The Therapeutic Potential of Neutrophil Extracellular Traps and NLRP3 Inflammasomes in Mycoplasma pneumoniae Pneumonia.

INTRODUCTION: Mycoplasma pneumoniae (MP) is the most common pathogen of community-acquired pneumonia in children. However, the role of neutrophil extracellular traps (NETs) in the pathogenesis of MP is unclear. METHODS: Both the level of NETs were detected between the 60 MP pneumonia patients and 20 healthy controls, whose the clinical characteristics were compared. Additionally, NETs formation induced by community-acquired respiratory distress syndrome (CARDS) toxin was also analyzed through transcriptome sequencing. RESULTS: The levels of cell-free DNA, Cit-H3, and MPO-DNA complexes were significantly increased in the patients with MP pneumonia. Importantly, both cell-free DNA and LDH were higher in hospitalized patients with severity than those without severity. In addition, CARDS toxin induced the NETs formation in vitro and in vivo. Transcriptomics GO and KEGG pathway analysis indicate that NOD like receptor signaling pathway and Toll-like receptor signaling pathway are significantly enriched. Finally, we found that DNase I significantly attenuated the higher levels of Cit-H3, and up-regulation of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) by down-regulating the expression of NLRP3 and Caspase1(p20) in the lung tissues. DISCUSSION: These results indicate that inhibiting excessive activation of NLRP3 inflammasomes, and NETs formation may alleviate MP pneumonia.

An Exploratory Analysis of Preclinical and Clinical Factors Associated With Sleep Disturbance Assessed via the Neuro-QoL After Hemorrhagic Stroke.

Background and Purpose: Sleep disturbance after hemorrhagic stroke (intracerebral or subarachnoid hemorrhage) can impact rehabilitation, recovery, and quality of life. We sought to explore preclinical and clinical factors associated with sleep disturbance after hemorrhagic stroke assessed via the Quality of Life in Neurological Disorders (Neuro-QoL) short form sleep disturbance inventory. Methods: We telephonically completed the Neuro-QoL short form sleep disturbance inventory 3-months and 12-months after hemorrhagic stroke for patients >18-years-old hospitalized between January 2015 and February 2021. We examined the relationship between sleep disturbance (T-score >50) and social and neuropsychiatric history, systemic and neurological illness severity, medical complications, and temporality. Results: The inventory was completed for 70 patients at 3-months and 39 patients at 12-months; 18 (26%) had sleep disturbance at 3-months and 11 (28%) had sleep disturbance at 12-months. There was moderate agreement (κ = .414) between sleep disturbance at 3-months and 12-months. Sleep disturbance at 3-months was related to unemployment/retirement prior to admission (P = .043), lower Glasgow Coma Scale score on admission (P = .021), higher NIHSS score on admission (P = .041) and infection while hospitalized (P = .036). On multivariate analysis, sleep disturbance at 3-months was related to unemployment/retirement prior to admission (OR 3.58 (95% CI 1.03-12.37), P = .044). Sleep disturbance at 12-months was related to premorbid mRS score (P = .046). Conclusion: This exploratory analysis did not demonstrate a sustained relationship between any preclinical or clinical factors and sleep disturbance after hemorrhagic stroke. Larger studies that include comparison to patients with ischemic stroke and healthy individuals and utilize additional techniques to evaluate sleep disturbance are needed.

Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex.

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh3)3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.

Relationship Between Hemorrhage Type and Development of Emotional and Behavioral Dyscontrol After Hemorrhagic Stroke.

OBJECTIVE: Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS: The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS: The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS: Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.

Neutrophil extracellular traps induce pyroptosis of pulmonary microvascular endothelial cells by activating the NLRP3 inflammasome.

