Sensory circuitry controls cytosolic calcium-mediated phytochrome B phototransduction.

Although Ca2+ has long been recognized as an obligatory intermediate in visual transduction, its role in plant phototransduction remains elusive. Here, we report a Ca2+ signaling that controls photoreceptor phyB nuclear translocation in etiolated seedlings during dark-to-light transition. Red light stimulates acute cytosolic Ca2+ increases via phyB, which are sensed by Ca2+-binding protein kinases, CPK6 and CPK12 (CPK6/12). Upon Ca2+ activation, CPK6/12 in turn directly interact with and phosphorylate photo-activated phyB at Ser80/Ser106 to initiate phyB nuclear import. Non-phosphorylatable mutation, phyBS80A/S106A, abolishes nuclear translocation and fails to complement phyB mutant, which is fully restored by combining phyBS80A/S106A with a nuclear localization signal. We further show that CPK6/12 function specifically in the early phyB-mediated cotyledon expansion, while Ser80/Ser106 phosphorylation generally governs phyB nuclear translocation. Our results uncover a biochemical regulatory loop centered in phyB phototransduction and provide a paradigm for linking ubiquitous Ca2+ increases to specific responses in sensory stimulus processing.

Integration of light and temperature sensing by liquid-liquid phase separation of phytochrome B.

Light and temperature in plants are perceived by a common receptor, phytochrome B (phyB). How phyB distinguishes these signals remains elusive. Here, we report that phyB spontaneously undergoes phase separation to assemble liquid-like droplets. This capacity is driven by its C terminus through self-association, whereas the intrinsically disordered N-terminal extension (NTE) functions as a biophysical modulator of phase separation. Light exposure triggers a conformational change to subsequently alter phyB condensate assembly, while temperature sensation is directly mediated by the NTE to modulate the phase behavior of phyB droplets. Multiple signaling components are selectively incorporated into phyB droplets to form concentrated microreactors, allowing switch-like control of phyB signaling activity through phase transitions. Therefore, light and temperature cues are separately read out by phyB via allosteric changes and spontaneous phase separation, respectively. We provide a conceptual framework showing how the distinct but highly correlated physical signals are interpreted and sorted by one receptor.

Out-of-sync evolutionary patterns and mutual interplay of major and minor capsid proteins in norovirus GII.2.

Human noroviruses are the most common cause of viral gastroenteritis, resulting annually in 219 000 deaths and a societal cost of $60 billion, and no antivirals or vaccines are available. The minor capsid protein may play a significant role in the evolution of norovirus. GII.4 is the predominant genotype of norovirus, and its VP2 undergoes epochal co-evolution with the major capsid protein VP1. Since the sudden emergence of norovirus GII.2[P16] in 2016, it has consistently remained a significant epidemic strain in recent years. In the construction of phylogenetic trees, the phylogenetic trees of VP2 closely parallel those of VP1 due to the shared tree topology of both proteins. To investigate the interaction patterns between the major and minor capsid proteins of norovirus GII.2, we chose five representative strains of GII.2 norovirus and investigated their evolutionary patterns using a yeast two-hybrid experiment. Our study shows VP1-VP2 interaction in GII.2, with critical interaction sites at 167-178 and 184-186 in the highly variable region. In the intra-within GII.2, we observed no temporal co-evolution between VP1 and VP2 of GII.2. Notable distinctions were observed in the interaction intensity of VP2 among inter-genotype (P<0.05), highlighting the divergent evolutionary patterns of VP2 within different norovirus genotypes. In summary, the interactions between VP2 and VP1 of GII.2 norovirus exhibit out-of-sync evolutionary patterns. This study offered valuable insights for further understanding and completing the evolutionary mechanism of norovirus.

Global prevalence of norovirus in cases of acute gastroenteritis from 1997 to 2021: An updated systematic review and meta-analysis.

