A fish herpesvirus highlights functional diversities among Zα domains related to phase separation induction and A-to-Z conversion.

Zalpha (Zα) domains bind to left-handed Z-DNA and Z-RNA. The Zα domain protein family includes cellular (ADAR1, ZBP1 and PKZ) and viral (vaccinia virus E3 and cyprinid herpesvirus 3 (CyHV-3) ORF112) proteins. We studied CyHV-3 ORF112, which contains an intrinsically disordered region and a Zα domain. Genome editing of CyHV-3 indicated that the expression of only the Zα domain of ORF112 was sufficient for normal viral replication in cell culture and virulence in carp. In contrast, its deletion was lethal for the virus. These observations revealed the potential of the CyHV-3 model as a unique platform to compare the exchangeability of Zα domains expressed alone in living cells. Attempts to rescue the ORF112 deletion by a broad spectrum of cellular, viral, and artificial Zα domains showed that only those expressing Z-binding activity, the capacity to induce liquid-liquid phase separation (LLPS), and A-to-Z conversion, could rescue viral replication. For the first time, this study reports the ability of some Zα domains to induce LLPS and supports the biological relevance of dsRNA A-to-Z conversion mediated by Zα domains. This study expands the functional diversity of Zα domains and stimulates new hypotheses concerning the mechanisms of action of proteins containing Zα domains.

Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: A meta-analysis of 15 randomized controlled trials.

OBJECTIVE: To compare the effectiveness and safety of ketamine and morphine in adult patients with acute pain in emergency department (ED) by using a meta-analysis method. METHODS: This study was based on the Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study, with an experimental group that received low-dose ketamine and a control group that received morphine. The participants were adults who had acute pain in the ED. The primary outcome measures were the numeric rating scale (NRS) and visual analog scale (VAS). The secondary outcome measures were the complete resolution of pain, NRS reduction ≥3 points, NRS reduction ≥50% or 60%, change of NRS score, change of VAS score, rescue analgesia, satisfaction and adverse events. Subgroup analysis was performed for studies with intravenous and intranasal administration of ketamine. The Review Manager Database was used to analyze the included studies. RESULTS: 15 RCTs involving 1768 patients were included. The ketamine group had lower NRS scores than morphine group at 30 min (MD, -0.77 [95% CI, -0.93 to -0.61]; p < 0.00001), while the morphine had better analgesic effects at 120 min after treatment (MD, 0.33 [95% CI, 0.15 to 051]; p = 0.0003). The subjects of complete resolution of pain in the ketamine group performed better than those in the morphine group at 15 min (RR 3.18, 95% CI 1.75 to 5.78; p = 0.0001). Compared with the morphine group, the ketamine group had a lower incidence of adverse events requiring intervention (RR, 0.34 [95% CI, 0.18 to 0.66]; p = 0.001). Subgroup analysis of intravenous ketamine showed that ketamine had lower VAS score than the morphine group at 30 min. However, also on the 30-min VAS score, intranasal ketamine analgesia was less effective than morphine. CONCLUSIONS: Ketamine had better analgesic effects in the early stages after treatment, while morphine maintained more durable effects. Compared with morphine, ketamine had a lower incidence of adverse events requiring intervention. The results of subgroup analysis showed that intravenous administration of ketamine was more effective than intranasal administration.

Study on the correlation of C-reactive protein/albumin ratio with sudden sensorineural hearing loss complicated by hypertension: a prospective study.

