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A trimetallic dendritic Au@PdPt nanparticles (Au@PdPt NPs) with intrinsic peroxidase-like catalytic activity were fabricated by a facile method. Au@PdPt NPs catalyzed the reduction of H 2 O 2 with the help of the electron mediator (thionine), which produced the electrochemical signals dramatically amplified. A sandwiched sensor was designed and implemented in the paper chip device for the determination of K-562 cells. The surface of dendritic Au@PtPd NPs was linked with folic acid by click chemistry. Folic acid was attached to the folate receptor (FR) of cell surface with high affinity. So, K-562 cells could be assayed based on folic acid-functionalized Au@PtPd NPs. On the other hand, folic acid-functionalized Au-paper working electrode on origami electrochemical device was fabricated, which could be used to capture K-562 cells. The twice utilization of folic acid for the capture of K-562 cells as well as the attachment of dendritic Au@PtPd NPs nanoprobe, which enhanced the selectivity of sensor for the determination of cells. The proposed biosensor exhibited excellent analytical performance toward the cytosensing of K562 cells with a wide detection linear range from 1.0 × 10 2 to 2.0 × 10 7 cells mL −1 and a detection limit of 31 cells mL −1 . Further, the proposed electrochemical sensor was applied to monitor cells. Au@PtPd NPs nonenzymatic catalysts could be used as signal-amplifying nanoprobes for ultrasensitive electrochemical sensing. [ABSTRACT FROM AUTHOR]

[Display omitted] • The immune response and inflammation in pulmonary hypertension (PH) have been systematically summarized based on recent studies. • The relationship between CC chemokines and the pathogenesis of pH is summarized in clinical and animal models. • We found that although the immune response serves as an important potential factor in the pathogenesis of PH, less attention has been paid to CC chemokines and their receptors. • We believe that a greater understanding of the relationship between PH and CC chemokines and their receptors is a pressing issue. • We believe that we need to further clarify the pathogenesis of pH and provide basis for the clinical treatment of PH. Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. Aim of review : In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is an immune system reaction that occurs soon after eating certain food, which severely damages the health of allergic patients. Since medical approaches for FA may trigger severe adverse effects, the natural substances with anti-allergy functions have received more and more attention. This paper reviewed the natural bioactive substances with anti-allergic properties in food allergy, which mainly include polyphenols, polysaccharides, oligosaccharides, traditional Chinese medicine (TCM) and probiotics. Moreover, this paper analyzed the limitations of current investigations and provided future outlook for the development of anti-allergic products. This paper extensively reviews the natural substances with anti-allergy functions. As the results, the polyphenols could inhibit the formation of allergen-IgE complex, influence the allergen-IgE complex bind to the receptor (FcϵRI) on the surface of effector cells (e.g. mast cells and basophils). The polysaccharides and oligosaccharides could inhibit the secretion of allergic mediators and cytokines, suppressing Th2 responses and promoting Th1/Treg responses. The TCM could reduce allergen presentation to dendritic cell, weaken the secretion of allergen-specific IgE and the degranulation of mast cell, upregulate Th1 cytokines (e.g. IL-12, IFN-γ) and downregulate Th2 cytokines (e.g. IL-4, IL-13). The probiotics could help maintain the integrity of intestinal epithelial barriers by promoting mucus production via goblet cells, which could reduce the intestinal permeability and improved mucus generation to decrease the risk of food allergen into immune systems. This review could provide a better understanding and future outlook on the natural anti-allergy substances and supply a novel insight into their potential application for FA prevention and treatment. • Polyphenols, polysaccharides and probiotics are beneficial to alleviate food allergy. • Polyphenols could inhibit the IgE secretion and degranulation of effector cells. • Polysaccharides could inhibit the secretion of allergic mediators and cytokines. • Probiotics maintain intestinal epithelial barrier integrity and help prevent allergens. [ABSTRACT FROM AUTHOR]

Despite the global administration of approved COVID-19 vaccines (e.g., ChAdOx1 nCoV-19®, mRNA-1273®, BNT162b2®), the number of infections and fatalities continue to rise at an alarming rate because of the new variants such as Omicron and its subvariants. Including COVID-19 vaccines that are licensed for human use, most of the vaccines that are currently in clinical trials are administered via parenteral route. However, it has been proven that the parenteral vaccines do not induce localized immunity in the upper respiratory mucosal surface, and administration of the currently approved vaccines does not necessarily lead to sterilizing immunity. This further supports the necessity of a mucosal vaccine that blocks the main entrance route of COVID-19: nasal and oral mucosal surfaces. Understanding the mechanism of immune regulation of M cells and dendritic cells and targeting them can be another promising approach for the successful stimulation of the mucosal immune system. This paper reviews the basic mechanisms of the mucosal immunity elicited by mucosal vaccines and summarizes the practical aspects and challenges of nanotechnology-based vaccine platform development, as well as ligand hybrid nanoparticles as potentially effective target delivery agents for mucosal vaccines. This review shows the induction of mucosal immunity efficiently induces secretory IgA and IgG in the upper respiratory tract and systemic immunity via intranasal administration of nanovaccine. [Display omitted] [ABSTRACT FROM AUTHOR]

• Impulsive differential equations are used to capture the characteristics of intermittent androgen deprivation therapy. • The dynamics of tumours are sensitive to stochastic noise and tumour antigenicity. • The sufficient conditions for the existence of ergodic stationary distribution are established. • The results show that comprehensive therapy is more effective than a single therapy. Intermittent androgen deprivation therapy is one of the most commonly used therapeutic regimens for treating prostate cancer. Immunotherapy with dendritic cells, which act as the most robust antigen-presenting cells, are regarded as an effective method for the treatment of advanced prostate cancer. This paper utilizes impulsive differential equations to describe the combinations of a dendritic cell vaccine and intermittent androgen therapy with white noise. The tumour-free solution is obtained and the unique global positive solution of the system is explored. Then it is proved that the solutions of the system are stochastic ultimately bounded and stochastically permanent. In addition, threshold conditions for the extinction and persistence of prostate cancer cells are derived, and the stationary distribution and ergodicity of the system are investigated. Finally, numerical studies and the biological significance of the results are discussed. [ABSTRACT FROM AUTHOR]

