A stochastic block Ising model for multi-layer networks with inter-layer dependence.

Community detection has attracted tremendous interests in network analysis, which aims at finding group of nodes with similar characteristics. Various detection methods have been developed to detect homogeneous communities in multi-layer networks, where inter-layer dependence is a widely acknowledged but severely under-investigated issue. In this paper, we propose a novel stochastic block Ising model (SBIM) to incorporate the inter-layer dependence to help with community detection in multi-layer networks. The community structure is modeled by the stochastic block model (SBM) and the inter-layer dependence is incorporated via the popular Ising model. Furthermore, we develop an efficient variational EM algorithm to tackle the resultant optimization task and establish the asymptotic consistency of the proposed method. Extensive simulated examples and a real example on gene co-expression multi-layer network data are also provided to demonstrate the advantage of the proposed method.

Role of arachidonic acid lipoxygenase pathway in Asthma.

The arachidonic acid (AA) metabolism pathways play a key role in immunological response and inflammation diseases, such as asthma, etc. AA in cell membranes can be metabolized by lipoxygenases (LOXs) to a screen of bioactive substances that include leukotrienes (LTs), lipoxins (LXs), and eicosatetraenoic acids (ETEs), which are considered closely related to the pathophysiology of respiratory allergic disease. Studies also verified that drugs regulating AA LOXs pathway have better rehabilitative intervention for asthma. This review aims to summarize the physiological and pathophysiological importance of AA LOXs metabolism pathways in asthma and to discuss its prospects of therapeutic strategies.

Discovery of a novel GLP-1/GIP dual receptor agonist CY-5 as long-acting hypoglycemic, anti-obesity agent.

Glucagon-like peptide-1 (GLP-1) receptor agonists as an effective approach for type 2 diabetes mellitus (T2DM) has been explored extensively, multi agonists based on GLP-1 may have better clinical benefits on obesity, Nonalcoholic steatohepatitis (NASH) and other metabolic diseases. To get multi agonists based on GLP-1, 15 conjugates were designed, synthesized, and tested for biological activity. GLP-1/glucagon dual receptor agonist E1 showed moderate long-acting hypoglycemic effect, CY-5 and CY-16 with GLP-1/GIP dual receptor agonistic activity exhibited longer duration of continuous blood glucose stabilization. The long-acting hypoglycemic effect was equal to that of semaglutide. Although they have lost the agonistic activity on glucagon receptor, chronic in vivo studies on T2DM mice and diet-induced obesity (DIO) mice showed that CY-5 can effectively reduce food intake, inhibit body weight gain, repair islets damage and improve the glucose tolerance. One month treatment on NASH mice showed that CY-5 can significantly lower the TG, TC, AST, ALT and LDL-C and increase the HDL-C. CY-5 can also improve the liver vacuolation, reduce fat accumulation and delay the process of the fibrosis. The liver protection effect is better than that of semaglutide. In summary, CY-5 is a promising candidate for the treatment of metabolic diseases and worthy for further development.

INSL-3 protein expression in normal and cryptorchid testes of Ziwuling black goats.

Ziwuling black goats are typically found in loess plateaus regions and the Ziwuling Nature Reserve. Cryptorchidism is a common disease in this inbred goat, and its pathogenesis has been linked with the expression of insulin-like factor 3 (INSL-3). Therefore, this study aimed to investigate anatomical alterations caused by cryptorchism and the expression and distribution of INSL-3 in normal and cryptorchid testicular tissues. The testicular tissues of 6-month-old Ziwuling black goats were collected for microscopic analyses using histochemical, immunohistochemical, immunofluorescence and biometrical methods, as well as Western blotting to compare the expression and distribution of INSL-3. A lower expression of INSL-3 was observed in cryptorchid compared with normal testicular tissues (p < .01). Cryptorchidism caused a significant reduction in layers of spermatogenic epithelium and tubule areas in Ziwuling black goat (p < .01). The interstitial to seminiferous tubule area ratio was larger in cryptorchid than in normal group. Periodic Acid-Schiff (PAS) staining revealed pronounced positive bands in the interstitial tissue, while positive Alcian blue (AB) staining was not clear, and AB-PAS staining revealed a positive red band in the basement membrane of cryptorchid group. Immunofluorescence revealed a strong signal of INSL-3 expression in Sertoli and peritubular myoid cells, and moderate signal in Leydig and spermatogenic cells in the normal group. However, in cryptorchid testicular tissues, the signal of INSL-3 expression was strong in primary spermatocytes, occasional in Sertoli cells, limited in Leydig cells and absent in peritubular myoid cells. Furthermore, immunohistochemistry showed that INSL-3 expression was higher in normal testes compared with cryptorchid testicular tissues (p < .05), especially in primary spermatocytes and Sertoli cells. Collectively, our results indicate that cryptorchidism is closely related to the disorder of acid glycoprotein metabolism and the reduction in release of INSL-3 from Leydig cells. Moreover, Sertoli and peritubular myoid cells are crucial for INSL signalling and could underpin further research on the mechanism of cryptorchidism in animal.

