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Abstract: Improving cancer immunotherapy by targeting T cell network also triggers autoimmunity. We disrupted regulatory T cell (Treg) function to probe the balance between breast cancer vaccination and autoimmune thyroiditis (EAT) in four models, with particular attention to MHC-associated susceptibility, EAT induction with mouse thyroglobulin (mTg) without adjuvant, and tolerance to Her-2/neu in transgenic mice. 1) In EAT-resistant BALB/c mice, Treg depletion enhanced tumor regression, and facilitated mild thyroiditis induction. 2) In Her-2 tolerant C57BL/6 mice expressing HLA-DR3, an EAT-susceptibility allele, Her-2 DNA vaccinations must follow Treg depletion for (Her-2xDR3)F1 mice to resist tumor challenge; thyroiditis incidence was moderated by the EAT-resistant IAb allele. 3) In neu tolerant, EAT-resistant BALB/c mice, implanted neu+ tumor also regressed only after Treg depletion and DNA vaccinations. Tumor immunity was long-term, providing protection from spontaneous tumorigenesis. In all three, immune stimuli from concurrent tumor regression and EAT development have a noticeable, mutually augmenting effect. 4) In Treg-depleted, EAT-susceptible CBA/J mice, strong tumor protection was established by immunization with a cell vaccine. mTg injections led to greater thyroiditis incidence and severity. Combination models with MHC class II diversity should facilitate autoimmunity risk assessment and management while generating tumor immunity. [Copyright &y& Elsevier]

The number of CD8+ T lymphocytes (CD8 cells) in peripheral blood can directly reflect the immune status of the body and is widely used for auxiliary diagnosis and prognostic evaluation of diseases. There is an urgent need to develop a simple CD8 cell-counting platform to meet clinical needs. Our group designed a paper-based cell-counting method based on a blocking competition strategy. In addition, we developed a time-resolved fluorescence-blocking competitive lateral flow immunoassay (TRF-BCLFIA) for point-of-care CD8 cell counting that functions by measuring europium nanoparticle (EuNP)-labeled CD8 antibody probes that are not captured by CD8 cells, and we indirectly calculated the concentration of CD8 cells in samples. Within 30 min, four operation steps can provide an accurate CD8 cell count for a 75-μL whole-blood sample, and this approach can be implemented on a handheld device. The TRF-BCLFIA reliably quantified CD8 cells in whole-blood samples, in which the assay exhibited a linear correlation (R2 = 0.989) readout for CD8 cell concentrations ranging from 137 to 821 cells/μL. To validate this approach, our newly developed CD8 cell-counting tool was used to assess 33 tumor patient blood samples. The results showed a high consistency with a flow cytometry-based absolute count. This analysis approach is a promising alternative for the costly standard flow cytometry-based tools for CD8 cell counting in tumor patients in community clinics, small hospitals, and low medical resource regions. This technology would deliver simple diagnostics to patients anywhere in the world, regardless of geography or socioeconomic status. [Display omitted] • We developed a CD8 cell-counting tool that called time-resolved fluorescence-blocking competitive lateral flow immunoassay. • The probes labeled CD8 antibody was europium nanoparticle (EuNP). • Within 30 min, the TRF-BCLFIA reliably quantified CD8 cells in whole-blood samples with a good a linear correlation. • The TRF-BCLFIA showed a high consistency with a flow cytometry-based absolute count. [ABSTRACT FROM AUTHOR]

The CD58-CD2 axis regulates T cell-mediated cancer immunity, but little is known about the regulation of CD58. In two recent papers pubished in Cancer Cell , Miao et al. and Ho et al. define a mechanism of CD58 regulation by CMTM6 and show an unexpected yin-yang link between PD-L1 and CD58. The CD58-CD2 axis regulates T cell-mediated cancer immunity, but little is known about the regulation of CD58. In two recent papers published in Cancer Cell , Miao et al. and Ho et al. define a mechanism of CD58 regulation by CMTM6 and show an unexpected yin-yang link between PD-L1 and CD58. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes recognize and kill cancer cells when the latter present antigenic epitopes complexed with MHC class I molecules on their surface. In a recent Science paper, Mangalhara et al. show that alterations of the mitochondrial electron flow upregulate multiple factors involved in antigen presentation via a succinate-dependent epigenetic mechanism. Cytotoxic T lymphocytes recognize and kill cancer cells when the latter present antigenic epitopes complexed with MHC class I molecules on their surface. In a Science paper, Mangalhara et al. show that alterations of the mitochondrial electron flow upregulate multiple factors involved in antigen presentation via a succinate-dependent epigenetic mechanism. [ABSTRACT FROM AUTHOR]

Whether prostate brachytherapy (BT) results in opportunistic biological changes that can improve clinical outcomes is not well studied. We sought to investigate the impact of prostate BT on the immune system. A scoping review was performed using PubMed/Scopus for papers published between 2011-2021. Search terms were "brachytherapy" AND "immune" AND "prostate". A total of 81 records were identified and 6 were selected for further review. 2 low-dose-rate BT papers (n=68) evaluated changes in the peripheral blood following I-125 monotherapy. Both showed significant increases in peripheral CD3+ and CD4+ T cells post-BT. One also demonstrated significant increases in Treg subsets up to 150 days post-BT. 4 high-dose-rate (HDR) studies (n=37) were identified, and all were done in combination with EBRT. The largest study (n=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature when comparing a pre-BT biopsy to one prior to a second HDR fraction. Prostate BT can invoke an immune activating phenotype; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to promote synergy between BT and the immune system. [ABSTRACT FROM AUTHOR]

• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]