Scheme 1. Schematic illustration of CRT valgus CT-26 tumor cell membranes-coated bacterial whole peptidoglycan (CPW/SR) combined with radiotherapy for cancer immunotherapy. (A) Preparation process of CPW/SR. (B) CPW/SR can activate the innate immunity by inducing DCs maturation, subsequently activate the adaptive immunity to play a role in cancer immunotherapy. [Display omitted] Immunotherapy has achieved some success in preclinical and clinical studies, but the immunosuppressive tumor microenvironment (TME) leads to a low response rate of this therapy. In this paper, we describe a calreticulin (CRT) valgus CT-26 tumor cell membranes-coated bacterial whole peptidoglycan (WPG) from P. aeruginosa (CPW/SR) with a high rate of the STING agonist loading. In the construct, WPG from P. aeruginosa (P.WPG) was used as a carrier with the immunoadjuvant function while synergistically promoting the maturation of dendritic cells (DCs) through the delivery of the STING agonist SR-717. CRT valgus tumor cell membranes were identified and internalized by DCs via CRT on the surface. In addition, this construct was able to reverse the immunosuppressive TME in vivo and achieve synergies with radiotherapy by creating a personalized tumor vaccine, therefore achieving more resultful antitumor efficacy. In conclusion, CPW/SR constructed in this paper provides a new approach for achieving efficient cancer immunotherapy and combination therapy. [ABSTRACT FROM AUTHOR]

Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine. • LMSN with different small particle sizes for oral delivery of split vaccine. • The effect of nanoparticle size on mucosal immunization and adjuvant efficacy. • Reasons for different immunization effects caused by nanoparticle size was studied. • Providing a scientific reference for adjuvant design of oral vaccine. [ABSTRACT FROM AUTHOR]

• The electrochemical conversion of quinoxaline and 1,2,3,4-tetrahydroquinoxaline reached 90% and 100%, respectively. • The established hydrogen storage system exhibited excellent reversibility under mild conditions. • Dendritic P-WO 3 /NF was employed as an efficient dual-functional electrode. • The hydrogenation reaction was completed without an external hydrogen supply. Liquid organic hydrogen carrier (LOHC) has been recognized as a highly promising candidate for hydrogen storage materials in addressing hydrogen utilization issues. However, the hydrogenation and dehydrogenation of LOHC typically require noble metal catalysts and harsh reaction conditions. In this paper, we proposed an efficient reversible electrochemical hydrogen storage system based on a nitrogen heterocyclic organic hydrogen carrier, quinoxaline, in which water was used as the solvent and hydrogen source for quinoxaline hydrogenation, and a self-supporting dendritic P-WO 3 /NF electrode was employed as the electrocatalyst. The catalytic properties of P-WO 3 /NF for electrochemical hydrogenation of quinoxaline and dehydrogenation of 1,2,3,4-tetrahydroquinoxaline were studied in 1 M KOH solution under mild conditions. The results showed that the hydrogenation conversion of quinoxaline was 90%, the selectivity was 99%, and the dehydrogenation conversion of 1,2,3,4-tetrahydroquinoxaline was 100%, the selectivity was 100%. This indicates that the system has high conversion efficiency, outstanding selectivity, and good reversibility. Meanwhile, the P-WO 3 /NF electrode adapted to the system exhibited good catalytic stability. In addition, no pre-prepared external hydrogen was required in the electrochemical hydrogenation reaction involving water, which gave the system an excellent safety profile. The reversible electrochemical hydrogen storage system established by this work broadens the vision of LOHC in hydrogen storage applications. [Display omitted] [ABSTRACT FROM AUTHOR]

In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs. [ABSTRACT FROM AUTHOR]

Dendritic spines are tiny membranous protrusions from neuron's dendrites. They play a very important role in the nervous system. A number of mental diseases such as Alzheimer's disease and mental retardation are revealed to have close relations with spine morphologies or spine number changes. Spines have various shapes, and spine images are often not of good quality; hence it is very challenging to detect spines in neuron images. This paper presents a novel pipeline to detect dendritic spines in 2D maximum intensity projection (MIP) images and a new dendrite backbone extraction method is developed in the pipeline. The strategy for the backbone extraction approach is that it iteratively refines the extraction result based on directional morphological filtering and improved Hessian filtering until a satisfactory extraction result is obtained. A shortest path method is applied along a backbone to extract the boundary of the dendrites. Spines are then segmented from the dendrites outside the extracted boundary. Touching spines will be split using a marker-controlled watershed algorithm. We present the results of our algorithm on real images and compare our algorithm with two other spine detection methods. The results show that the proposed approach can detect dendrites and spines more accurately. Measurements and classification of spines are also made in this paper. [ABSTRACT FROM AUTHOR]

• Nanocellulose is a biocompatible material, suitable for biomedical applications. • Cellulose Nanocrystals can induce proinflammatory response by activating macrophages. • Cellulose Nanofibers can induce tolerogenic properties of dendritic cells. • Surface modification of nanocellulose changes its immunomodulatory properties. Cellulose is the most abundant natural polymer in the world. Nanoscale forms of cellulose, including cellulose nanofibers (CNF), cellulose nanocrystals (CNC) and bacterial nanocellulose (BC), are very attractive in industry, medicine and pharmacy. Biomedical applications of nanocellulose in tissue engineering, regenerative medicine, and controlled drug delivery are the most promising. Nanocellulose is considered a biocompatible nanomaterial and relatively safe for biomedical applications. However, more studies are needed to prove this hypothesis, especially those related to chronic exposure to nanocellulose. Besides toxicity, the response of the immune system is of particular importance in this sense. This paper provides a comprehensive and critical review of the current-state knowledge of the impact of nanocellulose on the immune system, especially on macrophages and dendritic cells (DC), as the central immunoregulatory cells, which has not been addressed in the literature sufficiently. Nanocellulose, especially CNC, can induce the inflammatory response upon the internalization by macrophages, but this reaction may be significantly modulated by introducing different functional groups on their surface. Our original results showed that nanocellulose has a potent immunotolerogenic potential. Native CNF potentiated the capacity of DC to induce conventional Tregs. When carboxyl groups were introduced on the CNF surface, the tolerogenic potential of DC was shifted towards the induction of regulatory CD8+ T cells, whereas the introduction of phosphonates on CNF surface potentiated DCs' capacity to induce both regulatory CD8+ T cells and Type 1 regulatory (Tr-1) cells. These results are extremely important when considering the application of nanocellulose in vivo , especially for tissue regeneration and wound healing. [ABSTRACT FROM AUTHOR]

Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed. Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed. From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias. This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays. • Chimerism- and non-chimerism-based immune tolerance strategies were reviewed in transplant recipients • Both strategies allowed for safe discontinuation of immunosuppressive medications with comparable rejection rates and allograft survival • The myelosuppression-related risk tended to be lower in non-chimerism-based tolerance regimens • Most studies reviewed were limited by small sample sizes, and only a few examined cost implications and immune surveillance techniques • Further validation of the tolerogenic protocols is warranted in large-scale studies [ABSTRACT FROM AUTHOR]

This paper presents a new protection method for LVDC ring-bus microgrid systems based on Multi-Criterion System (MCS) and Neural Network (NN). The proposed method aimed at high-speed detecting line-to-ground (LG) and line-to-line (LL) low impedance faults without using a definite threshold of differential current by using specific rules and multi-criterion system. MCS protection showed speed and accuracy compared to differential protection. Also, NN estimated fault location in percent of line length acceptably as a secondary controller. In order to evaluate the reliability and the enforceability of fault detection and location schemes, simulated network and protection algorithms are implemented and tested in laboratory-scale. The implementation results indicate that the MCS and NN protection scheme can consistently detect and estimate fault locations in the order of a few milliseconds. To reach this goal, a loop type LVDC microgrid with proper power electronic equipment like solid-state bidirectional breakers and the multi-level inverter is fulfilled. • Protection of DC microgrid is highly challenging, unlike conventional AC system. • A novel protection scheme based on MCS is proposed for DC microgrids. • An accurate fault location scheme based on NN is presented for DC microgrids. • The MCS, NN schemes and simulated network is implemented in laboratory-scale. • MCS implementation leads to the reduction of the protective system cost. [ABSTRACT FROM AUTHOR]

Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection. [ABSTRACT FROM AUTHOR]

Abstract Gambogenic acid (GNA) is one of the main components of Gamboge, and its anti-cancer effects have been well confirmed by previous researches. Nasopharyngeal carcinoma (NPC) has not been thoroughly studied, and the pathogenesis of NPC is unclear. Scientists have neither discovered effective therapies nor achieved a desirable prognosis. Some studies have found that the regulation of intra- and extracellular ion channels hinges directly on cell apoptosis, and treatment with GNA brings changes to the volume-sensitive outwardly rectifying chloride (VSOR Cl−) current of CNE-2Z cells recorded by the patch clamp method. Nevertheless, rarely have any researchers probed into the relevance between this variation and the anti-tumor mechanism of GNA. This paper is suggested that 2.0 μmol/L GNA activates VSOR Cl− currents on CNE-2Z cell membranes and that the activation of VSOR Cl− currents by GNA in CNE-2Z cells is blocked by the chloride channel blockers DIDS (400 μmol/L) and DCPIB (20 μmol/L). MQAE experiment further proves that GNA leads to the opening of chloride ion channel, which in turn results in the efflux of VSOR Cl− current; GNA induces the downregulation of GRP78 and the upregulation of ATF4 and CHOP proteins. These effects are correlated with endoplasmic reticulum (ER) stress. GNA can activate VSOR Cl− channels, leading to ER stress, inducing apoptosis and inhibiting proliferation in CNE-2Z cells. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract The skin is the first anatomical region that dengue virus (DENV) encounters during the natural infection. Although the role of some skin resident cells like dendritic cells and fibroblasts has been demonstrated to be crucial to elucidate the role of resident cells and molecules participating during the early events of the innate immune response, the participation of keratinocytes during DENV infection has not been fully elucidated. In this paper we aimed to evaluate the use of the HaCaT cell line as a model to study the immune responses of skin keratinocytes to DENV infection. We demonstrated productive DENV-2 infection of HaCaT cells and their capability to establish an antiviral response through production of type I and type III interferons (IFN-β and IFN-λ). The production of these cytokines by HaCaT cells correlated with upregulation of IFN-inducible transmembrane protein-3 (IFITM3) and viperin in bystander, uninfected cells. We also observed an increase in secretion of IL-6 and IL-8. Skin keratinocytes are known to secrete antimicrobial peptides (AMPs) during viral infections. In our model, DENV-2 infected HaCaT cells upregulate the production of cytoplasmic LL-37. We evaluated the dual role of LL-37, HBD2, and HBD3 antiviral activity and immunoregulation during DENV-2 infection of HaCaT cells and found that LL-37 significantly reduced DENV-2 replication. This indicates that the HaCaT cell line can be used as a model for studying the innate response of keratinocytes to DENV infection. Our results also suggest that skin keratinocytes play an important role in the skin microenvironment after DENV infection by secreting molecules like type I and type III IFNs, pro-inflammatory molecules, and LL-37, which may contribute to the protection against arboviral infections. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the deadliest and most common type of primary brain tumor in adults with a grim prognosis despite multimodal treatments. Dendritic cell (DC)-based immunotherapy has emerged as a promising therapeutic modality for GBM, whose efficacy is nonetheless fundamentally undermined by GBM-induced immunosuppression. Inducing emission of damage associated molecular patterns (DAMPs) is a highly effective strategy to subvert tumor-associated immunosuppression. The present work was carried out to explore the idea of subverting the GBM immunosuppressive microenvironment through DC-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites (Nano-DOX), a potent DAMPs inducer demonstrated by our previous study, and thereby eliciting enhanced DC-driven anti-GBM immune response. In the in-vitro work on human cell models, Nano-DOX-loaded DC were shown to be functionally viable and release cargo drug to co-cultured GBM cells (GC). Nano-DOX-treated GC displayed not only profuse DAMPs emission but also antigen release. Enhanced activation and acquisition and presentation of GC-derived antigen were then demonstrated in DC in co-culture with GC and Nano-DOX. Consistently, co-culture with GC and Nano-DOX also activated mouse bone marrow-derived DC (mDC) which in turn stimulated mouse spleen-derived lymphocytes which ultimately suppressed co-cultured GC. Next, athymic mice bearing orthotopic human GBM xenografts were intravenously injected with Nano-DOX-loaded mDC and, 48 h later, spleen-derived lymphocytes. The presence of Nano-DOX, DAMPs emission and enhanced infiltration and activation of mDC and lymphocytes were detected in the GBM xenografts. Taken together, our results demonstrate the efficacy of DC-mediated delivery of Nano-DOX to stimulate GC immunogenicity and elicit anti-cancer immune response in the GBM. By this work, we present a novel approach with great application potential to subverting the GBM immunosuppressive microenvironment and to anti-GBM immunotherapy. Investigation has also been conducted probing the mechanisms by which Nano-DOX stimulates GC immunogenicity, which is described in a follow-up paper. [ABSTRACT FROM AUTHOR]

