Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells.

Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

A chemical probe to modulate human GID4 Pro/N-degron interactions.

The C-terminal to LisH (CTLH) complex is a ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via its substrate receptor Glucose-Induced Degradation 4 (GID4), but its function and substrates in humans remain unclear. Here, we report PFI-7, a potent, selective and cell-active chemical probe that antagonizes Pro/N-degron binding to human GID4. Use of PFI-7 in proximity-dependent biotinylation and quantitative proteomics enabled the identification of GID4 interactors and GID4-regulated proteins. GID4 interactors are enriched for nucleolar proteins, including the Pro/N-degron-containing RNA helicases DDX21 and DDX50. We also identified a distinct subset of proteins whose cellular levels are regulated by GID4 including HMGCS1, a Pro/N-degron-containing metabolic enzyme. These data reveal human GID4 Pro/N-degron targets regulated through a combination of degradative and nondegradative functions. Going forward, PFI-7 will be a valuable research tool for investigating CTLH complex biology and facilitating development of targeted protein degradation strategies that highjack CTLH E3 ligase activity.

Imaging classification of pancreatic ductal adenocarcinoma with histological large duct pattern.

OBJECTIVES: To investigate the imaging features of pancreatic ductal adenocarcinoma (PDAC) with histological large duct pattern. METHODS: Our study included 37 patients (mean age, 66.5 years; 22 women) with surgically proven PDAC with histological large duct pattern, whose imaging features were classified into four types: Type I, solid mass; Type II, predominantly cystic mass with intracystic solid components; Type III, predominantly solid mass with intratumoral cysts; and Type IV, solid mass with peritumoral retention cysts or pseudocysts. Two radiologists independently analyzed both CT and MRI images for the morphological type, presence of abrupt main pancreatic duct (MPD) cutoff, adjacent vascular invasion, diffusion restriction, and reached consensus. RESULTS: On CT, 26 patients (70.3%) had Type I tumors, five (13.5%) had Type II, three (8.1%) had Type III, and three (8.1%) had Type IV. Among the 26 patients with Type I tumors on CT, 16 had tumors with multiple intratumoral cysts within the solid mass on MRI and were subsequently classified as Type III. Accordingly, 10 patients (27.0%) were classified as Type I, five (13.5%) as Type II, 19 (51.7%) as Type III, and three (8.1%) as Type IV on MRI. Of the 37 patients, 27 (73.0%) had an abrupt MPD cutoff, 15 (40.5%) had adjacent vascular invasion, and 25 (67.6%) had diffusion restriction on MRI. CONCLUSIONS: Predominantly solid pancreatic masses with small intratumoral cysts visualized on MRI may be a characteristic imaging finding of PDAC with histological large duct pattern, and differentiate it from conventional PDAC or other cystic pancreatic tumors. CLINICAL RELEVANCE STATEMENT: Radiologists should be familiar with the various imaging features of PDAC with histological large duct pattern and should be aware that it may mimic other solid or cystic tumors of the pancreas. KEY POINTS: Imaging features of pancreatic ductal adenocarcinoma with histological large duct pattern can be classified into four types. This pathology more frequently appears as a predominantly solid mass with intratumoral cysts on MRI than on CT. Adding MRI to CT may help identify pancreatic ductal adenocarcinoma with histological large duct pattern.

A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety.

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

Chemical tools for the Gid4 subunit of the human E3 ligase C-terminal to LisH (CTLH) degradation complex.

We have developed a novel chemical handle (PFI-E3H1) and a chemical probe (PFI-7) as ligands for the Gid4 subunit of the human E3 ligase CTLH degradation complex. Through an efficient initial hit-ID campaign, structure-based drug design (SBDD) and leveraging the sizeable Pfizer compound library, we identified a 500 nM ligand for this E3 ligase through file screening alone. Further exploration identified a vector that is tolerant to addition of a linker for future chimeric molecule design. The chemotype was subsequently optimized to sub-100 nM Gid4 binding affinity for a chemical probe. These novel tools, alongside the suitable negative control also identified, should enable the interrogation of this complex human E3 ligase macromolecular assembly.

Nano-Priming for Inducing Salinity Tolerance, Disease Resistance, Yield Attributes, and Alleviating Heavy Metal Toxicity in Plants.

In today's time, agricultural productivity is severely affected by climate change and increasing pollution. Hence, several biotechnological approaches, including genetic and non-genetic strategies, have been developed and adapted to increase agricultural productivity. One of them is nano-priming, i.e., seed priming with nanomaterials. Thus far, nano-priming methods have been successfully used to mount desired physiological responses and productivity attributes in crops. In this review, the literature about the utility of nano-priming methods for increasing seed vigor, germination, photosynthetic output, biomass, early growth, and crop yield has been summarized. Moreover, the available knowledge about the use of nano-priming methods in modulating plant antioxidant defenses and hormonal networks, inducing salinity tolerance and disease resistance, as well as alleviating heavy metal toxicity in plants, is reviewed. The significance of nano-priming methods in the context of phytotoxicity and environmental safety has also been discussed. For future perspectives, knowledge gaps in the present literature are highlighted, and the need for optimization and validation of nano-priming methods and their plant physiological outcomes, from lab to field, is emphasized.

