A combined extract containing Schisandra chinensis (SCE) reduced hepatic triglyceride accumulation in rats fed a high-sucrose diet.

Excessive hepatic lipid accumulation is closely linked to inflammation, insulin resistance, and metabolic syndromes. We hypothesized that a combined extract containing Schisandra chinensis (SCE) could alleviate hepatic lipid accumulation. Male Sprague-Dawley rats fed a high-sucrose diet (HSD) were randomly assigned to three groups (n = 6): normal diet (ND), HSD (60% kcal from sucrose), and HSD + SCE (HSD with 2.44% SCE). Liquid chromatography-tandem mass spectrometry revealed that SCE contains chlorogenic acid (5.514 ± 0.009 mg/g) and schisandrin (0.179 ± 0.002 mg/g) as bioactive components. SCE did not alter the body weight, fat mass, lean mass, or glucose levels. Strikingly, SCE effectively reduced the plasma triglyceride (TG) and hepatic TG levels compared to the HSD group. Adiposity reduction is due to decreased activity of hepatic de novo lipogenic enzymes. These results indicated that SCE has nutraceutical potential for the prevention and treatment of hepatic steatosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01464-1.

Effect of fasting glucose levels on carotid intima-media thickness in premenopausal versus postmenopausal women.

Objective: To investigate the relationship between fasting blood glucose (FBG) and carotid intimamedia thickness (IMT) in premenopausal and postmenopausal women. Subjects and methods: The study enrolled 2,959 women seen at the Maanshan People's Hospital of Anhui Province from December 2013 to December 2018. Carotid IMT was measured using Doppler ultrasound. Linear regression and R smoothing curves were used to analyze the relationship between blood glucose level and carotid IMT in the premenopausal and postmenopausal groups. Results: Postmenopausal compared with premenopausal women had higher mean IMT (mIMT; 0.81 ± 0.23 mm versus 0.70 ± 0.14 mm, respectively, p < 0.001) and maximum IMT (maxIMT; 0.86 ± 0.35 mm versus 0.74 ± 0.16 mm, respectively, p < 0.001) values. On linear regression analysis, mIMT values increased with increasing FBG values when FBG level was ≤ 7 mmol/L, but no significance was found between FBG and maxIMT. After stratification by menopausal status, mIMT and maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group. In the postmenopausal group, mIMT and maxIMT increased with increasing FBG. After adjustment for covariate factors, the relationship between FBG and mIMT remained the same as before the adjustment, but when FBG was ≤ 11 mmol/L, the maxIMT increased with increasing FBG. In the stratification analysis, maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group, while both mIMT and maxIMT increased with increasing FBG when FBG was > 10 mmol/L in the postmenopausal group. Conclusion: Levels of FBG contributed more to increased IMT in postmenopausal than premenopausal women. The influence of FBG was greater on maxIMT than mIMT. Additionally, FBG was helpful in assessing focal thickening of the carotid intima.

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.

The structural characteristic of acidic-degraded polysaccharides from seeds of Plantago ovata Forssk and its biological activity.

In this study, a response surface methodology (RSM) was used to determine the best combination for acid degradation parameters to reduce the viscosity of Plantago ovata Forssk seed polysaccharide (POFP). Then, the two major homogeneous polysaccharides (AH-POFP1 and AH-POFP3) were obtained by DEAE-650 M and Sephadex G-100 column chromatography. The apparent structure of the main fraction AH-POFP1 was characterized by SEM, TG and XRD, and the linkage of AH-POFP1 was determined by a combination of partial acidolysis, Smith's degradation, methylation analysis and 2D NMR analysis. Structural analysis showed that AH-POFP1 was mainly composed of xylose, with a molecular weight of 618.1 kDa, and had a backbone of 1 â†’ 4-linked Xylp, as well as branches of T-linked Xylp, 1 â†’ 4-linked Xylp attached to the O-2 position. The antioxidant activity assays showed that the both AH-POFP1 and AH-POFP3 possess strong scavenging radical ability. Moreover, AH-POFP1 inhibits the secretion of pro-inflammatory factors, and promotes the secretion of anti-inflammatory factors, thereby exerting anti-inflammatory effects. These findings may help to guide future applications of Plantago ovata Forssk in the fields of food, health care, and pharmacy.

A patient with Owren disease requires pancreatic surgery: A case report.