Alpha-fetoprotein (AFP) is a glycoprotein that has many important physiological functions, including transportation, immunosuppression, and induction of apoptosis by T lymphocytes. AFP is closely related to the development of hepatocellular carcinoma and many kinds of tumors, all of which can show high concentrations, so it is used as a positive test indicator for many kinds of tumors. This paper reviews recent advances in the detection of the tumor marker AFP based on three immuno-biosensors: electrochemical (EC), photoelectrochemical (PEC), and electrochemical luminescence (ECL). The electrodes are modified by different materials or homemade composites, different signaling molecules are selected as single probes or dual probes for the detection of AFP. The detection limit was as low as 3 fg/mL, which indicated that the AFP immunosensor had achieved highly sensitive detection. In addition, we also reviewed and summarized the current development status and application prospect of AFP immunoelectrochemical sensors. There are not too many researches on immunosensors based on dual-signal ratios, and the commonly used probes are methylene blue (MB) and ferrocene (Fc). It would be more innovative to have more novel signaling molecules as probes to prepare dual-signal ratio sensors. This paper reviews recent advances in the detection of the tumor marker AFP in recent years based on three different types of electrochemical biosensors: electrochemical (EC) immunosensors, photoelectrochemical (PEC) sensors, and electrochemical luminescence (ECL) sensors. Among them, EC sensors are classified as single-probe and dual-probe. [Display omitted] • This manuscript reviews recent research on the detection of AFP. • The review describes three immunobiosensors: EC, PEC and ECL. • A comprehensive summary and comparison of three sensors for AFP detection. • This review provides guidelines for future research on immunobiosensors. [ABSTRACT FROM AUTHOR]

The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphatic transport of MPA-related species 83-fold and increased MLN concentrations of MPA >20 fold, when compared to MPA alone, for up to 4 h in mice. At the same time, the plasma exposure of MPA and MPA-TG was similar, limiting the opportunity for systemic side effects. Confocal microscopy and flow cytometry studies with a fluorescent model prodrug (Bodipy-TG) revealed that the prodrug accumulated in the MLN cortex and paracortex at 5 and 10 h following administration and was highly associated with B cells and T cells that are found in these regions of the MLN. Finally, we demonstrated that MPA-TG was significantly more effective than MPA at inhibiting CD4+ and CD8+ T cell proliferation in the MLN of mice in response to an oral ovalbumin antigen challenge. In contrast, MPA-TG was no more effective than MPA at inhibiting T cell proliferation in peripheral LN when mice were challenged via SC administration of ovalbumin. This paper provides the first evidence of an in vivo pharmacodynamic benefit of targeting the MLN using a TG mimetic prodrug approach. The TG mimetic prodrug technology has the potential to benefit the treatment of a range of conditions where aberrant immune responses are initiated in gut-associated lymphoid tissues. [Display omitted] • Targeting lymphocytes in the mesenteric lymph nodes (MLN) enhances immunomodulation. • An oral triglyceride based prodrug promoted lymphatic transport and MLN targeting. • The prodrug also enhanced drug exposure to MLN lymphocytes. • A prodrug of mycophenolic acid suppressed lymphocyte proliferation in antigen challenge studies. • Triglyceride-based prodrugs may provide a means to enhance intestinal immunomodulation. [ABSTRACT FROM AUTHOR]

As transistors shrink in size, the integration density of memory circuits like Static Random Access Memory (SRAM) cells rises, making them increasingly susceptible to Single Event Effects (SEE). In the space environment, memory circuits face stability and reliability challenges due to the presence of various charged particles such as α-particles, neutrons, electrons, heavy ions, and photons. These high-energy particles create ion tracks when they strike the memory device, leading to upsets in the storage bits. Conventional 6 T SRAM cells are susceptible to these upsets. As a solution this paper proposes a new Radiation Tolerable (RT 13 T) SRAM cell that is better suited for deep-space applications compared to other memory cell. RT13T has been validated to withstand radiation hazards through Critical Charge (Q Crit) analysis, which shows that it exhibits 1.17×, 1.1×, 1.94× and 1.06× highest Q Crit than QUCCE 10 T/12 T,traditional 6 T and LIOR 13 T memory cells, respectively. As the comparison made, our Proposed RT 13 T saved by5.1 %,9.9 %, 20.1 % and 7 % of the power consumption compared to QUCCE10T/12 T/LIOR 13 T/SERSC-16 T SRAM cells at a nominal supply voltage of 0.7 V. It also exhibits shorter read delay (T RA) 10.6 %, 1.34 %, 9.6 %, 22.16 %compared to QUCCE 10 T/12 T,6T, SERSC-16Tmemory cells, respectively. In terms of stability,our proposed RT13T SRAM cell exhibits 2.32×/2.05×/2.9×/1.05×/1.01 × higher read stability as compared with QUCCE10T/12 T/6T/LIOR 13 T/SERSC-16 T memory cells during the read operation. The our proposed RT13T shows improvements in design metrics are at the expense of a longer write delay. To characterize the performances of the proposed RT13T, 16-nm CMOS predictive technology model and validated through extensive simulation with licensed PrimeSim HSPICE of Synopsys. The results of our proposed RT13T cell are compared with some other previously proposed memory cells such as 6 T, QUCCE 10 T, QUCCE 12 T, LIOR 13 T and SERSC-16 T memory cells. The obtained results are tabulated and plotted for graphical analysis. In terms of area consumption our proposed 13 T consumes 0.9×/0.6 × lesser area than QUCCE 12 T/SERSC-16 T memory cells but our proposed circuit consumes 3.1×/1.08×/1.05 × more area than QUCCE10T/conventional 6 T/LIOR 13 T because QUCCE10T and 6 T consist of less number of transistors in memory cells.The cell proposed in this paper demonstrates strong radiation-hardened capabilities and excellent overall performance, making it well-suited for aerospace electronic devices and ensuring stable operation in space radiation environments. [ABSTRACT FROM AUTHOR]

Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. [ABSTRACT FROM AUTHOR]

Inflammation is the result of acute and chronic stresses, caused by emotional or physical trauma, or nutritional or environmental pollutants, and brings serious harm to human life and health. As an important cellular component of the innate immune barrier, the macrophage plays a key role in maintaining tissue homeostasis and promoting tissue repair by controlling infection and resolving inflammation. Several studies suggest that V Set and Ig domain-containing 4 is specifically expressed in tissue macrophages and is associated with a variety of inflammatory diseases. In this paper, we mainly summarize the recent research on V Set and Ig domain-containing 4 structures, functions, function and roles in acute and chronic inflammatory diseases, and provide a novel therapeutic avenue for the treatment of inflammatory diseases, including nervous system, urinary, respiratory and metabolic diseases. [ABSTRACT FROM AUTHOR]

This section presents abstracts of oncology-related topics including the kinetics of tumor growth, the effectiveness of bevacizumab in reducing the growth rate of renal carcinoma and the role of beta-catenin in regulating acute adult T cell leukemia/lymphoma.