Highlights • Dendritic cells with overexpression of SOCS1 are constructed with lentivirus encoding SOCS1. • SOCS1 could block maturation process of Dendritic cells through inhibition of JAK/STAT pathway signaling. • Dendritic cells with increased expression of SOCS1 could ameliorate LPS/D-GalN induced acute liver failure. Abstract Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/ d -galactosamine induced acute liver failure via inhibition of TLR4 pathway. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are highly specialized antigen-presenting cells (APCs) able to induce both specific immunity and immune tolerance. Using information gathered from the tissue where they reside, DCs adjust their functional activity to ensure that protective immunity is favoured while unwanted or exaggerated immune responses are prevented. The remarkable ability of these cells to induce, enhance and orient the immune response, while at the same time maintaining self-tolerance, makes them key players in the immune system. Despite the fact that the role of Ca 2+ has been clearly established in human DC functions, the link between ion homeostasis, mainly Ca 2+ , and DC functions is not fully understood. After all, a growing number of works clearly show the role of SOCE and associated channels in the maturation step, and those of K + channels in migration. This review highlights the key papers published over the past few years and summarizes prospects for the near future. [ABSTRACT FROM AUTHOR]

The aim of this paper was to perform a comprehensive characterization of polysaccharides isolated from the interior (IOI) and exterior (IOE) parts of the fungus Inonotus obliquus. Pre-extraction with DCM and MeOH, followed by water and alkali extraction and ethanol precipitation gave two water extracts and two alkali extracts. Neutral and acidic polysaccharide fractions were obtained after anion-exchange chromatography of the water extracts. The neutral polysaccharides (60–73 kDa) were heterogeneous and branched and consisted of a (1 → 3)-linked β-Glc backbone with (1 → 6)-linked kinks in the chain at approximately every fifth residue, with branches of (1 → 6)-linked β-Glc in addition to substantial amounts of (1 → 6)-linked α-Gal with 3- O- methylation at about every third Gal residue. The acidic polysaccharide fractions (10–31 kDa) showed similar structural motifs as the neutral fractions differing mainly by the presence of (1 → 4)-linked α-GalA and α-GlcA. β-Xyl, α-Man and α-Rha were also present in varying amounts in all fractions. No major structural differences between the IOI and IOE fractions were observed. An alkaline polysaccharide fraction (>450 kDa) was obtained from the IOI alkali extract, and consisted mainly of (1 → 3)- and (1 → 6)-linked β-Glc and (1 → 4)-linked β-Xyl. Several of the fractions showed in vitro immunomodulatory effect by increasing NO production in the murine macrophage and dendritic cell lines J774.A1 and D2SC/1. Most fractions managed to increase NO production only at the highest concentration tested (100 μg/ml), while the neutral fraction IOE-WN activated potent NO production at 10 μg/ml and was considered the most promising immunomodulating fraction in this study. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a lethal disease and remains one of the most resistant cancers to traditional therapies. New therapeutic modalities are urgently needed, particularly immunotherapy, which has shown promise in numerous animal model studies. Dendritic cell (DC)-based immunotherapy has been used in clinical trials for various cancers, including PC, because DCs are the most potent antigen-presenting cell (APC), which are capable of priming naive T cells and stimulating memory T cells to generate antigen-specific responses. In this paper, we review the preclinical and clinical efforts towards the application of DCs for PC. [ABSTRACT FROM AUTHOR]

The utilization of the cationic lipid R -DOTAP as immune cell stimulant (e.g. its stimulating effects on immature dendritic cells) and correspondingly as possible adjuvant for vaccination is well known. Likewise, it is described in literature that solid polymer particles loaded with antigens can be size-tailored in a manner to be suitable for phagocytosis by antigen presenting cells. The effects of DOTAP-microparticle combinations, however, are not well understood. This study aimed therefore to explore the potential of R -DOTAP stabilized microparticles (MP) to act as a carrier platform for antigens e.g. for cancer vaccination. It was investigated whether or not a combination of R -DOTAP and PLGA leads to a boosted adjuvant effect in dendritic cell maturation. For proper comparison, neutral and negatively charged MPs of comparable sizes were developed. Toxicity, uptake, routing and maturation of the MP platform was assessed in-vitro on human immature dendritic cells (iDCs). Interestingly, none of the tested placebo formulations (without antigen) was capable to induce DC maturation when compared to LPS as positive control. This is in contrast to experiments previously reported in literature, where R -DOTAP (e.g. in liposomal form) triggered iDC maturation even without antigen. Possible reasons and further approaches are discussed in the paper. [ABSTRACT FROM AUTHOR]

