Antibody-based cancer immunotherapy by targeting regulatory T cells

Regulatory T cells (Tregs) are among the most abundant suppressive cells, which infiltrate and accumulate in the tumor microenvironment, leading to tumor escape by inducing anergy and immunosuppression. Their presence has been correlated with tumor progression, invasiveness and metastasis. Targeting tumor-associated Tregs is an effective addition to current immunotherapy approaches, but it may also trigger autoimmune diseases. The major limitation of current therapies targeting Tregs in the tumor microenvironment is the lack of selective targets. Tumor-infiltrating Tregs express high levels of cell surface molecules associated with T-cell activation, such as CTLA4, PD-1, LAG3, TIGIT, ICOS, and TNF receptor superfamily members including 4-1BB, OX40, and GITR. Targeting these molecules often attribute to concurrent depletion of antitumor effector T-cell populations. Therefore, novel approaches need to improve the specificity of targeting Tregs in the tumor microenvironment without affecting peripheral Tregs and effector T cells. In this review, we discuss the immunosuppressive mechanisms of tumor-infiltrating Tregs and the status of antibody-based immunotherapies targeting Tregs

Age-specific reference values for low psoas muscle index at the L3 vertebra level in healthy populations: A multicenter study

Background and aimsThe progressive and generalized loss of skeletal muscle mass, strength and physical function is defined as sarcopenia. Sarcopenia is closely related to the prognosis of patients. Accurate diagnosis and adequate management of sarcopenia are crucial. The psoas muscle mass index taken at the third lumbar vertebra (L3-PMI, cm2/m2) is one of the established methods for evaluating skeletal muscle mass. However, the cutoff values of L3-PMI for diagnosis of sarcopenia are not yet to be clarified in Asian populations. We attempted to establish reference values for low L3-PMI that would be suitable for defining sarcopenia in the Northern Chinese population.MethodsThis was a retrospective, multicenter cross-sectional study. A search of abdominal CT imaging reports was conducted in four representative cities in northern China. Transverse CT images were measured using the analysis software Slice-O-Matic. Low psoas muscle index was defined as the 5th percentile or mean-2SD of the study group.Results1,787 healthy individuals in the study were grouped by age. The sex and number of people in each group were similar. L3-PMI had a negative linear correlation with age, and a strong correlation with the skeletal muscle index taken at the third lumbar vertebrae (L3-SMI, cm2/m2). The L3-PMI reference values in males were 5.41 cm2/m2 for 20–29 years, 4.71 cm2/m2 for 30–39 years, 4.65 cm2/m2 for 40–49 years, 4.10 cm2/m2 for 50–59 years and 3.68 cm2/m2 for over 60 years by using 5th percentile threshold. Similarly, the reference values in females were 3.32, 3.40, 3.18, 2.91, and 2.62 cm2/m2. When using mean-2SD as the reference, the values for each age group were 4.57, 4.16, 4.03, 3.37, and 2.87 cm2/m2 for males and 2.79, 2.70, 2.50, 2.30, and 2.26 cm2/m2 for females, respectively.ConclusionWe defined the reference values of age-specific low skeletal muscle mass when simply evaluated by L3-PMI. Further studies about the association of sarcopenia using these reference values with certain clinical outcomes or diseases are needed

Immune-Enhancing Activity of Aqueous Extracts from Artemisia rupestris L. via MAPK and NF-kB Pathways of TLR4/TLR2 Downstream in Dendritic Cells

Artemisia rupestris L. has long been used as a traditional herbal medicine owing to its immunomodulatory activity. Aqueous extracts of Artemisia rupestris L. (AEAR) contain the main functional component and can activate the maturation of dendritic cells (DCs) and enhance the adaptive immunity as the adjuvant against infections. To explore the underlying mechanism of immunomodulatory activities of AEAR, DCs were produced from bone-marrow cells of mice and the effects of AEAR on cell viability were assessed by the Cell Counting Kit 8 (CCK8) method and annexin V/propidium iodide staining assays. Then, the effects of AEAR on the morphology, maturation, and function of DCs were detected using a microscope, flow cytometry-based surface receptor characterization, and endocytosis assays. The secretion levels of cytokines were then analyzed with enzyme-linked immunosorbent assay (ELISA). The activation state of DCs was evaluated by the mixed lymphocyte reaction (MLR). The activity of MAPKs and NF-κB pathways, which were involved in the regulation of AEAR on DCs, was further detected by Western blot. AEAR did not have a cytotoxic effect on DCs or mouse splenocytes. AEAR remarkably enhanced the phenotypic maturation of DCs and promoted the expression of costimulatory molecules and the secretion of cytokines in DCs. AEAR also significantly decreased the phagocytic ability of DCs and augmented the abilities of DCs to present antigens and stimulate allogeneic T-cell proliferation. Simultaneously, AEAR potently activated toll-like receptor (TLR)4-/TLR2-related MAPKs and induced the degradation of IκB and the translocation of NF-κB. In short, AEAR can profoundly enhance the immune-modulating activities of DCs via TLR4-/TLR2-mediated activation of MAPKs and NF-κB signaling pathways and is a promising candidate immunopotentiator for vaccines

Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo.