This study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. An asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor β1 (TGF-β1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ , Il-4 , Tgf-β1 , Il-6 , Il-10 , Tnf-α , Il-13 , and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. Our study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. PE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance. [Display omitted] • This paper is the first to explore the intervention effect and mechanism of polysaccharides in Ephedrae Herba on OVA-induced allergic asthma. • Ephedrae Herba polysaccharides may treat OVA-induced allergic asthma by modulating inflammation and immunity. [ABSTRACT FROM AUTHOR]

Leukaemia is diagnosed conventionally by observing the peripheral blood and bone marrow smear using a microscope and with the help of advanced laboratory tests. Image processing-based methods, which are simple, fast, and cheap, can be used to detect and classify leukemic cells by processing and analysing images of microscopic smear. The proposed study aims to classify Acute Lymphoblastic Leukaemia (ALL) by Deep Learning (DL) based techniques. The study used Deep Convolutional Neural Networks (DNN s) to classify ALL according to WHO classification scheme without using any image segmentation and feature extraction that involves intense computations. Images from an online image bank of American Society of Haematology (ASH) were used for the classification. A classification accuracy of 94.12% is achieved by the study in isolating the B-cell and T-cell ALL images using a pretrained CNN AlexNet as well as LeukNet , a custom-made deep learning network designed by the proposed work. The study also compared the classification performances using three different training algorithms. The paper detailed the use of DNNs to classify ALL, without using any image segmentation and feature extraction techniques. Classification of ALL into subtypes according to the WHO classification scheme using image processing techniques is not available in literature to the best of the knowledge of the authors. The present study considered the classification of ALL only, and detection of other types of leukemic images can be attempted in future research. • Deep Learning based classification of ALL. • Classification of ALL based on WHO scheme. • ALL is classified into B – cell lymphoblasts and T – cell lymphoblasts. • Use of Convolutional Neural Networks (CNN) for leukaemia classification. • Leukaemia classification without image segmentation and feature extraction. [ABSTRACT FROM AUTHOR]

Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, survival for this stage of disease remains very low. Activating the immune system has incredible promise since it has the potential to be curative. However, immune checkpoint blockade (ICB) which works through T cells has been largely disappointing for metastatic breast cancer. One reason for this is a suppressive myeloid immune compartment that is unaffected by ICB. Cholesterol metabolism and proteins involved in cholesterol homeostasis play important regulatory roles in myeloid cells. Here, we demonstrate that NR0B2, a nuclear receptor involved in negative feedback of cholesterol metabolism, works in several myeloid cell types to impair subsequent expansion of regulatory T cells (T regs); T regs being a subset known to be highly immune suppressive and associated with poor therapeutic response. Within myeloid cells, NR0B2 serves to decrease many aspects of the inflammasome, ultimately resulting in decreased IL1β; IL1β driving T reg expansion. Importantly, mice lacking NR0B2 exhibit accelerated tumor growth. Thus, NR0B2 represents an important node in myeloid cells dictating ensuing T reg expansion and tumor growth, thereby representing a novel therapeutic target to re-educate these cells, having impact across different solid tumor types. Indeed, a paper co-published in this issue demonstrates the therapeutic utility of targeting NR0B2. • Regulatory T cells (Tregs) are associated with poor prognosis in several tumor types including breast cancer. • NR0B2 in myeloid cells suppresses several aspects of the inflammasome, culminating in decreased IL1β. • IL1β works to promote T reg expansion. • Loss of NR0B2 results in increased growth of mammary and melanoma tumors in mice. • NR0B2 represents a way to re-educate myeloid immune cells and relieve the immune-suppressive microenvironment of solid tumors. [ABSTRACT FROM AUTHOR]

The interaction between the immune system and the tumor matrix has a huge impact on the progression and treatment of cancer. This paper summarizes and discusses the crosstalk between T cells and cancer-associated fibroblasts (CAFs). CAFs can also produce inhibitors that counteract the function of T cells and promote tumor immune escape, while T cells can also engage in complex two-way interactions with CAFs through direct cell contact, the exchange of soluble factors such as cytokines, and the remodeling of the extracellular matrix. Precise targeted intervention can effectively reverse tumor-promoting crosstalk between T cells and CAFs, improve anti-tumor immune response, and provide a new perspective for cancer treatment. Therefore, it is important to deeply understand the mechanism of crosstalk between T cells and CAFs. This review aims to outline the underlying mechanisms of these interactions and discuss potential therapeutic strategies that may become fundamental tools in the treatment of cancer, especially hard-to-cure cancers. • CAFs regulate T cell infiltration and function through multiple pathways. • T cells modulate CAF functions through feedback mechanisms. • Crosstalk between CAFs and T cells reveals potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Stable fault self-healing ensures the smooth operation of intelligent industrial manufacturing processes. However, current research, while capable of inferring fault propagation paths or individually controlling manufacturing processes, still faces some challenges and limitations in addressing issues within manufacturing processes. In particular, it is easy to overlook the impact of fault variables on normal causal relationships in the manufacturing process and how to achieve adaptive fault repair from the source of faults. The biological immune system possesses sensitive nodes and a neuro-endocrine-immune network with interconnected functionalities, bearing remarkable resemblance to the sensor arrays, information networks, and intelligent controller systems in modern self-healing control systems. These problem domains have significant practical implications in industrial manufacturing processes and urgently require new methods and technologies to address them. To address the issue of root cause fault self-healing in intelligent industrial manufacturing processes, this paper proposes an innovative method that utilizes root cause inference and bio-inspired heuristic reinforcement learning models to achieve fault self-healing in industrial processes. First, innovatively introduce the Variational Autoencoder (VAE) into the Time Convolutional Network (TCN) to construct the TCN-VAE network. By performing feature reconstruction, the network's feature extraction capability is enhanced, further exploring the relationships between latent variables, and consequently building a causal graph of faults. A multi-head attention mechanism is introduced into the network, and the inference process is quantitatively evaluated, thereby improving the generalization and accuracy of root cause inference. Root cause determination rules are established to identify the fundamental reasons for fault occurrence, ensuring self-healing from the source of faults. Next, we developed for the first time a fault self-healing model based on reinforcement learning, utilizing the immune repair process of effector T cells to characterize the fault self-healing process. It effectively adapts to eliminate various levels of faults based on the state transition process of antigens in T helper cells. Additionally, stability control analysis is performed on the proposed model. The average reward function curve and Sobol sensitivity index demonstrates the model's strong robustness in practical applications. The validation results from case studies on the Tennessee Eastman (TE) and Continuous Stirred Tank Reactor (CSTR) show that the average improvement in fault repair F1 score was 0.0941 and 0.105 respectively, and the fastest improvement in fault repair response time was 0.266s and 0.258s respectively. It was confirmed that the root cause inference and fault repair results align with the actual mechanisms of the manufacturing processes. The proposed method has been verified to achieve stable and accurate root cause fault repair in real-world intelligent industrial manufacturing systems, making a significant contribution to achieving stable and accurate root cause fault repair in intelligent industrial manufacturing systems. • TCN-VAE enables feature reconstruction and latent variable exploration for root cause reasoning. • Multi-head attention enhances generality and accuracy in root cause reasoning. • Effector T-cell immune-inspired RL adapts to eliminate faults effectively. • The fault self-healing model exhibits strong reliability and robustness. • Method validated on Tennessee Eastman and continuous stirred-tank reactor datasets. [ABSTRACT FROM AUTHOR]

