Surpassing millisecond coherence in on chip superconducting quantum memories by optimizing materials and circuit design.

The performance of superconducting quantum circuits for quantum computing has advanced tremendously in recent decades; however, a comprehensive understanding of relaxation mechanisms does not yet exist. In this work, we utilize a multimode approach to characterizing energy losses in superconducting quantum circuits, with the goals of predicting device performance and improving coherence through materials, process, and circuit design optimization. Using this approach, we measure significant reductions in surface and bulk dielectric losses by employing a tantalum-based materials platform and annealed sapphire substrates. With this knowledge we predict the relaxation times of aluminum- and tantalum-based transmon qubits, and find that they are consistent with experimental results. We additionally optimize device geometry to maximize coherence within a coaxial tunnel architecture, and realize on-chip quantum memories with single-photon Ramsey times of 2.0 - 2.7 ms, limited by their energy relaxation times of 1.0 - 1.4 ms. These results demonstrate an advancement towards a more modular and compact coaxial circuit architecture for bosonic qubits with reproducibly high coherence.

Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial.

BACKGROUND: The rapid worldwide spread of COVID-19 has caused a global health challenge with high mortality of severe or critically ill patients with COVID-19. To date, there is no specific efficient therapeutics for severe or critically ill patients with COVID-19. It has been reported that androgen is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide as an androgen receptor antagonist has shown potential treatment effects on COVID-19 patients. Thus, this trial is designed to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. METHODS: This single-arm, open-label, single-center prospective exploratory trial is planned to recruit 64 severe or critically ill patients with COVID-19 in China. Recruitment started on 16 May 2022 and is foreseen to end on 16 May 2023. Patients will be followed-up until 60 days or death, whichever comes first. The primary outcome is the 30-day all-cause mortality. Secondary endpoints included 60-day all-cause mortality, rate of clinical deterioration within 30 days after administration, time to sustain clinical recovery (determined using an 8-point ordinal scale), mean change in the Acute Physiology and Chronic Health Evaluation II scores, change in oxygenation index, changes in chest CT scan, percentage of patients confirmed negative for SARS-CoV-2 by nasopharyngeal swab, change in Ct values of SARS-CoV-2 and safety. Visits will be performed on days 1 (baseline), 15 or 30, 22, and 60. DISCUSSION: The trial is the first to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. The findings of this study might lead to the development of better treatment for COVID-19 and provide convincing evidence regarding the efficacy and safety of proxalutamide. TRIAL REGISTRATION: This study was registered on 18 June 2022 at the Chinese Clinical Trial Registry (ChiCTR2200061250).

Chemical Profiles of the Oxides on Tantalum in State of the Art Superconducting Circuits.

Over the past decades, superconducting qubits have emerged as one of the leading hardware platforms for realizing a quantum processor. Consequently, researchers have made significant effort to understand the loss channels that limit the coherence times of superconducting qubits. A major source of loss has been attributed to two level systems that are present at the material interfaces. It is recently shown that replacing the metal in the capacitor of a transmon with tantalum yields record relaxation and coherence times for superconducting qubits, motivating a detailed study of the tantalum surface. In this work, the chemical profile of the surface of tantalum films grown on c-plane sapphire using variable energy X-ray photoelectron spectroscopy (VEXPS) is studied. The different oxidation states of tantalum that are present in the native oxide resulting from exposure to air are identified, and their distribution through the depth of the film is measured. Furthermore, it is shown how the volume and depth distribution of these tantalum oxidation states can be altered by various chemical treatments. Correlating these measurements with detailed measurements of quantum devices may elucidate the underlying microscopic sources of loss.

Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Formyl peptide receptor 2 activation by mitochondrial formyl peptides stimulates the neutrophil proinflammatory response via the ERK pathway and exacerbates ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) is an inevitable process in renal transplantation that significantly increases the risk of delayed graft function, acute rejection, and even graft loss. Formyl peptide receptor 2 (FPR2) is an important receptor in multiple septic and aseptic injuries, but its functions in kidney IRI are still unclear. This study was designed to reveal the pathological role of FPR2 in kidney IRI and its functional mechanisms. METHODS: To explore the mechanism of FPR2 in kidney IRI, the model rats were sacrificed after IRI surgery. Immunofluorescence, enzyme-linked immunosorbent assays, and western blotting were used to detect differences in the expression of FPR2 and its ligands between the IRI and control groups. WRW4 (WRWWWW-NH2), a specific antagonist of FPR2, was administered to kidney IRI rats. Kidney function and pathological damage were detected to assess kidney injury and recovery. Flow cytometry was used to quantitatively compare neutrophil infiltration among the experimental groups. Mitochondrial formyl peptides (mtFPs) were synthesized and administered to primary rat neutrophils together with the specific FPR family antagonist WRW4 to verify our hypothesis in vitro. Western blotting and cell function assays were used to examine the functions and signaling pathways that FPR2 mediates in neutrophils. RESULTS: FPR2 was activated mainly by mtFPs during the acute phase of IRI, mediating neutrophil migration and reactive oxygen species production in the rat kidney through the ERK1/2 pathway. FPR2 blockade in the early phase protected rat kidneys from IRI. CONCLUSIONS: mtFPs activated FPR2 during the acute phase of IRI and mediated rat kidney injury by activating the migration and reactive oxygen species generation of neutrophils through the ERK1/2 pathway.