BACKGROUND: The worldwide response towards the acute gastroenteritis epidemic was well known, but the absence of an updated systematic review of global norovirus epidemiology in cases of gastroenteritis existed. We aimed to conduct and update a systematic review and meta-analysis of studies assessing norovirus prevalence among gastroenteritis patients worldwide. METHODS: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched for epidemiological papers from 2014 to 2021 which applied the PCR method to access the prevalence of norovirus in acute gastroenteritis patients more than a full year. Statistical analysis was conducted using R-4.0.0 software. RESULTS: A total of 405 records with 842, 926 cases were included. The pooled prevalence of norovirus was 16% (95%CI 15, 17). Children under 5 years old were at a higher risk with norovirus. A higher prevalence was seen in South America (22%, 95% CI 18, 27), while other continents showed a similar result with the overall prevalence of norovirus. No association was found between national income level and norovirus prevalence. A gradient of decreasing prevalence was noticed from community (20%, 95% CI 16, 24) to outpatients (18%, 95% CI 16, 20) to hospital setting (included both in- and outpatients, 17%, 95% CI 16, 19) to inpatients (15%, 95% CI 13, 17). CONCLUSION: Norovirus were associated with 16% acute gastroenteritis globally. To fully understand the prevalence of norovirus worldwide, the continual surveillance of norovirus epidemics was required.

Mutations in eIF5B Confer Thermosensitive and Pleiotropic Phenotypes via Translation Defects in Arabidopsis thaliana.

The conserved eukaryotic translation initiation factor 5B, eIF5B, is a GTPase that acts late in translation initiation. We found that an Arabidopsis thaliana mutant sensitive to hot temperatures 3 (hot3-1), which behaves as the wild type in the absence of stress but is unable to acclimate to high temperature, carries a missense mutation in the eIF5B1 gene (At1g76810), producing a temperature sensitive protein. A more severe, T-DNA insertion allele (hot3-2) causes pleiotropic developmental phenotypes. Surprisingly, Arabidopsis has three other eIF5B genes that do not substitute for eIF5B1; two of these appear to be in the process of pseudogenization. Polysome profiling and RNA-seq analysis of hot3-1 plants show delayed recovery of polysomes after heat stress and reduced translational efficiency (TE) of a subset of stress protective proteins, demonstrating the critical role of translational control early in heat acclimation. Plants carrying the severe hot3-2 allele show decreased TE of auxin-regulated, ribosome-related, and electron transport genes, even under optimal growth conditions. The hot3-2 data suggest that disrupting specific eIF5B interactions on the ribosome can, directly or indirectly, differentially affect translation. Thus, modulating eIF5B interactions could be another mechanism of gene-specific translational control.

Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in Guangzhou, China, 2013-2015.

Norovirus diarrhea is a great threat to public health worldwide. To characterize the prevalence of circulating noroviruses associated with sporadic gastroenteritis cases in Guangzhou, 215 stool specimens were collected during two consecutive cold seasons in 2013-2015. Noroviruses were detected in 25 (11.63 %) samples, and GII.4 (6/9) and GII.17 (10/16) were identified as the most predominant variants of each of those seasons. The remaining strains belonged to the genotypes GII.P12/GII.3, GII.2, and GI.Pb/GI.6. The phylogenetic relationships of the GII.17 strains were analyzed based on their capsid protein sequences. This study suggests a significant shift of predominant variants associated with sporadic gastroenteritis in Guangzhou.

Comparative genome analysis of a norovirus GII.4 strain GZ2013-L10 isolated from South China.

In this study, the genome sequence of a norovirus GII.4 strain isolated from South China was comparatively analyzed. The RNA genome of the strain GZ2013-L10 was composed of 7513 nucleotides. Phylogenetic analyses based on three ORFs confirmed its genotype as GII.Pe/GII.4-2012. Compared with other 22 genomes of the same variant, nine distinct nucleotide substitutions were found in the new genome, which resulted in three amino acid changes. All 138 capsid protein VP1 sequences of GII.4-2012 variants were also collected, and multiple alignments revealed 35 variable codons. Evolutionary analyses of GII.4-2012 variants were performed against previous pandemic GII.4 variants, and 2 distinctive changes were identified on epitopes A and E (E368, T413), which resulted in an obvious variation of their solvent-accessible surface areas. Therefore, the genome of GZ2013-L10 was extensively characterized, and new emerging variations on viral epitopes were predicted to contribute to NoV persistence in humans.