BACKGROUND: Understanding the pathophysiology of sudden sensorineural hearing loss (SSNHL) and identifying its clinical symptoms and associated risk factors are crucial for doctors in order to create effective prevention and therapeutic methods for this prevalent otolaryngologic emergency. METHODS: This study focuses on investigating the correlation between the C-reactive protein/albumin ratio (CAR) and SSNHL complicated by hypertension. In this study, 120 patients diagnosed with SSNHL were divided into groups with and without hypertension, and propensity score matching was used to compare and analyze the severity, type, prognosis, and CAR levels in SSNHL. RESULTS: The results showed that the SSNHL group with hypertension had significantly higher CAR levels, age, hearing curve abnormalities, and more severe hearing loss compared to the control group with isolated SSNHL. These differences were statistically significant (p < 0.001). Among different subtypes of SSNHL, CAR levels increased progressively with the advancement of the condition, and these differences were also statistically significant (p < 0.001). CONCLUSION: In summary, in patients with SSNHL, those with hypertension had higher CAR levels than those without a history of hypertension, and they experienced more severe hearing loss. Moreover, there was a clear correlation between CAR levels and the extent of SSNHL, indicating that greater CAR levels in patients with SSNHL are connected to more severe hearing loss in various hearing patterns and perhaps indicative of a poorer prognosis.

Maize (Zea mays L.) genotypes induce the changes of rhizosphere microbial communities.

Plant-microbe interactions affect ecosystem function, and plant species influence relevant microorganisms. However, the different genotypes of maize that shape the structure and function of the rhizosphere microbial community remain poorly investigated. During this study, the structures of the rhizosphere microbial community among three genotypes of maize were analyzed at the seedling and maturity stages using high-throughput sequencing and bioinformatics analysis. The results demonstrated that Tiannuozao 60 (N) showed higher bacterial and fungal diversity in both periods, while Junlong1217 (QZ) and Fujitai519 (ZL) had lower diversity. The bacterial community structure among the three varieties was significantly different; however, fewer differences were found in the fungal community. The bacterial community composition of N and QZ was similar yet different from ZL at the seedling stage. The bacterial networks of the three cultivars were more complex than the fungal networks, and the networks of the mature stages were more complex than those of the seedling stages, while the opposite was true for the fungi. FAPROTAX functional and FUNGuild functional predictions revealed that different varieties of maize were different in functional abundance at the genus level, and these differences were related to breeding characteristics. This study suggested that different maize genotypes regulated the rhizosphere bacterial and fungal communities, which would help guide practices.

Roles of Neuropeptides in Sleep-Wake Regulation.

Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides can bind to specific surface receptors and subsequently regulate neuronal activities. For example, orexin is a crucial component for the maintenance of wakefulness and the suppression of rapid eye movement (REM) sleep. In addition to orexin, melanin-concentrating hormone, and galanin may promote REM sleep. These results suggest that neuropeptides play an important role in sleep-wake regulation. These neuropeptides can be divided into three categories according to their effects on sleep-wake behaviors in rodents and humans. (i) Galanin, melanin-concentrating hormone, and vasoactive intestinal polypeptide are sleep-promoting peptides. It is also noticeable that vasoactive intestinal polypeptide particularly increases REM sleep. (ii) Orexin and neuropeptide S have been shown to induce wakefulness. (iii) Neuropeptide Y and substance P may have a bidirectional function as they can produce both arousal and sleep-inducing effects. This review will introduce the distribution of various neuropeptides in the brain and summarize the roles of different neuropeptides in sleep-wake regulation. We aim to lay the foundation for future studies to uncover the mechanisms that underlie the initiation, maintenance, and end of sleep-wake states.

Complete genome sequence of Bacillus velezensis YYC, a bacterium isolated from the tomato rhizosphere.

The Bacillus velezensis YYC strain was isolated from the tomato rhizosphere. In a previous experiment, it increased tomato growth and induced systemic resistance against Ralstonia solanacearum. However, information on its genomic content is lacking. The complete genome sequence of the bacterium was described in this study. The genome size was 3,973,236 bp and consisted of 4034 genes in total, with a mean G + C content of 46.52%. In addition, 86 tRNAs and 27 ribosomal RNAs were identified. Fourteen clusters of secondary metabolites were identified. The KEGG database analysis showed that 69 genes were related to quorum sensing, which were important for microbe-plant interaction. In addition, genes involved in promoting plant growth and triggering plant immunity were identified from the genome. Based on digital DNA-DNA hybridizations (dDDH), B. velezensis YYC was most closely related with B. velezensis FZB42. The complete genome data of B. velezensis YYC will provide a basis for explanation of its growth-promoting mechanism and biocontrol mechanism.