Adoptive T cell therapy has undergone remarkable advancements in recent decades; nevertheless, the rapid and effective ex vivo expansion of tumor-reactive T cells remains a formidable challenge, limiting their clinical application. Artificial antigen-presenting substrates represent a promising avenue for enhancing the efficiency of adoptive immunotherapy and fostering T cell expansion. These substrates offer significant potential by providing flexibility and modularity in the design of tailored stimulatory environments. Polydimethylsiloxane (PDMS) silicone elastomer stands as a widely utilized biomaterial for exploring the varying sensitivity of T cell activation to substrate properties. This paper explores the optimization of PDMS surface modification and formulation to create customized stimulatory surfaces with the goal of enhancing T cell expansion. By employing soft PDMS elastomer functionalized through silanization and activating agent, coupled with site-directed protein immobilization techniques, a novel T cell stimulatory platform is introduced, facilitating T cell activation and proliferation. Notably, our findings underscore that softer modified elastomers (Young' modulus E∼300 kPa) exhibit superior efficacy in stimulating and activating mouse CD4+ T cells compared to their stiffer counterparts (E∼3 MPa). Furthermore, softened modified PDMS substrates demonstrate enhanced capabilities in T cell expansion and Th1 differentiation, offering promising insights for the advancement of T cell-based immunotherapy. [Display omitted] • Chemically modified layers and Protein A enhance antibody density and stability. • Softer elastomers better stimulate CD4+ T cells compared to stiffer ones. • Softened PDMS substrates enhance T cell expansion and Th1 differentiation. • Study shows surface chemistry and mechanical cues influence T cell behavior. [ABSTRACT FROM AUTHOR]

In this Q&A, Cell Press Community Review Scientific Editor Leia Judge talks to Dr. Clint Allen and Dr. Sandro Santagata about their new papers "Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer" and "Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma" and their experiences with publishing through Cell Press Community Review. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive methodology to characterize the mission profile of photovoltaic systems, through which a powerful set of relevant information may be obtained and used in order to improve the design of power converters. Characterizing a photovoltaic system accurately is not trivial and this paper aims to present a detailed methodology on how to obtain a PV real field mission profile. Three cities with different climate were considered and a large dataset of four variables was used: global horizontal, direct, and diffuse irradiances and ambient temperature. Data were measured at one-minute intervals over multiple years. For each location, four scenarios of panel orientation were analyzed: horizontal position, fixed tilt, 1-axis and 2-axis mechanical tracker. A mathematical model to estimate instantaneous in-plane irradiance based on measured data and mounting type was used. An average profile of solar energy and ambient temperature for each city were built; these profiles were used as input for estimation of annual energy yield of a commercial photovoltaic panel, which was mathematically modeled and validated. Current and power processing throughout a year in a one-minute resolution were investigated, along with the most frequent and most significant operating points in each scenario. Panel operating temperature related to ambient conditions and its relation to energy yield were also studied. Finally, a comprehensive discussion to understand how different mission profiles affect power processing of photovoltaic power converters and the way this characterization can aid in pre-sizing and lifetime analysis of power electronics is presented. [ABSTRACT FROM AUTHOR]

Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis , proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro : P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN−) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. We aimed to use a mouse model to elucidate the molecular mechanisms of immune-related hepatitis, one of the common irAEs associated with ICIs. Immune phenotyping and molecular profiling were performed on Pdcd1 -/- mice treated with anti-CTLA4 and/or the IDO1 inhibitor epacadostat or a 4-1BB agonistic antibody. ICI combination-induced hepatitis and 4-1BB agonist-mediated hepatitis share similar features yet maintain distinct immune signatures. Both were characterized by an expansion of periportal infiltrates and pan-zonal inflammation albeit with different morphologic characteristics. In both cases, infiltrates were predominantly CD4+ and CD8+ T cells with upregulated T-cell activation markers, ICOS and CD44. Depletion of CD8+ T cells abolished ICI-mediated hepatitis. Single-cell transcriptomics revealed that the hepatitis induced by combination ICIs is associated with a robust immune activation signature in all subtypes of T cells and T helper 1 skewing. Expression profiling revealed a central role for IFNγ and liver monocyte-derived macrophages in promoting a pro-inflammatory T-cell response to ICI combination and 4-1BB agonism. We developed a novel mouse model which offers significant value in yielding deeper mechanistic insight into immune-mediated liver toxicity associated with various immunotherapies. Hepatitis is one of the common immune-related adverse events in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. The mechanisms of ICI-induced hepatitis are not well understood. In this paper, we identify key molecular mechanisms mediating immune intracellular crosstalk between liver T cells and macrophages in response to ICI in a mouse model. [Display omitted] • P dcd 1 -/- mouse can be utilized as a model for immune checkpoint inhibitor-mediated liver injury. • Single-cell immune transcriptional profiling revealed a landscape of molecular pathways responding to inhibition of PD1, CTLA4 and IDO1. • We identified a subset-specific T cell activation signature and common IFNγ signature. • Monocyte-derived macrophages coordinate the T cell response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