In this paper, the microstructure formation mechanism of an AlSi10Mg alloy prepared by laser directed energy deposition (DED-LB) and its influence on the mechanical properties was fully studied. The relationships between the microstructure characteristic scale, the molten pool solidification/thermal cycle conditions, and the tensile mechanical properties were established by combining the numerical simulation, theoretical calculation, and experimental validation. The as-deposited microstructure consists of the columnar α-Al dendritic array growing epitaxially along the building direction with the primary dendritic arm spacing of 18 ± 4.5 µm, the dendritic arm cell of 3 ± 1 µm surrounded by the refined eutectic network, and the Si precipitation of 17.7 ± 0.8 nm dispersed in the α-Al dendritic trunk. The feature size of the primary dendritic arm spacing and the dendritic arm cell size can be well predicted using the Kurz-Fisher and KGT dendritic growth models. The formation and size evolution of the Si precipitation was well described by the non-isothermal aging KWN model for the first time. The as-DED-LB-processed AlSi10Mg alloy exhibits a good comprehensive mechanical property with a yield strength of 187 ± 1.5 MPa and elongation to fracture of 7.4 ± 0.5%. The boundary strengthening from the eutectic phase network, the load-bearing capacity for dislocations caused by refined dendritic arms, and the precipitation strengthening of nano-Si particles play a major role in the improvement of the tensile strength and hardening ability. As a result, a quantitative relationship of the processing–microstructure–performance has been systematically investigated and established, which explores a method for the precision control and large-scale application of DED-AlSi10Mg alloys. [Display omitted] • Experiments and simulations of directed energy deposition AlSi10Mg parts. • Validity of theoretical solidification models on the microstructure. • Linking non-isothermal aging model to precipitated phase. • Quantitative relationships of processing–microstructure–performance. [ABSTRACT FROM AUTHOR]

In vitro approaches to address key events in chemical-induced skin sensitization have been developed, but there is still uncertain how they will be useful to predict the potency for an effective risk assessment. Keratinocytes (KCs) play a key role in all phases of skin sensitization. Dendritic cells (DCs) activation and maturation require the binding of cytokines produced by KC as a result of initial chemical exposure. We previously identified interleukin-18 (IL-18) as useful marker for determination of skin sensitization potential of chemicals. The aim of this paper was to mimic the interaction between KCs and DCs using a co-culture of NCTC 2544 and THP-1 cells. Three selected contact allergens of different potency (Bandrowski's base, diethyl maleate, and imidazolidinyl urea) were tested in time-course experiments (24, 48 and 72 h). Cell surface markers expression (CD80, CD86, and HLA-DR) was determined by flow cytometry analysis while IL-18 production was evaluated with specific sandwich ELISA. Results obtained from this simple in vitro co-culture system show the possibility to study the contribution of KCs in DCs activation through the analysis of HLA-DR expression. Results obtained demonstrate the ability of the KCs to favor the full maturation of the DCs in the presence of moderate and weak allergens, while the extreme allergen induced a complete maturation of DC alone without the need of KCs. • This paper describes the possible cross-talk between DCs and KCs (NCTC 2544) in ACD through a simple in vitro co-culture system. • The aim of this work was to better understand the in vitro behavior of moderate and weak sensitizers. • KCs favor the full maturation of the DCs in the presence of moderate and weak allergens [ABSTRACT FROM AUTHOR]

In the last 10 years, there has been a considerable increase in the number of studies on the development of multiplier circuits based on spiking neural P systems with the aim of taking advantage of their intrinsic distributed parallel computing characteristics. Nevertheless, these efforts have had difficulties in adequately exploiting parallel data processing because they are designed to process the input data using a sequential protocol and thus suffer from the resulting increase in processing time. This paper develops a novel parallel multiplier that is based on spiking neural P systems and is capable of multiplying two natural numbers with many digits in parallel. The proposed method employs the divide and conquer strategy (i.e., segmenting the numbers into units, tens, hundreds, thousands, etc.), to optimize the processing time of the arithmetic operations, and every two units are treated by a single neuron that can calculate up to 9 × 9 sequentially. The use of one neuron to perform a sequential multiplication represents the best improvement in terms of the number of neurons that has been reported to date. [ABSTRACT FROM AUTHOR]

Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably “yes”. Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine- mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger- associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned “local-synthesis-for-local function” paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular. [ABSTRACT FROM AUTHOR]

Immunotherapy is an entirely advanced class of cancer treatment which has been highly active and exciting field in clinical therapeutics. In numerous procedures, cancer immunotherapy demands a laborious practice to recognise and count Dendritic Cells (DCs) in the vaccine preparation. Conventionally, the laser-based technologythat provides a rapid analysis such as Flow Cytometrycan affect the DCs viability as the staining procedure is involved. Another highly promising method which is Phase Contrast Microscopy (PCM) involves experienced pathologists to visually examine the respective microscopy images. In facts, PCM confronts complex issues regarding to imaging artifacts which can deteriorate the recognition process.As the DCs counting is crucial in cancer treatment procedures, this paper proposes a pioneering system called CasDC which implement an image processing algorithm to recognise and count DCs with a label-free method. The aim of developing this system is to establish a reliable and time saving-tool as a second reader in the clinical practice. In the meantime, the treatment procedure can be administered and therefore, improve the patient's survival rate. Our proposed system has an enormous potential towards helping Cancer Research Institute in which the system offers rapid and high throughput cancer immunotherapy vaccine preparation and automated live cell investigation. [ABSTRACT FROM AUTHOR]

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

A numerically efficient 3D transient thermal-based computational framework was developed to predict the microstructure and morphology within the molten pool. The results show that a transition from curved cellular to columnar morphologies occurred while moving from the molten pool edge toward its tail, which was correlated with the ratio of local thermal gradient and the solidification rate. The higher cooling rates, at the melt pool center, are seem to favour the fine microstructure. The obtained cooling rates not only appeared to control the size of the microstructural grains but also the dendritic cell spacing within the melt pool. The microstructural features like dendrite cell spacing and the microhardness was predicted using the developed framework and validated within an error range of 7–12% and 4–6%, respectively. Moreover, a parametric study performed to investigate the effect of laser speed and power revealed that the microstructural variation was more sensitive to the scanning speed than to the input power of the simulated heat source. The obtained results from the developed numerical framework were validated with the experimentally observed values and are discussed in this paper. [Display omitted] • A FE-based framework to predict microstructural features has been developed. • Simulated thermal profile was coupled with the solidification curves of IN718. • The FE-results were validated successfully with CFD-based and experimental results. • High and low cooling rates implied finer and coarser microstructure, respectively. • The microstructural features were more sensitive to scanning speed than laser power. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

