Risk analysis of the association between different hemoglobin glycation index and poor prognosis in critical patients with coronary heart disease-A study based on the MIMIC-IV database.

BACKGROUND: The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database. METHODS: The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A Kaplan‒Meier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group. RESULTS: A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable. CONCLUSION: There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.

Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis.

BACKGROUND: In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. METHODS: Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed. RESULTS: A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876-0.919), and 0.896 (95% CI: 0.866-0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups. CONCLUSION: The prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.

Transient Dynamic Operation of G-Quadruplex-Gated Glucose Oxidase-Loaded ZIF-90 Metal-Organic Framework Nanoparticle Bioreactors.

Glucose oxidase-loaded ZIF-90 metal-organic framework nanoparticles conjugated to hemin-G-quadruplexes act as functional bioreactor hybrids operating transient dissipative biocatalytic cascaded transformations consisting of the glucose-driven H2O2-mediated oxidation of Amplex-Red to resorufin or the glucose-driven generation of chemiluminescence by the H2O2-mediated oxidation of luminol. One system involves the fueled activation of a reaction module leading to the temporal formation and depletion of the bioreactor conjugate operating the nickase-guided transient biocatalytic cascades. The second system demonstrates the fueled activation of a reaction module yielding a bioreactor conjugate operating the exonuclease III-dictated transient operation of the two biocatalytic cascades. The temporal operations of the bioreactor circuits are accompanied by kinetic models and computational simulations enabling us to predict the dynamic behavior of the systems subjected to different auxiliary conditions.

Effects of yak rumen anaerobic fungus Orpinomyces sp. YF3 fermented on in vitro wheat straw fermentation and microbial communities in dairy goat rumen fluid, with and without fungal flora.

Rumen fungi play an essential role in the breakdown of dietary fibrous components, facilitating the provision of nutrients and energy to the host animals. This study investigated the fermentation characteristics and effects on rumen microbiota of yak rumen anaerobic fungus Orpinomyces sp. YF3 in goat rumen fluid, both with and without fungal flora, utilizing anaerobic fermentation bottles. Crushed and air-dried wheat straw served as the fermentation substrate, and cycloheximide was used to eradicate microorganisms from the rumen fluid of dairy goats. The experiment compromised four treatment groups (2×2 factorial design): control (C); yak fungus group (CF, Orpinomyces sp. YF3); goat fungi eliminated group (CA, antibiotic: 0.25 mg/mL cycloheximide); goat fungi eliminated+yak fungus group (CAF). Each treatment had six replicates. Fermentation characteristics and microbial composition of the fermentation media were analyzed using one-way analysis of variance and high-throughput sequencing technology. The findings revealed that in the Orpinomyces sp. YF3 addition group (CF and CAF groups), there were significant increases in ammonia nitrogen concentration by 70%, total volatile fatty acids (VFA) by 53%, as well as acetate, isobutyrate, and valerate concentrations, and the ratio of acetate to propionate (p < 0.05), while the propionate proportion declined by 13%, alongside a reduction of butyrate concentration (p < 0.05). Similarly, in the CF and CAF groups, there were a notable increase in the relative abundance of Bacteroidota, Synergistota, Desulfobacterota, Actinobacteria, and Fusobacteriota, alongside a decrease in the relative abundance of Fibrobacterota and Proteobacteria (p < 0.05). Bacteria exhibiting increased relative abundance were positively correlated with the activity of carboxymethyl cellulase and avicelase, total VFA concentration, and acetate proportion, while showing a negatively correlation with propionate proportion. In conclusion, supplementing rumen fermentation media with yak rumen anaerobic fungus Orpinomyces sp. YF3 led to an increase in bacteria associated with fibre degradation and acetic acid production, a decrease in propionate-producing bacteria, enhanced the activity of plant cell wall degrading enzymes, and promoted cellulose degradation, ultimately elevating total VAF concentration and acetate proportion. This presents a novel approach to enhance roughage utilization in ruminants.

Spatial-temporal evolution characteristics of PM2.5 and its driving mechanism: spatially explicit insights from Shanxi Province, China.