Enteral Nutrition in Critically Ill Patient With Septic Shock Requiring Vasopressor: Case Report.

Nutritional support in critically ill patients is an essential aspect of treatment. In particular, the benefits of enteral nutrition (EN) are well recognized, and various guidelines recommend early EN within 48 hours in critically ill patients. However, there is still controversy regarding EN in critically ill patients with septic shock requiring vasopressors. Therefore, this case report aims to provide basic data for the safe and effective nutritional support in septic shock patients who require vasopressors. A 62-year-old male patient was admitted to the intensive care unit with a deep neck infection and mediastinitis that progressed to a septic condition. Mechanical ventilation was initiated after intubation due to progression of respiratory acidosis and deterioration of mental status, and severe hypotension required the initiation of norepinephrine. Due to hemodynamic instability, the patient was kept nil per os. Subsequently, trophic feeding was initiated at the time of norepinephrine dose tapering and was gradually increased to achieve 75% of the energy requirement through EN by the 7th day of enteral feeding initiation. Although there were signs of feeding intolerance during the increasing phase of EN, adjusting the rate of EN resolved the issue. This case report demonstrates the gradual progression and adherence to EN in septic shock patient requiring vasopressors, and the progression observed was relatively consistent with existing studies and guidelines. In the future, further case reports and continuous research will be deemed necessary for safe and effective nutritional support in critically ill patients with septic shock requiring vasopressors.

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer.

BACKGROUND: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). AIM: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT. METHODS: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT. RESULTS: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes. CONCLUSION: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

Assessing the impact of mRNA vaccination in chronic inflammatory murine model.

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma: A case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that originates in the central nervous system (CNS) and is exclusively limited to the CNS. Although most PCNSLs are diffuse large B-cell lymphomas, primary CNS T-cell lymphomas (PCNSTLs) are rare. PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, non-enhancing PCNSTL has not been reported previously. CASE SUMMARY: A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks. Initial MRI showed asymmetric T2-hyperintense lesions within the brain. No enhancement was observed on the contrast-enhanced T1 image. The initial diagnosis was neuro-Behçet's disease. Despite high-dose steroid therapy, no alterations in the lesions were identified on initial MRI. The patient's symptoms deteriorated further. An MRI performed one month after the initial scan revealed an increased lesion extent. Subsequently, brain biopsy confirmed the diagnosis of PCNSTL. The patient underwent definitive combined chemo-radiotherapy. However, the patient developed bacteremia and died of septic shock approximately three months after diagnosis. CONCLUSION: The absence of enhancement in the lesion did not rule out PCNSTL. A biopsy approach is advisable for pathological confirmation.

A metal-free strategy to construct fluoroalkyl-olefin linkages using fluoroalkanes.

We present a metal-free strategy to access fluoroalkyl-olefin linkages from fluoroalkane precursors and vinyl-pinacol boronic ester (BPin) reagents. This reaction sequence is templated by the boron reagent, which induces C-C bond formation upon oxidation. We developed this strategy into a one-pot synthetic protocol using RCF2H precursors directly with vinyl-BPin reagents in the presence of a Brønsted base, which tolerated oxygen- and nitrogen-containing heterocycles, and aryl halogens. We also found that HCF3 (HCF-23; a byproduct of the Teflon industry) and CH2F2 (HCF-32; a low-cost refrigerant) are amenable to this protocol, representing distinct strategies to generate RCF2H and RCF3 molecules. Finally, we demonstrate that the vinyldifluoromethylene products can be readily derivatized, representing an avenue for late-stage modification after installing the fluoroalkyl unit.

Moderating Effects of Individual Traits on the Association Between Nature and Patient Wait Experiences.

OBJECTIVES: We empirically investigated to what extent plants in the emergency department (ED) waiting areas influence patient wait experiences (i.e., anxiety, perceived service quality, and perception of wait time) depending on individual differences in cognitive thinking styles and one's bonds with the natural world. BACKGROUND: Positive effects of nature on patient experiences in healthcare environments are well established by empirical research findings. However, evidence is scarce on the impact of nature on patient wait experiences and the roles of patient traits often related to their backgrounds. METHODS: A within-subjects study was conducted (N = 116) with two virtually built ED waiting rooms: with versus without indoor and outdoor plants. RESULTS: Findings confirmed that plants lower anxiety and improve perceptions of service quality and wait time. Cognitive thinking style significantly moderated how plants affected patient wait experiences. Although participants with higher connectedness to nature showed more positive responses to the nature condition, connectedness to nature did not significantly affect the association between nature and wait experiences. CONCLUSIONS: This study contributes to the existing body of knowledge on nature's effects in healthcare environments by examining the roles of individual differences in patients' and visitors' cognitive styles and connectedness to nature. Results highlighted the impact of these differences in patient experiences for effective implications of nature in waiting areas of healthcare facilities.

Post-surgical thyroid bed myofibroma simulating a recurrent papillary thyroid carcinoma: A case report and review of the literature.