Associations between Visual Acuity and Cognitive Decline in Older Adulthood: A 9-Year Longitudinal Study.

OBJECTIVE: Emerging evidence suggests low vision may be a modifiable risk factor for cognitive decline. We examined effects of baseline visual acuity (VA) on level of, and change in, cognitive test performance over 9 years. METHOD: A population-based sample of 1,621 participants (average age 77 years) completed a comprehensive neuropsychological evaluation and VA testing at baseline and reassessed at nine subsequent annual visits. Linear regression modeled the association between baseline VA and concurrent cognitive test performance. Joint modeling of a longitudinal sub-model and a survival sub-model to adjust for attrition were used to examine associations between baseline VA and repeated cognitive test performance over time. RESULTS: Better baseline VA was associated cross-sectionally with younger age, male sex, greater than high school education, and higher baseline neuropsychological test scores on both vision-dependent (B coefficient range -0.163 to -0.375, p = .006 to <.001) and vision-independent tests (-0.187 to -0.215, p = .003 to .002). In longitudinal modeling, better baseline VA was associated with slower decline in vision-dependent tests (B coefficient range -0.092 to 0.111, p = .005 to <.001) and vision-independent tests (-0.107 to 0.067, p = .007 to <.001). CONCLUSIONS: Higher VA is associated with higher concurrent cognitive abilities and slower rates of decline over 9 years in both vision-dependent and vision-independent tests of memory, language, and executive functioning. Findings are consistent with emerging literature supporting vision impairment in aging as a potentially modifiable risk factor for cognitive decline. Clinicians should encourage patient utilization of vision assessment and correction with the added aim of protecting cognition.

Predictors of Driving Cessation in Older Adults: A 12-year Population-based Study.

BACKGROUND: Changes in physical health and cognition during aging can result in some older adults to stop driving. In this population-based longitudinal study, we describe potential predictors of driving cessation in older adults. METHODS: Age-stratified random population cohort of 1982 adults aged 65 years and older drawn from voter registration lists. Participant characteristics were measured using demographics, physical and self-rated health, sleeping habits, driving status, cognitive screening, modified Center for Epidemiologic Studies-Depression scale, clinical dementia rating, and mini-mental state examination. RESULTS: Over 12 years of follow-up, 390 participants stopped driving. These individuals were older, more likely to be women and to have a clinical dementia rating score ≥1, had worse self-reported health, and more symptoms of depression, compared with those who were still driving. In addition, individuals with lower test performance in all cognitive domains, loss of visual acuity and fields, and bilateral hearing loss were more likely to stop driving. CONCLUSIONS: Age, sex, cognitive impairments, physical health, and depressive symptoms were associated with driving cessation in this cohort. By identifying potential driving cessation predictors, health care providers and families may better recognize these risk factors and begin the driving cessation discussion early.

Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM.

Renal fibrosis is a common pathological feature and outcome of almost all chronic kidney diseases, and it is characterized by metabolic reprogramming toward aerobic glycolysis. Mesenchymal stem cell-derived exosomes (MSC-Exos) have been proposed as a promising therapeutic approach for renal fibrosis. In this study, we investigated the effect of MSC-Exos on glycolysis and the underlying mechanisms. We demonstrated that MSC-Exos significantly ameliorated unilateral ureter obstruction (UUO)-induced renal fibrosis by inhibiting glycolysis in tubular epithelial cells (TECs). miRNA sequencing showed that miR-21a-5p was highly enriched in MSC-Exos. Mechanistically, miR-21a-5p repressed the expression of phosphofructokinase muscle isoform (PFKM), a rate-limiting enzyme of glycolysis, thereby attenuating glycolysis in TECs. Additionally, knockdown of miR-21a-5p abolished the renoprotective effect of MSC-Exos. These findings revealed a novel role for MSC-Exos in the suppression of glycolysis, providing a new insight into the treatment of renal fibrosis.

