Investigation of autophagy­related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation.

The present study aimed to elucidate the role of autophagy-related genes (ARGs) in calcific aortic valve disease (CAVD) and their potential interactions with immune infiltration via experimental verification and bioinformatics analysis. A total of three microarray datasets (GSE12644, GSE51472 and GSE77287) were obtained from the Gene Expression Omnibus database, and gene set enrichment analysis was performed to identify the relationship between autophagy and CAVD. After differentially expressed genes and differentially expressed ARGs (DEARGs) were identified using CAVD samples and normal aortic valve samples, a functional analysis was performed, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, protein-protein interaction network construction, hub gene identification and validation, immune infiltration and drug prediction. The results of the present study indicated a significant relationship between autophagy and CAVD. A total of 46 DEARGs were identified. GO and pathway enrichment analyses revealed the complex roles of DEARGs in regulating CAVD, including multiple gene functions and pathways. A total of 10 hub genes were identified, with three (SPP1, CXCL12 and CXCR4) consistently upregulated in CAVD samples compared with normal aortic valve samples in multiple datasets and experimental validation. Immune infiltration analyses demonstrated significant differences in immune cell proportions between CAVD samples and normal aortic valve samples, thus showing the crucial role of immune infiltration in CAVD development. Furthermore, therapeutic drugs were predicted that could target the identified hub genes, including bisphenol A, resveratrol, progesterone and estradiol. In summary, the present study illuminated the crucial role of autophagy in CAVD development and identified key ARGs as potential therapeutic targets. In addition, the observed immune cell infiltration and predicted autophagy-related drugs suggest promising avenues for future research and novel CAVD treatments.

A Reaction-based Ratiometric Fluorescent Probe with Large STOKES Shift for Cu2+ in Neat Aqueous Solution.

A novel reaction-based ratiometric fluorescent probe 1 for Cu2+ using picolinate as the reaction site and hemicyanine as the fluorophore was developed. 1 displayed maximum absorption peak at 355 nm and fluorescence emission peak at 500 nm, with large Stokes shift of 145 nm. Upon reaction with Cu2+, the maximum absorption and fluorescence emission peaks red-shifted to 390 nm and 570 nm respectively, owing to Cu2+-induced hydrolysis of the picolinate moiety in 1. Meanwhile, the solution of 1 turned from green to orange under a 365 nm UV lamp. 1 not only could detect Cu2+ ratiometrically by the ratios of both absorbance (A390 nm/A355 nm) and fluorescence intensity (F570 nm/F500 nm), but also displayed large Stokes shift, fast response, high sensitivity and excellent selectivity over other metal ions in neat aqueous solution.

Analysis of post-market adverse events of istradefylline: a real-world study base on FAERS database.

Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

A highly sensitive, long-time stable Ag/AgCl ultra-micro sensor for in situ monitoring chloride ions inside the crevice using SECM.

Tracking the variation of Cl- timely within the crevice is of great significance for comprehending the dynamic mechanism of crevice corrosion. The reported chloride ion selective electrodes are difficult to realize the long-time Cl- detection inside the confined crevice, due to their millimeter size or a relative limited lifespan. For this purpose, an Ag/AgCl ultra-micro sensor (UMS) with a radius of 12.5 µm was fabricated and optimized using laser drawing and electrodeposition techniques. Results show the AgCl film's structure is significantly impacted by the deposited current density, and further affects the linear response, life span and stability of Ag/AgCl UMS. The UMS prepared at current density of 0.1 mA/cm2 for 2 h shows a rapid response (several seconds), excellent stability and reproducibility, strong acid/alkali tolerance, sufficient linearity (R2 > 0.99), and long lifespan (86 days). Moreover, combined with the potentiometric mode of scanning electrochemical microscope (SECM), the Ag/AgCl UMS was successfully applied to monitor the in-situ radial Cl- concentration in micro-regions inside a 100 µm gap of stainless steel. The findings demonstrated that there was obvious radial difference in Cl- concentration inside the crevice, where the fastest rise in Cl- concentration was at the opening. The proposed method which combines the UMS with SECM has attractive practical applications for microzone Cl- monitoring in real time inside crevice. It may further promote the study of other localized corrosion mechanism and the development of microzone ions detection method.

Comparison of Physical Activity and Sedentary Behavior between Work in Office and Work From Home: A Self-controlled Study.