Complete remission of gallbladder neuroendocrine carcinoma with liver metastasis by tislelizumab plus chemotherapy: a case report.

Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established. Case presentation: A 52-year-old woman was admitted to our hospital with the chief complaint of "almost 1 month after palliative surgery for metastatic gallbladder carcinoma." According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1-3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last follow-up, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future.

Development and clinical validation of a dual ddPCR assay for detecting carbapenem-resistant Acinetobacter baumannii in bloodstream infections.

Objective: Acinetobacter baumannii (A. baumannii, AB) represents a major species of Gram-negative bacteria involved in bloodstream infections (BSIs) and shows a high capability of developing antibiotic resistance. Especially, carbapenem-resistant Acinetobacter baumannii (CRAB) becomes more and more prevalent in BSIs. Hence, a rapid and sensitive CRAB detection method is of urgent need to reduce the morbidity and mortality due to CRAB-associated BSIs. Methods: A dual droplet digital PCR (ddPCR) reaction system was designed for detecting the antibiotic resistance gene OXA-23 and AB-specific gene gltA. Then, the specificity of the primers and probes, limit of detection (LOD), linear range, and accuracy of the assay were evaluated. Furthermore, the established assay approach was validated on 37 clinical isolates and compared with blood culture and drug sensitivity tests. Results: The dual ddPCR method established in this study demonstrated strong primer and probe specificity, distinguishing CRAB among 21 common clinical pathogens. The method showed excellent precision (3 × 10-4 ng/µL, CV < 25%) and linearity (OXA-23: y = 1.4558x + 4.0981, R2 = 0.9976; gltA: y = 1.2716x + 3.6092, R2 = 0.9949). While the dual qPCR LOD is 3 × 10-3 ng/µL, the dual ddPCR's LOD stands at 3 × 10-4 ng/µL, indicating a higher sensitivity in the latter. When applied to detect 35 patients with BSIs of AB, the results were consistent with clinical blood culture identification and drug sensitivity tests. Conclusion: The dual ddPCR detection method for OXA-23 and gltA developed in this study exhibits good specificity, excellent linearity, and a higher LOD than qPCR. It demonstrates reproducibility even for minute samples, making it suitable for rapid diagnosis and precision treatment of CRAB in BSIs.

The variation of antigenic and histo-blood group binding sites synergistically drive the evolution among chronologically emerging GII.4 noroviruses.

Norovirus, commonly found on shellfish and vegetables, is a foodborne virus with GII.4 as the dominant genotype responsible for widespread outbreaks since 1995. Continuous variation of major capsid protein VP1 can lead to changes in the immunogenicity and host receptor binding ability of norovirus, which is an important evolutionary mechanism. Therefore, analyzing the immunogenicity of VP1 and its binding ability to various HBGAs in GII.4 variants could improve our understanding of the persistent prevalence of GII.4. Here, the results suggest that GII.4 has gradually enhanced its HBGAs binding ability over time for various types of receptors. Variants exhibit significantly stronger immune response to homologous mouse antiserum than heterologous ones, highlighting the importance of variation of antigenic and histo-blood group binding sites in driving the evolution of GII.4. These synergistic forces constantly lead to antigenic drift and changes in receptor binding, resulting in continuous emergence of new variant strains and sustained prevalence.

Complete genome analysis of a novel norovirus GII.4 variant identified in China.

The complete genome sequence of a novel norovirus strain GZ2010-L87 identified in Guangzhou was analyzed phylogenetically in this study. The RNA genome of the GZ2010-L87 strain is composed of 7,559 nucleotides. The phylogenetic analysis based on open reading frame (ORF) 2 revealed that the strain belongs to the GII.4 genotype, forming the new cluster GII.4-2009 which was also identified in Asia and the USA since 2009. Furthermore, phylogenetic analyses of the full genome and the different open reading frame sequences of GZ2010-L87 and other representative strains suggested that the novel strain did not undergo recombination. Comparative analysis with the consensus sequence of 31 completely sequenced norovirus GII.4-2009 genomes showed 86 mismatched nucleotides (56 in ORF1, 16 in ORF2, and 14 in ORF3), resulting in 19 amino acid changes (9 in ORF1, 3 in ORF2, and 7 in ORF3). Furthermore, 12 variable sites were found on the capsid protein of norovirus GII.4-2009, and most were located at the P2 domain. Meanwhile, based on comparison with other GII.4 clusters, 14 sites were shown specific to the novel cluster. In summary, the genome of the new GII.4-2009 variant GZ2010-L87, which was first identified in China, was extensively characterized with a large panel of genetically diverse noroviruses. The genomic information obtained from the novel variant can be used not only as a full-length norovirus sequence standard in China but also as reference data for future evolution research.

