Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

BACKGROUND: Toll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via the adaptor protein MyD88. However, the specific sequence and structural requirements of the CpG DNA for the recognition of and binding to TLR9 are unknown. Moreover, the 3D structures of TLR9 and the TLR9-ODN complex have not been determined. In this study, we propose a reliable model of the interaction of the TLR9 ECD with CpG ODN using bioinformatics tools. RESULTS: The three-dimensional structures of two TLR9 ECD-CpG ODN complexes were constructed using a homology modelling and docking strategy. Based on the models of these complexes, the TLR9 ECD-CpG ODN interaction patterns were calculated. The results showed that the interface between the human TLR9 and the CpG ODN molecule is geometrically complementary. The computed molecular interactions indicated that LRR11 is the main region of TLR9 that binds to CpG ODN and that five positively charged residues within LRR11 are involved in the binding of the TLR9 ECD to the CpG ODN. Observations in the close-up view of these interactions indicated that these five positively charged residues contribute differently to the binding region within the TLR9 ECD-CpG ODN complex. 337Arg and 338Lys reside in the binding sites of ODN, forming hydrogen bonds and direct contacts with the CpG ODN, whereas 347Lys, 348Arg, and 353His do not directly contact the CpG ODN. These results are in agreement with previously reported experimental data. CONCLUSION: In this study, we present two structural models for the human and mouse TLR9 ECD in a complex with CpG ODN. Some features predicted by this model are consistent with previously reported experimental data. This complex model may lead to a better understanding of the function of TLR9 and its interaction with CpG ODN and will improve our understanding of TLR9-ligand interaction in general

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses

Effect of Cryogenic Treatment on Friction and Wear Properties of 20CrNiMo Carburized Steel

In order to improve the friction and wear properties of 20CrNiMo carburized steel, the cryogenic treatment was carried out on it for different durations and different cycles. The changes of microstructure, hardness and impact toughness before and after cryogenic treatment were analyzed by means of scanning electron microscope and Rockwell hardness tester. The friction and wear properties of samples before and after cryogenic treatment were compared and investigated by friction and wear testing machine. Results showed that the cryogenic treatment had a limited effect on the surface hardness of 20CrNiMo carburized steel. The impact toughnesses of the samples were significantly improved after cryogenic treatment, and the impact toughness was the highest when the sample was treated with a single cycle of 6 h cryogenic treatment, which was increased by 10.9% compared with the un - cryogenic sample (QT). The average friction coefficient and relative wear rate of cryogenic samples were significantly reduced. The samples treated with a single cycle of 6 h cryogenic treatment and 3 cycles of 3 h cryogenic treatment had better friction and wear properties, and the average friction coefficient were 0.50 and 0.52 respectively. Compared with the QT samples, the wear rates were reduced by 25.9% and 23.3% respectively

Left-Invariant PID Control Almost Globally Stabilizes Rigid-Body Attitudes with Right-Invariant Biases

This paper studies the robust stabilization of rigid-body attitudes represented by a special orthogonal matrix. A geometric proportional–integral–derivative (PID) controller is proposed with all the input commands defined in the dual space so*(3) of a Lie algebra for left-invariant systems evolving on a Lie group SO(3). Almost global asymptotic stability (AGAS) of the close system is proved by constructing a gradient-descent Lyapunov function after explicitly performing two stages of variable change. The attitudes are stabilized to the stable equilibrium despite the influence of inertially fixed biases. The convergent behaviors and the robustness to biases are verified by numerical simulations

Harmony in Extraction: A Variable Weight Theory Approach to Unraveling the Ecological Security Veins in China's Rare Earth Mining Under Variable Pressures