Excessive formation of neutrophil extracellular traps (NETs) may lead to myositis-related interstitial lung disease (ILD). There is evidence that NETs can directly injure vascular endothelial cells and play a pathogenic role in the inflammatory exudation of ILD. However, the specific mechanism is unclear. This study aimed to investigate the specific mechanism underlying NET-induced injury to human pulmonary microvascular endothelial cells (HPMECs). HPMECs were stimulated with NETs (200 ng/ml) in vitro. Cell death was detected by propidium iodide staining. The morphological changes of the cells were observed by transmission electron microscopy (TEM). Pyroptosis markers were detected by western blot, immunofluorescence, and quantitative real-time polymerase chain reaction, and the related inflammatory factor Interleukin-1ß (IL-1ß) was verified by enzyme-linked immunosorbent assay (ELISA). Compared with the control group, HPMECs mortality increased after NET stimulation, and the number of pyroptosis vacuoles in HPMECs was further observed by TEM. The pulmonary microvascular endothelial cells (PMECs) of the experimental autoimmune myositis mouse model also showed a trend of pyroptosis in vivo. Cell experiment further confirmed the significantly high expression of the NLRP3 inflammasome and pyroptosis-related markers, including GSDMD and inflammatory factor IL-1ß. Pretreated with the NLRP3 inhibitor MCC950, the activation of NLRP3 inflammasome and pyroptosis of HPMECs were effectively inhibited. Our study confirmed that NETs promote pulmonary microvascular endothelial pyroptosis by activating the NLRP3 inflammasome, suggesting that NETs-induced pyroptosis of PMECs may be a potential pathogenic mechanism of inflammatory exudation in ILD.

Novel salty peptides derived from bovine bone: Identification, taste characteristic, and salt-enhancing mechanism.

Excessive sodium intake is a major contributor to the incidence of cardiovascular diseases. The objective of this study was to prepare, isolate, and characterize peptides from bovine bone protein and investigate the salty/salt-enhancing mechanism of peptides. 1032 peptides were identified in the enzymatic hydrolysates of bovine bone protein and were further screened by the composition of amino acid residues and molecular docking analysis. 5 peptides were finally selected for solid-phase synthesis, and KER showed a better salty taste by sensory verification. Moreover, the synergistic effect of KER in NaCl and MSG solution could enhance the salty intensity by 65.26 %. The binding of KER to the salty receptor (TMC4) was driven by hydrogen bonding and electrostatic interactions with a binding energy of -88.0734 kcal/mol. This work may provide a new approach to efficiently screen salty peptides from natural food materials, which were expected as a taste enhancer used in salt-reducing foods.

Tethered Trimeric Small-molecular Acceptors through Aromatic-core Engineering for Highly Efficient and Thermally Stable Polymer Solar Cells.

Polymer solar cells (PSCs) rely on a blend of small molecular acceptors (SMAs) with polymer donors, where thermodynamic relaxation of SMAs poses critical concerns on operational stability. To tackle this issue, tethered SMAs, wherein multiple SMA-subunits are connected to the aromatic-core via flexible chains, are proposed. This design aims to an elevated glass transition temperature (Tg) for a dynamical control. However, attaining an elevated Tg value with additional SMA subunits introduces complexity to the molecular packing, posing a significant challenge in realizing both high stability and power conversion efficiency (PCE). In this study, we initiate isomer engineering on the benzene-carboxylate core and find that meta-positioned dimeric BDY-ß exhibits more favorable molecular packing compared to its para-positioned counterpart, BDY-α. With this encouraging result, we expand our approach by introducing an additional SMA unit onto the aromatic core of BDY-ß, maintaining a meta-position relative to each SMA unit location in the tethered acceptor. This systematic aromatic-core engineering results in a star-shaped C3h-positioned molecular geometry. The supramolecular interactions of SMA units in the trimer contribute to enhancements in Tg value, crystallinity, and a red-shifted absorption compared to dimers. These characteristics result in a noteworthy increase in PCE to 18.24 %, coupled with a remarkable short-circuit current density of 27.06 mA cm-2. More significantly, the trimer-based devices delivered an excellent thermal stability with over 95 % of their initial efficiency after 1200 h thermal degradation. Our findings underscore the promise and feasibility of tethered trimeric structures in achieving highly ordered aggregation behavior and increased Tg value in PSCs, simultaneously improving in device efficiency and thermal stability.

Factors Associated With Anxiety After Hemorrhagic Stroke.

OBJECTIVE: A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS: Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS: Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS: Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.

Use of Carotid Web Angioarchitecture for Stroke Risk Assessment.

