate whether TMPA could ameliorate liver lipid accumulation under the stimulation of free fatty acids (FFAs) in vitro. METHODS: We evaluated differences of Nur77 and AMPK pathway in mice fed a high-fat diet and those fed a normal diet. In vitro, TMPA was added to HepG2 cells and primary hepatocytes before FFAs stimulation. Oil red O staining, Nile red staining were used to evaluate lipid deposition. Western blot and immunofluorescence were used to quantify related proteins. RESULTS: Nur77, AMPKα, LKB1, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), acetyl-CoA carboxylase phosphorylation (p-ACC), and carnitine palmitoyltransferase 1 (CPT1A) showed significant differences in vivo. Under the intervention of TMPA, HepG2 cells and primary hepatocytes showed considerable amelioration of lipid deposition and improved the expression of phosphorylated (p)-AMPKα (p-AMPKα), p-LKB1, p-ACC, and CPT1A. Furthermore, Western blotting and immunofluorescence studies indicated that LKB1 dramatically increased expression in the cytoplasm but decreased in the nucleus. Further, AMPKα phosphorylation (p-AMPKα) also showed a higher expression in cytoplasm instead of the nucleus. CONCLUSION: TMPA ameliorated lipid accumulation by influencing the stability of Nur77-LKB1 in vitro.