Simulation and calibration of radiation monitoring of nuclear power plant containment sump waste liquid.

Waste liquid stored in the containment sumps of nuclear power plants may contain a variety of radionuclides. Real-time monitoring of containment sump waste liquid can ensure that accidents, such as leakage of cooling water, can be avoided. This paper presents the design of a radioactive monitoring system for waste liquid in a containment sump. The detector and the lead-shield in the measurement unit are optimized through Monte Carlo simulations. Experimental verification showed that the background count rate of the measurement chamber in the system was 418.3 cps, and the detection limit of the detection system was 3.01 Bq/L. Distinct gamma-ray characteristic peaks were also observable, demonstrating the system's ability to identify radioactive nuclides in the waste.

Five glycosylation-related gene signatures predict the prognostic risks of lung adenocarcinoma.

This study aimed to identify glycosylation-related genes associated with lung adenocarcinoma (LUAD) prognosis through comprehensive bioinformatic analysis. Glycosylation-related genes were identified from the Human Gene Nomenclature Committee, and LUAD prognostic genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)-GSE68465 datasets. Glycosylation risk score (GLRS) was calculated to predict LUAD prognostic risk. Samples were grouped into GLRS-high and GLRS-low and compared. The Tumor Immune Dysfunction and Exclusion (TIDE) score was computed to assess the antitumor immune escape possibility after immunotherapy. From 213 glycosylation-related genes, five gene signatures served as prognostic LUAD predictors using univariate and stepwise Cox regression analyses. GLRS-based models were constructed using TCGA and GSE68465 samples; their sensitivity and specificity in predicting LUAD prognosis were confirmed. GLRS was an independent LUAD prognostic factor and contributed to the nomogram to predict patient survival. High GLRS was associated with advanced tumor stage and higher mutation frequencies, estimate scores, and TIDE scores. GLRS-high and GLRS-low patients differed in immune cell infiltration and epithelial-mesenchymal transition (EMT)-related gene expression. Thus, we propose five glycosylation-related gene signatures to predict overall survival and prognostic risks of LUAD. Their regulatory roles may be related to immune invasion, immunotherapy response, mutation, and EMT.

Application and outlook of electrochemical technology in single-cell analysis.

Cellular heterogeneity, especially in some important diseased cells like tumor cells, acts as an invisible driver for disease development like cancer progression in the tumor ecosystem, contributing to differences in the macroscopic and microscopic detection of disease lesions like tumors. Traditional analysis techniques choose group information masked by the mean as the analysis sample, making it difficult to achieve precise diagnosis and target treatment, on which could be shed light via the single-cell level determination/bioanalysis. Hence, in this article we have reviewed the special characteristic differences among various kinds of typical single-cell bioanalysis strategies and electrochemical techniques, and then focused on the recent advance and special bio-applications of electrochemiluminescence and micro-nano electrochemical sensing mediated in single-cell bioimaging & bioanalysis. Especially, we have summarized the relevant research exploration of the possibility to establish the in-situ single-cell electrochemical methods to detect cell heterogeneity through determination of specific biomolecules and bioimaging of some important biological processes. Eventually, this review has explored some important advances of electrochemical single-cell detection techniques for the real-time cellular bioimaging and diagnostics of some disease lesions like tumors. It raises the possibility to provide the specific in-situ platform to exploit the versatile, sensitive, and high-resolution electrochemical single-cell analysis for the promising biomedical applications like rapid tracing of some disease lesions or in vivo bioimaging for precise cancer theranostics.

Effects of low molecular weight heparin combined with hyperbaric oxygen on neurologic function and coagulation factors in patients with intracranial venous thrombosis.