OBJECTIVE: To examine the usefulness of carotid web (CW), carotid bifurcation and their combined angioarchitectural measurements in assessing stroke risk. METHODS: Anatomic data on the internal carotid artery (ICA), common carotid artery (CCA), and the CW were gathered as part of a retrospective study from symptomatic (stroke) and asymptomatic (nonstroke) patients with CW. We built a model of stroke risk using principal-component analysis, Firth regression trained with 5-fold cross-validation, and heuristic binary cutoffs based on the Minimal Description Length principle. RESULTS: The study included 22 patients, with a mean age of 55.9 ± 12.8 years; 72.9% were female. Eleven patients experienced an ischemic stroke. The first 2 principal components distinguished between patients with stroke and patients without stroke. The model showed that ICA-pouch tip angle (P = 0.036), CCA-pouch tip angle (P = 0.036), ICA web-pouch angle (P = 0.036), and CCA web-pouch angle (P = 0.036) are the most important features associated with stroke risk. Conversely, CCA and ICA anatomy (diameter and angle) were not found to be risk factors. CONCLUSIONS: This pilot study shows that using data from computed tomography angiography, carotid bifurcation, and CW angioarchitecture may be used to assess stroke risk, allowing physicians to tailor care for each patient according to risk stratification.

The phonological congruency modulated long-term form priming of Chinese characters.

Elucidating the interaction between lexical processing and word learning is essential for a complete understanding of the underlying mechanisms of each of them. Long-term priming for words reflects an interplay between lexical processing and word learning. Although robust long-term priming effects have been found between two occurrences of the same word and between semantically similar words, it remains unclear whether long-term priming between orthographically similar words (i.e., long-term form priming) is a reliable effect. Following the theoretical analysis based on the connectionist framework, we articulated the possibility that long-term form priming might be modulated by the phonological congruency between the prime and target words, and that if this modulator was under control, reliable effects of long-term form priming would emerge. However, this hypothesis has not been adequately tested empirically. The present study tested this hypothesis by using Chinese phonograms and the phonetic radicals embedded in them as the prime and target items. In three experiments that varied in the types of stimuli and testing tasks, we consistently found that when the prime and target had the same phonology, naming the prime facilitated later processing of the target, while when they had different phonologies, the priming effect was inhibitory. These observations were consistent with the connectionist account of long-term priming for words. Our findings help confirm the reliability, generalizability, and robustness of long-term form priming and elucidate its underlying mechanisms, and suggesting promising future directions on the interactions between lexical processing and word learning.

Analysis of Variables Associated with Positive Micro-Embolic Signals Detected by Transcranial Doppler in Patients with Atrial Fibrillation and Their Predictive Value for Embolic Risk.

Objective: This study examined the factors associated with positive micro-embolic signals (MES) on transcranial Doppler monitoring in patients with atrial fibrillation (AF), as well as the predictive value of MES for the risk of embolism in AF. Methods: Sixty-six patients who had micro emboli with AF were included in the positive group, and 75 patients who did not have micro emboli with AF served as the control group. The clinical data, congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74, female (CHA2DS2-VASc) score, D-dimer (D-d) level, echocardiography results, and brain magnetic resonance imaging (MRI) findings were compared between the two groups. Logistic regression models were used to analyze the relationship between positive micro emboli with CHA2DS2-VASc score, D-d, left atrial anteroposterior diameter (LAD), and silent cerebral ischemia (SCI) occurrence. Results: The CHA2DS2-VASc score, D-d level, and LAD were significantly higher in the positive group than in the control group (P < 0.05) and were accompanied by a higher detection rate of SCI by brain MRI (P < 0.01). Elevated D-d levels, increased LAD, and the detection rate of SCI were all highly positively correlated with positive micro emboli. Also, CHA2DS2-VASc score ≥ 2 showed a significant positive correlation with positive micro emboli, and the higher CHA2DS2-VASc score was associated with a stronger correlation. The multivariate regression analysis demonstrated that positive micro-embolic was independently associated with SCI and a CHA2DS2-VASc score of ≥ 4. Conclusion: Positive micro emboli in patients with persistent AF are consistent with an increased risk of embolism, and are independently associated with a higher CHA2DS2-VASc score and SCI, which can be used as an indicator of individual embolic risk in patients with AF.

