Social Inequities in the Survival of Liver Cancer: A Nationwide Cohort Study in Korea, 2007-2017.

BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

Correlation Between Computed Tomography Findings and the Laboratory Test-Derived Severity Score in Patients With Severe Acute Alcoholic Hepatitis.

OBJECTIVE: This study aimed to compare computed tomography (CT) findings between patients with severe and nonsevere acute alcoholic hepatitis (AAH). METHODS: We included 96 patients diagnosed with AAH between January 2011 and October 2021 who underwent 4-phase liver CT and laboratory blood tests. Two radiologists reviewed the initial CT images with respect to distribution and grade of hepatic steatosis; transient parenchymal arterial enhancement (TPAE); and presence of cirrhosis, ascites, and hepatosplenomegaly. A Maddrey discriminant function score (4.6 × [patient's prothrombin time - control] + total bilirubin [mg/mL]) was used as cutoff indicator for severity, with a score of 32 or higher indicating severe disease. The image findings were compared between the severe (n = 24) and nonsevere (n = 72) groups using the χ 2 test or Fisher exact test. After univariate analysis, the most significant factor was identified using a logistic regression analysis. RESULTS: In the univariate analysis, there were significant between-group differences in the TPAE, liver cirrhosis, splenomegaly, and ascites ( P < 0.0001, P < 0.0001, P = 0.0002, and P = 0.0163, respectively). Among them, TPAE was the only significant factor for severe AAH ( P < 0.0001; odds ratio, 48.1; 95% confidence interval, 8.3-280.6). Using this single indicator, the estimated accuracy, positive predictive, and negative predictive values were 86%, 67%, and 97%, respectively. CONCLUSIONS: Transient parenchymal arterial enhancement was the only significant CT finding in severe AAH.

Widening Social Inequalities in Cancer Mortality of Children Under 5 Years in Korea.

BACKGROUND: To investigate the effect of parental social class on cancer mortality in children under 5 in Korea, two birth cohorts were constructed by linking national birth data to under-5 death data from the Statistics Korea for 1995-1999 (3,323,613 births) and 2010-2014 (2,297,876 births). METHODS: The Cox proportional hazards model adjusted for covariates was used in this study. RESULTS: Social inequalities of under-5 cancer mortality risk in paternal education and paternal employment status were greater in 2010-2014 than in 1995-1999. The gap of hazard ratio (HR) of under-5 cancer mortality between lower (high school or below) and higher (university or higher) paternal education increased from 1.23 (95% confidence interval, 1.041.46) in 1995-1999 to 1.45 (1.11-1.97) in 2010-2014; the gap of HR between parents engaged in manual work and non-manual work increased from 1.32 (1.12-1.56) in 1995-1999 to 1.45 (1.12-1.89) in 2010-2014 for fathers, and from 1.18 (0.7-1.98) to 1.69 (1.03-2.79) for mothers. When the parental social class was lower, the risk of under-5 cancer mortality was higher in not only adverse but normal births. CONCLUSION: Social inequalities must be addressed to reduce the disparity in cancer mortality of children under 5 years old.

Development of aptamers for rapid airborne bacteria detection.

Airborne microbes can rapidly spread and cause various infectious diseases worldwide. This necessitates the determination of a fast and highly sensitive detection method. There have been no studies on receptors targeting Citrobacter braakii (C. braakii), a pathogenic bacterium which can exist in the air. In this study, we rapidly isolate an aptamer, a nucleic acid molecule that can specifically bind to C. braakii by centrifugation-based partitioning method (CBPM) reported previously by our groups as omitting the repeated rounds of binding incubation, separation, and amplification that are indispensable for SELEX. The binding affinity and specificity of isolated aptamers are checked using bacteria in liquid culture and recollection solution from aerosolized bacteria. Recollection solutions of the recovered bacteria are obtained by nebulizing, drying, and recapturing with a biosampler. The CB-5 aptamer shows high affinity and specificity for C. braakii (Kd: 16.42 in liquid culture and 26.91 nM in recollection from aerosolized sample). Our results indicate the current protocol can be employed for the rapid development of reliable diagnostic receptors targeting airborne bacteria.

An Innovative Way to Turn Catalyst into Substrate for Highly Efficient Water Splitting.

The energy-efficiency loss with high overpotential during hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), as well as economic inefficiencies including high-cost materials and complicated processes, is considered the major challenge to the implementation of electrochemical water splitting applications. The authors present a new platform for electrocatalysts that functions in an unprecedented way to turn a catalyst into substrate. The NiFe alloy catalyzed substrate (NiFe-CS) described herein is substantially active and stable electrocatalyst for both HER and OER, with low overpotential of 33 and 191 mV at 10 mA cm-2 for HER and OER, respectively. This structure enables not only the maximization of electrochemically active sites, but also the formation of hydroxyl species on the surface as the active phase. These outstanding results provide a new pathway for the development of electrocatalysts used in energy conversion technology.