Estimation of Mycophenolic Acid Exposure in Chinese Renal Transplant Patients by a Joint Deep Learning Model.

BACKGROUND: To predict mycophenolic acid (MPA) exposure in renal transplant recipients using a deep learning model based on a convolutional neural network with bilateral long short-term memory and attention methods. METHODS: A total of 172 Chinese renal transplant patients were enrolled in this study. The patients were divided into a training group (n = 138, Ruijin Hospital) and a validation group (n = 34, Zhongshan Hospital). Fourteen days after renal transplantation, rich blood samples were collected 0-12 hours after MPA administration. The plasma concentration of total MPA was measured using an enzyme-multiplied immunoassay technique. A limited sampling strategy based on a convolutional neural network-long short-term memory with attention (CALS) model for the prediction of the area under the concentration curve (AUC) of MPA was established. The established model was verified using the data from the validation group. The model performance was compared with that obtained from multiple linear regression (MLR) and maximum a posteriori (MAP) methods. RESULTS: The MPA AUC 0-12 of the training and validation groups was 54.28 ± 18.42 and 41.25 ± 14.53 µg·ml -1 ·h, respectively. MPA plasma concentration after 2 (C 2 ), 6 (C 6 ), and 8 (C 8 ) hours of administration was the most significant factor for MPA AUC 0-12 . The predictive performance of AUC 0-12 estimated using the CALS model of the validation group was better than the MLR and MAP methods in previous studies (r 2 = 0.71, mean prediction error = 4.79, and mean absolute prediction error = 14.60). CONCLUSIONS: The CALS model established in this study was reliable for predicting MPA AUC 0-12 in Chinese renal transplant patients administered mycophenolate mofetil and enteric-coated mycophenolic acid sodium and may have good generalization ability for application in other data sets.

Assessing Social Cognition in Older Adults: A Population-Based Study.

OBJECTIVES: In a population-based study of mild cognitive impairment (MCI), to validate the assessment of social cognition in older adults. METHODS: Cross-sectional study of 902 adults aged 65+ with mean age 76.6 years (SD 8.06). We created a social cognition composite comprising standardized z scores on the Social Norms Questionnaire and the 10-item Reading the Mind in the Eyes Test. We identified associated factors and compared sensitivity, specificity, and the area under the curve of social cognition, for MCI defined as Clinical Dementia Rating (CDR)=0.5, to those of other cognitive domains. We calculated the impact of including social cognition on the proportion neuropsychologically classified as MCI. RESULTS: Better social cognition was associated with younger age, female sex, higher education, better general cognition (mini-mental state examination), fewer depressive symptoms, and lower CDR. Adjusting for demographics, associations with mini-mental state examination, depressive symptoms, anxiety symptoms, and subjective cognitive complaints remained significant. The sensitivity and specificity of social cognition for CDR=0.5 were comparable to those of the traditional 5 cognitive domains. Including social cognition as a sixth domain of cognition resulted in a 5% increase in the proportion classified as MCI. CONCLUSIONS: Brief objective assessment of social cognition may enhance cognitive assessment of older adults.

Driving Habits of Older Adults: A Population-based Study.

OBJECTIVES: To describe factors associated with driving history, habits, and self-reported driving difficulties of 1982 older adults in a population-based survey. SETTING: This was a community setting. PARTICIPANTS: Age-stratified random population sample drawn from publicly available voter registration list. DESIGN: Participants underwent assessments including cognitive testing and self-reported current and past driving status, instrumental activities of daily living, self-rated health, social supports, physical limitations, and depressive symptoms. We built multivariable logistic regression models to identify factors associated with never having driven, having ceased driving, and reporting difficulties while driving. RESULTS: In the multivariable model, "never drivers" were more likely than "ever drivers" to be older, female, less educated and to leave home less frequently. Former drivers were significantly older, more likely to be women, have lower test performance in the cognitive domain of attention, have more instrumental activity of daily living difficulties, leave home less frequently and have visual field deficits in the right eye than current drivers. Current drivers with reported driving difficulties were more likely than those without difficulties to have lower test performance in attention but higher in memory, were more likely to report depressive symptoms and to have both vision and hearing loss. CONCLUSION: Age, female sex, marital status, and education appear to be associated with driving cessation. Cognitive and functional impairments, mood symptoms and physical health also seem to influence driving cessation and reduction. Our findings may have implications for clinicians in assessing and educating their patients and families on driving safety.

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation.