OBJECTIVE: To compare physical activity levels and sedentary behavior between individuals working in the office and those working from home, with the aim of elucidating the potential implications on employees' health. METHODS: We used triaxial accelerometers to assess the physical activity levels of 94 white-collar employees from a large-scale manufacturing company in Japan. They were instructed to wear the accelerometers during their working hours, which included the commuting time on work-in-office days. RESULTS: The mean energy expenditure on work in office was 426 kcal for individuals, while it was 228 kcal on work from home (P < 0.01). In addition, not including commuting, the time spent sedentary on work-from-home days was higher than that on work-in-office days by 20 minutes. CONCLUSIONS: Work from home decreases physical activity and increases sedentary time compared with work in office.

Exploring differences in substance use behaviours among gender minority and non-gender minority youth: a cross-sectional analysis of the COMPASS study. / Exploration des différences dans les comportements liés à la consommation de substances chez les jeunes faisant partie de minorités de genre et les jeunes ne faisant pas partie de minorités de genre : analyse transversale de l'étude COMPASS.

INTRODUCTION: Research characterizing substance use disparities between gender minority youth (GMY) and non-GMY (i.e. girls and boys) is limited. The aim of this study was to examine the differences in substance use behaviours among gender identity (GI) groups and identify associated risk and protective factors. METHODS: Cross-sectional data from Canadian secondary school students (n = 42 107) that participated in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study were used. Hierarchal logistic regression models estimated current substance use (cigarettes, e-cigarettes, binge drinking, cannabis and nonmedical prescription opioids [NMPOs]). Predictor variables included sociodemographics, other substances, mental health outcomes, school connectedness, bullying and happy home life. Interaction terms were used to test mental health measures as moderators in the association between GI and substance use. RESULTS: Compared to non-GMY, GMY reported a higher prevalence for all substance use outcomes. In the adjusted analyses, GMY had higher odds of cigarette, cannabis and NMPO use and lower odds for e-cigarette use relative to non-GMY. The likelihood of using any given substance was higher among individuals who were involved with other substances. School connectedness and happy home life had a protective effect for all substances except binge drinking. Bullying victimization was associated with greater odds of cigarette, e-cigarette use and NMPOs. Significant interactions between GI and all mental health measures were detected. CONCLUSION: Findings highlight the importance of collecting a GI measure in youth population surveys and prioritizing GMY in substance use-related prevention, treatment and harm reduction programs. Future studies should investigate the effects of GI status on substance use onset and progression among Canadian adolescents over time.

Exploring ncRNA-Drug Sensitivity Associations Via Graph Contrastive Learning.

Increasing evidence has shown that noncoding RNAs (ncRNAs) can affect drug efficiency by modulating drug sensitivity genes. Exploring the association between ncRNAs and drug sensitivity is essential for drug discovery and disease prevention. However, traditional biological experiments for identifying ncRNA-drug sensitivity associations are time-consuming and laborious. In this study, we develop a novel graph contrastive learning approach named NDSGCL to predict ncRNA-drug sensitivity. NDSGCL uses graph convolutional networks to learn feature representations of ncRNAs and drugs in ncRNA-drug bipartite graphs. It integrates local structural neighbours and global semantic neighbours to learn a more comprehensive representation by contrastive learning. Specifically, the local structural neighbours aim to capture the higher-order relationship in the ncRNA-drug graph, while the global semantic neighbours are defined based on semantic clusters of the graph that can alleviate the impact of data sparsity. The experimental results show that NDSGCL outperforms basic graph convolutional network methods, existing contrastive learning methods, and state-of-the-art prediction methods. Visualization experiments show that the contrastive objectives of local structural neighbours and global semantic neighbours play a significant role in contrastive learning. Case studies on two drugs show that NDSGCL is an effective tool for predicting ncRNA-drug sensitivity associations. Source code and datasets can be available on https://github.com/altriavin/NDSGCL.

Role of ArcA in the regulation of antibiotic sensitivity in avian pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) is one of the common extraintestinal infectious disease pathogens in chickens, geese, and other birds, inducing serious impediments to the development of the poultry industry. Hence, investigating how bacteria regulate themselves amidst different challenging conditions is immense essential in prevention and treatment for bacterial pathogen infections. The ArcA regulatory factor has been reported to regulate oxygen availability in strains, but its role in regulation of antibiotics resistance in APEC is unclear. This study delved into understanding how ArcA regulates antibiotic resistance in APEC. An E. coli APEC40 arcA knockout strain was constructed, and the regulatory mechanism of arcA on APEC antibiotic susceptibility was identified by drug sensitivity test, colony counting assay, real-time quantitative PCR, ß-galactosidase assays and electrophoretic mobility shift assay (EMSA). The results showed that ArcA directly binds to the promoter region of the outer membrane protein OmpC/OmpW and regulates bacterial susceptibility to kanamycin and penicillin G. At the same time, the double knockout of ompW and ompW/arcA resulted in an increase in resistance to kanamycin compared to the deletion of the arcA gene. This outcome provided experimental proof suggesting that the outer membrane protein OmpW could serve as a crucial pathway for the ingress of kanamycin into cells. These results confirmed the important regulatory role of ArcA transcription factors under APEC antibiotic stress.