Correction: Specific detection of Cronobacter sakazakii in powdered infant formula using ssDNA aptamer.

Correction for 'Specific detection of Cronobacter sakazakii in powdered infant formula using ssDNA aptamer' by Hye Ri Kim et al., Analyst, 2021, 146, 3534-3542, DOI: .

Specific detection of Cronobacter sakazakii in powdered infant formula using ssDNA aptamer.

Cronobacter sakazakii (C. sakazakii) is a foodborne pathogen associated with bacterial meningitis, sepsis, and necrotizing enterocolitis in premature and immuno-compromised infants. C. sakazakii is typically acquired by ingesting contaminated powdered infant formula (PIF). The growing demand for a safe food supply requires rapid detection of foodborne pathogens for delivering safe-to-consume food to consumers. In the present study, we isolated C. sakazakii-specific aptamers using a centrifugation-based partitioning method (CBPM) instead of systematic evolution of ligands by exponential enrichment (SELEX) process. Unlike SELEX, the CBPM reduces the evolution-loop time to obtain enriched probes, allowing the isolation of target-specific aptamers in a shorter time. The two aptamers (SC25 and SC45) isolated using the CBPM showed high affinity and specificity for C. sakazakii (Kd: 34 and 66 nM). Among the two aptamers, SC25 aptamer detected efficiently C. sakazakii in PIF with less cross-reactivity. Our results indicate that the isolated aptamers could be used for detecting C. sakazakii in PIF and reducing the overall testing time compared with the conventional C. sakazakii detection method.

Rapid isolation of bacteria-specific aptamers with a non-SELEX-based method.

Usually, isolation of bacteria-specific aptamers by SELEX is a time-consuming process due to the required repeated rounds of binding, separation, and amplification of the probes to target bacteria. Here, we show that it is possible to isolate bacteria-specific DNA aptamers omitting the repeated rounds of binding incubation, separation, and amplification that are indispensable for SELEX. The serial removal of unbound DNAs to the bacterial cells from an initial mixture of bacteria and DNA libraries through serial centrifugation, one-time separation, and further one-time amplification of DNA bound to the target bacterial cells applied in this non-SELEX-based method allows successful aptamer isolation.

Effects of Repetitive Transcranial Magnetic Stimulation on Improvement of Mental Health and Clinical Parameters in Depressed Hemodialysis Patients: a Pilot Study.

BACKGROUND: This study aimed to evaluate the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacologic treatment in depressed hemodialysis patients. METHODS: Patients who scored ≥ 5 on the Patient Health Questionnaire-9 were randomized to either the rTMS (n = 7) or sham group (n = 7). The rTMS group was stimulated with a 110% motor threshold and 10 Hz on the left dorsolateral prefrontal cortex for 20 minutes, three times a week, for 4 weeks. In the sham group, the "1-wing 90-degree method" was used. We analyzed clinical indices before and after the intervention, as well as data from quantitative electroencephalography (frontal alpha asymmetry [FAA]), and various psychiatric questionnaires (Beck Depression Inventory-II, Beck Anxiety Inventory [BAI], Symptom Checklist-90-Revised Somatization Subscale [SCL-90R-SOM]), and Perceived Stress Scale. RESULTS: One month after rTMS, the changes in hemoglobin A1c levels in the rTMS group were significantly greater than those in the sham group (F = 6.687, P = 0.032). The changes in BAI scores in the rTMS group were significantly greater than those in the sham group (F = 6.700, P = 0.025), and the changes in SCL-90R-SOM scores in the rTMS group were greater than those in the sham group (F = 4.943, P = 0.048). In addition, the changes in the FAA value at the F7 and F8 electrodes in the rTMS group were greater than those in the sham group (F = 6.468, P = 0.027). CONCLUSION: In depressed hemodialysis patients, rTMS may improve anxiety and somatization symptoms, which may lead to improvements in clinical measures. Trial Registration Clinical Research Information Service Identifier: KCT0004082.

Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a pilot randomized controlled trial.