Evasion mechanisms of the type I interferons responses by influenza A virus.

The type I interferons (IFNs) represent the first line of host defense against influenza virus infection, and the precisely control of the type I IFNs responses is a central event of the immune defense against influenza viral infection. Influenza viruses are one of the leading causes of respiratory tract infections in human and are responsible for seasonal epidemics and occasional pandemics, leading to a serious threat to global human health due to their antigenic variation and interspecies transmission. Although the host cells have evolved sophisticated antiviral mechanisms based on sensing influenza viral products and triggering of signalling cascades resulting in secretion of the type I IFNs (IFN-α/ß), influenza viruses have developed many strategies to counteract this mechanism and circumvent the type I IFNs responses, for example, by inducing host shut-off, or by regulating the polyubiquitination of viral and host proteins. This review will summarise the current knowledge of how the host cells recognise influenza viruses to induce the type I IFNs responses and the strategies that influenza viruses exploited to evade the type I IFNs signalling pathways, which will be helpful for the development of antivirals and vaccines.

Novel glucagon- and OXM-based peptides acting through glucagon and GLP-1 receptors with body weight reduction and anti-diabetic properties.

Oxyntomodulin (OXM) is an endogenous gastrointestinal hormone, which activates both the Glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). However, OXM has shortcomings including poor GLP-1R agonism to control glycemia, short half-life and others. Inspired from the sequence relationship between OXM and glucagon, in this study, we introduced different C-terminus residues of GLP-1, exenatide and OXM to glucagon to get a series of hybrid peptides with enhanced GLP-1R activation. The formed glucagon-exenatide hybrid peptide shows higher GLP-1R activation properties than OXM. Then the peptides based on the glucagon-exenatide hybrid peptide were coupled with fatty acid side chains to prolong their half-lives. As a result, the most potent compound 16a could stimulate insulin secretion and maintain blood glucose in normal level for ~42.6 h in diabetic mice. 16a exhibited reduced HbA1c level in diabetic mice, lowered body weight significantly in obesity mice on chronic treatment assay. 16a, combined efficient GCGR/GLP-1R activity, is potential as novel treatment for obesity and diabetes. This finding provides new insights into balancing GLP-1/GCGR potency of glucagon-exenatide hybrid peptide and is helpful for discovery of novel anti-diabetic and bodyweight-reducing drugs.

A new fruit fly optimization algorithm enhanced support vector machine for diagnosis of breast cancer based on high-level features.

BACKGROUND: It is of great clinical significance to develop an accurate computer aided system to accurately diagnose the breast cancer. In this study, an enhanced machine learning framework is established to diagnose the breast cancer. The core of this framework is to adopt fruit fly optimization algorithm (FOA) enhanced by Levy flight (LF) strategy (LFOA) to optimize two key parameters of support vector machine (SVM) and build LFOA-based SVM (LFOA-SVM) for diagnosing the breast cancer. The high-level features abstracted from the volunteers are utilized to diagnose the breast cancer for the first time. RESULTS: In order to verify the effectiveness of the proposed method, 10-fold cross-validation method is used to make comparison among the proposed method, FOA-SVM (model based on original FOA), PSO-SVM (model based on original particle swarm optimization), GA-SVM (model based on genetic algorithm), random forest, back propagation neural network and SVM. The main novelty of LFOA-SVM lies in the combination of FOA with LF strategy that enhances the quality for FOA, thus improving the convergence rate of the FOA optimization process as well as the probability of escaping from local optimal solution. CONCLUSIONS: The experimental results demonstrate that the proposed LFOA-SVM method can beat other counterparts in terms of various performance metrics. It can very well distinguish malignant breast cancer from benign ones and assist the doctor with clinical diagnosis.