Synthetic lethality strategies: Beyond BRCA1/2 mutations in pancreatic cancer.

Cancer cells are often characterized by abnormalities in DNA damage response including defects in cell cycle checkpoints and/or DNA repair. Synthetic lethality between DNA damage repair (DDR) pathways has provided a paradigm for cancer therapy by targeting DDR. The successful example is that cancer cells with BRCA1/2 mutations are sensitized to poly(adenosine diphosphate [ADP]-ribose)polymerase (PARP) inhibitors. Beyond the narrow scope of defects in the BRCA pathway, "BRCAness" provides more opportunities for synthetic lethality strategy. In human pancreatic cancer, frequent mutations were found in cell cycle and DDR genes, including P16, P73, APC, MLH1, ATM, PALB2, and MGMT. Combined DDR inhibitors and chemotherapeutic agents are under preclinical or clinical trials. Promoter region methylation was found frequently in cell cycle and DDR genes. Epigenetics joins the Knudson's "hit" theory and "BRCAness." Aberrant epigenetic changes in cell cycle or DDR regulators may serve as a new avenue for synthetic lethality strategy in pancreatic cancer.

A novel TLR7 agonist as adjuvant to stimulate high quality HBsAg-specific immune responses in an HBV mouse model.

BACKGROUND: The global burden of hepatitis B virus (HBV) infection in terms of morbidity and mortality is immense. Novel treatments that can induce a protective immune response are urgently needed to effectively control the HBV epidemic and eventually eradicate chronic HBV infection. METHODS: We designed and evaluated an HBV therapeutic vaccine consisting of a novel Toll-like receptor 7 (TLR7) agonist T7-EA, an Alum adjuvant and a recombinant HBsAg protein. We used RNA-seq, ELISA and hTLR7/8 reporting assays to characterize T7-EA in vitro and real-time PCR to evaluate the tissue-retention characteristics in vivo. To evaluate the adjuvant potential, we administrated T7-EA intraperitoneally in a formulation with an Alum adjuvant and HBsAg in normal and HBV mice, then, we evaluated the HBsAg-specific immune responses by ELISA and Elispot assays. RESULTS: T7-EA acted as an hTLR7-specific agonist and induced a similar gene expression pattern as an unmodified TLR7 ligand when Raw 264.7 cells were exposed to T7-EA; however, T7-EA was more potent than the unmodified TLR7 ligand. In vivo studies showed that T7-EA had tissue-retaining activity with stimulating local cytokine and chemokine expression for up to 7 days. T7-EA could induce Th1-type immune responses, as evidenced by an increased HBsAg-specific IgG2a titer and a T-cell response in normal mice compared to mice received traditional Alum-adjuvant HBV vaccine. Importantly, T7-EA could break immune tolerance and induce persistent HBsAg-specific antibody and T-cell responses in an HBV mouse model. CONCLUSIONS: T7-EA might be a candidate adjuvant in a prophylactic and therapeutic HBV vaccine.

Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak.

We developed a chemiluminescence immunoassay method based on the recombinant nucleocapsid antigen and assessed its performance for the clinical diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections by detecting SARS-CoV-2-specific IgM and IgG antibodies in patients. Full-length recombinant nucleocapsid antigen and tosyl magnetic beads were used to develop the chemiluminescence immunoassay approach. Plasmas from 29 healthy cohorts, 51 tuberculosis patients, and 79 confirmed SARS-CoV-2 patients were employed to evaluate the chemiluminescence immunoassay method performance for the clinical diagnosis of SARS-CoV-2 infections. A commercial ELISA kit (Darui Biotech, China) using the same nucleocapsid antigen was used for the in-parallel comparison with our chemiluminescence immunoassay method. The IgM and IgG manner of testing in the chemiluminescence immunoassay method showed a sensitivity and specificity of 60.76% (95% CI 49.1 to 71.6) and 92.25% (95% CI 83.4 to 97.2) and 82.28% (95% CI 72.1 to 90.0) and 97.5% (95% CI 91.3 to 99.7), respectively. Higher sensitivity and specificity were observed in the chemiluminescence immunoassay method compared with the Darui Biotech ELISA kit. The developed high sensitivity and specificity chemiluminescence immunoassay IgG testing method combined with the RT-PCR approach can improve the clinical diagnosis for SARS-CoV-2 infections and thus contribute to the control of COVID-19 expansion.