STUDY DESIGN: A pilot randomized controlled trial. OBJECTIVES: To evaluate the clinical efficacy of upper limb robotic therapy in people with tetraplegia. SETTING: Inpatient rehabilitation hospital in Seoul, Korea. METHODS: Participants were randomly allocated to a robotic therapy (RT) or occupational therapy (OT) group. Both groups received usual care plus 30 min of additional therapy per day for 4 weeks. The additional therapy provided to the OT group was OT, and the additional therapy provided to RT group was RT using the Armeo Power. Primary outcomes were the Medical Research Council scale of each key muscle and Upper Extremity Motor Score (UEMS) for the trained arm. Secondary outcomes were the Spinal Cord Independence Measurement version III (SCIM-III) subscale and total score. Evaluations were performed at baseline and 4 weeks. RESULTS: A total of 34 individuals with tetraplegia were included; 17 in each group. At 4 weeks, the median (IQR) change in UEMS in the RT group was 1/25 (0 to 3) points compared with 0/25 (-1 to 1) points in the OT group (p = 0.03). The median (IQR) change in total SCIM-III score in the RT group was 7/100 (1.5 to 11) points compared with 0/100 (-8 to 4) points in the OT group (p < 0.01). CONCLUSIONS: There were small improvements in motor strength and SCIM-III scores in the RT group, but there were no statistically significant differences between the groups. Further studies are required for a better understanding of the effects of RT for people with tetraplegia.

Correction: Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a pilot randomized controlled trial.

In the original version of the article the authors incorrectly stated that: "One case study provided evidence of some improvements in motor performance and spasticity [19], while several other studies only provided evidence on the feasibility of UER as an assessment tool; however, the fact that the manufacturer funded these studies lessens their objectivity [15, 20-24]." This is not correct as the manufacturers did not fund the studies. The correct phrase therefore should have read: "One case study provided evidence of some improvements in motor performance and spasticity [19], while several other studies provided evidence focusing more on the feasibility of UER rather than the clinical efficacy [15, 20-24]." The authors would like to apologise for this error.This has been corrected in both the PDF and HTML versions of the Article.

A Fluorescent Probe for Stimulated Emission Depletion Super-Resolution Imaging of Vicinal-Dithiol-Proteins on Mitochondrial Membrane.

Realizing the significant roles of vicinal-dithiol proteins (VDPs) in maintaining the cellular redox homeostasis and their implication in many diseases, we synthesized a smart arsenate based fluorescent probe 1 which can preferentially target the mitochondrial membrane-bound vicinal dithiol proteins (VDPs), especially voltage-dependent anion channel (VDAC2). The probe targetability was demonstrated by in vitro studies such as colocalization, stimulated emission depletion (STED) super-resolution imaging, proteomic MS/MS analysis, and Western blot analysis. The probe represents a rare example of fluorescence labeling of mitochondrial membrane-bound VDPs and can provide a new way to construct VDPs-specific fluorescent probes to gain deeper understanding of their roles in mitochondrial-related disorders.

Character strengths as protective factors against depression and suicidality among male and female employees.

BACKGROUND: So far, studies on workplace mental health have only focused on work-related environmental risk factors, disregarding both protective and individual factors of employees. Therefore, we aimed to identify character strengths that act as protective factors against depressive moods and suicidality in Korean employees. METHODS: In total, 84 male and 151 female employees (aged 19-50 years) reported their sociodemographic characteristics; depressive symptoms, as measured by the Beck Depression Inventory-II; suicidality, as measured by the Korean version of the MINI International Neuropsychiatric Interview suicidality module; and character strengths, as measured by the 24 Character Strength Alphas on the Values in Action Survey-72. We conducted a hierarchical logistic regression, in which depressive mood and suicidality served as the categorical outcome variables. RESULTS: In females, scores on the "curiosity" (B = 1.107, Wald = 10.207, odds ratio = 3.026, p = .001) and "love" (B = .862, Wald = 5.767, odds ratio = 2.367, p = .016) sub scales of the 24 Character Strength Alphas on the Values in Action Survey-72 were statistically significant predictors of having depressive mood. Additionally, females' scores on "judgment" (B = - 1.405, Wald = 5.663, odds ratio = .245, p = .017) and "kindness" (B = - 1.456, Wald = 6.486, odds ratio = .233, p = .011) were protective factors against suicidality. In males, the "love" (B = 1.746, Wald = 4.279, odds ratio = 5.729, p = .039) score was a predictor of having depressive mood, while "teamwork" (B = - 2.204, Wald = 4.666, odds ratio = .110, p = .031) and "creativity" (B = - 1.384, Wald = 4.202, odds ratio = .251, p = .040) scores were protective factors against having depressive mood and suicidality, respectively. CONCLUSIONS: We suggest that focusing on "judgement" and "kindness" in female employees, and "teamwork" and "creativity" in male employees, and engaging in activities that use these strengths at the workplace can be protective factors against depression and suicidality. Future research should focus on developing interventions to promote these character strengths among employees at the workplace.