In this paper, two approaches are proposed and compared for the detection and identification of aircraft subsystem failures based on the artificial immune system paradigm combined with the hierarchical multiself strategy. The first approach relies on the heuristic ranking of lower order self/non-self projections and the generation of selective immunity identifiers through structuring of the non-self. The second approach is based on an information processing algorithm inspired by the functionality of the dendritic cells. The artificial dendritic cell is defined as a computational unit that centralizes, fuses, and interprets information from the multiple selves to produce a unique detection and identification outcome. A hierarchical multi-self strategy is used with both approaches considering 2-dimensional self/non-self projections or subselves. A mathematical formulation of the concepts and detailed implementation algorithms are presented. The proposed methodologies are demonstrated and compared using simulation data for a supersonic fighter from a motion-based flight simulator at nominal conditions, under failures of actuators, malfunction of sensors, and wing damage. In all cases considered, both detection and identification schemes achieve excellent detection and identification rates with practically no false alarms. [ABSTRACT FROM AUTHOR]

While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1−/− T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1 − / − T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1 − / − T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation. [ABSTRACT FROM AUTHOR]

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) – absolute requirements for vaccine design – were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo , inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. From the Clinical Editor The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. [ABSTRACT FROM AUTHOR]

The C-type lectin domain containing (CLEC) receptors including CD209 are expressed in vivo by monocytes, monocyte-derived macrophages and dendritic cells and by in vitro generated monocyte-derived cells. This paper reports the cloning and sequencing of a lectin molecule, CLEC4T1, in rainbow trout that is a homologue of the CLEC4 family. The expression pattern of the CLEC4T1 was investigated in vivo after infection with a bacterial pathogen and in cultured macrophages after modulation with microbial mimics. Trout CLEC4T1 was highly expressed in spleen and head kidney following infection with Yersinia ruckeri . Expression could also be induced in macrophage cultures by LPS but not by Poly I:C, and suggests that the regulation of CLEC4T1 expression in trout varies according to the nature of the stimulant. A polyclonal CLEC4T1 antibody was generated and validated by Western blotting for use in evaluation of CLEC4T1 + cells by flow cytometry analysis. Freshly isolated adherent trout head kidney cultures, potentially containing macrophages and dendritic cell precursors, showed an increase of CLEC4T1 + cells (assessed by flow cytometry) upon stimulation with recombinant interleukin-4/13A. The results suggest that CLEC4T1 is a useful marker for further characterisation of monocyte derived antigen presenting cells in fish. [ABSTRACT FROM AUTHOR]

Targeting of specific receptors on antigen-presenting cells is an appealing prospect in the production of novel nanoparticulate vaccines. In particular, the targeting of vaccines to dendritic cell (DC) subsets has been shown in models to significantly improve the induction of immune responses. This paper describes the evaluation of natural ligands, mannan and chitosan, and monoclonal antibodies as targeting motifs to enhance uptake of PLGA nanoparticle carriers by bovine DCs. To assess enhancement of uptake after the addition of natural ligands a bovine monocyte derived DC (MoDC) model was used. For the assessment of monoclonal antibody targeting, the model was expanded to include afferent lymph DCs (ALDCs) in a competitive uptake assay. Mannan, proved unsuccessful at enhancing uptake or targeting by MoDCs. Chitosan coated particle uptake could be impeded by the addition of mannan suggesting uptake may be mediated through sugar receptors. Inclusion of monoclonal antibodies specific for the DEC-205 (CD205) receptor increased the number of receptor expressing DCs associated with particles as well as the number of particles taken up by individual cells. These results support the further evaluation of active targeting of nanovaccines to DCs to enhance their immunogenicity in cattle and other large mammalian species including humans. [ABSTRACT FROM AUTHOR]

A failure of central immune tolerance driven by autoantigen specific T regulatory (Treg) cells is a major cause of many autoimmune diseases. Restoration of proper autoantigen Treg specific response holds promise as a highly effective, long-term therapy for a wide variety of autoimmune diseases. Generating autoantigen specific Tregs remains a challenge due to the non-specific nature of most tolerizing agents and the complexities of generating Tregs in vivo. Here we show a new push/pull method for inducing antigen-specific Treg tolerance via induction of tolerogenic dendritic cells (tolDCs). We identified a combination of three tolerogenic drugs, dexamethasone, simvastatin and SC-514, which when used in combination with toll-like-receptor (TLR) agonists induces an active tolDC phenotype. When the tolerogenic combination was packaged into a liposome with a model antigen such as ovalbumin (OVA), these tolDCs induce differentiation of OVA specific Tregs both ex vivo and in vivo. We examined the tolerizing potential of the combination in an experimental autoimmune encephalomyelitis (EAE) disease model. Given the antigen specificity of this technique, this paper presents an attractive preclinical autoimmune therapy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditional Chinese herbal medicine (CHM) has a long-history for treatment of various human diseases including tumors, infection, autoimmune diseases in Asian countries, especially in China, Japan, Korea and India. CHM was traditionally used as water extracts and many Chinese herbs were considered to be good for health, which can regulate immune system to protect host from diseases. With the progress of technology, the components of CHM were identified and purified, which included polysaccharides, saponins, phenolic compounds, flavonoids and so on. Recently, accumulating evidence indicates that CHM and its components can regulate immune system through targeting dendritic cells (DCs). We hereby reviewed the immunoregulatory effects of CHM on the maturation, cytokine production and function of DCs. This should help to shed light on the potential mechanism of CHM to improve the usage and clinical efficacy of CHM. Materials and methods Literatures about the effects of CHM on DCs were searched in electronic databases such as Pubmed, Google Scholar and Scopus from 2000 to 2014. ‘CHM’, ‘DC’ or ‘immune’ were used as keywords for the searches. We only reviewed literatures published in English. Results Over 600 publications were found about ‘CHM&immune’ and around 120 literatures about ‘CHM&DC’ were selected and reviewed in this paper. All publications are backed by preclinical or clinical evidences both in vitro and in vivo . Some CHM and its components promote the maturation, pro-inflammatory cytokine production and function of DCs and as the adjuvant enhance immune responses against tumor and infection. In contrast, other CHM and its components suppress the activation status of DCs to induce regulatory T cells, inhibit allergic and inflammatory responses, ameliorate autoimmune diseases, and prolong the allograft survival. A large body of evidence shows that CHM and its components regulate the activation status of DCs through TLRs, NF-κB, MAPK signaling pathways. Conclusion This review provides useful information for understanding the mechanism of CHM on the treatment of diseases, which facilitates to improve the efficacy of CHM. Based on the immunoregulatory effects of CHM on DCs, it indicated that some CHM and its components could be use to develop adjuvant to enhance antigen-specific immune responses or tolerogenic adjuvant to generate antigen-specific immune tolerance. [ABSTRACT FROM AUTHOR]