The Astragalus membranaceus polysaccharide (APS4) with direct cytotoxicity on various cancer cells has been prepared in our previous study, while the underlying therapeutic role of APS4 on solid tumors in vivo hasn't been investigated yet. Therefore, in this paper, the lymphocytes-mediated antitumor and immunoregulatory activities of APS4 were researched by establishing S180 tumor-bearing mice model. Flow cytometry analysis revealed that APS4 could effectively regulate the percentages of CD3+, CD4+, CD8+ T cells and CD19+ B cells in thymus, peripheral blood and spleen of S180 tumor-bearing mice, dose-dependently. H&E staining and cell cycle determination of solid tumors manifested that APS4 treatment could significantly inhibit the growth of solid tumors by inducing cells apoptosis. Furthermore, two-dimensional electrophoresis and western blot analysis further demonstrated that APS4 could activate antitumor-related immune cells and promote anaerobic metabolism of tumor microenvironment, thereby causing the apoptosis of S180 tumor cells. These data implicated that APS4 could be used as a potential dietary supplement for immune enhancement. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8+ T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields. [Display omitted] [ABSTRACT FROM AUTHOR]

The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of ‘technology identity’ and ‘development space’ to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a ‘point-of-care’ cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways. [ABSTRACT FROM AUTHOR]

Despite recent breakthroughs of immune-checkpoint inhibitors in the management of bladder cancer (BC), only 20% of patients with non-muscle invasive BC (NMIBC) completely respond, leaving room for improvement. Due to challenges in developing a preclinical model which reflects the heterogeneity and biology of bladder tumors, patient-derived xenograft (PDX) models were created. PDX models involve implanting tumor extracted from patients into immunocompromised mice, which therefore keep the morphology and genomic fidelity of their parental patient cancers. The state of immunodeficiency, however, precludes study of immunotherapy and consequently humanized mice models engrafted with a human immune system were developed, though this led to spontaneous xenogenic graft vs host disease (GVHD). As a potential solution to GVHD in humanized mouse models, this paper describes successful creation of a double-humanized mouse (DHM) by simultaneously engrafting human immune cells and human tumors from the same donor. BC tissue was processed +/- digested into single-cell suspensions (SCS, F0 tissue) and injected orthotopically or subcutaneously into flanks of NSG™ mice. Subsequent tumor growth (PDX-F1) was measured, and PDX-F1 tumors reaching >200mm3 were processed into SCS and reimplanted subcutaneously into a new NSG™ (PDX-F2). Continuous passages (PDX-Fn) were repeated.; Extra SCS-F1 and Fn was analyzed for human epithelial cell adhesion molecule (EpCAM) expression. From an individual F1, a stable cell line (PDX257S) was cultured, and also analyzed for EpCAM expression by flow cytometry. For the DHM model, autologous γδ T-cells expanded in vitro from PDX257S donors were injected with PDX257S cells (effector: target = 2:1) into the NSG™ flanks and were observed for body condition/hematuria for 45 days. Total RNA-sequencing was performed on F0, PDX-Fn and PDX257S cell line. Tumor growth curves were analyzed with 2-way analysis of variance (ANOVA). F0 tissue was obtained from 60 patients. Tumor acceptance in orthotopic injection was not observed in the first 11 suitable tumors, and this method was ceased. Subcutaneous tumor acceptance rate improved with digestion and processing of F0 rather than processing alone (11% vs 5%). EpCAM expression was 98% vs 70% in PDX257S vs its F1 tissue, and < 30% in F1 tissue from other donors that did not yield further passages. In the DHM, while tumor growth was significantly reduced compared to control group after 45 days (mean vol 200 mm3 vs 580 mm3, p=0.02) post injection, it was not completely suppressed. RNA sequencing revealed increased expression of genes including BCL2L1, KRAS, MYC, E2F1, and E2F4 in both PDX257 subcutaneous tumor and cell line compared with donor tumor tissue, and very low/no expression of CDKN2A and FHIT genes in both PDX257 cell line and donor tumor tissue. Creation of a double-humanized mouse model is feasible, and tumor growth is not completely suppressed with the addition of autologous γδ T-cells. PDX257S tumor and cell line is associated with increased EpCAM expression and on RNA sequencing, increased expression of BCL2L1, KRAS, MYC, E2F1, and E2F4. [ABSTRACT FROM AUTHOR]

Highly expressed azo-reductase (AZOR) selectively reduces Azo-DON to DON in hypoxic tumor environments, impair glutamine metabolism in cancer cells, and promote tumor cell death without affecting T cell metabolism and proliferation, thereby generating strong antitumor immune responses. CB-PLG nanoparticles (CBP) mentioned in the paper can enhance the degree of hypoxia in normoxic tumors, which is conducive to efficient reduction of Azo-DON at tumor sites. [Display omitted] • Azo-DON is a novel hypoxia-active prodrug of glutamine antagonist. • Azo-DON selectively blocks tumor glutamine metabolism after reducing to DON. • T cells continue to proliferate and remain active when Azo-DON is reduced to DON. • CBP nanoparticles increase tumor hypoxia and facilitate the reduction of Azo-DON. Glutamine antagonists, such as 6-diazo-5-oxo-L-norleucine (DON), have demonstrated remarkable anti-tumor effects by blocking tumor glutamine metabolism, but their use is frequently causing toxicity. Despite the existence of multiple glutamine antagonist prodrug designs, a tumor-selective prodrug has yet to be developed. Herein, a novel prodrug of DON, Azo-DON, has been developed, which remains stable and inactive in normal tissues with sufficient oxygen levels, while can be selectively reduced to DON by highly expressed azo-reductase in hypoxic tumor environments. This leads to blockade of glutamine metabolism in cancer cells and promotes cell death without affecting T cell proliferation. In a high-hypoxic H22 hepatoma cancer model, Azo-DON showed a 1.8-fold enhancement in glutamine blockade compared to the control group, resulting in a tumor suppression rate (TSR) of 84.2% in vivo with no significant weight loss. In a low-hypoxic CT26 colon cancer model, when combined with vascular disrupting agent nanoparticles (CBP) to induce a hypoxic environment, Azo-DON exhibited a 4.6-fold enhancement in glutamine blockade over the control group, resulted in a remarkable TSR of 96.6% in vivo. This innovative approach represents a promising strategy for the application of broad-spectrum metabolic inhibitors in the field of precision cancer treatment. [ABSTRACT FROM AUTHOR]