RATIONALE: Coagulation factor V deficiency is rare, and perioperative management of patients with this condition is particularly important, especially during major abdominal surgery. We present a case of a patient with pancreatic duct stones combined with coagulation factor V deficiency. We share our perioperative management experience. PATIENT CONCERNS: A 31-year-old man presented with recurrent upper abdominal pain for 2 years. DIAGNOSES: The diagnosis of pancreatic duct stones in the patient has been established through abdominal computed tomography and magnetic resonance imaging examinations. The diagnosis of factor V deficiency was initially identified through coagulation function tests, revealing significant prolongation of both aPTT and PT. Subsequent testing of coagulation factors and inhibitors demonstrated that the patient has a deficiency in coagulation factor V. Finally, genetic testing revealed that the factor V deficiency in this case is hereditary. INTERVENTIONS: The patient underwent a partial resection of the pancreatic head, and FFP was infused 1 hour before surgery. 600 mL of FFP was instilled 1 hour before the start of surgery along with 10 U of cryoprecipitate. and 600 ml of FFP were added during surgery. Postoperative treatment included intermittent FFP supplemental infusion in the first 5 days after surgery while monitoring the coagulation function. OUTCOMES: The patient underwent a successful surgery without any abnormal bleeding or oozing during the procedure. The postoperative recovery was smooth, with no abnormal bleeding. LESSONS: Patients with a deficiency of coagulation factor V are not contraindicated for surgery. Appropriate Fresh Frozen Plasma (FFP) replacement therapy can ensure the safe conduct of the surgical procedure. For patients with abnormal blood coagulation function, we recommend testing for coagulation factors and inhibitors, as well as performing genetic testing for abnormal coagulation factors, which can provide guidance on marriage and childbirth.

Comparative analyses of bat genomes identify distinct evolution of immunity in Old World fruit bats.

Bats have been identified as natural reservoir hosts of several zoonotic viruses, prompting suggestions that they have unique immunological adaptations. Among bats, Old World fruit bats (Pteropodidae) have been linked to multiple spillovers. To test for lineage-specific molecular adaptations in these bats, we developed a new assembly pipeline to generate a reference-quality genome of the fruit bat Cynopterus sphinx and used this in comparative analyses of 12 bat species, including six pteropodids. Our results reveal that immunity-related genes have higher evolutionary rates in pteropodids than in other bats. Several lineage-specific genetic changes were shared across pteropodids, including the loss of NLRP1, duplications of PGLYRP1 and C5AR2, and amino acid replacements in MyD88. We introduced MyD88 transgenes containing Pteropodidae-specific residues into bat and human cell lines and found evidence of dampened inflammatory responses. By uncovering distinct immune adaptations, our results could help explain why pteropodids are frequently identified as viral hosts.

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.

Robust SSRL analysis framework for intervention strategy construction in CSCL environment.

While the importance of socially shared regulatory of learning (SSRL) in computer-supported collaborative learning (CSCL) environments has increasingly been emphasized, a surge of research has been conducted to identify socially shared regulation activities and their transition sequences. However, little research has been carried out on constructing a systematic framework in which significant regulation activities and transition sequences can be mined automatically with high reliability. Moreover, though efforts have been made, the current SSRL analysis neither serves the construction of downstream teaching intervention strategy nor explores how SSRL analysis results can be utilized conversely for refining the intervention strategy. Based on advanced machine learning techniques, this work proposes a robust framework on SSRL analysis, aiming to find the optimal teaching intervention strategy to improve learners' performance in CSCL by analyzing the SSRL process. In particular, our framework can automatically identify significant SSRL regulation activities along with high-contribution activity transition sequences. The proposed Ensemble Learning-based classification model with four distilled additional regulation activities can ensure the high reliability of our framework. The framework serves to construct a downstream teaching intervention strategy, while the strategy is updated and verified based on empirical and experimental statistical results within five rounds of iterative experiments. Extensive theoretical analysis and experimental results both confirm the effectiveness of our framework. Meanwhile, the attempt to leverage advanced machine learning algorithms to enhance SSRL analysis in this work can provide a nontrivial contribution to the literature.

The nucleoprotein of influenza A virus inhibits the innate immune response by inducing mitophagy.

Mitophagy is a form of autophagy that plays a key role in maintaining the homeostasis of functional mitochondria in the cell. Viruses have evolved various strategies to manipulate mitophagy to escape host immune responses and promote virus replication. In this study, the nucleoprotein (NP) of H1N1 virus (PR8 strain) was identified as a regulator of mitophagy. We revealed that NP-mediated mitophagy leads to the degradation of the mitochondria-anchored protein MAVS, thereby blocking MAVS-mediated antiviral signaling and promoting virus replication. The NP-mediated mitophagy is dependent on the interaction of NP with MAVS and the cargo receptor TOLLIP. Moreover, Y313 of NP is a key residue for the MAVS-NP interaction and NP-mediated mitophagy. The NPY313F mutation significantly attenuates the virus-induced mitophagy and the virus replication in vitro and in vivo. Taken together, our findings uncover a novel mechanism by which the NP of influenza virus induces mitophagy to attenuate innate immunity.Abbreviations: ACTB: actin beta; ATG7: autophagy related 7; ATG12: autophagy related 12; CCCP: carbonyl cyanide 3-chlorophenyl hydrazone; co-IP: co-immunoprecipitation; COX4/COXIV: cytochrome c oxidase subunit 4; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; EID50: 50% egg infective dose; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HEK: human embryonic kidney; hpi: hours post-infection; IAV: influenza A virus; IFN: interferon; IP: immunoprecipitation; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MLD50: 50% mouse lethal dose; MOI: multiplicity of infection; NBR1: NBR1 autophagy cargo receptor; NP: nucleoprotein; PB1: basic polymerase 1; RFP: red fluorescent protein; RIGI: RNA sensor RIG-I; RIGI-N: RIGI-CARD; SeV: Sendai virus; SQSTM1/p62: sequestosome 1; TIMM23: translocase of inner mitochondrial membrane 23; TOLLIP: toll interacting protein; TOMM20: translocase of outer mitochondrial membrane 20; TUBA: tubulin alpha; Vec: empty vector; vRNP: viral ribonucleoprotein.