Successful fault-tolerant control strategies often require vital tools that can accurately detect the failure, identify its root cause, and evaluate its nature and severity. Most of the existing methodologies in the field of failure detection, identification, and evaluation are limited to few subsystems with reduced number of features. Due to the complexity and multidimensionality of the aircraft system, new methodologies that are robust, accurate, and fast enough need to be developed for such systems. The biological immune system is a natural system that possesses vigorous peculiarities in protecting the mammalian body from harmful intruders and, therefore, may represent a rich source of inspiration to solve anomaly problems. This paper presents a novel integrated scheme for aircraft sub-system failure detection, identification, and evaluation based on the functionality of the biological dendritic cells and their interactions with the various components of the immune system. The proposed approach relies on using the self/nonself discrimination principle with the hierarchical multiself strategy to overcome the multidimensionality issues. The information collected by the artificial dendritic cells is fused in a way that convert the identification and evaluation problem into a pattern recognition problem. The proposed scheme was successfully tested for a supersonic fighter aircraft in a motion-based flight simulator with high detection, identification, and evaluation rates and practically zero false alarms. [ABSTRACT FROM AUTHOR]

Summary The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n = 67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver. [ABSTRACT FROM AUTHOR]

Under ultra-low fuel stoichiometry condition, direct methanol fuel cell (DMFC) suffers from severe methanol crossover in the inlet region and methanol shortage in the outlet region, which results in significant performance drop. In order to improve uniformity of fuel distribution, this paper proposes an anode structure which has a dead-end fuel chamber with a porous fuel distributor, so called interdigitated anode. Comparative study between the conventional cell and the interdigitated cell was conducted with multi-dimensional model. Calculation result shows the interdigitated structure mitigates anode non-uniformity by switching fuel transport mechanism from diffusion to convection, which leads to enhancement of both cell voltage and fuel efficiency. [ABSTRACT FROM AUTHOR]

Three major active polysaccharides isolated from Pholiota nameko (PNPS), including PNPS-1, PNPS-2 and PNPS-3, had been proved to inhibit the maturation of the murine bone marrow-derived dendritic cells (BMDCs). This paper recognized the affinity bind between PNPS and the five receptors (TLR2, TLR4, CD14, Dectin-1 and Mannose receptor) on BMDCs, using the bio-layer interferometry (BLI)-based biosensor technology developed by ForteBio on Octet RED system (Fortebio, Inc.). From the primary binding experiment, the gradient binding experiment and the inhibition binding experiment between the receptor proteins and PNPS, combined with the binding experiment between PNPS and the BMDCs membranes, we found that PNPS-1, PNPS-2 and PNPS-3 presented strong affinity bind with both TLR2 and Dectin-1 on BMDCs, only PNPS-3 with Mannose receptor. These data confirmed that PNPS could interact with TLR2, Dectin-1 and Mannose receptor that were very important for the affinity bind of these receptors and PNPS, which triggered the further stimulation on BMDCs. [ABSTRACT FROM AUTHOR]

Decidualization of endometrium, which is characterized by endometrial stromal cell (ESC) decidualization, vascular reconstruction, immune cell recruitment, and plentiful molecule production, is a crucial step for uterus to become receptive for embryo. When implantation takes place, ESCs surround and directly interact with embryo. Decidualized stromal cells (DSCs) are of great importance in endometrial decidualization, having a broad function in regulating immune activity and vascular remodeling of uterus. DSCs are shown to have a higher metabolic level and looser cytoskeleton than ESCs. What's the origin of ESCs and how ESCs successfully transform into DSCs had puzzled scientists in the last decades. Breakthrough had been achieved recently, and many studies had elucidated some of the characters and functions of DSCs. However, several questions still remain unclear. This paper reviews current understanding of where ESCs come from and how ESCs differentiate into DSCs, summarizes some characters and functions of DSCs, analyzes current studies and their limitations and points out research areas that need further investigation. [ABSTRACT FROM AUTHOR]