In China, despite the fact that the atmospheric environment quality has continued to improve in recent years, the PM2.5 pollution still had not been controlled fundamentally and its driving mechanism was complex which remained to be explored. Based on the 1-km ground-level PM2.5 datasets of China from 2000 to 2020, this study combined spatial autocorrelation, trend analysis, geographical detector, and multi-scale geographically weighted regression (MGWR) model to explore the spatial-temporal evolution of PM2.5 in Shanxi Province and revealed its complex driving mechanism behind this process. The results reflected that (1) there was a pronounced spatial clustering of PM2.5 concentration within Shanxi Province, with PM2.5 concentrations decreasing from southwest to northeast. From 2000 to 2020, the levels of PM2.5 pollution demonstrated a decline over time, with its concentrations decreasing by 9.15 µg/m3 overall. The Hurst exponent indicated a projected decrease in PM2.5 concentrations in the central and northern areas of Shanxi Province, contrasting with an anticipated increase in other regions. (2) The geographical detector indicated that all drivers had significant influences on PM2.5 concentrations, with meteorological factors exerting the greatest effects then followed by human activity and vegetation cover showing the least effects. (3) Both gross domestic product and population density exhibited positive correlations with PM2.5 concentration, while vegetation fractional cover, wind speed, precipitation, and elevation exerted negative influences on PM2.5 concentration all over the space. This study enriched the research content and ideas on the driving mechanism of PM2.5 and provided a reference for similar studies.

Regulating Reactive Oxygen Intermediates of Fe-N-C SAzyme via Second-Shell Coordination for Selective Aerobic Oxidation Reactions.

Reactive oxygen species (ROS) regulation for single-atom nanozymes (SAzymes), e.g., Fe-N-C, is a key scientific issue that determines the activity, selectivity, and stability of aerobic reaction. However, the poor understanding of ROS formation mechanism on SAzymes greatly hampers their wider deployment. Herein, inspired by cytochromes P450 affording bound ROS intermediates in O2 activation, we report Fe-N-C containing the same FeN4 but with tunable second-shell coordination can effectively regulate ROS production pathways. Remarkably, compared to the control Fe-N-C sample, the second-shell sulfur functionalized Fe-N-C delivered a·2.4-fold increase of oxidase-like activity via the bound Fe=O intermediate. Conversely, free ROS (•O2-) release was significantly reduced after functionalization, down to only 17% of that observed for Fe-N-C. The detailed characterizations and theoretical calculations revealed that the second-shell sulfur functionalization significantly altered the electronic structure of FeN4 sites, leading to an increase of electron density at Fermi level. It enhanced the electron transfer from active sites to the key intermediate *OOH, thereby ultimately determining the type of ROS in aerobic oxidation process. The proposed Fe-N-Cs with different second-shell anion were further applied to three aerobic oxidation reactions with enhanced activity, selectivity, and stability.

Identification of Hub Genes Correlated with the Initiation and Development in Chronic Kidney Disease via Bioinformatics Analysis.

INTRODUCTION: Chronic kidney disease (CKD) is a major public health issue worldwide, which is characterized by irreversible loss of nephron and renal function. However, the molecular mechanism of CKD remains underexplored. METHODS: This study integrated three transcriptional profile datasets to investigate the molecular mechanism of CKD. The differentially expressed genes (DEGs) between Sham control (Con) and unilateral ureteral obstruction (UUO)-operated mice were analyzed by utilizing the limma package in R. The shared DEGs were analyzed by Gene Ontology and functional enrichment. Protein-protein interactions (PPIs) were constructed by utilizing the STRING database. Hub genes were analyzed by MCODE and Cytohubba. We further validated the gene expression by using the other dataset and mouse UUO model. RESULTS: A total of 315 shared DEGs between Con and UUO samples were identified. Gene function and KEGG pathway enrichment revealed that DEGs were mainly enriched in inflammatory response, immune system process, and chemokine signaling pathway. Two modules were clustered based on PPI network analysis. Module 1 contained 13 genes related to macrophage activation, migration, and chemotaxis. Ten hub genes were identified by PPI network analysis. Subsequently, the expression levels of hub genes were validated with the other dataset. Finally, these four validated hub genes were further confirmed by our UUO mice. Three validated hub genes, Gng2, Pf4, and Ccl9, showed significant response to UUO. CONCLUSION: Our study reveals the coordination of genes during UUO and provides a promising gene panel for CKD treatment. GNG2 and PF4 were identified as potential targets for developing CKD drugs.

Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients.