Influence of Major Coping Strategies on Treatment Non-adherence and Severity of Comorbid Conditions in Hemodialysis Patients.

BACKGROUND: Non-adherence and comorbidities are prevalent among hemodialysis patients and are associated with increased mortality and financial burden. We aimed to investigate the influence of major coping strategies (CSs) on non-adherence and comorbidities in hemodialysis patients. METHODS: A total of 49 patients were enrolled. We collected participant data including CS measured by a Korean version of the ways of coping questionnaire (K-WCQ), comorbidities measured by age-adjusted Charlson comorbidity index (CCI), and adherence measured by the 8-item Morisky medication adherence scale (MMAS-8). RESULTS: Regarding major CS, 61.2% of participants reported use of support-seeking CS (SUP group), 14.3% reported use of problem-focused CS (PRO group), and 24.5% reported use of hopeful-thinking CS (HOP group). The mean MMAS-8 score was higher in the PRO group than in the HOP group (P = 0.024). The mean CCI score was lower in the PRO group than in the HOP group (P = 0.017). In the HOP group, the severity of somatic symptoms was positively correlated with the scores for the emotion-focused CS subscale (r = 0.39, P = 0.029) and the hopeful-thinking CS subscale (r = 0.38, P = 0.036) of the K-WCQ. The level of life satisfaction positively correlated with the score for the problem-focused CS subscale in the HOP group (r = 0.40, P = 0.027). CONCLUSION: We should pay more attention to the CSs of hemodialysis patients and provide interventions that promote problem-focused CSs, especially for nonadherent patients with high comorbidity rates who mainly use a hopeful-thinking CS.

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 (306VQIVYK311) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aß-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aß plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease.

BACKGROUND: PEA-15 is abundantly expressed in both neurons and astrocytes throughout the brain. It is a multifunctional protein with the ability to increase cell survival via anti-apoptotic and anti-proliferative properties. However, the function of PEA-15 in neuronal diseases such as Parkinson's disease (PD) remains unclear. In this study, we investigated the protective effects of PEA-15 on neuronal damage induced by MPP(+) in neuroblastoma SH-SY5Y and BV2 microglia cells and in a MPTP-induced PD mouse model using cell-permeable PEP-1-PEA-15. METHODS: PEP-1-PEA-15 was purified using affinity chromatography. Cell viability and DNA fragmentation were examined by MTT assay and TUNEL staining. Dopaminergic neuronal cell death in the animal model was examined by immunohistochemistry. RESULTS: PEP-1-PEA-15 transduced into the SH-SY5Y and BV2 cells in a time- and dose-dependent manner. Transduced PEP-1-PEA-15 protected against MPP(+)-induced toxicity by inhibiting intracellular ROS levels and DNA fragmentation. Further, it enhanced the expression levels of Bcl-2 and caspase-3 while reducing the expression levels of Bax and cleaved caspase-3. We found that PEP-1-PEA-15 transduced into the substantia nigra and prevented dopaminergic neuronal cell death in a MPTP-induced PD mouse. Also, we showed the neuroprotective effects in the model by demonstrating that treatment with PEP-1-PEA-15 ameliorated MPTP-induced behavioral dysfunctions and increased dopamine levels in the striatum. CONCLUSIONS: PEP-1-PEA-15 can efficiently transduce into cells and protects against neurotoxin-induced neuronal cell death in vitro and in vivo. GENERAL SIGNIFICANCE: These results demonstrate the potential for PEP-1-PEA-15 to provide a new strategy for protein therapy treatment of a variety of neurodegenerative diseases including PD.

Side population in LX2 cells decreased by transforming growth factor-ß.

AIM: Side population (SP) cells are known to be enriched in stem/progenitor-like cells. Transforming growth factor (TGF)-ß signaling is associated with extracellular matrix (ECM) production in hepatic stellate cells. We hypothesized that the SP fraction in LX2 cells is associated with ECM deposition, which is regulated through TGF-ß signaling. METHODS: We investigated the relationship between SP cells and TGF-ß signaling in the hepatic stellate cell line LX2. The effects of TGF-ß and SB431542 on the SP fraction and expression of collagen type I and phospho-Smad2 was determined. RESULTS: We identified 0.8-3% SP cells in LX2 cells. The growth rate of sorted SP and non-SP cells was similar to that of the original LX2 population, but population of the G0/G1 phase was increased in SP cells. Treatment of LX2 cells with TGF-ß decreased the SP fraction in a dose-dependent manner and increased the production of collagen type I. Treatment of LX2 cells with SB431542 blocked the effect of TGF-ß on the SP fraction and the expression of collagen type I. We cultured LX2 cells on collagen-coated dishes to observe the effect of ECM deposition on the SP fraction. The growth rate and cell cycle distribution was similar to that observed on normal tissue culture dishes, but the SP fraction was decreased when LX2 cells were cultured on collagen-coated plates. CONCLUSION: These results show that LX2 cells contain an SP fraction and that TGF-ß signaling is involved in the induction of ECM deposition as well as the number of SP cells.