OBJECTIVE: To investigate the effects of low molecular weight heparin (LMWH) combined with hyperbaric oxygen (HBO) on the neurologic function and coagulation factors of patients with intracranial venous thrombosis (ICVT). METHODS: The clinical data of 80 patients with ICVT admitted to the No. 2 Hospital of Baoding from February 2020 to January 2021 were retrospectively analyzed. Patients were assigned to a control group (n=32) and a research group (n=48) according to different treatment methods. The neurological function score, and the levels of D-dimer (D-D), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were compared between the two groups. The two groups were also compared regarding the curative effect, toxic and side effects, as well as quality of life (QoL). RESULTS: After treatment, the National Institutes of Health Stroke Scale (NIHSS) score was significantly lower in the research group compared to the control group. At 1, 2 and 3 weeks after treatment, the levels of D-D and FIB, as well as inflammatory factors TNF-α and CRP were lower in the research group compared to the control group. The overall response rate was significantly higher in the research group compared to the control group, while there was no significant difference in the total incidence of toxic and adverse effects between the two groups. After treatment, the QoL of patients assessed by the Generic Quality of Life Inventory-74 (GQOLI-74) from the domains of physical, social, and psychological function as well as material life status was significantly better in the research group. CONCLUSIONS: LMWH combined with HBO can effectively improve the clinical efficacy and neurologic function of patients with ICVT and reduce the levels of coagulation factors and inflammatory factors.

Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth.

BACKGROUND: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. METHODS: The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin. RESULTS: Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death. CONCLUSIONS: Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate.

Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: a network meta-analysis.

BACKGROUND: Long-term antiviral treatments are associated with a significantly lower hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients by reducing HBV DNA concentrations. However, it is still controversial whether antiviral strategies affect HCC development in antiviral treatment-naïve CHB patients. This study aimed to estimate the incidence of HCC in antiviral treatment-naïve CHB patients who were treated with Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF) and compare the efficacy of two treatment regimens in HCC reduction. METHODS: The PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were systematically searched until June 24, 2021. The pooled incidence and 95% confidence interval of HCC were calculated by the Freeman-Tukey double arcsine transformation method. The efficacies of ETV and TDF treatments in HCC reduction were compared through a network meta-analysis. RESULTS: A total of 27 studies were identified as eligible for this systematic review. The incidence densities in the ETV and TDF treatment groups were 2.78 (95% CI: 2.21-3.40) and 2.59 (95% CI: 1.51-3.96) per 100 persons-year among patients with preexisting cirrhosis and 0.49 (95% CI: 0.32-0.68) and 0.30 (95% CI: 0.06-0.70) per 100 persons-year among patients without preexisting cirrhosis. As the proportion of CHB patients with preexisting cirrhosis increased, the incidence density of HCC also increased gradually. Compared with other Nucleos(t)ide analogs (NAs) treatments, ETV and TDF treatments significantly lowered the risk of HCC, with hazard ratios (HRs) of 0.60 (95% CI: 0.40-0.90) and 0.56 (95% CI: 0.35-0.89), respectively. However, there was no difference in the incidence density of HCC between ETV and TDF treatments (HR = 0.92, 95% CI: 0.71-1.20) regardless of preexisting cirrhosis. CONCLUSION: ETV and TDF treatments were associated with significantly lower risks of HCC than other NAs treatments. However, no difference was observed between ETV and TDF treatments in the risk of HCC development regardless of preexisting cirrhosis among treatment-naïve CHB patients.

CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial-mesenchymal transition (EMT). METHODS: qRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The migration ability of OC cell was determined using wound healing. The protein expressions of CXCL14 and ß-catenin in OC tissues were determined by immumohistochemical staining. RESULTS: We demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth, migration and invasion of OC cell in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/ß-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness. CONCLUSION: These data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/ß-catenin signaling pathway.

Relationship between the structure and function of the transcriptional regulator E2A.

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.

Nuclear translocation of ATG5 induces DNA mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) via interacting with Mis18α in colorectal cancer.

BACKGROUND AND PURPOSE: It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. EXPERIMENTAL APPROACH: Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18α overexpression were analysed in ATG5high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29atg5 and SW480atg5 cancer cells. KEY RESULTS: In ATG5high colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5+/- and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5-Mis18α complex and MMR-D/MSI-H. CONCLUSIONS AND IMPLICATIONS: Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18α in ATG5high colorectal cancer cells. We suggest that ATG5-Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR-296-5p/Bax axis.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA-296-5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR-296-5p in neuroblastoma (NB) cells. By performing quantitative real-time PCR (qRT-PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR-296-5p mimics or inhibitor. Pathway-specific PCR array allowed us to identify the target genes of miR-296-5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR-296-5p. The binding of KCNQ1OT1 and miR-296-5p was validated via RNA immunoprecipitation and Biotin pull-down assays. We also demonstrate that miR-296-5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR-296-5p directly bound the 3'UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR-296-5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR-296-5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.