Cortical F-actin plays important roles during HIV-1 infection. A recent paper in Cell highlights the involvement of F-actin in enhancing dendritic cell (DC)-mediated HIV-1 infection of T cells. Such a critical mechanism of HIV-1 trans -enhancement between human DCs and T cells had not been analyzed in molecular detail before this work. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans; therefore, a range of DC-based approaches have been established to promote an immune response against cancer cells. The efficacy of DC-based immunotherapeutic approaches is markedly affected by the immunosuppressive factors related to the tumor microenvironment, such as adenosine. In this paper, based on immunological theories and experimental data, a hybrid model is designed that offers some insights into the effects of DC-based immunotherapy combined with adenosine inhibition. The model combines an individual-based model for describing tumor-immune system interactions with a set of ordinary differential equations for adenosine modeling. Computational simulations of the proposed model clarify the conditions for the onset of a successful immune response against cancer cells. Global and local sensitivity analysis of the model highlights the importance of adenosine blockage for strengthening effector cells. The model is used to determine the most effective suppressive mechanism caused by adenosine, proper vaccination time, and the appropriate time interval between injections. [Display omitted] • We propose a hybrid model to describe the immunosuppressive function of adenosine in tumor micro environment. • Our model provides immunologists with a new level of insight into the role of immunosuppressive factors of the immune system. • Our model highlights the importance of adenosine blockage for strengthening effector cells and suppressing Treg cells. • Model simulations are compatible with in vivo experimental data. • The results reveals that the appropriate time interval for administration of adenosine inhibitor is between 2 and 4 days. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a pivotal role in initiating antigen-specific tumor immunity. However, the abnormal function of DCs owing to the immunosuppressive tumor microenvironment (TME) and the insufficient number of tumor infiltrating DCs could promote immune tolerance and tumor immune escape. Thus, there is great potential to employ DCs to induce efficient antitumor immunity. In this paper, we developed intelligent DCs (iDCs), which consist of nanoparticles loaded with photothermal agents (IR-797) and coated with a mature DC membrane. The DC cell membrane on the surface of iDCs preserves the ability to present antigens and prime T cells. The iDCs can also enter the lymph node and stimulate T cells. The activated T cells reduced the expression of heat shock proteins (HSPs) in tumor cells, rendering them more sensitive to heat stress. Subsequently, we used mild photothermal therapy (42–45 °C) to induce immunogenic cell death and contribute to a synergistic antitumor effect. iDCs as a refined and precise system in combination with DC-based immunotherapy and thermal therapy can be stored long-term and on a large scale, so they can be applied in many patients. [ABSTRACT FROM AUTHOR]

• The phenotype of human CD303+ pDC subsets is investigated in this paper. Four new subpopulations of CD303 pDCs expressing CD205 and/or CD103 are found in human peripheral blood. • Non-small-cell lung cancer (NSCLC) modulates the differentiation of CD303+ pDC subsets expressing CD103 and CD205 in vitro and ex vivo. • Co-culture with primary NSCLC cells or NSCLC cell line (H1299) in vitro leads to abnormal expression of co-stimulatory molecules/MHC II (CD40, CD80, CD86 and HLA-DR) and production of pro-/anti-inflammatory cytokines (IL-6, IL-10, IL-12, IL-23, IL-27 and TGF-β) by CD303+ pDCs. • Our data indicated that NSCLC cells generate immune tolerogenic CD303+ pDC subsets in vitro. This may be one part of immune suppressive microenvironment induced by NSCLC in vivo. CD303+ plasmacytoid dendritic cells (pDCs) play an important role in the induction of immune tolerance and antitumor immunity. Here, we focused on the effect of NSCLC cells on the development of CD303+ pDC subsets expressing CD205 and/or CD103. The NSCLC cell line H1299 and primary NSCLC cells were incubated with DCs. The protein expression of costimulatory molecules on CD303+ pDCs, the production of pro-inflammatory and anti-inflammatory cytokines by CD303+ pDCs and the development of CD303+ pDC subsets were detected by using flow cytometry. Coculture with NSCLC cells modulates the protein expression of CD86 and HLA-DR on CD303+ pDCs. Moreover, NSCLC cells suppressed the production of IL-12 and IL-23 but facilitated the secretion of IL-27 and TGF-β by CD303+ pDCs. There were new CD303+ pDC subsets expressing CD205 and/or CD103 in healthy donors and NSCLC patients: CD303+CD205+CD103+, CD303+CD205+CD103-, CD303+CD205-CD103+ and CD303+CD205-CD103- pDCs. NSCLC cells modulated the differentiation of CD303+ pDC subpopulations by regulating the protein expression of CD205 and/or CD103 on CD303+ pDCs. NSCLC cells may regulate the immune functions of CD303+ pDCs by modulating the expression of costimulatory molecules on DCs and the production of pro-inflammatory/anti-inflammatory cytokines by DCs. NSCLC cells also regulate the development of CD303+ pDC subsets expressing CD205 and/or CD103. These outcomes may reveal a new cellular mechanism leading to the NSCLC-induced immune-suppressive microenvironment. [ABSTRACT FROM AUTHOR]

The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell , two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by CD103 expression, dependence on transcription factors Batf3 and Irf8, and interleukin-12 production. [ABSTRACT FROM AUTHOR]

Artificial immune system (AIS) as a good prototype for developing Machine Learning (ML) is a promising candidate to design Intrusion Detection System (IDS). Two of its prevalent paradigms, the negative selection, and the danger theory, inspired by immunity responses of the powerful human immune system (HIS) are being widely used in this case. In this paper, we proposed a novel sophisticated hybrid method including two defensive lines by using two aforesaid mechanisms. In the proposed method, decentralized cooperation of dendritic cells together with mature detectors acts as a stimulator to generate efficient and accurate detectors and retain memory in the long-term that meant security control via ensuring immunity. Simulating such a system was applicable only by establishing artificial life cycles in the MATLAB environment. Experimental consequences demonstrate that the present schema gradually ameliorates its overall performance during the incipient stages of life cycles and also it is more capable than the previous ones found in the literature. [Display omitted] [ABSTRACT FROM AUTHOR]

The efficiency of the promising deterministic dendritic cell algorithm (dDCA) in terms of anomaly detection has been demonstrated in large number of studies. However, the results of these studies also show that the signal calculation phase of dDCA depends on artificial experience, while the algorithm also lacks adaptability. To overcome these limitations, we propose a new approach for anomaly detection based on dDCA, in which numerical differential and immune responses are applied. The numerical differential is introduced to provide a new method of calculating the signal values that is independent of artificial experience. In the immune response method, moreover, the immune nonlinear model is adopted to adjust the weight signal matrix of dDCA. The experimental results show that the proposed algorithm has significant advantages over the compared immune anomaly detection approaches in terms of signal calculation and adaptability. • A dDCA with numerical differentiation and immune response is proposed in this paper. • Numerical differentiation is used for signal extraction. • An immune dynamic model of nonlinear model is used to adjust the weights in dDCA. • Experimental results show that the proposed algorithm achieves a better performance. [ABSTRACT FROM AUTHOR]