Identification of the crp gene in avian Pasteurella multocida and evaluation of the effects of crp deletion on its phenotype, virulence and immunogenicity.

BACKGROUND: Pasteurella multocida (P. multocida) is an important veterinary pathogen that can cause severe diseases in a wide range of mammals and birds. The global regulator crp gene has been found to regulate the virulence of some bacteria, and crp mutants have been demonstrated to be effective attenuated vaccines against Salmonella enterica and Yersinia enterocolitica. Here, we first characterized the crp gene in P. multocida, and we report the effects of a crp deletion. RESULTS: The P. multocida crp mutant exhibited a similar lipopolysaccharide and outer membrane protein profile but displayed defective growth and serum complement resistance in vitro compared with the parent strain. Furthermore, crp deletion decreased virulence but did not result in full attenuation. The 50 % lethal dose (LD50) of the Δcrp mutant was 85-fold higher than that of the parent strain for intranasal infection. Transcriptome sequencing analysis showed that 92 genes were up-regulated and 94 genes were down-regulated in the absence of the crp gene. Finally, we found that intranasal immunization with the Δcrp mutant triggered both systematic and mucosal antibody responses and conferred 60 % protection against virulent P. multocida challenge in ducks. CONCLUSION: The deletion of the crp gene has an inhibitory effect on bacterial growth and bacterial resistance to serum complement in vitro. The P. multocida crp mutant was attenuated and conferred moderate protection in ducks. This work affords a platform for analyzing the function of crp and aiding the formulation of a novel vaccine against P. multocida.

Identification of the Avian Pasteurella multocida phoP Gene and Evaluation of the Effects of phoP Deletion on Virulence and Immunogenicity.

Pasteurella multocida (P. multocida) is an animal pathogen of worldwide economic significance that causes fowl cholera in poultry and wild birds. Global gene regulators, including PhoP are important in regulating bacterial virulence and are good targets for developing attenuated vaccines against many pathogenic bacteria. However, the biological significance of phoP gene has not been identified in P. multocida. Here, we identified the phoP gene in P. multocida, and we evaluated the roles of phoP in P. multocida by deleting the phoP gene. The P. multocida phoP mutant exhibited similar growth curves and lipopolysaccharide and outer membrane protein profiles but displayed defective polymyxin resistance in vitro compared with the parent strain. Additionally, the phoP deletion resulted in decreased virulence. The LD50 of the ΔphoP mutant was 32- and 154-fold higher than the parent strain via the oral and intranasal routes, respectively. Transcriptome sequencing analysis showed that 161 genes were up-regulated and 173 genes were down-regulated in the absence of the phoP gene. Finally, the immunogenicity and protective efficacy of the ΔphoP mutant were evaluated. Immunized ducks produced significantly higher levels of serum IgY and bile IgA compared to the control ducks, and immunization with the ΔphoP mutant conferred 54.5% protection efficiency against challenge with the virulent P. multocida. This work provides a platform to dissect the function of phoP and develop a new vaccine against P. multocida.

Persistent Colonization of Ciprofloxacin-Resistant and Extended-Spectrum ß-Lactamase (ESBL)-Producing Salmonella enterica Serovar Kentucky ST198 in a Patient with Inflammatory Bowel Disease.