Group selective aptamers: Broad-spectrum recognition of target groups in Cronobacter species and implementation of electrochemical biosensors as receptors.

Aptamers are a versatile class of receptors with a high affinity and selectivity for specific targets. Although their ability to recognize individual targets has been extensively studied, some scenarios require the development of receptors capable of identifying all target groups. This study investigated the use of aptamers to achieve the broad-spectrum recognition of groups instead of individual targets. Aptamers were screened for selectively distinct groups of Cronobacter species associated with foodborne diseases. Seven Cronobacter spp. were divided into Group A (C. sakazakii, C. malonaticus, C. turicensis, and C. muytjensii) and Group B (C. dublinensis, C. condimenti, and C. universalis). Aptamers with exclusive selectivity for each group were identified, allowing binding to the species within their designated group while excluding those from the other group. The screened aptamers demonstrated reliable affinity and specificity with dissociation constants ranging from 1.3 to 399.7 nM for Group A and 4.0-24.5 nM for Group B. These aptamers have also been successfully employed as receptors in an electrochemical biosensor platform, enabling the selective detection of each group based on the corresponding aptamer (limit of detection was 7.8 and 3.2 CFU for Group A and Group B, respectively). The electrochemical sensor effectively detected the extent of infection in each group in powdered infant formula samples. This study highlights the successful screening and application of group-selective aptamers as sensing receptors, emphasizing their potential for diverse applications in different fields such as food safety, environmental monitoring, and clinical diagnostics, where the selective biosensing of target groups is crucial.

Evaluation of Extra-Prostatic Extension on Deep Learning-Reconstructed High-Resolution Thin-Slice T2-Weighted Images in Patients with Prostate Cancer.

The aim of this study was to compare diagnostic performance for extra-prostatic extension (EPE) and image quality among three image datasets: conventional T2-weighted images (T2WIconv, slice thickness, 3 mm) and high-resolution thin-slice T2WI (T2WIHR, 2 mm), with and without deep learning reconstruction (DLR) in patients with prostatic cancer (PCa). A total of 88 consecutive patients (28 EPE-positive and 60 negative) diagnosed with PCa via radical prostatectomy who had undergone 3T-MRI were included. Two independent reviewers performed a crossover review in three sessions, in which each reviewer recorded five-point confidence scores for the presence of EPE and image quality using a five-point Likert scale. Pathologic topographic maps served as the reference standard. For both reviewers, T2WIconv showed better diagnostic performance than T2WIHR with and without DLR (AUCs, in order, for reviewer 1, 0.883, 0.806, and 0.772, p = 0.0006; for reviewer 2, 0.803, 0.762, and 0.745, p = 0.022). The image quality was also the best in T2WIconv, followed by T2WIHR with DLR and T2WIHR without DLR for both reviewers (median, in order, 3, 4, and 5, p < 0.0001). In conclusion, T2WIconv was optimal in regard to image quality and diagnostic performance for the evaluation of EPE in patients with PCa.

Autophagy suppresses interleukin-1ß (IL-1ß) signaling by activation of p62 degradation via lysosomal and proteasomal pathways.

ATG16L1 is an essential component of the autophagasome. The T300A allele of ATG16L1 is associated with the increased susceptibility to Crohn disease. In this study, we identified a novel function of ATG16L1, which suppresses signaling of the pro-inflammatory cytokine IL-1ß. Deletion of ATG16L1 in mouse embryonic fibroblasts significantly amplifies IL-1ß signal transduction cascades. This amplification is due to elevated p62 levels in ATG16L1-deficient cells. We found that ATG16L1 regulates p62 levels via both autolysosomal and proteasomal pathways. For proteasomal degradation, we found that Cullin-3 (Cul-3) is a E3 ubiquitin ligase of p62 and that ATG16L1 is essential for neddylation of Cul-3, a step required for Cul-3 activation. Taken together our data indicate that loss-of-function of ATG16L1 results in a hyper-responsiveness to the IL-1ß signaling because of the increased p62 level.