The unique mining process of China's ion-adsorption rare earth (RE) mines has changed the structure of the mine ecosystem, and the interplay between the natural red soil characteristics and economic and social activities has exacerbated environmental problems such as the degradation of regional vegetation cover and soil erosion. These issues have had a profound and detrimental impact on the ecological security (ES) of the mining areas. The existing static evaluation study cannot comprehensively assess the ES status and dynamic evolution trend of the mining area, and cannot meet the needs of the complex ecosystem in the mining area. Therefore, this article constructs an ES evaluation index system based on the driver-pressure-state-impact-response-management causal framework model, and uses the variable weight (VW) theory to formulate a penalty-dominated state VW function to calculate the weight values of the indicators in different contexts of each year and evaluation unit. Finally, a dynamic evaluation of the spatial and temporal evolution trend of the ES of the Lingbei RE mining area is carried out during the period from 2000 to 2020. The geodetector model is then applied to reveal the driving factors impacting the ES of the mining area in different time periods. The results show that 1) Compared to the constant weight method, VW can provide a more detailed distribution of the ES level in the mining area, which has good application value in the small and dispersed ionic RE mining area. 2) The overall ES status of the Lingbei mining area shows a dynamic trend of deterioration followed by improvement and finally stabilization. 3) The vegetation health status is one of the most important driving factors of ES in the mine site, and the interaction between any two factors is greater than the explanatory power of the individual factors. This study provided insights into the ES and sustainable development of mining areas

Face Recognition Based on Optimized Projections for Distributed Intelligent Monitoring Systems

Compressive sensing (CS), as a new theory of signal processing, has found many applications. This paper deals with a CS-based face recognition system design. A novel framework, called projection matrix optimization- (PMO-) based compressive classification, is proposed for distributed intelligent monitoring systems. Unlike the sparse preserving projection (SPP) approach, the projection matrix is designed such that the coherence between different classes of faces is reduced and hence a higher recognition rate is expected. The optimal projection matrix problem is formulated as identifying a matrix that minimizes the Frobenius norm of the difference between a given target Gram and that of the equivalent dictionary. A class of analytical solutions is derived. With the PMO-based CS system, two frameworks are proposed for compressive face recognition. Experiments are carried out with five popularly utilized face databases (i.e., ORL, Yale, Yale Extend, CMU PIE, and AR) and simulation results show that the proposed approaches outperform those existing compressive ones in terms of the recognition rate and reconstruction error

Effects of dietary supplemented with a combination of magnolol, palmatine and β-glucan on growth rate, antioxidant activity, immune response and resistance to Aeromonas hydrophila in tilapia (Oreochromis niloticus)

This study evaluated the effects of dietary additions of magnolol, palmatine and β-glucan mixture on growth rate, antioxidant capacity, immune response and resistance to Aeromonas hydrophila in tilapia (Oreochromis niloticus). Four experimental diets were formulated with 0 %, 0.24 %, 0.48 % and 0.96 % compound additives (magnolol: palmatine: β-glucan = 1:1:10) and fed for ten weeks. The addition of compound additives did not affect the growth indices but improved the protein efficiency ratio of tilapia. Feeding 0.24 % or 0.48 % compound additives increased the blood leukocyte and basophil as well as erythrocyte and hemoglobin contents, respectively. However, the addition of 0.24–0.96 % compound additives decreased the serum total cholesterol and LDL-C levels, as well as the LDL-C/HDL-C and AST/ALT ratios. In addition, supplementation with 0.24–0.48 % compound additives increased the activities of glutathione reductase, superoxide dismutase, peroxidase and total antioxidant capacity in the intestine, plasma, and liver, but reduced the content of malondialdehyde, thereby enhancing the antioxidant capacity of tilapia. Further, the inclusion of 0.24–0.48 % compound additives enhanced the plasma immunoglobulin M, complement 4, complement 3 levels as well as lysozyme activity. The phagocytic activity of head kidney macrophages was improved by supplementation with 0.48 % compound additives. Besides, the addition of 0.48 % compound additives reduced the cumulative mortality and thereby increased the relative protection rate of tilapia infected with A. hydrophila. Under the present experimental conditions, the addition of 0.24–0.48 % compound additives was effective in improving the antioxidant capacity, immune response and anti-disease capacity of tilapia while maintaining good growth performance