Sequencing of the grxB gene of Cronobacter spp. and the development of a PCR assay for its identification.

Cronobacter spp. (formerly Enterobacter sakazakii), a foodborne pathogen linked to powdered infant formula, is a rare cause of invasive infection with a high mortality rate in neonates. In this study, the Cronobacter sakazakii ATCC 29544 and C. muytjensii ATCC 51329 glutaredoxin 2 (grxB) genes were cloned and sequenced. Based on the unique regions of the Cronobacter grxB genes, two primers were synthesized to develop and optimize a Cronobacter-specific polymerase chain reaction (PCR) method. The PCR assay amplified a 378-bp DNA product from all positive controls, which are composed of 45 strains of Cronobacter spp., but not from any of 45 non-Cronobacter bacterial strains. The detection limits of this method are 10(4) colony-forming units (CFU)/mL of Cronobacter spp. in infant formula directly and 10(0) CFU/mL after an 8-h enrichment step. In summary, we have developed a PCR assay based on the grxB sequence. Combined with enrichment culturing, this technique offers a rapid and sensitive method for the detection of Cronobacter spp.

Genetic analysis of noroviruses associated with sporadic gastroenteritis during winter in Guangzhou, China.

Noroviruses are regarded as the major causes of acute gastroenteritis worldwide, but their prevalence in sporadic diarrhea in South China remains unclear. This study was performed to characterize the genotypes of circulating norovirus strains associated with sporadic diarrhea cases in Guangzhou from November 2010 to January 2011. Among fecal specimens collected from 89 patients with acute diarrhea, nine samples (10.11%) were norovirus positive and 32 samples (35.96%) were rotavirus positive. The partial polymerase and the capsid regions of these norovirus samples were sequenced and phylogenetically analyzed. Three genotypes (GII.4, GII.6, and GII.b/GII.3) were identified, among which GII.4-2006b was the most predominant genotype (4/9, 44.4%), followed by GII.6 (3/9, 33.3%). A novel GII.4-2010 variant was first detected in China. Furthermore, the near full-length genome of the GZ2010-L26 strain, which belonged to GII.4-2006b, was sequenced and analyzed. Thus, the results of this study suggested that, second to rotavirus, noroviruses are the important pathogens responsible for sporadic acute gastroenteritis during winter in Guangzhou, and the GII.4-2006b variant remains the predominant genotype.

Epochal coevolution of minor capsid protein in norovirus GII.4 variants with major capsid protein based on their interactions over the last five decades.

Norovirus is a leading cause of viral gastroenteritis outbreaks worldwide, with GII.4 responsible for the majority of infections. Minor capsid protein VP2 has been found to have functions such as stabilizing virus particles, and VP2 is one of the highly variable proteins of norovirus, similar to major capsid protein VP1. However, whether the variation of VP2 is functionally driven still remains unclear. In this study, VP2 showed a higher evolutionary rate (2.642×10-3 substitutions/site/year) than VP1 (1.587×10-3 substitutions/site/year), and a hypervariable region in VP2 in a serial of norovirus GII.4 over the past 50 years had been observed. Notably, the high variation of VP2 was not haphazard. The evolutionary process of VP2 is similar to that of VP1 with comparable topologies when the phylogenetic trees were constructed. Moreover, VP2 was found to interact with VP1 among epidemic variants of GII.4 using the yeast two-hybrid experiments. The results of interactions were grouped into time-adjacent (e.g. Ancestral-VP1 plus US95-VP2) and non-adjacent (e.g. Ancestral-VP1 plus Sydney-VP2) according to the epochal chronologically based prevalence of GII.4 norovirus. Interestingly, the interaction of the former group was significantly stronger than that of the latter group (P=0.0001). Furthermore, the interaction regions on VP2 (residues 131-160 and 171-180) were mapped to the hypervariable region. And these interaction regions did show an important role in the evolutionary process of VP2, which was consistent with that of VP1. In summary, the minor capsid protein VP2 of GII.4 noroviruses had shown the epochal coevolution with VP1 based on their interactions over the past 50 years. The findings of this study provided valuable information for further understanding and completing the evolutionary mechanism of norovirus.