Arbutin attenuates LPS-induced lung injury via Sirt1/ Nrf2/ NF-κBp65 pathway.

The main goal of this study was to evaluate the effects of arbutin (AR) on lipopolysaccharide (LPS)-induced lung injury. A lung injury rat model was established by intravenous LPS administration. We found that levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) in both serum and lung tissue were significant increased after LPS challenge. In addition, pathological conditions were examined in rat lungs, and it was demonstrated that AR-pretreatment reduced LPS-induced malondialdehyde (MDA) levels and increased LPS-induced superoxide dismutase (SOD) activity. Moreover, the expression of sirtuin1 (SIRT1), nuclear erythroid factor 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) as well as the phosphorylation of NF-κBp65 and IκBα were increased with LPS-induced lung injury, and were significantly restored by AR treatment. Together, our results indicated that SIRT1 is a potential therapeutic target in LPS-induced lung injury, and that AR may be a novel therapeutic in patients with acute lung injury.

Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties.

Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1-39)-NH2, Cys40-Exenatide (1-39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1-39)-NH2 and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1-39)-NH2 were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugation C2 was selected for further investigation. Glucoregulatory and insulin secretion assay and hypoglycemic duration test were accessed and showed that C2 was capable of comparable insulinotropic activities and glucose-lowering abilities with those of liraglutide and exenatide. Cell protective effects in INS-1 cells confirmed that C2 had relatively protection effects. Meanwhile, once daily injection of C2 to STZ-induced diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. Acute feeding studies were evaluated in DIO mice. These results suggested that C2 is a promising agent for further investigation of its potential to treat diabetes patients with obese.

Synthesis and evaluation of redox-sensitive gonadotropin-releasing hormone receptor-targeting peptide conjugates.

Lytic peptides have been demonstrated to exhibit obvious advantages in cancer therapy with binding ability toward tumor cells via electrostatic attractions, which are lack of active targeting and aggregation to tumor tissue. In the present study, five conjugated lytic peptides were redesigned and constructed to target gonadotropin releasing hormone receptors (GnRHr), meanwhile, the disulfide bridge was introduced to achieve redox sensitive delivery based on the experience from the preliminary work of lytic peptides P3 and P7. YX-1, was considered to be the most promising for in-depth study. YX-1 possessed high potency (IC50 = 3.16 ±â€¯0.3 µM), low hemolytic effect, and cell membrane permeability in human A2780 ovarian cancer cells. Moreover, YX-1 had prominent pro-apoptotic activity by activating the mitochondria-cytochrome c-caspase apoptotic pathway. The study yielded the conjugate YX-1 with superior properties for antineoplastic activity, which makes it a promising potential candidate for targeting cancer therapy.

Effects of breathing exercises using home-based positive pressure in the expiratory phase in patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) commonly have higher intrinsic positive end-expiratory pressure (PEEPi). A breathing exercise programme strategy employing an appropriate PEEP may improve their pulmonary functional capacity, exercise tolerance and health-related quality of life. Breathing with an expiratory resistive load, which is a method of modulating spontaneous breathing against PEEPi, has not been fully studied in patients with COPD. The objective of this study was to investigate the role of changing spontaneous breathing in home-based conditions and regulating spontaneous breathing with breathing exercises in patients with COPD. METHODS: This was a prospective randomised trial including 64 patients with a diagnosis of stage III or IV COPD. Patients were randomised into two groups: standard treatment and standard treatment combined with breathing exercise rehabilitation. The effects of the treatments on the COPD assessment test (CAT) score, 6-minute walk test (6MWT) results and pulmonary function were compared at 0, 6, 12 and 18 months within and between the two groups. RESULTS: All outcomes showed no significant differences between the two groups at the beginning of the study, while the 6MWT and CAT scores exhibited clinically and statistically significant improvements (p<0.001) by the end of the study. At month 18, the change in the predicted percentage of forced expiratory volume in 1 s (FEV1%pred) differed between the two groups (p<0.05). In addition, there were statistically significant differences in the 6MWT results, CAT scores and FEV1%pred values between the baseline and month 18 (p<0.0001) in the intervention group. CONCLUSIONS: Improvements in 6MWT results, pulmonary function and CAT scores are associated with a successful response to breathing against PEEPi in patients with COPD. TRIAL REGISTRATION: This trial was registered at research registry.com (identifier research registry 4816).