OBJECTIVES: Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis. METHODS: 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated. RESULTS: The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p < 0.05, respectively), and more changes in pulmonary CT scanning images in terms of patched/striped compact opacity, alveolar hemorrhage, bronchiectasis, pleural effusion, as well as mediastinal lymphadenopathy (89.71% vs 52.00%, 11.76% vs 2.00%, 22.06% vs 8.00%, 50.00% vs 20.00%, 48.53% vs 24.00%, p < 0.05, respectively). In addition, patients in the lung infection group had significantly higher levels of serum pro-calcitonin (PCT), C-reactive protein (CRP), amyloid A (SAA), blood neutrophil-to-lymphocyte ratio (NLCR), erythrocyte sedimentation rate (ESR), as well as Birmingham vasculitis activity score (BVAS) than patients in the other two groups (p < 0.05). Among all biomarkers, PCT exhibited the highest diagnostic efficacy (0.928; 95%CI 0.89-0.97) for pulmonary infected AAV patients at a cut-off score of 0.235 ng/ml with 85.3% sensitivity and 84% specificity. Moreover, the composite biomarker of PCT-CRP-NLCR showed more diagnostic efficacy (0.979; 95% CI 0.95-1.00) in distinguishing the infectious and non-infectious lung injuries in AAV patients. CONCLUSIONS: AAV patients with lung infection manifested more clinical symptoms and prominent lung image changes. The PCT and composite biomarker PCT-CRP-NLCR showed high diagnostic efficacy for a lung infection in AAV patients. Pulmonary lesion caused by either infection or AAV involvement is commonly seen and difficult to distinguish. We aim to identify the biomarkers that can be applied in the differentiation diagnosis of pulmonary lesions in AAV patients.

Insight into Iron Leaching from an Ascorbate-Oxidase-like Fe-N-C Nanozyme and Oxygen Reduction Selectivity.

Ascorbate (H2 A) is a well-known antioxidant to protect cellular components from free radical damage and has also emerged as a pro-oxidant in cancer therapies. However, such "contradictory" mechanisms underlying H2 A oxidation are not well understood. Herein, we report Fe leaching during catalytic H2 A oxidation using an Fe-N-C nanozyme as a ferritin mimic and its influence on the selectivity of the oxygen reduction reaction (ORR). Owing to the heterogeneity, the Fe-Nx sites in Fe-N-C primarily catalyzed H2 A oxidation and 4 e- ORR via an iron-oxo intermediate. Nonetheless, trace O2 ⋅- produced by marginal N-C sites through 2 e- ORR accumulated and attacked Fe-Nx sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H2 A concentration increased to 2 mM. As a result, a substantial fraction (ca. 40 %) of the N-C sites on Fe-N-C were activated, and a new 2+2 e- ORR path was finally enabled, along with Fenton-type H2 A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N-C sites stopped at H2 O2 production, which was the origin of the pro-oxidant effect of H2 A.

Elucidating Electrocatalytic Oxygen Reduction Kinetics via Intermediates by Time-Dependent Electrochemiluminescence.

Facile evaluation of oxygen reduction reaction (ORR) kinetics for electrocatalysts is critical for sustainable fuel-cell development and industrial H2 O2 production. Despite great success in ORR studies using mainstream strategies, such as the membrane electrode assembly, rotation electrodes, and advanced surface-sensitive spectroscopy, the time and spatial distribution of reactive oxygen species (ROS) intermediates in the diffusion layer remain unknown. Using time-dependent electrochemiluminescence (Td-ECL), we report an intermediate-oriented method for ORR kinetics analysis. Owing to multiple ultrasensitive stoichiometric reactions between ROS and the ECL emitter, except for electron transfer numbers and rate constants, the potential-dependent time and spatial distribution of ROS were successfully obtained for the first time. Such exclusively uncovered information would guide the development of electrocatalysts for fuel cells and H2 O2 production with maximized activity and durability.

Lighting Up Electrochemiluminescence-Inactive Dyes via Grafting Enabled by Intramolecular Resonance Energy Transfer.

Due to near-zero optical background and photobleaching, electrochemiluminescence (ECL), an optical phenomenon excited by electrochemical reactions, has drawn extensive attention, especially for ultrasensitive bioassays. Developing diverse ECL emitters is crucial to unlocking their multiformity and performances but remains a formidable challenge due to the rigorous requirements for ECL. Herein, we report a general strategy to light up ECL-inactive dyes in an aqueous solution via grafting, a well-developed concept for plant propagation since 500 BCE. As a proof of concept, a series of luminol donor-dye acceptor-based ECL emitters were grafted with near-unity resonance energy transfer (RET) efficiency and coarse/fine-tunable emission wavelengths. Rather than the sophisticated design of new skeleton-based molecules to meet all of the prerequisites for ECL in a constrained manner, each unit in the proposed ECL ensemble performed its functions maximally. As a result, beyond traditional two-dimensional (2D) ones, a three-dimensional (3D) coordinate biosensing system, simultaneously showing a calibration curve and selectivity, was established using the new ECL emitter. This lighting up strategy would generally address the scarcity of ECL emitters and enable unprecedented functions.