With the success of immunosuppressive checkpoint in tumor therapy, the corresponding adverse response and drug resistance defects have been exposed. T cells and NK cells are the body's immune system of the two substantial main forces. in recent years, study of T cell checkpoints appeared a certain block, such as PD-1 the effect not benign, on the distribution of NK cell surface excitatory and inhibitory receptors under normal conditions to maintain steady, could be targeted in the tumor treatment blockade have therapeutic effect. This paper reviews the function of NK cells and the effects of corresponding receptors in various types of tumors, providing a direction for the selection of appropriate gate control sites for future treatment. [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]

• We first described the S.maltophilia immunosuppressive effect on T cells and it is meaningful for immunosuppressed patients or co-infections. • T cells stimulated by S.maltophilia with CD4 and CD8 degraded via PD-1/PD-L1 pathway, which led to the massive apoptosis of T cells. • T cells were stimulated by S. maltophilia to secrete IFN-γ. Blocking the PD-1/PD-L1 pathway, apoptosis was suppressed. • S.maltophilia down-regulates host immunity by inhibiting immune cells. Smalotrophomonas maltophilia (S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ. S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells. T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells. These indicates that T cells are inhibited after being stimulated by S. maltophilia , and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered. [ABSTRACT FROM AUTHOR]

In the present paper, a HIV - 1 infection of CD 4 + T-cells with the impact of drug treatment model of arbitrary order have been examined with the aid of Legendre wavelet operational matrix method. The technique employed to convert differential equations of arbitrary order into the linear or nonlinear algebraic equations, which are easy to handle by mathematical software. The comparison among the discussed methods with RK4, homotopy perturbation scheme, homotopy analysis approach, Laplace adomian-decomposition technique and Adam-Bashforth predictor-corrector scheme divulge that the present technique is authentic and valid for other engineering problems. It is noticed that the suggested scheme are more efficient and effective. [ABSTRACT FROM AUTHOR]

Presentation of exogenous antigens loaded on major histocompatibility complex class I molecules by antigen presenting cells, termed cross-presentation, is essential for the induction of CD8+ T cells and is performed mainly by specialized dendritic cell subsets. Research into this field has described two main mechanisms of cross-presentation, the cytosolic pathway and the vacuolar pathway. As the first step in cross-presentation, surface receptors relating to cross-presentation are required in the recognition and uptake of Ags, which include C-type lectin receptors, immunoglobulin γ Fc region receptor, chemokine receptor, scavenger receptor etc. After uptake by the cells, there are also many molecules that enable Ags to participate in cross-presentation pathways. By this approach, exogenous Ags can induce CD8+ T cells into cytotoxic T lymphocytes, which is of great significance to induce antitumor and antiviral immune responses, and the molecular mechanism would facilitate the development of related adjuvants. However, the detailed mechanisms of cross-presentation still remain unknown. In this paper, some latest researches, including two major pathways, DC surface receptors and application prospects are summarized. [ABSTRACT FROM AUTHOR]

Nocardia affects immunocompromised human host exhibiting an altered cell-mediated immunity. Infectious risk after allogeneic hematopoietic cell transplantation (AHCT) is significantly correlated to the recovery status of donor-derived immune system, especially CD4+ T-cells reconstitution and thymopoiesis. The purpose of this paper is to highlight a lack of cell-mediated immunity recovery for patients presenting a nocardiosis compared to a control cohort. This is a case control retrospective monocentric study. We retrospectively analyzed a monocentric cohort of 15 cases of nocardiosis after AHCT and we explored the degree of patients' immunosuppression by phenotyping circulating lymphoid subpopulations, including NK cells, CD8+ T-cells, CD4+ T-cells and CD19+ B-cells. We focused on CD4+ T-cell subsets to appreciate thymic output, especially on naive CD4+ T-cells (NTE, CD45RA+/RO− CD4+ T-cells) and recent thymic emigrants (RTE, CD4+CD45RA+/RO−/CD31+). Infected patients were paired with a control cohort of patients with identical transplantation characteristics screened on hematological disease, AHCT conditioning, primary graft- versus -host disease (GHVD) prophylaxis, graft type, sex, age, and season at the AHCT and data concerning immunological reconstitution were compared. At onset of nocardiosis, circulating lymphocytes and CD4+ T-cells means count were respectively 730/μL and 162/μL. CD8+ T-cells, CD56+ NK cells and CD19+ B-cells means count were respectively 362/μL, 160/μL, 112/μL. CD4+ T-cells subpopulations, naïve CD4+ T-cells production was impaired with NTE and RTE means count at 26/μL and 11/μL respectively. Comparison between nocardiosis cohort and control cohort over time highlight significant lower cellular count for lymphocytes, CD4+ T-cells, NTE and RTE with p = 0.001, p < 0.001, p < 0.001, p < 0.001 respectively. Immune recovery monitoring follow-up after AHCT is of particular importance to identify patients susceptible to develop Nocardiosis. Efficient microbiological investigations toward Nocardia such PCR should be used in case of compatible clinical presentation. [ABSTRACT FROM AUTHOR]

Early embryonic exogenous feeding of bioactive substances is a topic of interest in poultry production, potentially improving gastrointestinal tract (GIT) development, stimulating immunization, and maximizing the protection capability of newly hatched chicks. However, the biophysiological actions and effects of in ovo administered bioactive substances are inconsistent or not fully understood. Thus, this paper summarizes the functional effects of bioactive substances and their interaction merits to augment GIT development, the immune system, and microbial homeostasis in newly hatched chicks. Prebiotics, probiotics, and synbiotics are potential bioactive substances that have been administered in embryonic eggs. Their biological effects are enhanced by a variety of mechanisms, including the production of antimicrobial peptides and antibiotic responses, regulation of T lymphocyte numbers and immune-related genes in either up- or downregulation fashion, and enhancement of macrophage phagocytic capacity. These actions occur directly through the interaction with immune cell receptors, stimulation of endocytosis, and phagocytosis. The underlying mechanisms of bioactive substance activity are multifaceted, enhancing GIT development, and improving both the innate and adaptive immune systems. Thus summarizing these modes of action of prebiotics, probiotics and synbiotics can result in more informed decisions and also provides baseline for further research. [ABSTRACT FROM AUTHOR]

Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune diseases is difficult because of its only partially understood immune-mediated mechanisms. The literature concerning the innate and adaptive immune system activation in PMR was systematically reviewed highlighting the relative weight of autoinflammation and autoimmunity in its pathogenesis and disease progression. A literature search on PubMed Central and Embase scientific databases was performed by two independent reviewers. To be eligible, the studies needed to fully satisfy our initial PICO framework: a primary diagnosis of PMR as a population, the search for immune/inflammatory cells, cytokines and autoantibodies as an intervention, a control group consisting in healthy controls, patients with other inflammatory rheumatic diseases or PMR patients in remission after treatment and as outcomes the results of the investigations in the analyzed tissue samples. The most relevant data of the included papers were extracted by using a standardized template. Of the 933 screened abstracts, 52 papers were included in the systematic review and categorized depending on their primary research objectives. The hyper-activity of neutrophils and monocytes, expressing toll-like receptor 7 in active disease, an impaired phagocytosis and endothelial dysfunction, as well as an increased count of innate T cells in patients with remission emerged among the major derangements of the innate immune response in PMR. Among the cytokines profile, interleukin-6 plays a key role but other pro-inflammatory mediators and angiogenesis markers such as chemokines, B-cell activating factor, vascular endothelial growth factor and angiopoietins seem to be involved in refractory or glucocorticoid-resistant PMR. The aberrant adaptive immune response was documented by tissue and serum findings of polarized T cells towards T helper 1 and 17 phenotypes, an increased expression of immunosenescent surface markers and a downregulated immunoregulatory response. The altered distribution of peripheral B cells, detected during active disease, suggested their peripheral migration towards unidentified sites. The interaction between innate and adaptive immune response was documented by a synovial infiltrate of macrophages and T cells. Despite multiple autoantibodies have been detected in PMR patients, none proved to correlate with disease activity seeming to be reactive to the marked inflammation or antigenic determinants provided by environmental triggers or tissue/cell damage. The complex network between innate and adaptive immune system in PMR is supported by findings at molecular and cellular levels. By considering both the ends of the pathophysiological spectrum of immune-mediated rheumatic diseases, PMR may be regarded as an inflammatory immune-mediated disease with mixed mechanisms in a background of genetic and epigenetic factors together with immunological and endocrine senescence. • High concentrations of serum pro-inflammatory cytokines and cell growth factors identify active PMR patients • Innate immune cells might play a role both in PMR disease activity and sub-clinical ongoing inflammation. • T cells are dysregulated in PMR for a hyper-expression of immunosenescent markers and deficient immunoregulatory pathways. • B cells peripheral distribution is altered during active disease suggesting an inflammatory-driven compartmentalization. • Autoantibodies do not seem pathogenetic in PMR but may be reactive to external triggers or damaged tissues self-antigens. [ABSTRACT FROM AUTHOR]

Abstract: The Negative Selection Algorithm developed by Forrest et al. was inspired by the way in which T-cell lymphocytes mature within the thymus before being released into the blood system. The mature T-cell lymphocytes exhibit an interesting characteristic, in that they are only activated by non-self cells that invade the human body. The Negative Selection Algorithm utilises an affinity matching function to ascertain whether the affinity between a newly generated (NSA) T-cell lymphocyte and a self-cell is less than a particular threshold; that is, whether the T-cell lymphocyte is activated by the self-cell. T-cell lymphocytes not activated by self-sells become mature T-cell lymphocytes. A new affinity matching function termed the feature-detection rule is introduced in this paper. The feature-detection rule utilises the interrelationship between both adjacent and non-adjacent features of a particular problem domain to determine whether an antigen is activated by an artificial lymphocyte. The performance of the feature-detection rule is contrasted with traditional affinity matching functions, currently employed within Negative Selection Algorithms, most notably the r-chunks rule (which subsumes the r-contiguous bits rule) and the hamming distance rule. This paper shows that the feature-detection rule greatly improves the detection rates and false alarm rates exhibited by the NSA (utilising the r-chunks and hamming distance rule) in addition to refuting the way in which permutation masks are currently being applied in artificial immune systems. [Copyright &y& Elsevier]

Abstract: In this paper, we introduce fractional-order into a model of HIV infection of CD4+ T-cells. We show that the model established in this paper possesses non-negative solutions, as desired in any population dynamics. We also carry out a detailed analysis on the stability of equilibrium. Numerical simulations are presented to illustrate the results. [Copyright &y& Elsevier]

• This paper compares and analyzes the difference of immune status of T lymphocytes and their subsets in hepatitis B patients under different ALT conditions for the first time. • For the first time, this paper reveals the changes of immune status and the effects of antiviral therapy on immune function when ALT is greater than or equal to 2 times the normal upper limit. • This paper puts forward for the first time the significance of using ALT as a node to judge the immune function of the body. The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point. [ABSTRACT FROM AUTHOR]

Anaplasma Marginale, a rickettsial gram-negative bacterium, is responsible for causing bovine anaplasmosis which has widely spread among the different parts of the world causing death among cattle. It is mainly spread through the transmission of infected ticks. The manifestation of infected ticks could be controlled to a limited extent. However, subsequently, it is very much necessary for the cattle to develop strong immunity against A. marginale. It could be possible if a subunit vaccine is created against the rickettsial bacteria and introduced into the blood of the cattle for trials. In this paper, we have conducted a study to develop a multi-epitope subunit vaccine against A.marginale by using reverse vaccinology process. Five highly immunogenic outer membrane proteins of A. marginale were selected such as MSP1a, MSP2, Vir B10, OMP1 and OMP11. These proteins bind to the MHC class I molecules of the epithelial cells of mammals and MHC class II molecules of the antigen-presenting cells such as B-cells. The MHC class I molecules present antigens to the cytotoxic t-lymphocytes whereas the MHC class II molecules present antigens to the helper t-lymphocytes thus, initiating a strong immune response among the bovine species. We constructed three vaccine sequences from which two vaccine constructs V2 and V3, were found to be stable with high solubility and negative allergenicity. We also performed molecular docking of the two refined vaccine constructs with Rp-105 (30% resemblance in sequence to TLR4) and TLR-9. The vaccines interacted with the receptors with high binding energy. The best-designed vaccine construct was then reverse transcribed and adapted for the host E.coli K12 strain. The reverse transcribed sequence was later inserted into the pET28a (+) vector for the cloning and expression of the vaccine. The study could be a better initiative for in vitro and in vivo practice in developing an effective vaccine against A. marginale. • The five Outer surface proteins- MSP1a, MSP2, Vir B10, OMP1, and OMP11 were the most antigenic. • The proposed epitopes displayed high antigenic scores, high conservancy and non allergenicity. • Both the modeled vaccine V2 and V3 interacted with the bovine receptors rp-105 (TLR4) and TLR9 with high binding energy. • The designed construct, V3 was adapted for E. coli (K12) for cloning and expression. • Sequence of vaccine constructs showed no similarity with human proteins. [ABSTRACT FROM AUTHOR]