Radiofrequency ablation vs. surgical resection for resectable hepatocellular carcinoma: A systematic review and meta-analysis.

The treatment of hepatocellular carcinoma (HCC) is a significant challenge. Although radiofrequency ablation (RFA) has emerged as a popular therapeutic option for patients with resectable HCC, whether it can achieve comparable survival outcomes compared with surgical resection (RES) remains unclear. The aim of the present study was to conduct a meta-analysis to assess the survival outcomes of RFA vs. RES in patients with early resectable HCC tumors. A Medline, Embase, and Cochrane Library search was performed for data published between January 2000 and February 2018. A meta-analysis of the efficacy of RFA compared with RES for HCC was subsequently performed, with particular emphasis on overall survival and disease-free survival (DFS) rates. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. In the present study, a total of 13,147 patients with HCC were included; of which, 6,727 were treated with RFA and 6,420 were treated with RES. The overall survival rates (OR1-year, 0.757, 95% CI, 0.578-0.989; OR3-year, 0.530, 95% CI, 0.401-0.700; OR5-year, 0.566, 95% CI, 0.423-0.758) and the DRS rates (OR1-year, 0.569, 95% CI, 0.456-0.711; OR3-year, 0.418, 95% CI, 0.267-0.653; OR5-year, 0.374, 95% CI, 0.231-0.606) of RES were significantly higher than those of RFA. The results indicate that RES is superior to RFA for promoting the survival of selected patients with resectable HCC. However, future randomized controlled trials are required to investigate the specific relevance of these modalities in the treatment of HCC.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

PURPOSE: To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. METHODS: Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. RESULTS: During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. CONCLUSIONS: Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

Insulin Resistance in Polycystic Ovary Syndrome Improved by Chinese Medicine Dingkun Pill (): A Randomized Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L2, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05). CONCLUSION: DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).

Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells.

Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression. Furthermore, hnRNPK knockdown affected the migration ability of H1299 and A549 cells which could be rescued by ectopic expression of GSN in those cells. Conversely, GSN knockdown in hnRNPK-overexpressing cells could abort the stimulatory effect of hnRNPK on the cell migration. These results suggest that hnRNPK function in the regulation of cell migration is GSN-dependent. Taken together, these data unveiled a new mechanism of regulation of the GSN expression by hnRNPK and provides new clues for the discovery of new anti-metastatic therapy.

Effects of Postoperative Parenteral Nutrition Enhanced by Multivitamin on Metabolic Phenotype in Postoperative Gastric Cancer Patients.

SCOPE: To investigate the effects of postoperative parenteral nutrition (PN) with multivitamins supplementation on oxidative stress and metabolism. METHODS AND RESULTS: The participants are randomly assigned in a 1:1 ratio to groups: total nutrient admixture (TNA) + multivitamin (n = 14, Group A) and TNA + normal saline (n = 16, Group B). The levels of blood vitamins, ILs, and MDA are assessed and the dysregulation of metabolism is analyzed using nontargeted metabolite profiling. The degree of postoperative stress in Group A is significantly lower than that in Group B by analyzing changes in the levels of IL-8 and MDA. A set of 43 features are qualified to have a variable importance parameter score of >1.5 of a partial least-squares discriminate analysis model and fold change of >1.5 at p-value <0.05 between Groups A and B. The principal metabolic alternations in Group A include increased tricarboxylic acid cycle and ketogenesis with reduced plasma-free amino acids. Backing the results of clinical biomarkers, increased levels of antioxidative molecules, together with decreased levels of inflammatory related polyunsaturated fatty acids, are observed. CONCLUSION: Postoperative PN enhanced by multivitamins can alleviate traumatic stress and improve metabolic transition from catabolism to anabolism in gastric cancer patients.

YWHAZ Binds to TRIM21 but Is Not Involved in TRIM21-stimulated Osteosarcoma Cell Proliferation.

OBJECTIVE: Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation. METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ. RESULTS: TRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21. CONCLUSION: Our results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.