The relationship between family socioeconomic status and the young children's number sense development: The mediating role of parent-child activities.

This study examines the relationship between family socioeconomic status, parent-child activities, and young children's digital development. Using the Family SES questionnaire, the parent-child activities questionnaire, and the 5 to 6 year old children's number sense development scale as research instruments, 314 young children (M = 70.42, SD = 3.47). The results show that: (1) Family Socioeconomic Status can significantly positively predict the young children's number sense development; (2) Parent-child activities play a partial mediating role in the relationship between family socioeconomic status and the young children's number sense development. This study provides specific guidelines and recommendations for improving the young children's number sense development.

Mining and analysis of security alert signals of valbenazine based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.

Diagnostic features emerging in near-infrared reflectance spectroscopy for low petroleum hydrocarbon pollution after spectral subtraction.

Diagnostic features in near-infrared reflectance spectroscopy (NIRS) are the foundation of knowledge-based approach of petroleum hydrocarbon determination. However, a significant challenge arises when analyzing samples with low levels of petroleum hydrocarbon pollution, as they often lack distinctive diagnostic features in their sample NIRS spectra, limiting the effectiveness of this approach. To address this issue, we have developed a technical workflow for diagnostic spectrum construction and parameterization based on spectral subtraction. This method was applied on a set of NIRS spectra from soil samples that were contaminated with petroleum hydrocarbons (ranged between 178 and 1716 mg/kg of total petroleum hydrocarbon). Then two diagnostic features for low-level petroleum hydrocarbon pollution were found: (1) An overall downward concave emerged on diagnostic spectrum within both 2290-2370 nm and 1700-1780 nm for all low pollution levels even below 200 mg/kg; (2) An indicative pattern of asymmetric "W-shaped" double absorption valley occurred for those exceeding 1000 mg/kg, and its valleys located near 2310 nm, 2348 nm or 1727 nm, 1762 nm stably. These two features on diagnostic spectrum could be parameterized to detect, and the detection limit was at least about 10-50 times lower than that based on sample spectrum. These findings update our understanding on the detectability of spectral response from low petroleum hydrocarbon pollution, and widely extend the application of knowledge-based NIRS approach in either field detection or remote sensing identification for environmental management.

Thioketal-Based Electrochemical Sensor Reveals Biphasic Effects of l-DOPA on Neuroinflammation.

Neuroinflammation is linked closely to neurodegenerative diseases, with reactive oxygen species (ROS) exacerbating neuronal damage. Traditional electrochemical sensors show promise in targeting cellular ROS to understand their role in neuropathogenesis and assess therapies. Nevertheless, these sensors face challenges in mitigating the ROS oxidation overpotential. We herein introduce an ROS oxidation-independent nucleic acid sensor for in situ ROS analysis and therapeutic assessment. The sensor comprises ionizable and thioketal (TK)-based lipids with methylene blue-tagged nucleic acids on a glass carbon electrode. ROS exposure triggers cleavage within the sensor's thioketal moiety, detaching the nucleic acid from the electrode and yielding quantifiable results via square-wave voltammetry. Importantly, the sensor's low potential window minimizes interference, ensuring precise ROS measurements with high selectivity. Using this sensor, we unveil levodopa's dose-dependent biphasic effect on neuroinflammation: low doses alleviate oxidative stress, while high doses exacerbate it. The TK-based sensor offers a promising methodology for investigating neuroinflammation's pathogenesis and screening potential treatments, advancing neurodegenerative disease research.

Incident Functional Limitations Among Older Adults With Diabetes During the COVID-19 Pandemic: An Analysis of Prospective Data From the Canadian Longitudinal Study on Aging.

OBJECTIVES: The objectives of this study were: 1) to examine and compare changes in functional limitations during the COVID-19 pandemic among older adults with and without diabetes; and 2): to identify key risk factors associated with developing functional limitations among older adults with and without diabetes during the pandemic. METHODS: We analyzed data collected from the Canadian Longitudinal Study on Aging. The analysis was restricted to those with no functional limitations in the follow-up 1 wave (2015 to 2018) (final sample N=6,045). Regression models were used to describe associations between diabetic status and functional limitation outcomes. We conducted stratified analyses to evaluate whether these associations varied by sociodemographic indicators. We also predicted the probability of the development of ≥1 functional limitation among those with and without diabetes for various patient profiles. RESULTS: Older adults with diabetes were 1.28-fold (95% confidence interval 1.02 to 1.60) more likely to develop ≥1 functional limitation than older adults without diabetes after controlling for relevant sociodemographic and health covariates. Risk factors for incident functional limitations among older adults, both with and without diabetes, include increasing age, low socioeconomic status, obesity, multimorbidity, and physical inactivity. CONCLUSIONS: Our findings indicate that older adults with diabetes were at an increased risk of developing functional limitations during the pandemic when compared with older adults without diabetes, even when controlling for several key risk factors. Targetting modifiable risk factors, such as physical activity, may help to reduce the risk of functional limitations among older adults with diabetes.