The Regulation of Ferroptosis by Noncoding RNAs.

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which is different from other regulated cell death forms morphologically, biochemically, and immunologically. Ferroptosis is regulated by iron metabolism, lipid metabolism, and antioxidant defense systems as well as various transcription factors and related signal pathways. Emerging evidence has highlighted that ferroptosis is associated with many physiological and pathological processes, including cancer, neurodegeneration diseases, cardiovascular diseases, and ischemia/reperfusion injury. Noncoding RNAs are a group of functional RNA molecules that are not translated into proteins, which can regulate gene expression in various manners. An increasing number of studies have shown that noncoding RNAs, especially miRNAs, lncRNAs, and circRNAs, can interfere with the progression of ferroptosis by modulating ferroptosis-related genes or proteins directly or indirectly. In this review, we summarize the basic mechanisms and regulations of ferroptosis and focus on the recent studies on the mechanism for different types of ncRNAs to regulate ferroptosis in different physiological and pathological conditions, which will deepen our understanding of ferroptosis regulation by noncoding RNAs and provide new insights into employing noncoding RNAs in ferroptosis-associated therapeutic strategies.

Geometry design of tethered small-molecule acceptor enables highly stable and efficient polymer solar cells.

With the power conversion efficiency of binary polymer solar cells dramatically improved, the thermal stability of the small-molecule acceptors raised the main concerns on the device operating stability. Here, to address this issue, thiophene-dicarboxylate spacer tethered small-molecule acceptors are designed, and their molecular geometries are further regulated via the thiophene-core isomerism engineering, affording dimeric TDY-α with a 2, 5-substitution and TDY-ß with 3, 4-substitution on the core. It shows that TDY-α processes a higher glass transition temperature, better crystallinity relative to its individual small-molecule acceptor segment and isomeric counterpart of TDY-ß, and a more stable morphology with the polymer donor. As a result, the TDY-α based device delivers a higher device efficiency of 18.1%, and most important, achieves an extrapolated lifetime of about 35000 hours that retaining 80% of their initial efficiency. Our result suggests that with proper geometry design, the tethered small-molecule acceptors can achieve both high device efficiency and operating stability.

Ferroptosis Regulated by Hypoxia in Cells.

Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which is associated with many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, and immunologically distinct from other regulated cell death forms. Ferroptosis is regulated by iron metabolism, lipid metabolism, anti-oxidant defense systems, as well as various signal pathways. Hypoxia, which is found in a group of physiological and pathological conditions, can affect multiple cellular functions by activation of the hypoxia-inducible factor (HIF) signaling and other mechanisms. Emerging evidence demonstrated that hypoxia regulates ferroptosis in certain cell types and conditions. In this review, we summarize the basic mechanisms and regulations of ferroptosis and hypoxia, as well as the regulation of ferroptosis by hypoxia in physiological and pathological conditions, which may contribute to the numerous diseases therapies.

A Comparative Study of Pickled Salted Eggs by Positive and Negative Pressure-Ultrasonic Method.

In this study, the positive and negative pressure-ultrasonic method was applied to salted egg pickling, compared with traditional pickled salted eggs by various physical and chemical indicators. Results indicated the salt content of egg white and egg yolk increased rapidly in the salt-preserved salted egg with the positive and negative pressure-ultrasonic method, and the moisture content decreased rapidly. In addition, the oil yield of egg yolk was marinated for 12 days compared with the normal method of 35 days, and the ripening time of salted eggs was shortened by 2/3. There was no obvious difference in the microscopical structure of the egg yolk between the two methods of pickling. Moreover, the pores on the eggshell of the salted egg that was marinated by the positive and negative pressure-ultrasonic method had big cracks, which was beneficial to the substance exchange of the eggs and the outside. The common volatile flavor substances were detected by GC-MS, and a total of 33 flavor constituents were detected. There was no significant difference between the content of alcohols, aldehydes, and ketones, which contributed greatly to the flavor. Overall, the results indicated that this innovative salted eggs method can significantly reduce the curing time while ensuring the quality of salted eggs.