Genomic mutation characteristics and prognosis of biliary tract cancer.

BACKGROUND: The incidence of biliary system cancer is higher in the Chinese population than in the West. The overall prognosis of gallbladder cancer and cholangiocarcinoma is poor, and the current treatment is limited. In order to explore the pathogenesis of biliary tract cancers and potential targeted therapies, we mapped the mutation landscape of biliary tract cancer in the Chinese population and analyzed the molecular mechanism related to prognosis. METHODS: A total of 59 formalin fixed paraffin-embedded (FFPE) tissue samples were obtained from patients with operable biliary tract cancer. We conducted targeted capture sequencing of 620 genes through high-throughput sequencing technology and analyzed the fusion information of 13 genes. RESULTS: Mutations were detected in 88% samples, and the most frequent mutation base was C>T. Genes with higher single nucleotide variations (SNV) and copy number variations (CNV) frequency are TP53, KRAS, ARID1A, VEGFA, cyclin family related genes and cyclin-dependent kinase genes. Actionable mutations were detected in 59.3% samples, and germline mutations were detected in 22% samples. Patients with KRAS mutations, VEGFA pathway mutations and higher tumor mutation burden (TMB) may have poor prognosis. CONCLUSIONS: We explored the mutation characteristics and prognostic mechanism of biliary tract cancers in the Chinese population. This study provides potential evidence for targeted therapy and immunotherapy of biliary tract cancers.

Identification of a Two-lncRNA Signature with Prognostic and Diagnostic Value for Hepatocellular Carcinoma.

Background: Accumulating evidence has revealed the important role of long noncoding RNAs (lncRNA) in tumorigenesis and progression of hepatocellular carcinoma (HCC). This study aimed to identify potential lncRNAs that can serve as diagnostic and prognostic signatures for HCC. Methods: Expression profiling analysis was performed to identify differentially expressed lncRNAs (DElncRNA) between HCC and matched normal samples by integrating two independent microarray datasets. Functional Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were explored by Gene Set Variation Analysis. The prognostic and diagnostic models were developed based on two DElncRNAs. Real-time PCR was used to quantify the relative expressions of candidate lncRNAs. Results: Two robust DElncRNAs were identified and verified by quantitative PCR between HCC and matched normal samples. Function enrichment analysis revealed that they were associated with the wound healing process. The two lncRNAs were subsequently used to construct a prognostic risk model for HCC. Patients with high-risk scores estimated by the model showed a shorter survival time than low-risk patients (P < 0.001). Besides, the two lncRNA-based HCC diagnostic models exhibited good performance in discriminating HCC from normal samples on both training and test sets. The values of area under the curve (AUC) for early (I-II) and late (III-IV) HCC detection were 0.88 and 0.93, respectively. Conclusions: The two wound healing-related DElncRNAs showed robust performance for HCC prognostic prediction and detection, implying their potential role as diagnostic and prognostic markers for HCC.

The VP2 protein exhibits cross-interaction to the VP1 protein in norovirus GII.17.

Norovirus is a major cause of acute gastroenteritis worldwide. Like the major capsid protein (VP1), the minor capsid protein (VP2) also contains a hypervariable domain. Generally, a hypervariable domain is functionally driven. However, many functions of VP2 remain unknown and worth exploring. Without sufficient sequences and an available crystallographic model, it is difficult to explore VP2's mysteries. As a helper of stabilizing and coordinating the formation of virus-like particles (VLPs), we asked whether VP2 interacted with the major capsid protein (VP1) in GII.17 and if so, what the key interaction residues were. Here, we reported cross-interaction among four strains represented four clusters of GII.17, and the VP1 interaction domain of VP2 (174-179aa) was found. However, the VP1 interaction domain of VP2 was not universal in different clusters of GII.17. VP2 might evolve in a different pattern from VP1. Additionally, in contrast to previous reports, we found that VP2 localized in the cytoplasm. More possibilities of VP2 should be further explored.