Highlights • Few paper investigates the role of CD8+CD28+ T cells in patients with AMI. • The frequency of CD8+CD28+ T cells in patients with AMI were significant increased. • In patients with AMI, frequency of CD8+CD28+ T cells was positively correlated with TNI and negatively associated with LVEF. • The CD8+ CD28+ T cell might participate in the process of myocardial damage. Abstract CD8+ T cells accumulate in the necrotic myocardium of acute myocardial infarction (AMI). It is unclear whether CD8+CD28+ T cells, a specific subset of CD8+ T cells, contribute to myocardial injury. In this study, 92 consecutive patients with AMI and 28 healthy control subjects were enrolled. The frequency of CD8+CD28+ T cells in peripheral blood samples was assayed by flow cytometry. Plasma cardiac troponin I (TNI) and left ventricular ejection fraction (LVEF) were determined. Long-term prognosis of the patients was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period. Our findings indicated that patients with AMI who presented with high numbers of CD8+CD28+ T cells had an increased infarction size and aggravated ventricular function. We proposed that cytotoxic CD8+CD28+ T cell-mediated myocardial necrosis may act as a novel and alternative pathway of AMI. [ABSTRACT FROM AUTHOR]

Diagnosing acute leukemia is the necessary prerequisite to treating it. Multi-classification on the gene expression data of acute leukemia is help for diagnosing it which contains B-cell acute lymphoblastic leukemia (BALL), T-cell acute lymphoblastic leukemia (TALL) and acute myeloid leukemia (AML). However, selecting cancer-causing genes is a challenging problem in performing multi-classification. In this paper, weighted gene co-expression networks are employed to divide the genes into groups. Based on the dividing groups, a new regularized multinomial regression with overlapping group lasso penalty (MROGL) has been presented to simultaneously perform multi-classification and select gene groups. By implementing this method on three-class acute leukemia data, the grouped genes which work synergistically are identified, and the overlapped genes shared by different groups are also highlighted. Moreover, MROGL outperforms other five methods on multi-classification accuracy. [ABSTRACT FROM AUTHOR]

Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. [ABSTRACT FROM AUTHOR]

Sensitive and specific detection of DNA is of great significance for clinical diagnosis. In this paper, an effective cascade signal amplification strategy was introduced into photoelectrochemical (PEC) biosensor for ultrasensitive detection of human T-cell lymphotropic virus type I (HTLV-I) DNA. This proposed signal amplification strategy integrates λ-exonuclease (λ-Exo) aided target recycling with hybridization chain reaction (HCR) and enzyme catalysis. In the presence of target DNA (tDNA) of HTLV-I, the designed hairpin DNA (h 1 DNA) hybridized with tDNA, subsequently recognized and cleaved by λ-Exo to set free tDNA. With the λ-Exo aided tDNA recycling, an increasing number of DNA fragments (output DNA, oDNA) were released from the digestion of h 1 DNA. Then, triggered by the hybridization of oDNA with capture DNA (cDNA), numerous biotin-labeled hairpin DNAs (h 2 DNA and h 3 DNA) could be loaded onto the photoelectrode via the HCR. Finally, avidin-labeled alkaline phosphatase (avidin-ALP) could be introduced onto the electrode by specific interaction between biotin and avidin. The ALP could catalyze dephosphorylation of phospho-L-ascorbic acid trisodium salt (AAP) to generate an efficient electron donor of ascorbic acid (AA), and thereby greatly increasing the photocurrent signal. By utilizing the proposed cascade signal amplification strategy, the fabricated PEC biosensor exhibited an ultrasensitive and specific detection of HTLV-I DNA down to 11.3 aM, and it also offered an effective strategy to detect other DNAs at ultralow levels. [ABSTRACT FROM AUTHOR]

Abstract Introduction Invariant natural killer T cells (iNKTs) are a rare but vital subset of immunomodulatory T cells and play an important role in allogeneic hematopoietic stem cell trans-plantation (HSCT). The association of donor characteristics with the number and frequency of the iNKTs subsets in allografts remains poorly understood. In this paper, we prospectively investigate the association of donor characteristics with iNKTs dose and frequency in granulocyte–colony-stimulating factor (G-CSF) mobilized marrow and peripheral blood harvests. Materials and methods 100 bone marrow (BM) units and 100 peripheral blood (PB) units from 100 healthy donors were examined. Parameters including donor age, sex, weight, height, BMI and blood count [including white blood cells (WBCs), lymphocytes and monocytes] at three time points [donor's steady state before G-CSF administration, the day of G-BM harvesting and the day of G-PB apheresis] were analyzed to explore the impact of donor characteristics on iNKTs composition in BM and PB grafts. Results Multivariate analysis showed monocyte counts before G-BM harvest could predict higher frequency of iNKTs in WBC (OR = 2.593, 95%CI: 1.128–5.961, p = 0.025), higher total CD4+ iNKTs dose (OR = 2.250, 95%CI: 1.011–5.008, p = 0.047) and higher total iNKTs dose (OR = 2.662, 95%CI: 1.187–5.970, p = 0.017) in mixture allografts. Discussion The results suggested that monocyte counts pre G-BM harvest could predict the yield of total CD4+ iNKTs and total iNKTs in mixture allografts. The male and older donors were associated with a higher dose of total CD4− iNKTs in mixture allografts. Highlights • Monocyte before G-BM harvest predicted iNKT/WBC, iNKT/T and iNKTs dose in allograft. • Weight and monocyte pre-mobilization were positively associated with iNKT/T. • Allografts from male and elder donors contained higher dose of CD4− iNKTs. • 100 G-BM and 100 G-PB units from 100 healthy donors examined in this study. [ABSTRACT FROM AUTHOR]