A safe and effective vaccine adjuvant is important in modern vaccines. Various Chinese herbal polysaccharides can activate the immune system. Cistanche deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo. In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments. In addition, its immunomodulatory activity was also observed in mice. WPCD effectively improved the titers of IgG, IgG1 and IgG2a and markedly enhanced the proliferation of T and B cells, the production of IFN-γ and IL-4 in CD4+ T cells and the expression level of IFN-γ in CD8+ T cells better than Alum. Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and CD80 on DCs in spleen and down-regulate the Treg frequency. The study suggests that polysaccharides of Cistanche deserticola are a safe and effective vaccine adjuvant for eliciting both humoral immunity and cellular immunity by activating DCs via TLR4 signaling pathway

Projecting potential evapotranspiration change and quantifying its uncertainty under future climate scenarios: A case study in southeastern Australia

Projecting the likely change of potential evapotranspiration (ETp) under future climate scenarios is crucial for quantifying the impacts of climate change on the hydrologic cycle and aridity conditions. However, there are different sources of uncertainty in projecting future ETp that may arise from global climate models (GCMs), emission scenarios, and multiple ETp models used. In this study, we developed three random forest-based (RF-based) ETp models with solar radiation and air temperature at eight climatic stations in southeastern Australia. With Penman model as the benchmark, their performance was firstly compared with four empirical models (Jensen-Haise, Makkink, Abtew, and Hargreaves), which requires the same meteorological inputs. In general, the RF-based ETp models showed better performance in ETp estimates across all stations, with coefficients of determination (R2) ranging from 0.68 to 0.92, root mean square errors (RMSE) ranging from 0.58 mm day−1 to 1.46 mm day−1, and relative mean bias errors (rMBE) ranging from −16.10% to 9.73%. The RF-based and empirical models were then used to project future ETp for the eight stations based on statistically downscaled daily climatic data from 34 GCMs under two different representative concentration pathways (RCP4.5 and RCP8.5). All models indicated that ETp was likely to increase at the eight stations. The ensemble increases of mean ETp across eight stations ranged from 33 mm year−1 (2.1%, 2040s) to 129 mm year−1 (9.2%, 2090s) and from 43 mm year−1 (2.8%, 2040s) to 248 mm year−1 (17.6%, 2090s) under RCP4.5 and under RCP8.5, respectively. In addition, we also quantified uncertainties in ETp projections originating from ETp models, GCMs, RCPs, and their combined effects using the analysis of variance (ANOVA) method. Results showed that RCP-related uncertainty contributed the most to projected ETp uncertainty (around 40% for most stations) while GCM-related and ETp model-related uncertainties accounted for roughly equal amounts of projected ETp uncertainty (10%–30%). This study demonstrated the better performance of RF-based ETp models. It is advisable to use multiple ETp models driven by various GCMs under different RCPs to produce reliable projections of future ETp

Synthesis and Applications of Silver Nanowires for Transparent Conductive Films

Flexible transparent conductive electrodes (TCEs) are widely applied in flexible electronic devices. Among these electrodes, silver (Ag) nanowires (NWs) have gained considerable interests due to their excellent electrical and optical performances. Ag NWs with a one-dimensional nanostructure have unique characteristics from those of bulk Ag. In past 10 years, researchers have proposed various synthesis methods of Ag NWs, such as ultraviolet irradiation, template method, polyol method, etc. These methods are discussed and summarized in this review, and we conclude that the advantages of the polyol method are the most obvious. This review also provides a more comprehensive description of the polyol method for the synthesis of Ag NWs, and the synthetic factors including AgNO3 concentration, addition of other metal salts and polyvinyl pyrrolidone are thoroughly elaborated. Furthermore, several problems in the fabrication of Ag NWs-based TCEs and related devices are reviewed. The prospects for applications of Ag NWs-based TCE in solar cells, electroluminescence, electrochromic devices, flexible energy storage equipment, thin-film heaters and stretchable devices are discussed and summarized in detail

Enhanced Red Emissions of Europium (III) Chelates in RNA–OTMA Complexes

In recent years, biopolymers have been widely used in optoelectronic devices because of their unique structure, novel optical and physical properties. In this paper, novel RNA-based photofunctional materials were fabricated by associating an RNA–OTMA (octadecyltrimethylammonium chloride) lipid complex with a luminescent Eu (III) complex. The fluorescence emission intensity, fluorescence quantum yield and fluorescence lifetime were characterized in both solution and thin film states, and the interaction between the RNA–OTMA lipid complex and Eu (III) complexes was analyzed. This study suggests that the luminescence performance of the Eu (III) complexes doped with RNA–OTMARNA–OTMA was significantly enhanced compared with those of the complex in a conventional poly (methyl methacrylate) matrix, thereby providing an important basis for the application of biomaterials in optoelectronic devices

Effects of WPCD on the splenocyte proliferation.

<p>Single splenocyte was isolated from mice immunized on day 21 after the first vaccination and splenocyte proliferation was determined by the MTT assay and expressed as SI. OVA-antigen stimulated splenocyte proliferation <b>(A)</b>. OVA^323-339-antigen stimulated splenocyte proliferation <b>(B).</b> ConA-mitogen stimulated splenocyte proliferation <b>(C)</b>. LPS-mitogen splenocyte proliferation <b>(D)</b>. Data are expressed as mean ± SD (n = 5) from 3 independent experiments. *<i>P</i> < 0.05, ** <i>P</i> < 0.01 compared with the OVA group; ^#<i>P</i> < 0.05, ^##<i>P</i> < 0.01 compared with the OVA/Alum group.</p

Effects of subcutaneous administration of WPCD on the mean body weight.

<p>Effects of subcutaneous administration of WPCD on the mean body weight.</p