BACKGROUND: In the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model. METHODS: Microarray data of rat gene expression profiles under accession number GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba. RESULTS: Three hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes. CONCLUSIONS: These key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.

CYP4B1 is a prognostic biomarker and potential therapeutic target in lung adenocarcinoma.

CYP4B1 belongs to the mammalian CYP4 enzyme family and is predominantly expressed in the lungs of humans. It is responsible for the oxidative metabolism of a wide range of endogenous compounds and xenobiotics. In this study, using data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database, a secondary analysis was performed to explore the expression profile of CYP4B1, as well as its prognostic value in patients with lung adenocarcinoma (LUAD). Based on the obtained results, a significantly decreased CYP4B1 expression was discovered in patients with LUAD when compared with their normal counterparts (p<0.05), and was linked to age younger than 65 years (p = 0.0041), history of pharmaceutical (p = 0.0127) and radiation (p = 0.0340) therapy, mutations in KRAS/EGFR/ALK (p = 0.0239), and living status of dead (p = 0.0026). Survival analysis indicated that the low CYP4B1 expression was an independent prognostic indicator of shorter survival in terms of overall survival (OS) and recurrence-free survival (RFS) in patients with LUAD. The copy number alterations (CNAs) and sites of cg23440155 and cg23414387 hypermethylation might contribute to the decreased CYP4B1 expression. Gene set enrichment analysis (GSEA) suggested that CYP4B1 might act as an oncogene in LUAD by preventing biological metabolism pathways of exogenous and endogenous compounds and enhancing DNA replication and cell cycle activities. In conclusion, CYP4B1 expression may serve as a valuable independent prognostic biomarker and a potential therapeutic target in patients with LUAD.

Microfluidics for the rapid detection of Escherichia coli O157:H7 using antibody-coated microspheres.

This study developed a novel method for the rapid detection of Escherichia coli (E. coli) O157:H7 on a microfluidic platform. First, the concentration of bacteria in a sample was determined with the adenosine triphosphate (ATP) method. Then, the specific detection of E. coli was achieved in a microfluidic chip by the immune-microsphere technique. The influences of the culture time, flow rate and capture time on the detection of the target bacteria were investigated systematically. Generally, with increasing capture time, more bacteria could be captured by the microspheres, which had a positive effect on bacterial detection. Furthermore, the sensitivity and specificity of the method were also tested. The results showed that this method could specifically detect E. coli with a sensitivity as high as 49.1 cfu/µL; the consumption of bacteria was 1 µL, and the reagent was at the microliter level. The testing time can be controlled within one and a half hours, and the cost of testing was approximately RMB 10. The method described in this article is simple and accurate and has great application value in bacterial detection for medical diagnostics.

Cause-specific quantile regression on inactivity time.

In time-to-event analysis, the traditional summary measures have been based on the hazard function, survival function, quantile event time, restricted mean event time, and residual lifetime. Under competing risks, furthermore, typical summary measures have been the cause-specific hazard function and cumulative incidence function. Recently inactivity time has recaptured attention in the literature, being interpreted as life lost. In this paper, we further interpret it as quality of life reduced and time period after transition to a drug, and propose a quantile regression model to associate the inactivity time with potential predictors under competing risks. We define the proper cumulative distribution function of the inactivity time distribution for each specific event type among those subjects who experience the same type of events during a follow-up period. A score function-type estimating equation is developed and asymptotic properties of the regression coefficient estimators are derived by assuming that competing events are censored at their occurrence times as in the cause-specific hazard analysis. The proposed approach reduces to a regular quantile regression on the inactivity time without competing risks when all types of competing events are collapsed into the same type. Due to difficulty in estimating the improper probability density function of the cause-specific inactivity distribution to evaluate the variance of the quantiles, a computationally efficient perturbation method is adopted to infer the regression coefficients. Simulation results show that our proposed method works well under the assumed finite sample settings. The proposed method is illustrated with a real dataset from a breast cancer study.

Cognitive Functions Predict Trajectories of Sleepiness Over 10 Years: A Population-Based Study.