Characterization of the complete mitochondrial genome sequence of Homalogaster paloniae (Gastrodiscidae, Trematoda) and comparative analyses with selected digeneans.

Gastrodiscidae species are neglected but significant paramphistomes in small ruminants, which can lead to considerable economic losses to the breeding industry of livestock. However, knowledge about molecular ecology, population genetics, and phylogenetic analysis is still limited. In the present study, we firstly sequenced and analyzed the full mitochondrial (mt) genome of Homalogaster paloniae (14,490 bp). The gene contents and organization of the H. paloniae mt genome is the same as that of other digeneans, such as Fasciola hepatica and Paramphistomum cervi. It is interesting that unlike other paramphistomes, H. paloniae is flat in shape which is similar with Fasciola, such as F. hepatica. Phylogenetic analysis of H. paloniae and other 17 selected digeneans using concatenated amino acid sequences of the 12 protein-coding genes showed that Gastrodiscidae is closely related to Paramphistomidae and Gastrothylacidae. The availability of the mt genome sequence of H. paloniae should provide an important foundation for further molecular study of Gastrodiscidae and other digeneans.

Optimized fuzzy K-nearest neighbor approach for accurate lung cancer prediction based on radial endobronchial ultrasonography.

Radial endobronchial ultrasonography (R-EBUS) has been a surge in the development of new ultrasonography for the diagnosis of pulmonary diseases beyond the central airway. However, it faces challenges in accurately pinpointing the location of abnormal lesions. Therefore, this study proposes an improved machine learning model aimed at distinguishing between malignant lung disease (MLD) from benign lung disease (BLD) through R-EBUS features. An enhanced manta ray foraging optimization based on elite perturbation search and cyclic mutation strategy (ECMRFO) is introduced at first. Experimental validation on 29 test functions from CEC 2017 demonstrates that ECMRFO exhibits superior optimization capabilities and robustness compared to other competing algorithms. Subsequently, it was combined with fuzzy k-nearest neighbor for the classification prediction of BLD and MLD. Experimental results indicate that the proposed modal achieves a remarkable prediction accuracy of up to 99.38%. Additionally, parameters such as R-EBUS1 Circle-dense sign, R-EBUS2 Hemi-dense sign, R-EBUS5 Onionskin sign and CCT5 mediastinum lymph node are identified as having significant clinical diagnostic value.

Enhanced differential evolution algorithm for feature selection in tuberculous pleural effusion clinical characteristics analysis.

Tuberculous pleural effusion poses a significant threat to human health due to its potential for severe disease and mortality. Without timely treatment, it may lead to fatal consequences. Therefore, early identification and prompt treatment are crucial for preventing problems such as chronic lung disease, respiratory failure, and death. This study proposes an enhanced differential evolution algorithm based on colony predation and dispersed foraging strategies. A series of experiments conducted on the IEEE CEC 2017 competition dataset validated the global optimization capability of the method. Additionally, a binary version of the algorithm is introduced to assess the algorithm's ability to address feature selection problems. Comprehensive comparisons of the effectiveness of the proposed algorithm with 8 similar algorithms were conducted using public datasets with feature sizes ranging from 10 to 10,000. Experimental results demonstrate that the proposed method is an effective feature selection approach. Furthermore, a predictive model for tuberculous pleural effusion is established by integrating the proposed algorithm with support vector machines. The performance of the proposed model is validated using clinical records collected from 140 tuberculous pleural effusion patients, totaling 10,780 instances. Experimental results indicate that the proposed model can identify key correlated indicators such as pleural effusion adenosine deaminase, temperature, white blood cell count, and pleural effusion color, aiding in the clinical feature analysis of tuberculous pleural effusion and providing early warning for its treatment and prediction.

A novel machine learning model for efficacy prediction of immunotherapy-chemotherapy in NSCLC based on CT radiomics.

