The tumor suppressor PTEN has a critical role in antiviral innate immunity.

The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-ß production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.

The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors.

Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate antiviral immune response. How the binding of viral RNA to and activation of the RLRs are regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co-receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune response to RNA virus.

Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation.

During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked ß-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response.

The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.

Influenza A virus (IAV) has evolved various strategies to counteract the innate immune response using different viral proteins. However, the mechanism is not fully elucidated. In this study, we identified the PB1 protein of H7N9 virus as a new negative regulator of virus- or poly(I:C)-stimulated IFN induction and specifically interacted with and destabilized MAVS. A subsequent study revealed that PB1 promoted E3 ligase RNF5 to catalyze K27-linked polyubiquitination of MAVS at Lys362 and Lys461. Moreover, we found that PB1 preferentially associated with a selective autophagic receptor neighbor of BRCA1 (NBR1) that recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation. The degradation cascade mediated by PB1 facilitates H7N9 virus infection by blocking the RIG-I-MAVS-mediated innate signaling pathway. Taken together, these data uncover a negative regulatory mechanism involving the PB1-RNF5-MAVS-NBR1 axis and provide insights into an evasion strategy employed by influenza virus that involves selective autophagy and innate signaling pathways.

Maternal seafood consumption and fetal growth: a birth cohort study in urban China.

BACKGROUND: Seafood is a good source of essential fatty acids which has a presumably beneficial effect on developing embryos and fetuses, although it is also a source of contaminants. In this context, pregnant women are faced with conflicting reports on the risk and benefits of seafood consumption. This study aims to assess whether the consumption of seafood during pregnancy was associated with fetal growth in an inland city in China. METHODS: This study included 10,179 women who delivered a singleton live birth in Lanzhou, China. Seafood consumption was assessed using a Food Frequency Questionnaire. Maternal data including birth outcomes and maternal complications information is extracted from the medical records. Associations between seafood consumption and fetal growth indicators were analyzed using multiple linear regression and multiple logistic regression. RESULTS: There was a positive association between total seafood consumption and birth weight (ß = 0.027, 95%CI:0.030-0.111) but no association concerning birth length or head circumference. Seafood consumption was associated with decreased risk of low birth weight (OR = 0.575, 95% CI: 0.480, 0.689). The frequency of seafood consumption during pregnancy showed a trend toward a positive association with low birth weight. Significantly reduced rates of low birth weight were found in women who consumed more than 75 g of seafood/week during pregnancy as compared to women with no or very low intakes (P for trend 0.021). A significant interaction was observed between pre-pregnancy BMI and seafood consumption on birth weight among underweight women, but not among overweight women. Gestational weight gain partially mediated the association between seafood consumption and birth weight. CONCLUSIONS: Maternal seafood consumption was associated with decreased risk of low birth weight and increased birth weight. This association was mainly driven by freshwater fish and shellfish. These results further corroborate the present dietary recommendation to the Chinese Nutrition Society for pregnant women, especially those with underweight pre-pregnancy BMI and inadequate GWG. In addition, our findings provide implications for future interventions to improve seafood consumption among pregnant women to prevent low birth weight babies in the inland city in China.

ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response.

The retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5), sense cytoplasmic viral RNA and initiate innate antiviral responses. How RIG-I and MDA5 are differentially regulated remains enigmatic. In this study, we identified the guanylate-binding protein (GBP) and zinc-finger FYVE domain-containing protein ZFYVE1 as a negative regulator of MDA5- but not RIG-I-mediated innate antiviral responses. ZFYVE1-deficiency promoted MDA5- but not RIG-I-mediated transcription of downstream antiviral genes. Comparing to wild-type mice, Zfyve1-/- mice were significantly protected from lethality induced by encephalomyocarditis virus (EMCV) that is sensed by MDA5, whereas Zfyve1-/- and Zfyve1+/+ mice were comparable to death induced by vesicular stomatitis virus (VSV) that is sensed by RIG-I. Mechanistically, ZFYVE1 interacted with MDA5 but not RIG-I. ZFYVE1 bound to viral RNA and decreased the ligand binding and oligomerization of MDA5. These findings suggest that ZFYVE1 acts as a specific negative regulator of MDA5-mediated innate immune responses by inhibiting its ligand binding and oligomerization.