RATIONALE: Myofibromas are rare benign spindle cell tumors of the soft tissue, bone, or internal organs that occur at any age. Here, we report a post-surgical thyroid bed myofibroma that mimicked a papillary thyroid carcinoma. PATIENT CONCERNS: A 56-year-old male presented with a mass in the thyroid surgical bed, detected 3 years post thyroidectomy following papillary carcinoma. DIAGNOSIS: Thyroid ultrasonography revealed a well-defined, lobulated, hypoechoic, solid nodule, with large rod-like echogenic foci in the thyroid surgical bed. The development of a postoperative suture granuloma was considered. However, ultrasonography performed 12 months later showed a marked increase in the lesion size. Two fine needle aspiration cytology yielded nondiagnostic results. INTERVENTION: Considering the possibility of local tumor recurrence, surgical resection was performed. OUTCOME: The diagnosis of a myofibroma was confirmed, and no additional treatment was administered. LESSONS: It is challenging to differentiate lesions occurring on the thyroid surgical bed after surgery, from recurrent thyroid cancer. A lesion measuring 6 mm, with a degree of punctate echogenicity, suggests tumor recurrence. Moreover, myofibromas are extremely rare. This case highlights that it is advisable to perform a core needle biopsy in cases of nondiagnostic fine needle aspiration results.

Preoperative prediction of early recurrence in resectable pancreatic cancer integrating clinical, radiologic, and CT radiomics features.

OBJECTIVES: To use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer. METHODS: We retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity. RESULTS: Early recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort. CONCLUSIONS: The CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.

Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report.

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma that predominantly consists of epithelioid cells and belongs to the perivascular epithelioid cell neoplasm (PEComa) family. The majority of EAMLs arise in the kidneys, and primary hepatic EAML appears to be much less common than renal EAML. Most PEComas arise sporadically, but may be associated with tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder characterized by germline mutations in the TSC1 or TSC2 genes. However, PEComas have previously been reported in five patients with Li-Fraumeni syndrome (LFS), which is an inherited cancer susceptibility disorder resulting from germline mutations in the TP53 tumor suppressor gene. CASE PRESENTATION: We report a 49-year-old female patient with hepatic EAML and pancreatic cancer. Because she had previously been diagnosed with bilateral breast cancer at the age of 30, we performed a comprehensive genetic analysis to identify genetic alterations associated with any cancer predisposition syndrome. Whole-exome sequencing of a blood sample identified a heterozygous germline variant of TP53 (NM_000546.5):c.708C>A, and targeted next-generation sequencing of liver EAML and pancreatic cancer tissue samples demonstrated the same TP53 (NM_000546.5):c.708C>A variant in both. This, plus the patient's history of early-onset breast cancer, met the 2015 version of the Chompret criteria for diagnosis of LFS. CONCLUSIONS: There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.

Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Water-extractable polysaccharide fraction PNE-P1 from Pinus koraiensis pine nut: Structural features and immunostimulatory activity.

The polysaccharide fraction PNE-P1 was isolated from hot water extract (PNE) of the defatted meal of pine nuts (Pinus koraiensis) using DEAE-cellulose column chromatography. This fraction had three components of molecular masses 1251, 616, and 303 g/mol consisting mainly of arabinose, xylose, and galacturonic acid at a molar ratio of 2:1.6:1. Structural analysis with FTIR/Raman, methylation and GC-MS, and NMR revealed that PNE-P1 is a cell wall polysaccharide complex including arabinan, heteroxylan, homogalacturonan (HM) and rhamnogalacturonan I (RG-I) parts. Being nontoxic to RAW 264.7 macrophages in the concentration range of 10-200 µg/mL, PNE-P1 promoted proliferation of these cells, significantly induced the secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (RANTES and MIP-1α) and enhanced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nitric oxide (NO). PNE-P1 also markedly induced macrophage-mediated phagocytosis of apoptotic Jurkat T cells. These results demonstrate that pine nuts Pinus koraiensis contain a complex of water-soluble plant cell wall polysaccharides, which can stimulate innate immunity by potentiating macrophage function.

USP13 deubiquitinates p62/SQSTM1 to induce autophagy and Nrf2 release for activating antioxidant response genes.

SQSTM1/p62 (sequestosome 1) is a multifunctional protein that serves as a receptor for selective autophagy and scaffold. In selective autophagy, p62 functions as a bridge between polyubiquitinated proteins and autophagosomes. Further, p62 acts as a signaling hub for many cellular pathways including mTORC1, NF-κB, and Keap1-Nrf2. Post-translational modifications of p62, such as ubiquitination and phosphorylation, are known to determine its binding partners and regulate their intracellular functions. However, the mechanism of p62 deubiquitination remains unclear. In this study, we found that ubiquitin-specific protease 13 (USP13), a member of the USP family, directly binds p62 and removes ubiquitin at Lys7 (K7) of the PB1 domain. USP13-mediated p62 deubiquitination enhances p62 protein stability and facilitates p62 oligomerization, resulting in increased autophagy and degradation of Keap1, which is a negative regulator of the antioxidant response that promotes Nrf2 activation. Thus, USP13 can be considered a therapeutic target as a deubiquitination enzyme of p62 in autophagy-related diseases.