Rapid screening for antigenic characterization of GII.17 norovirus strains with variations in capsid gene.

The emergence of the novel GII.17 Kawasaki 2014 norovirus variant raising the interest of the public, has replaced GII.4 as the predominant cause of noroviruses outbreaks in East Asia during 2014-2015. Antigenic variation of the capsid protein is considered as one of the key mechanisms of norovirus evolution. In this study, we screened a panel of GII.17 mutants. First, we produced norovirus P proteins using cell-free protein synthesis (CFPS) system, comparing the results to pure proteins expressed in a cell-based system. Next, we determined the binding capability of specific monoclonal antibody (mAb) 2D11 using a unique set of wild-type GII.17 strains. Results of the EIA involving a panel of mutant cell-free proteins indicated that Q298 was the key residue within loop 1. These data highlighted the essential residues in the linear antibody binding characteristics of novel GII.17. Furthermore, it supported the CFPS as a promising tool for rapidly screening mutants via the scalable expression of norovirus P proteins.

Over-expression of human carcinoma-associated antigen in intrahepatic cholangiocellular carcinoma.

OBJECTIVE: To investigate the expression status of human carcinoma antigen (HCA) in human cholangiocellular carcinomas, and to determine the relationship between HCA and clinical features. METHODS: Tissues from 60 intrahepatic cholangiocellular carcinoma (ICC) patients, and normal liver tissues from 20 hepatic hemangioma patients selected randomly were assayed for the expression of HCA by immunohistochemistry, and Western blots. Areas of poorly differentiated (n=20), moderately-well differentiated (n=30), highly differentiated tumors (n=10) from different cases were evaluated. Results were recorded as positive (≥5% of cells staining and staining intensity 2+ or 3+) or negative (<5% of cells staining and staining intensity<2+) and analyzed using the χ2 test. RESULTS: BCE075 and BDD048 antibodies showed similar staining patterns. The positive immunostaining of BCE075 was mainly localized in the cytoplasm and cell secretions. The staining was positive in 15% of poorly differentiated ICC, 72% of moderately-well differentiated, 100% of highly differentiated tumors. But, staining was not detected in adjacent normal tissue. The differences in HCA expression among these tissues were statistically significant. Also, we found expression of HCA to be closely associated with the degree of differentiation of ICC and tumor cell morphology. There was a correlation between expression of HCA and serum CA19-9. CONCLUSION: The data suggest that HCA is a potential marker for the diagnosis of cholangiocellular carcinoma.

Association of fucosyltransferase 2 gene with norovirus infection: A systematic review and meta-analysis.

BACKGROUND: Norovirus is a leading cause of viral gastroenteritis outbreaks worldwide. Histo-blood group antigens (HBGAs) are important host attachment factors in susceptibility to norovirus. In this study, the association of FUT2 gene, which participates in the biosynthesis of HBGAs, with norovirus infection has been investigated. METHODS: All relevant studies on the associations of FUT2 gene with norovirus were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence interval (CI) were used to analyze the extracted data. I2 statistic, sensitivity analysis and publication bias analysis were used to confirm the findings. Subgroup analyses were performed for races, genotypes, development degree of the countries, publication years, age and setting when heterogeneity was recorded. RESULTS: Twenty studies including 4066 participants were included for the meta-analysis. This analysis showed that there is a significant association between FUT2 gene and norovirus infection (OR = 3.02, 95%CI = 2.00-4.55, P < 0.001). Additionally, the ORs of norovirus infection among Chinese (OR = 4.49, 95%CI = 2.37-8.50, P < 0.001) were higher than those among Caucasian (OR = 3.23, 95%CI = 2.20-4.74, P < 0.001). CONCLUSIONS: The meta-analysis suggested that FUT2 gene is associated with susceptibility to norovirus infection.