Lung cancer is categorized into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer. Of these, NSCLC accounts for approximately 85% of all cases and encompasses varieties such as squamous cell carcinoma and adenocarcinoma. For patients with advanced NSCLC that do not have oncogene addiction, the preferred treatment approach is a combination of immunotherapy and chemotherapy. However, the progression-free survival (PFS) typically ranges only from about 6 to 8 months, accompanied by certain adverse events. In order to carry out individualized treatment more effectively, it is urgent to accurately screen patients with PFS for more than 12 months under this treatment regimen. Therefore, this study undertook a retrospective collection of pulmonary CT images from 60 patients diagnosed with NSCLC treated at the First Affiliated Hospital of Wenzhou Medical University. It developed a machine learning model, designated as bSGSRIME-SVM, which integrates the rime optimization algorithm with self-adaptive Gaussian kernel probability search (SGSRIME) and support vector machine (SVM) classifier. Specifically, the model initiates its process by employing the SGSRIME algorithm to identify pivotal image features. Subsequently, it utilizes an SVM classifier to assess these features, aiming to enhance the model's predictive accuracy. Initially, the superior optimization capability and robustness of SGSRIME in IEEE CEC 2017 benchmark functions were validated. Subsequently, employing color moments and gray-level co-occurrence matrix methods, image features were extracted from images of 60 NSCLC patients undergoing immunotherapy combined with chemotherapy. The developed model was then utilized for analysis. The results indicate a significant advantage of the model in predicting the efficacy of immunotherapy combined with chemotherapy for NSCLC, with an accuracy of 92.381% and a specificity of 96.667%. This lays the foundation for more accurate PFS predictions and personalized treatment plans.

Multi-step influenza forecasting through singular value decomposition and kernel ridge regression with MARCOS-guided gradient-based optimization.

This research delves into the significance of influenza outbreaks in public health, particularly the importance of accurate forecasts using weekly Influenza-like illness (ILI) rates. The present work develops a novel hybrid machine-learning model by combining singular value decomposition with kernel ridge regression (SKRR). In this context, a novel hybrid model known as H-SKRR is developed by combining two robust forecasting approaches, SKRR and ridge regression, which aims to improve multi-step-ahead predictions for weekly ILI rates in Southern and Northern China. The study begins with feature selection via XGBoost in the preprocessing phase, identifying optimal precursor information guided by importance factors. It decomposes the original signal using multivariate variational mode decomposition (MVMD) to address non-stationarity and complexity. H-SKRR is implemented by incorporating significant lagged-time components across sub-components. The aggregated forecasted values from these sub-components generate ILI values for two horizons (i.e., 4-and 7-weekly ahead). Employing the gradient-based optimization (GBO) algorithm fine-tunes model parameters. Furthermore, the deep random vector functional link (dRVFL), Ridge regression, and gated recurrent unit neural network (GRU) models were employed to validate the MVMD-H-SKRR-GBO paradigm's effectiveness. The outcomes, assessed using the MARCOS (Measurement of alternatives and ranking according to compromise solution) method as a multi-criteria decision-making method, highlight the superior accuracy of the MVMD-H-SKRR-GBO model in predicting ILI rates. The results clearly highlight the exceptional performance of the MVMD-H-SKRR-GBO model, with outstanding precision demonstrated by impressive R, RMSE, IA, and U95 % values of 0.946, 0.388, 0.970, and 1.075, respectively, at t + 7.

Roles of histone hypoacetylation in LAT expression on T cells and Th2 polarization in allergic asthma.

BACKGROUND: Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a role in T cell and mast cell function, while it remains unclear how histone modifications mediate LAT expression in allergic asthma. The present study aimed at understanding alterations of lymphocyte LAT in patients with asthma and potential mechanisms by which histone modulation may be involved in. METHOD: The expression of LAT mRNA was checked by Quantitative real-time PCR and histone hypoacetylation on LAT promoter was detected by Chromatin Immunoprecipitation. RESULTS: Our results demonstrated that the expression of LAT mRNA in peripheral blood T cells from patients with asthma decreased, as compared to healthy controls. Peripheral blood T cells were treated with pCMV-myc-LAT, pCMV-myc or LAT-siRNA plasmid. Over-expression of LAT mRNA and decrease of Th2 cytokine production were noted, which could be prevented by the inhibition of LAT. The further investigation of the role of histone was performed in an asthma model induced by allergen. Histone hypoacetylation on LAT promoter could inhibit LAT expression and enhanced Th2 differentiation, while trichostatin A, a histone deacetylase inhibitor, promoted LAT expression and inhibited Th2 cytokine production. CONCLUSION: Our results indicate that histone hypoacetylation may regulate LAT expression on T cells and modify Th2 polarization in allergic asthma.