Identification of a conserved neutralizing epitope in Seneca Valley virus VP2 protein: new insight for epitope vaccine designment.

BACKGROUND: Seneca Valley virus (SVV) is a picornavirus that causes vesicular disease in swine. Clinical characteristics of the disease are similar to common viral diseases such as foot-and-mouth disease virus, porcine vesicular disease virus, and vesicular stomatitis virus, which can cause vesicles in the nose or hoof of pigs. Therefore, developing tools for detecting SVV infection is critical and urgent. METHODS: The neutralizing antibodies were produced to detect the neutralizing epitope. RESULTS: Five SVV neutralizing monoclonal antibodies (mAb), named 2C8, 3E4, 4C3, 6D7, and 7C11, were generated by immunizing mouses with ultra-purified SVV-LNSY01-2017. All five monoclonal antibodies exhibited high neutralizing titers to SVV. The epitopes targeted by these mAbs were further identified by peptide scanning using GST fusion peptides. The peptide 153QELNEE158 is defined as the smallest linear neutralizing epitope. The antibodies showed no reactivity to VP2 single mutants E157A. Furthermore, the antibodies showed no neutralizing activity with the recombinant virus (SVV-E157A). CONCLUSIONS: The five monoclonal antibodies and identified epitopes may contribute to further research on the structure and function of VP2 and the development of diagnostic methods for detecting different SVV strains. Additionally, the epitope recognized by monoclonal antibodies against VP2 protein may provide insights for novel SVV vaccines and oncolytic viruses development.

Cascaded Nanozyme System with High Reaction Selectivity by Substrate Screening and Channeling in a Microfluidic Device.

Surpassing natural enzymes in cost, stability and mass production, nanozymes have attracted wide attention in fields from disease diagnosis to tumor therapy. However, nanozymes intrinsically have low reaction selectivity, which significantly restricts their applications. A general method is reported to address this challenge by following a biomimetic operation principle of substrates channeling and screening. Two oxidase- and peroxidase-like nanozymes (i.e., emerging N-doped carbon nanocages and Prussian blue nanoparticles), were cascaded as a proof of concept to improve the reaction selectivity in transforming the substrate into the targeted product by more than 2000 times. The cascaded nanozymes were also adopted to a spatially confined microfluidic device, leading to more than 100-fold enhancement of the reaction efficiency due to signal amplification.

Long Noncoding RNA PMS2L2 Downregulates miR-24 through Methylation to Suppress Cell Apoptosis in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colon. It has been reported that PMS2L2 plays protective roles in inflammatory injury. This study aimed to investigate the role of the long noncoding RNA PMS2L2 in UC. METHODS: Sixty-two patients with UC as well as 62 age- and gender-matched healthy controls were enrolled. Expressions of PMS2L2 and miR-24 in plasma from UC patients and healthy controls were determined by RT-qPCR. The interaction between PMS2L2 and miR-24 was predicted by bioinformatics and confirmed by RNA immunoprecipitation and RNA pull-down. The role of PMS2L2 in the regulation of miR-24 gene methylation was analyzed by methylation-specific PCR. The effects of PMS2L2 and miR-24 on the expressions of apoptosis-related proteins were detected by Western blots. RESULTS: PMS2L2 was downregulated in the plasma of UC patients compared to that in age- and gender-matched healthy control. In human colonic epithelial cells (HCnEpCs), PMS2L2 overexpression inhibited miR-24 expression via promoting the methylation of miR-24 gene. In contrast, miR-24 overexpression failed to affect PMS2L2. In the detection of cell apoptosis, PMS2L2 overexpression could promote the expression of Bcl-2 and inhibit Bax, cleaved-caspase-3, and cleaved-caspase-9 expressions stimulated by LPS. Flow cytometer revealed that PMS2L2 elevation suppressed the apoptosis of HCnEpCs induced by LPS, but miR-24 aggravated the apoptosis. PMS2L2 overexpression rescued the detrimental effect of miR-24 on cell apoptosis. CONCLUSION: PMS2L2 may downregulate miR-24 via methylation to suppress cell apoptosis in UC.

Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury.

OBJECTIVE: Acute kidney injury (AKI) usually occurs during sepsis. Inflammation factors, such as high-mobility group box 1 (HMGB1), are dramatically upregulated under septic conditions. In our current work, the functions of HMGB1 in AKI were explored. METHODS: An AKI model was induced by the lipopolysaccharide (LPS) challenge in C57 mice. Podocytes were challenged by LPS for different durations. Subsequently, podocytes transfected with HMGB1 siRNA were exposed to LPS for 24 h. The expressions of supernatant HMGB1 and cellular active caspase-3 were examined by Western blotting analysis. To explore the effect of HMGB1 on tubular epithelial cells (TECs), HK-2 cells were exposed to HMGB1 at various concentrations for 24 h. Epithelial-mesenchymal transition (EMT) of HK-2 cells was evaluated by Western blotting analysis. Mitochondrial division and apoptosis of HK-2 cells were assessed by MitoTracker Red and Western blotting analysis, respectively. RESULTS: Compared with the sham control group, the expression of HMGB1 was increased in the kidney of AKI mice. Moreover, the expression of supernatant HMGB1 was increased in LPS-challenged podocytes compared with the control group. Knockdown of HMGB1 attenuated LPS-induced podocyte injury. Besides, EMT in TECs was triggered by HMGB1. Mitochondrial damage and apoptosis of HK-2 cells exposed to HMGB1 were markedly elevated compared with the control group. CONCLUSIONS: Collectively, HMGB1 release in podocytes was induced by LPS, subsequently leading to exacerbated AKI.

Sirt6 attenuates hypoxia-induced tubular epithelial cell injury via targeting G2/M phase arrest.

Acute kidney injury (AKI) is a condition that has a high incidence and death rate. Unfortunately, the kidney may not recover completely after AKI, which then develops to chronic kidney disease (CKD). Therefore, it is necessary to identify potential curative targets to avoid its development to CKD. As an NAD+ -dependent deacetylase, sirtuin 6 (Sirt6) has been linked to different types of biological processes. In the present work, our group investigated the role of Sirt6 in tubular epithelial cells (TECs) under hypoxic stress. Sirt6 expression was examined in mouse kidney following ischemia/reperfusion (IR) injury and hypoxia-challenged TECs. Using Sirt6 plasmid and small interfering RNA, we also investigated how, in regard to inflammation and epithelial-to-mesenchymal transition, Sirt6 affects hypoxia-triggered injury. In addition, cell cycle was detected in hypoxia-challenged TECs. Sirt6 was downregulated in the kidney of mice with IR injury and hypoxia-challenged TECs. Consequently, Sirt6 depletion aggravated hypoxia-induced injury and G2/M phase arrest. Sirt6 overexpression attenuated hypoxia-triggered damage and G2/M phase arrest in TECs. Sirt6 prevented hypoxia-triggered TEC damage via suppressing G2/M phase arrest. Thus, Sirt6 is a possible candidate for alleviating the effects of kidney injury.

Identification of Long Non-Coding RNA and Circular RNA Expression Profiles in Atrial Fibrillation.

BACKGROUND: Long non-coding RNA (lncRNA) and circular RNA (circRNA) have both been found to play important roles in cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis. However, the role of lncRNA and circRNA in atrial fibrillation (AF) has rarely been investigated. This study aimed to identify lncRNA and circRNA expression profiles in AF patients. METHODS: Atrial tissues from seven patients with AF and seven matched controls were collected. The lncRNA and circRNA expression profiles of atrial tissues were identified using Hiseq/Proton RNA sequencing. Validation was performed by reverse transcription quantitative real-time PCR (qRT-PCR) on 35 pairs of AF patients and controls. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A competing endogenous RNA (ceRNA) network was constructed. RESULTS: A total of 557 lncRNAs and 280 circRNAs were significantly differentially expressed with fold change >1.5 (p<0.05). An lncRNA Voltage Dependent Anion Channel 2 Pseudogene 2 (VDAC2P2) and two circRNAs chr13_41887361_41865736_-21625 and chr13_100368574_100301460_-67114 were validated, using qRT-PCR, to have significantly different expression levels. GO and KEGG pathway analysis showed that some pathways such as ribosome and chromatin modification, Rap1 signalling and cardiac muscle contraction were involved in the pathogenesis of AF. Competing endogenous RNAs were predicted based on constructional network analysis. The LncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed by co-expressing lncRNA/circRNA and mRNAs, which were competitively combined with miRNAs. CONCLUSION: This study characterised lncRNA and circRNA expression and their interaction with mRNA and miRNA in AF.