The Nucleoprotein of H7N9 Influenza Virus Positively Regulates TRAF3-Mediated Innate Signaling and Attenuates Viral Virulence in Mice.

H7N9 influenza A virus (IAV) is an emerged contagious pathogen that may cause severe human infections, even death. Understanding the precise cross talk between virus and host is vital for the development of effective vaccines and therapeutics. In the present study, we identified the nucleoprotein (NP) of H7N9 IAV as a positive regulator of RIG-I like receptor (RLR)-mediated signaling. Based on a loss-of-function strategy, we replaced H1N1 (mouse-adapted PR8 strain) NP with H7N9 NP, by using reverse genetics, and found that the replication and pathogenicity of recombinant PR8-H7N9NP (rPR8-H7N9NP) were significantly attenuated in cells and mice. Biochemical and cellular analyses revealed that H7N9 NP specifically interacts with tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) after viral infection. Subsequently, we identified a PXXQXS motif in the H7N9 NP that may be a determinant for the NP and TRAF3 interaction. Furthermore, H7N9 NP stabilized TRAF3 expression via competitively binding to TRAF3 with cellular inhibitor of apoptosis 2 (cIAP2), leading to the inhibition of the Lys48-linked polyubiquitination and degradation of TRAF3. Taken together, these data uncover a novel mechanism by which the NP of H7N9 IAV positively regulates TRAF3-mediated type I interferon signaling. Our findings provide insights into virus and host survival strategies that involve a specific viral protein that modulates an appropriate immune response in hosts.IMPORTANCE The NS1, PB2, PA-X, and PB1-F2 proteins of influenza A virus (IAV) are known to employ various strategies to counteract and evade host defenses. However, the viral components responsible for the activation of innate immune signaling remain elusive. Here, we demonstrate for the first time that the NP of H7N9 IAV specifically associates with and stabilizes the important adaptor molecule TRAF3, which potentiates RLR-mediated type I interferon induction. Moreover, we reveal that this H7N9 NP protein prevents the interaction between TRAF3 and cIAP2 that mediates Lys48-linked polyubiquitination of TRAF3 for degradation. The current study revealed a novel mechanism by which H7N9 NP upregulates TRAF3-mediated type I interferon production, leading to attenuation of viral replication and pathogenicity in cells and mice. Our finding provides a possible explanation for virus and host commensalism via viral manipulation of the host immune system.

USP19 Inhibits TNF-α- and IL-1ß-Triggered NF-κB Activation by Deubiquitinating TAK1.

The dynamic regulations of ubiquitination and deubiquitination play important roles in TGF-ß-activated kinase 1 (TAK1)-mediated NF-κB activation, which regulates various physiological and pathological events. We identified ubiquitin-specific protease (USP)19 as a negative regulator of TNF-α- and IL-1ß-triggered NF-κB activation by deubiquitinating TAK1. Overexpression of USP19 but not its enzymatic inactive mutant inhibited TNF-α- and IL-1ß-triggered NF-κB activation and transcription of downstream genes, whereas USP19 deficiency had the opposite effects. Usp19-/- mice produced higher levels of inflammatory cytokines and were more susceptible to TNF-α- and IL-1ß-triggered septicemia death compared with their wild-type littermates. Mechanistically, USP19 interacted with TAK1 in a TNF-α- or IL-1ß-dependent manner and specifically deconjugated K63- and K27-linked polyubiquitin chains from TAK1, leading to the impairment of TAK1 activity and the disruption of the TAK1-TAB2/3 complex. Our findings provide new insights to the complicated molecular mechanisms of the attenuation of the inflammatory response.

Approach selection and outcomes of craniopharyngioma resection: a single-institute study.