BACKGROUND: Excessive daytime sleepiness is associated with chronic disorders of aging and mortality. Because longitudinal data are limited on the development of sleep disturbances and cognitive changes in older adults, we investigated the demographic, clinical, and cognitive predictors of self-reported daytime sleepiness over a period of 10 years. METHODS: We jointly modeled latent trajectories over time of sleepiness, cognitive domains, and informative attrition and then fit models to identify cognitive trajectories and baseline characteristics that predicted the trajectories of sleepiness. RESULTS: Three latent trajectory groups were identified: emerging sleepiness, persistent sleepiness, and consistently low daytime sleepiness accounting for attrition in all groups. Compared with low sleepiness, emerging sleepiness was significantly associated with declining attention and subjective memory complaints; persistent sleepiness was associated with lower baseline scores in all cognitive domains, declining language trajectory, and more subjective memory complaints. CONCLUSIONS: These findings suggest that persistent sleepiness and emerging daytime sleepiness are associated with cognitive decline and multiple morbidities, albeit more subtly in emerging daytime sleepiness. Furthermore, these data suggest that change in the cognitive domain of attention and subjective memory complaints may be early indicators of future sleep disturbance.

Aging and Functional Health Literacy: A Population-based Study.

OBJECTIVES: To investigate functional health literacy and its associated factors among older adults drawn from a disadvantaged area. DESIGN: Cross-sectional epidemiologic study. SETTING: Population-based cohort randomly selected from the voter registration lists. PARTICIPANTS: Individuals aged 65+ (N=1066). MEASUREMENTS: The Short Test of Functional Health Literacy in Adults (S-TOFHLA); demographics; self-rated health; number of prescription drugs; modified Center for Epidemiologic Studies- Depression scale; Mini-Mental State Examination; Wechsler Test of Adult Reading; Clinical Dementia Rating; cognitive domain composite scores; independence in Instrumental Activities of Daily Living and medication management; health services utilization (emergency/urgent care visits and hospitalizations). RESULTS: Low (inadequate or marginal) S-TOFHLA scores were obtained by 7.04% of the sample. In unadjusted analyses, participants with low S-TOFHLA scores were significantly more likely than those with higher scores to be older, male, non-White, with lesser education and lower household income, to have lower scores on the Wechsler Test of Adult Reading, the Mini-Mental State Examination, and all cognitive domains; to be more dependent in Instrumental Activities of Daily Living and be taking more prescription drugs. In a multiple regression model including all covariates, only older age, male sex, and lower reading level were independently associated with inadequate or marginal S-TOFHLA scores. CONCLUSION: In a population-based sample of older adults, low functional health literacy was associated with age, sex, education, and reading ability. Basic functional health literacy is essential for understanding health information and instructions. Clinicians should formally or informally assess health literacy in their older patients to ensure effective communication and enhance health outcomes.

Reading the Mind in the Eyes: A Population-Based Study of Social Cognition in Older Adults.

BACKGROUND: Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the social cognition mechanism which forms the root of empathy. OBJECTIVES: To describe the distribution of, and factors associated with, scores on a 10-item version of Reading the Mind in the Eyes Test (RMET-10) in older adults. DESIGN: Population-based cross-sectional study. SETTING: Small-town communities in Pennsylvania. PARTICIPANTS: Adults aged 66-105 years (N = 902, mean age = 76.6). MEASUREMENTS: The assessment included RMET-10, demographics, cognitive screening, literacy, depression symptoms, anxiety symptoms, cognitive composites derived from a neuropsychological test battery, Social Norms Questionnaire, and Clinical Dementia Rating (CDR). RESULTS: RMET-10 score was normally distributed in our overall study sample. Normative RMET-10 scores among those rated as CDR = 0 were calculated by age, sex, and education. RMET-10 score was significantly higher with younger age, higher education, white race, higher cognitive screening scores, literacy, social norms scores, higher scores in all five domains in cognitive composites, and lower CDR. RMET-10 score was also significantly higher with fewer depression and anxiety symptoms after adjusting for demographics. CONCLUSIONS: The RMET is a potentially useful measure of social cognition for use in the research assessment of older adults. With appropriate calibration it should also have utility in the clinical setting.

Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation.

Renal ischemia-reperfusion injury (IRI) after renal transplantation often leads to the loss of kidney graft function. However, there is still a lack of efficient regimens to prevent or alleviate renal IRI. Our study focused on the renoprotective effect of 3-Deazaneplanocin A (DZNep), which is a histone methylation inhibitor. We found that DZNep significantly alleviated renal IRI by suppressing nuclear factor kappa-B (NF-κB), thus inhibiting the expression of inflammatory factors in renal tubular epithelial cells in vivo or in vitro. After treatment with DZNep, T cell activation was impaired in the spleen and kidney, which correlated with the downregulated expression of T-cell immunoglobulin mucin (TIM)-1 on T cells and TIM-4 in macrophages. In addition, pretreatment with DZNep was not sufficient to protect the kidney, while administration of DZNep from before to after surgery significantly ameliorated IRI. Our findings suggest that DZNep can be a novel strategy for preventing renal IRI following kidney transplantation.