Plasma Level of Interferon-γ Predicts the Prognosis in Patients With New-Onset Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation are at increased risk of stroke and mortality. It is not clear if inflammatory biomarkers are associated with stroke and mortality in patients with atrial fibrillation. We aimed to evaluate the predictive value of three inflammatory biomarkers (interleukin [IL]-9, IL-10, and interferon [IFN]-γ) for stroke and mortality in atrial fibrillation. METHOD: A total of 232 patients with new-onset atrial fibrillation were enrolled and 217 patients were completely followed-up. Peripheral plasma concentrations of cytokines (IL-9, IL-10, and IFN-γ) were measured using Luminex xMAP assays. The association between dichotomous groups of cytokines and outcomes were evaluated by a Cox proportional hazards model. The incremental value of inflammatory biomarkers, in addition to the CHA2DS2-VASc score, was also assessed. RESULTS: Patients were followed-up for a median duration of 27 (interquartile range [IQR], 23-30) months. The elevated plasma level of IFN-γ was an independent risk factor for stroke (hazard ratio [HR], 4.02 [IQR, 1.06-15.34]; p=0.042) and all-cause mortality (HR, 3.93 [IQR, 1.43-10.78]; p=0.008) in patients with atrial fibrillation. Adding high IFN-γ to the CHA2DS2-VASc score showed improvement in discrimination and reclassification prediction for stroke and mortality. However, IL-9 and IL-10 had no statistically significant association with stroke and all-cause mortality in patients with atrial fibrillation. CONCLUSIONS: In this "real-world" cohort of patients with atrial fibrillation, we have shown for the first time that plasma levels of IFN-γ could provide incremental prognostic value supplementary to that obtained from the CHA2DS2-VASc scores for predicting of stroke and all-cause mortality.

The Fe-N-C Nanozyme with Both Accelerated and Inhibited Biocatalytic Activities Capable of Accessing Drug-Drug Interactions.

Emerging as a cost-effective and robust enzyme mimic, nanozymes have drawn increasing attention with broad applications ranging from cancer therapy to biosensing. Developing nanozymes with both accelerated and inhibited biocatalytic properties in a biological context is intriguing to peruse more advanced functions of natural enzymes, but remains challenging, because most nanozymes are lack of enzyme-like molecular structures. By re-visiting and engineering the well-known Fe-N-C electrocatalyst that has a heme-like Fe-Nx active sites, herein, it is reported that Fe-N-C could not only catalyze drug metabolization but also had inhibition behaviors similar to cytochrome P450 (CYP), endowing it a potential replacement of CYP for preliminary evaluation of massive potential chemicals, drug dosing guide, and outcome prediction. In addition, in contrast to electrocatalysts, the highly graphitic framework of Fe-N-C may not be obligatory for a competitive CYP-like activity.

Carbon Nitride Co-catalyst Activation Using N-Doped Carbon with Enhanced Photocatalytic H2 Evolution.

Photocatalytic water splitting holds huge potential to meet the current challenges of energy and environments. Among them, polymeric carbon nitride (CN) has drawn much attention as a promising metal-free photocatalyst. As it is known, a number of promising co-catalysts have been developed to improve catalytic reactions, Pt nanoparticles is still among the best co-catalysts for CN in photocatalytic H2 evolution, due to the suitable Fermi level to transfer excited electrons and the low overpotential for H2 reduction. Herein, we report the interface engineering of urea-derived bulk CN and Pt co-catalyst by using a small portion of N-doped carbon (N-C) as a transition layer with a boosted photocatalytic activity up to 7 times. It was revealed that the activation energy of the Pt co-catalyst for water reduction was lowered in the presence of N-C, and the intimate interaction between CN and N-C, ascribing to the similar elemental composition and crystal structure, promoted the efficient separation and migration of charge carriers. This study may open a new avenue to develop CN-based photocatalysts for solar fuel conversion with even higher activity by photocatalyst/co-catalyst interface engineering.