Since there are many approaches for successful craniopharyngioma resection, how to choose a suitable approach remains problematic. The aim of this study was to summarize experience of approach selection and outcomes of craniopharyngioma resection in our institute. The data of 182 primary craniopharyngiomas between January 2013 and June 2019 were retrospectively reviewed. Craniopharyngiomas were classified into intrasellar, intra-suprasellar, suprasellar, and intra-third ventricle types based on the location. The surgical approaches, extent of resection, endocrine and ophthalmological outcomes, and complications were evaluated. Gross total resection (GTR) was achieved in 158 (86.8%) patients, near-total resection (NTR) in 20 (11%), and partial resection (PR) in 4 (2.2%). New-onset hypopituitarism occurred in 90 (49.5%) and new-onset diabetes insipidus in 48 (26.4%). Visual function was improved in 110 of the 182 patients, unchanged in 52, and deteriorated in 20. For intra-suprasellar and suprasellar tumors, patients in the endoscopic endonasal approach (EEA) group had higher GTR rate, lower incidence of new-onset hypopituitarism, and better visual outcome than patients in transcranial approach group, but no significant difference in the incidence of new-onset diabetes insipidus was found. There were no surgery-related deaths, and the common complications included permanent oculomotor nerve palsy, hemorrhage, and cerebrospinal fluid leaks. During the follow-up period, tumor recurrence or regrowth occurred in 6.6% of the cases. Tumor location is key for choosing an optimal surgical approach for craniopharyngioma resection. The EEA should be considered as the first choice for intra-suprasellar and suprasellar craniopharyngiomas to achieve better visual outcomes and fewer pituitary hormonal disorders.

A Naturally Occurring Deletion in the Effector Domain of H5N1 Swine Influenza Virus Nonstructural Protein 1 Regulates Viral Fitness and Host Innate Immunity.

Nonstructural protein 1 (NS1) of influenza A virus regulates innate immune responses via various mechanisms. We previously showed that a naturally occurring deletion (the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus impairs the inhibition of type I interferon (IFN) in chicken fibroblasts and attenuates virulence in chickens. Here we found that the virus bearing this deletion in its NS1 effector domain showed diminished inhibition of IFN-related cytokine expression and attenuated virulence in mice. We further showed that deletion of the EALQR motif disrupted NS1 dimerization, impairing double-stranded RNA (dsRNA) sequestration and competitive binding with RIG-I. In addition, the EALQR-deleted NS1 protein could not bind to TRIM25, unlike full-length NS1, and was less able to block TRIM25 oligomerization and self-ubiquitination, further impairing the inhibition of TRIM25-mediated RIG-I ubiquitination compared to that with full-length NS1. Our data demonstrate that the EALQR deletion prevents NS1 from blocking RIG-I-mediated IFN induction via a novel mechanism to attenuate viral replication and virulence in mammalian cells and animals.IMPORTANCE H5 highly pathogenic avian influenza viruses have infected more than 800 individuals across 16 countries, with an overall case fatality rate of 53%. Among viral proteins, nonstructural protein 1 (NS1) of influenza virus is considered a key determinant for type I interferon (IFN) antagonism, pathogenicity, and host range. However, precisely how NS1 modulates virus-host interaction, facilitating virus survival, is not fully understood. Here we report that a naturally occurring deletion (of the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus disrupted NS1 dimerization, which diminished the blockade of IFN induction via the RIG-I signaling pathway, thereby impairing virus replication and virulence in the host. Our study demonstrates that the EALQR motif of NS1 regulates virus fitness to attain a virus-host compromise state in animals and identifies this critical motif as a potential target for the future development of small molecular drugs and attenuated vaccines.

Glycogen synthase kinase 3ß regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1.

Viral infection activates transcription factors IRF3 and NF-κB, which collaborate to induce type I interferons (IFNs). Here, we identified glycogen synthase kinase 3ß (GSK3ß) as an important regulator for virus-triggered IRF3 and NF-κB activation, IFN-ß induction, and cellular antiviral response. Overexpression of GSK3ß potentiated virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas reduced expression or deletion of GSK3ß impaired virus-induced IRF3 and NF-κB activation, transcription of the IFNB1 gene, as well as cellular antiviral response. GSK3ß physically associated with the kinase TBK1 in a viral infection-dependent manner. GSK3ß promoted TBK1 self-association and autophosphorylation at Ser172, which is critical for virus-induced IRF3 activation and IFN-ß induction. The effect of GSK3ß on virus-induced signaling is independent of its kinase activity. Our findings suggest that GSK3ß plays important roles in virus-triggered IRF3 activation by promoting TBK1 activation and provide new insights to the molecular mechanisms of cellular antiviral response.

TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction.

TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a Trim8 gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including TNF, Il6, Rantes, and Ifnb, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as Salmonella typhimurium infection-induced loss of body weight and septic shock. TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN-ß and mediated its K6- and K33-linked polyubiquitination, leading to disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-ß-TANK-binding kinase-1 association. Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses.

Duck Tembusu Virus Nonstructural Protein 1 Antagonizes IFN-ß Signaling Pathways by Targeting VISA.

Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-ß induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-ß expression by inhibiting retinoic acid-inducible gene I-like receptor signaling. Moreover, we found that DTMUV NS1 specifically interacted with the C-terminal domain of virus-induced signaling adaptor and impaired the association of retinoic acid-inducible gene I or melanoma differentiation-associated gene 5 and virus-induced signaling adaptor, thereby downregulating the retinoic acid-inducible gene I-like receptor-mediated signal transduction and cellular antiviral responses, leading to evasion of the innate immune response. Together, our findings reveal a novel mechanism manipulated by DTMUV to circumvent the host antiviral immune response.

WDFY1 mediates TLR3/4 signaling by recruiting TRIF.

Toll-like receptors (TLRs) are pattern recognition receptors that sense a variety of pathogens, initiate innate immune responses, and direct adaptive immunity. All TLRs except TLR3 recruit the adaptor MyD88 to ultimately elicit inflammatory gene expression, whereas TLR3 and internalized TLR4 use TIR-domain-containing adaptor TRIF for the induction of type I interferon and inflammatory cytokines. Here, we identify the WD repeat and FYVE-domain-containing protein WDFY1 as a crucial adaptor protein in the TLR3/4 signaling pathway. Overexpression of WDFY1 potentiates TLR3- and TLR4-mediated activation of NF-κB, interferon regulatory factor 3 (IRF3), and production of type I interferons and inflammatory cytokines. WDFY1 depletion has the opposite effect. WDFY1 interacts with TLR3 and TLR4 and mediates the recruitment of TRIF to these receptors. Our findings suggest a crucial role for WDFY1 in bridging the TLR-TRIF interaction, which is necessary for TLR signaling.

Krüppel-like factor 6 is a co-activator of NF-κB that mediates p65-dependent transcription of selected downstream genes.

The transcription factor NF-κB plays a pivotal role in a broad range of physiological and pathological processes, including development, inflammation, and immunity. How NF-κB integrates activating signals to expression of specific sets of target genes is of great interest. Here, we identified Krüppel-like factor 6 (KLF6) as a co-activator of NF-κB after TNFα and IL-1ß stimulation. Overexpression of KLF6 enhanced TNFα- and IL-1ß-induced activation of NF-κB and transcription of a subset of downstream genes, whereas knockdown of KLF6 had opposite effects. KLF6 interacted with p65 in the nucleus and bound to the promoters of target genes. Upon IL-1ß stimulation, KLF6 was recruited to promoters of a subset of NF-κB target genes in a p65-dependent manner, which was in turn required for the optimal binding of p65 to the target gene promoters. Our findings thus identified KLF6 as a previously unknown but essential co-activator of NF-κB and provided new insight into the molecular regulation of p65-dependent gene expression.

Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome.

Mutations in ANKRD11 have recently been reported to cause KBG syndrome, an autosomal dominant condition characterized by intellectual disability (ID), behavioral problems, and macrodontia. To understand the pathogenic mechanism that relates ANKRD11 mutations with the phenotype of KBG syndrome, we studied the cellular characteristics of wild-type ANKRD11 and the effects of mutations in humans and mice. We show that the abundance of wild-type ANKRD11 is tightly regulated during the cell cycle, and that the ANKRD11 C-terminus is required for the degradation of the protein. Analysis of 11 pathogenic ANKRD11 variants in humans, including six reported in this study, and one reported in the Ankrd11 (Yod/+) mouse, shows that all mutations affect the C-terminal regions and that the mutant proteins accumulate aberrantly. In silico analysis shows the presence of D-box sequences that are signals for proteasome degradation. We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.