Objective: Salmonella enterica serovar Kentucky ST198 has emerged as a global threat to humans. In this study, we aimed to characterize the prolonged carriage of ciprofloxacin-resistant and extended-spectrum ß-lactamase (ESBL)-producing S. Kentucky ST198 in a single patient with inflammatory bowel disease (IBD). Methods: Three S. Kentucky strains were collected from a single patient with IBD on 11th January, 23rd January, and 8th February, 2022, respectively. Antimicrobial susceptibility testing, whole-genome sequencing, and phylogenetic analysis with 38 previously described Chinese S. Kentucky ST198 strains from patients and food were performed. Results: All three S. Kentucky isolates belonged to ST198. They carried identical 16 resistance genes, such as blaCTX-M-55, tet(A), and qnrS1, and had identical mutations within gyrA (S83F and D87N) and parC (S80I). Therefore, they exhibited identical multidrug-resistant profiles, including the clinically important antibiotics cephalosporins (ceftazidime and cefepime), fluoroquinolones (ciprofloxacin and levofloxacin), and third-generation tetracycline (tigecycline). Our three S. Kentucky strains were classified into the subclade ST198.2-2, and were genetically identical (2-6 SNPs) to each other. They exhibited a close genetic similarity (15-20 SNPs) to the isolate NT-h3189 from a patient and AH19MCS1 from chicken meat in China, indicating a possible epidemiological link between these S. Kentucky ST198 isolates from the patients and chicken meat. Conclusion: Long-term colonization of ciprofloxacin-resistant and ESBL-producing S. Kentucky ST198 in a single patient is a matter of concern. Due to the potential transfer of S. Kentucky ST198 from food sources to humans, ongoing surveillance of this particular clone in animals, animal-derived food products, and humans should be strengthened.

Straw from Different Crop Species Recruits Different Communities of Lignocellulose-Degrading Microorganisms in Black Soil.

The biological degradation of plant residues in the soil or on the soil surface is an integral part of the natural life cycle of annual plants and does not have adverse effects on the environment. Crop straw is characterized by a complex structure and exhibits stability and resistance to rapid microbial decomposition. In this study, we conducted a microcosm experiment to investigate the dynamic succession of the soil microbial community and the functional characteristics associated with lignocellulose-degrading pathways. Additionally, we aimed to identify lignocellulose-degrading microorganisms from the straw of three crop species prevalent in Northeast China: soybean (Glycine max Merr.), rice (Oryza sativa L.), and maize (Zea mays L.). Our findings revealed that both the type of straw and the degradation time influenced the bacterial and fungal community structure and composition. Metagenome sequencing results demonstrated that during degradation, different straw types assembled carbohydrate-active enzymes (CAZymes) and KEGG pathways in distinct manners, contributing to lignocellulose and hemicellulose degradation. Furthermore, isolation of lignocellulose-degrading microbes yielded 59 bacterial and 14 fungal strains contributing to straw degradation, with fungi generally exhibiting superior lignocellulose-degrading enzyme production compared to bacteria. Experiments were conducted to assess the potential synergistic effects of synthetic microbial communities (SynComs) comprising both fungi and bacteria. These SynComs resulted in a straw weight loss of 42% at 15 days post-inoculation, representing a 22% increase compared to conditions without any SynComs. In summary, our study provides novel ecological insights into crop straw degradation by microbes.

Insight into mitigation mechanisms of N2O emission by biochar during agricultural waste composting.

The effects and mitigation mechanisms of biochar added at different composting stages on N2O emission were investigated. Four treatments were set as follows: CK: control, BB10%: +10 % biochar at beginning of composting, BB5%&T5%: +5% biochar at beginning and + 5 % biochar after thermophilic stage of composting, BT10%: +10 % after thermophilic stage of composting. Results showed that treatment BB10%, BB5%&T5%, and BT10% reduced total N2O emissions by 55 %, 37 %, and 36 %, respectively. N2O emission was closely related to most physicochemical properties, while it was only related to amoA gene and hydroxylamine oxidoreductase. Different addition strategies of biochar changed the contributions of physicochemical properties, functional genes and enzymes to N2O emission. Organic matter and C/N contributed 23.7 % and 27.6 % of variations in functional gene abundances (P < 0.05), respectively. pH and C/N (P < 0.05) contributed 37.3 % and 17.3 % of variations in functional enzyme activities. These findings provided valuable insights into mitigating N2O emissions during composting.

Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification.

Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5'-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.

Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2.

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCEMycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway.

The expression of type I interferon (IFN) is one of the most potent innate defences against viral infection in higher vertebrates. Borna disease virus (BDV) establishes persistent, noncytolytic infections in animals and in cultured cells. Early studies have shown that the BDV phosphoprotein can inhibit the activation of type I IFN through the TBK1-IRF3 pathway. The function of the BDV nucleoprotein in the inhibition of IFN activity is not yet clear. In this study, we demonstrated IRF7 activation and increased IFN-α/ß expression in a BDV-persistently infected human oligodendroglia cell line following RNA interference-mediated BDV nucleoprotein silencing. Furthermore, we showed that BDV nucleoprotein prevented the nuclear localisation of IRF7 and inhibited endogenous IFN induction by poly(I:C), coxsackie virus B3 and IFN-ß. Our findings provide evidence for a previously undescribed mechanism by which the BDV nucleoprotein inhibits type I IFN expression by interfering with the IRF7 pathway.

Dimethyl phthalate inhibits the growth of Escherichia coli K-12 by regulating sugar transport and energy metabolism.

Dimethyl phthalate (DMP) is one of the most widely used plasticizers, and it is easily released into the environment, posing a threat to microbes. In this study, the impact of DMP on the uptake and metabolism of sugars in E. coli K-12 was assessed using proteomics, computational simulation analysis, transcriptome analysis, and sugar utilization experiments. DMP contamination inhibited the growth of E. coli K-12 and downregulated the expression of proteins in ATP-binding cassette (ABC) transporters and the phosphotransferase (PTS) system of E. coli K-12, which are primarily involved in the transmembrane transport of sugars. DMP formed a stable complex with sugar transporters and changed the rigidity and stability of the proteins. Furthermore, DMP treatment decreased the utilization of L-arabinose, glucose, D-xylose, and maltose. Moreover, carbon metabolism and oxidative phosphorylation were also downregulated by DMP. Our study shows that DMP reduces the uptake of sugars and ATP production and subsequently inhibits the growth of E. coli K-12.

WDR76 regulates 5-fluorouracil sensitivity in colon cancer via HRAS.

BACKGROUND: WD repeat domain 76 (WDR76) has been reported in multiple tumors, while without relation to chemotherapy resistance. 5-fluorouracil (5-FU) is widely adopted in treating colon cancer. However, the resistance of WDR76 and 5-FU in colon cancer remains unclear. METHODS: Limma package in R software was employed to analyze the differentially expressed genes. Western blot or quantitative real-time PCR (qRT-PCR) were run to assessed the gene expression. The cytotoxic effect was determined according to cell viability assay, colony formation assay in vitro. Cell apoptosis was assayed using flow cytometry. GSEA analysis was performed to identify pathways related to the target gene. Xenografted mice model was employed to evaluate the tumor growth. RESULTS: Bioinformatic analysis revealed the higher expression of WDR76 in 5-FU sensitive colon cancer cells compared to resistant colon cancer cells, accompanied by the decreased mRNA expression of WDR76 in 5-FU resistant colon cancer cells. The overexpressed WDR76 resulted in the apoptosis and the downregulated colony numbers in 5-FU resistant colon cancer cells, leading to the elevated sensitivity of 5-FU. Meanwhile, knockdown of WDR76 enhances the resistance of 5-FU in colon cancer both in vitro and vivo, which was reversed by a specific inhibitor of HRAS, Kobe006. An important molecular mechanism of 5-FU resistance lies the degradation of HRAS induced by WDR76. CONCLUSION: Our findings demonstrated a role of WDR76 as a promising target for reversing the resistance of colon cancer to 5-FU.