Rapid quantification of royal jelly quality by mid-infrared spectroscopy coupled with backpropagation neural network.

Royal jelly is rich in nutrients but its quality is greatly affected by storage conditions. To determine the quality of royal jelly accurately and quickly, a qualitative discrimination model was established based on the fusion of conventional parameters and mid-infrared spectrum, using support vector machine. The prediction models for three representative quality parameters were developed by the backpropagation neural network with various algorithms. The results demonstrated that the recognition rate of the multi-source information fusion model was increased to 100% when compared with that of the spectral data preprocessed by Savitzky-golay smoothing (95.83%). The mean square errors of the constructed model for moisture, water-soluble protein, and total sugar were 0.0032, 0.0058, and 0.0069, respectively. The constructed model had an ensured accuracy for the calibration set, with the correlation coefficient of prediction maintained at 0.9353, 0.9533, and 0.9563, which could meet the requirement of non-destructive rapid detection of royal jelly quality.

Optimizing Levilactobacillus brevis NPS-QW 145 Fermentation for Gamma-Aminobutyric Acid (GABA) Production in Soybean Sprout Yogurt-like Product.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid with various physiological functions. Levilactobacillus brevis NPS-QW 145 strains active in GABA catabolism and anabolism can be used as a microbial platform for GABA production. Soybean sprouts can be treated as a fermentation substrate for making functional products. This study demonstrated the benefits of using soybean sprouts as a medium to produce GABA by Levilactobacillus brevis NPS-QW 145 when monosodium glutamate (MSG) is the substrate. Based on this method, a GABA yield of up to 2.302 g L-1 was obtained with a soybean germination time of one day and fermentation of 48 h with bacteria using 10 g L-1 glucose according to the response surface methodology. Research revealed a powerful technique for producing GABA by fermentation with Levilactobacillus brevis NPS-QW 145 in foods and is expected to be widely used as a nutritional supplement for consumers.

Influence of calcium sulfate incorporated with gluconolactone coagulant on the quality of whole soybean flour tofu.

This work proposes a novel method for whole soybean flour tofu preparation by combining calcium sulfate (CS) and glucose-delta-lactone (GDL) coagulation. Importantly, the characteristics of the synthesized gel and the quality were studied. MRI and SEM results showed that the whole soybean flour tofu possessed satisfactory water holding capacity and water content at a CS to GDL ratio of 3:2, significantly improving the cross-linking network gel in tofu and accounting for its similar color to soybeans. Furthermore, GC-IMS analysis showed that the whole soybean flour tofu prepared at a 3:2 ratio had more flavor components (51 types) than commercially available ones (CS or GDL tofu) and exhibited satisfactory results during consumer sensory evaluation. Overall, this method is effective and applicable for the industrial preparation of whole soybean flour tofu.

The ubiquitin ligase TRIM21 regulates mutant p53 accumulation and gain of function in cancer.

The tumor suppressor TP53 is the most frequently mutated gene in human cancers. Mutant p53 (mutp53) proteins often accumulate to very high levels in human cancers to promote cancer progression through the gain-of-function (GOF) mechanism. Currently, the mechanism underlying mutp53 accumulation and GOF is incompletely understood. Here, we identified TRIM21 as a critical E3 ubiquitin ligase of mutp53 by screening for specific mutp53-interacting proteins. TRIM21 directly interacted with mutp53 but not WT p53, resulting in ubiquitination and degradation of mutp53 to suppress mutp53 GOF in tumorigenesis. TRIM21 deficiency in cancer cells promoted mutp53 accumulation and GOF in tumorigenesis. Compared with p53R172H knockin mice, which displayed mutp53 accumulation specifically in tumors but not normal tissues, TRIM21 deletion in p53R172H knockin mice resulted in mutp53 accumulation in normal tissues, an earlier tumor onset, and a shortened life span of mice. Furthermore, TRIM21 was frequently downregulated in some human cancers, including colorectal and breast cancers, and low TRIM21 expression was associated with poor prognosis in patients with cancers carrying mutp53. Our results revealed a critical mechanism underlying mutp53 accumulation in cancers and also uncovered an important tumor-suppressive function of TRIM21 and its mechanism in cancers carrying mutp53.