FoxO1 negatively regulates cellular antiviral response by promoting degradation of IRF3.

Viral infection causes activation of the transcription factor IRF3, which is critical for production of type I interferons (IFNs) and innate antiviral immune response. How virus-induced type I IFN signaling is controlled is not fully understood. Here we identified the transcription factor FoxO1 as a negative regulator for virus-triggered IFN-ß induction. Overexpression of FoxO1 inhibited virus-triggered ISRE activation, IFN-ß induction as well as cellular antiviral response, whereas knockdown of FoxO1 had opposite effects. FoxO1 interacted with IRF3 in a viral infection-dependent manner and promoted K48-linked polyubiquitination and degradation of IRF3 in the cytosol. Furthermore, FoxO1-mediated degradation of IRF3 was independent of the known E3 ubiquitin ligases for IRF3, including RBCK1 and RAUL. Our findings thus suggest that FoxO1 negatively regulates cellular antiviral response by promoting IRF3 ubiquitination and degradation, providing a previously unknown mechanism for control of type I IFN induction and cellular antiviral response.

The expression of TGF-ß1, Smad3, phospho-Smad3 and Smad7 is correlated with the development and invasion of nonfunctioning pituitary adenomas.

BACKGROUND: Transforming growth factor ß (TGF-ß) signaling functions as a suppressor or a promoter in tumor development, depending on the tumor stage and type. However, the role of TGF-ß signaling in nonfunctioning pituitary adenomas (NFPAs) has not been explored. METHODS: TGF-ß1, Smad2, phospho-Smad2 (p-Smad2), Smad3, phospho-Smad3 (p-Smad3), Smad4, and Smad7 were detected in 5 cases of normal anterior pituitaries, 29 cases of invasive NFPAs, and 21 cases of noninvasive NFPAs by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. RESULTS: The Smad3 and p-Smad3 protein levels gradually decreased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. However, there were no significant differences in Smad2 (P = 0.122) and p-Smad2 protein levels (P = 0.101) or Smad2 mRNA level (P = 0.409). In addition, the TGF-ß1 mRNA level gradually decreased while the Smad7 mRNA level gradually increased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. Furthermore, proliferating cell nuclear antigen (PCNA) mRNA level was markedly increased in invasive NFPAs compared to noninvasive ones (P < 0.01), and its level was negatively correlated with Smad3 mRNA level (P < 0.01). CONCLUSION: The activity of TGF-ß signaling may be restrained in NFPAs and is correlated with the development and invasion of NFPAs.

Research on evaluation of university education informatization level based on clustering technique.

Today, the utilization of Information Technology tools is considered an inevitable path in the education system. In this regard, assessing the effective integration of Information Technology tools in the educational system holds significant importance. This process can be automated using artificial intelligence techniques, which are the subject of the current study. In this research, initially, a set of 14 indicators related to levels of Education Informatization (EI) in higher education is introduced. Subsequently, a clustering-based strategy is proposed to rank the indicators and determine an optimal subset of these features. Based on this framework, it is demonstrated that using 11 indicators related to educational behaviors can achieve the highest accuracy in evaluating EI levels. The proposed approach employs a group of Support Vector Machines (SVMs) for EI level assessment, where classifier hyperparameters are tuned using reinforcement learning strategy. The performance of the proposed method is evaluated on real-world data and compared with previous works. The results indicate that the proposed method can assess EI levels in universities with an average accuracy of 93.64 %, outperforming compared methods by at least 4.09 %.

The management of a duodenal fistula involving the right hepatic duct: a rare case report.

The formation of an internal fistula between the biliary system and the gastrointestinal tract is a rare condition with various etiologies, predominantly associated with recurrent chronic inflammation of the biliary system and tumors. Patients with this condition may lack specific clinical manifestations, presenting with symptoms such as abdominal pain, fever, jaundice, or may show no clinical signs at all. Common types of internal fistulas include cholecystoduodenal fistula, cholecystocolonic fistula, and choledochoduodenal fistula. Among these, the right hepaticoduodenal fistula is extremely rare and seldom reported in clinical literature. We herein report a case of right hepaticoduodenal fistula and analyze its mechanism, treatment principles, and preventive measures through a literature review.