In vitro activity of cefepime/taniborbactam and comparator agents against Gram-negative bacterial bloodstream pathogens recovered from patients with cancer.

Background: Taniborbactam is a ß-lactamase inhibitor that, when combined with cefepime, may offer a potential treatment option for patients with serious and resistant Gram-negative bacterial (GNB) pathogens. Objectives: This study evaluated in vitro activity of cefepime/taniborbactam and comparator agents against GNB pathogens isolated from patients with cancer at our institution. Methods: A total of 270 GNB pathogens (2019-23) isolated from patients with cancer were tested against cefepime/taniborbactam and comparator agents commonly used for these patients. CLSI-approved broth microdilution methods were used. MIC50, MIC90, MIC range and percentage of susceptibility calculations were made using FDA breakpoints when available. Results: Cefepime/taniborbactam showed highly potent activity against tested Enterobacterales, including isolates producing ESBLs and carbapenem-resistant Enterobacterales. At a provisional breakpoint of ≤16/4 mg/L, cefepime/taniborbactam inhibited most tested species of GNB pathogens, with overall 98.9% susceptibility, which was significantly (P < 0.0001) higher than the susceptibility of the GNB isolates to all other tested comparator agents, ranging from 39.6% for cefepime to 86.3% for ceftazidime/avibactam. Conclusions: Our results showed that taniborbactam in combination with cefepime improved in vitro activity against GNB pathogens isolated from patients with cancer, including MDR Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, ESBL-producing Enterobacterales and Stenotrophomonas maltophilia isolates, with highest activity compared with all tested comparator agents, including other ß-lactam/ß-lactamase inhibitor combinations. Further studies are warranted to explore the efficacy of cefepime/taniborbactam for empirical initial treatment of GNB infections in cancer patients with high rates of febrile neutropenia requiring hospitalization.

Mitigating the Overheat of Stretchable Electronic Devices Via High-Enthalpy Thermal Dissipation of Hydrogel Encapsulation.

The practical application of flexible and stretchable electronics is significantly influenced by their thermal and chemical stability. Elastomer substrates and encapsulation, due to their soft polymer chains and high surface-area-to-volume ratio, are particularly susceptible to high temperatures and flame. Excessive heat poses a severe threat of damage and decomposition to these elastomers. By leveraging water as a high enthalpy dissipating agent, here, a hydrogel encapsulation strategy is proposed to enhance the flame retardancy and thermal stability of stretchable electronics. The hydrogel-based encapsulation provides thermal protection against flames for more than 10 s through the evaporation of water. Further, the stretchability and functions automatically recover by absorbing air moisture. The incorporation of hydrogel encapsulation enables stretchable electronics to maintain their functions and perform complex tasks, such as fire saving in soft robotics and integrated electronics sensing. With high enthalpy heat dissipation, encapsulated soft electronic devices are effectively shielded and retain their full functionality. This strategy offers a universal method for flame retardant encapsulation of stretchable electronic devices.

Proteomic analysis of DEN and CCl4-induced hepatocellular carcinoma mouse model.

Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein-protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.

Investigating the Mechanism of Chufan Yishen Formula in Treating Depression through Network Pharmacology and Experimental Verification.

Objective: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.

ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.

The pathogenesis of inflammatory bowel disease (IBD) remains unclear and is associated with an increased risk of developing colitis-associated cancer (CAC). Under sustained inflammatory stimulation in the intestines, loss of early DNA damage response genes can lead to tumor formation. Many proteins are involved in the pathways of DNA damage response and play critical roles in protecting genes from various potential damages that DNA may undergo. ERCC4 is a structure-specific endonuclease that participates in the nucleotide excision repair (NER) pathway. The catalytic site of ERCC4 determines the activity of NER and is an indispensable gene in the NER pathway. ERCC4 may be involved in the imbalanced process of DNA damage and repair in IBD-related inflammation and CAC. This article primarily reviews the function of ERCC4 in the DNA repair pathway and discusses its potential role in the processes of IBD-related inflammation and carcinogenesis. Finally, we explore how this knowledge may open novel avenues for the treatment of IBD and IBD-related cancer.

SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.