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 RNA-binding protein LUC7L2 mediates MITA/STING intron retention to negatively regulate innate antiviral response.

MITA (also known as STING) is an ER-located adaptor protein, which mediates DNA-triggered innate immune response and is critically involved in autoimmune diseases and tumorigenesis. MITA is regulated by post-translational modifications, but how post-transcriptional mechanisms are involved in the regulation of MITA is still largely unknown. Here, we identified the RNA-binding protein LUC7L2 as a negative regulator of DNA virus-triggered innate immune response. LUC7L2-deficient mice exhibited resistance to lethal herpes simplex virus 1 (HSV-1) infection and reduced HSV-1 loads in the brain. Mechanistically, LUC7L2 directly bound to intron 3 of MITA precursor messenger RNA, inhibited its splicing and promoted its nonsense-mediated decay, leading to its downregulation at protein level. LUC7L2-deficient cells had markedly increased MITA level, leading to heightened innate antiviral response. Finally, LUC7L2 was induced following HSV-1 infection. Our findings reveal a feedback negative post-transcriptional regulatory mechanism for regulation of MITA-mediated innate immune response to viral and aberrant cellular DNA.

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.

PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA.

Cyclic GMP-AMP synthase (cGAS) is a key sensor critical for the recognition of DNA in the cytosol and catalyzes the synthesis of the second messenger cyclic GMP-AMP (cGAMP), which binds to the adapter protein MITA (also known as STING, MPYS, and ERIS) to initiate the innate immune response. How the binding of DNA to and the activation of cGAS are regulated remains poorly understood. Using a biochemical purification approach, we identified poly(rC)-binding protein 1 (PCBP1) as a cGAS-associated protein. PCBP1 was recruited to cGAS in a viral infection-dependent manner. PCBP1 directly bound to DNA and enhanced cGAS binding to its ligands, which was important for cGAS activation. Consistently, PCBP1 deficiency inhibited cytosolic DNA- and DNA virus-triggered transcription of downstream effector genes. These findings suggest that PCBP1 plays an important role in the cGAS-mediated innate immune response to DNA virus infection by promoting the binding of cGAS to viral DNA.

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.

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.

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.

TAK1-TABs Complex: A Central Signalosome in Inflammatory Responses.

Transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1) is a member of the MAPK kinase kinase (MAPKKK) family and has been implicated in the regulation of a wide range of physiological and pathological processes. TAK1 functions through assembling with its binding partners TAK1-binding proteins (TAB1, TAB2, and TAB3) and can be activated by a variety of stimuli such as tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), and toll-like receptor ligands, and they play essential roles in the activation of NF-κB and MAPKs. Numerous studies have demonstrated that post-translational modifications play important roles in properly controlling the activity, stability, and assembly of TAK1-TABs complex according to the indicated cellular environment. This review focuses on the recent advances in TAK1-TABs-mediated signaling and the regulations of TAK1-TABs complex by post-translational modifications.

The zinc-finger protein ZFYVE1 modulates TLR3-mediated signaling by facilitating TLR3 ligand binding.

Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to the induction of downstream antiviral effectors and the innate antiviral immune response. Here, we identified the zinc-finger FYVE domain-containing protein ZFYVE1, a guanylate-binding protein (GBP), as a positive regulator of TLR3-mediated signaling. Overexpression of ZFYVE1 promoted the transcription of downstream antiviral genes upon stimulation with the synthetic TLR3 ligand poly(I:C). Conversely, ZFYVE1 deficiency had the opposite effect. Zfyve1-/- mice were less susceptible than wild-type mice to inflammatory death induced by poly(I:C) but not LPS. ZFYVE1 was associated with TLR3, and the FYVE domain of ZFYVE1 and the ectodomain of TLR3 were shown to be responsible for their interaction. ZFYVE1 was bound to poly(I:C) and increased the binding affinity of TLR3 to poly(I:C). These findings suggest that ZFYVE1 plays an important role in the TLR3-mediated innate immune and inflammatory responses by promoting the ligand binding of TLR3.