Comprehensive analysis of cuproptosis-related genes in immune infiltration and prognosis in lung adenocarcinoma.

Copper-dependent cell death, called cuproptosis, is connected to tumor development, prognosis, and the immune response. Nevertheless, the function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) remains unknown. This work used R software packages to classify the raw data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases of LUAD patients. Afterward, the connections of the various subgroups, clinical pathological traits, and immune infiltration (IMIF) features with the TME mutation status were explored. Ultimately, a nomogram and calibration curve were developed, aiming at enhancing the clinical application of CRG scores and estimating the survival probability of patients. Moreover, the relationships between cuproptosis and the molecular traits, immune cell infiltration of tumor tissue, prognosis, and clinical treatment of patients were investigated in this work. Subsequently, the CRG score was established to predict overall survival (OS), and its credible predictive ability in LUAD patients was identified. Afterward, a highly credible nomogram was created to contribute to the clinical viability of the CRG score. Furthermore, as demonstrated, gene signatures could be applied in assessing tumor immune cell infiltration, clinical traits, and prognosis. In addition, high tumor mutation burden, immunological activity, and significant survival probability were characterized by low CRG scores, and high CRG scores were related to immunosuppression and stromal pathway activation. The current work also discovered a predictive CRG-related signature for LUAD patients, probably contributing to TME trait clarification and more potent immunotherapy strategy exploration.

Non-classical major histocompatibility complex class makes a crucial contribution to reproduction in the dairy cow.

The aim of this study was to evaluate the effect of classical and non-classical major histocompatibility complex (MHC) on the reproduction in the dairy cow. Nine pairs of MHC-I genes were chosen according to their homology and possible function, and their transcription levels in maternal peripheral blood mononuclear cells (PBMCs) from all three trimesters and transcription levels in fetal tissues were compared to evaluate their contributions to cattle reproduction. The results showed that three non-classical genes were variably expressed in PBMCs of pregnant cows. MICB was downregulated in the first and second trimesters (P<0.05), but recovered back to the level in replacement heifers in the last trimester (P>0.05). BoLA-NC1* was upregulated in the first and last trimesters (P<0.001) but no different in the second trimester (P>0.05). BoLA-NC3* was upregulated in all trimesters (P<0.001). On the other hand, MICB was upregulated in fetal ear tissues (P<0.001), and BoLA-NC1* was almost silent in both fetal placenta and ear tissues (P<0.001); however, BoLA-NC3* was upregulated in both the fetal placenta and ear tissues (P<0.001). These results suggested that non-classical gene BoLA-NC1* increased maternal immunity against the fetus, which was inhibited by BoLA-NC3*. BoLA-NC3* also inhibited fetal autoimmunity. Apoptosis of the fetal placenta could reduce itself expressing MICB, and upregulated expression of MICB in ear tissues was favorable for the fetus to escape autoimmunity. On the other hand, downregulated expression of MICB in the fetal placenta allows for placental decoherence from the maternal placentome, which was beneficial to fetus delivery. Although classical genes were expressed differentially, their effects were restricted because of heavy chain deficiency.

Influenza virus NS1 interacts with 14-3-3ε to antagonize the production of RIG-I-mediated type I interferons.

For influenza A viruses (IAVs), non-structural protein 1 (NS1) protein was recognized to be the key factor to enhance virulence by antagonizing host innate anti-viral responses. However, for the pathways allowing NS1 to regulate the type I interferon (IFN) response, the identification of the substrates was still incomplete. Here a recombinant IAV encoding a NS1 containing an affinity tag (NS1-Strep) was generated to capture the NS1-interactome in the lungs of infected mice. Several scaffold proteins of the 14-3-3 family were distinguished as the most potent candidates. Based on the conserved motif RxxTxxT of NS1, the interaction between NS1 and 14-3-3ε was enabled, which competed for the binding of RIG-I to 14-3-3ε and prevented RIG-I translocation to the adaptor MAVS, consequently inhibiting IFN-ß expression. A recombinant mutant IAV deficient in 14-3-3ε binding elicited a markable innate immune responses and showed impaired growth kinetics.