Effects of dietary β-glucan on growth rate, antioxidant status, immune response, and resistance against Aeromonas hydrophila in genetic improvement of farmed tilapia (GIFT, Oreochromis niloticus)

This study was conducted to assess the influences of dietary β-glucan on growth rate, antioxidant status, immunity response, and resistance against Aeromonas hydrophila of genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Four isonitrogenous and isoenergetic diets were formulated to contain 0%, 0.2%, 0.4%, and 0.8% β-glucan, respectively. Fish with similar size (average body weight, 3.43 ± 0.02 g) were randomly distributed into 12 tanks with 40 juveniles per tank and hand-fed to apparent satiation twice daily for 10 weeks. The fish were then challenged by A. hydrophila and their cumulative survival rate was recorded for the next week. No obvious influences on growth rate and feed utilization of GIFT were induced by dietary β-glucan addition (P > 0.05). However, dietary 0.4% β-glucan inclusion increased the serum high-density lipoprotein cholesterol level but decreased the triglyceride, total cholesterol and low-density lipoprotein cholesterol levels as well as alanine aminotransferase and aspartate aminotransferase activities (P < 0.05). Similarly, the increased intestinal superoxide dismutase (SOD), peroxidase and total antioxidant capacity (TAC) activities as well as the decreased intestinal malondialdehyde (MDA) and reactive oxygen species contents were also observed in GIFT fed diet with 0.4% β-glucan (P < 0.05). Dietary addition of 0.8% β-glucan increased the plasma SOD, glutathione peroxidase (GPx), catalase, and TAC activities, but reduced the plasma MDA content (P < 0.05). Dietary β-glucan inclusion regardless of levels improved the hepatic SOD, glutathione reductase, catalase, peroxidase, TAC, and acid phosphatase activities, but depressed the hepatic nitric oxide and MDA contents (P < 0.05). Plasma lysozyme activity was improved by the inclusion of 0.4% and 0.8% β-glucan (P < 0.05); plasma immunoglobulin M, complement 3 and complement 4 contents were improved by dietary β-glucan inclusion (P < 0.05); respiratory burst activity of macrophages was improved by the addition of 0.2% β-glucan (P < 0.05). Additionally, dietary β-glucan supplementation reduced the mortality rate and increased the relative percentage survival of GIFT challenged by A. hydrophila (P < 0.05). These results indicated that suitable β-glucan inclusion (0.4–0.8%) could promote the antioxidant status, immune response and disease resistance of GIFT, and β-glucan can be used as a feed additive for GIFT

Comparative Genomic Analysis of Vibrio cincinnatiensis Provides Insights into Genetic Diversity, Evolutionary Dynamics, and Pathogenic Traits of the Species

Vibrio cincinnatiensis is a poorly understood pathogenic Vibrio species, and the underlying mechanisms of its genetic diversity, genomic plasticity, evolutionary dynamics, and pathogenicity have not yet been comprehensively investigated. Here, a comparative genomic analysis of V. cincinnatiensis was constructed. The open pan-genome with a flexible gene repertoire exhibited genetic diversity. The genomic plasticity and stability were characterized by the determinations of diverse mobile genetic elements (MGEs) and barriers to horizontal gene transfer (HGT), respectively. Evolutionary divergences were exhibited by the difference in functional enrichment and selective pressure between the different components of the pan-genome. The evolution on the Chr I and Chr II core genomes was mainly driven by purifying selection. Predicted essential genes in V. cincinnatiensis were mainly found in the core gene families on Chr I and were subject to stronger evolutionary constraints. We identified diverse virulence-related elements, including the gene clusters involved in encoding flagella, secretion systems, several pili, and scattered virulence genes. Our results indicated the pathogenic potential of V. cincinnatiensis and highlighted that HGT events from other Vibrio species promoted pathogenicity. This pan-genome study provides comprehensive insights into this poorly understood species from the genomic perspective