The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines ...revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.
Photo-degradation mechanism of MB dye using sub-10 CdS/RGO nanocomposites under visible (sun) light irradiation.
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•Sub-10 sized CdS NPs evenly embedded on RGO matrix by thermal ...decomposition method.•Single source (CdDTC2) as precursor source for sub-10 CdS NPs.•The sub-10 CdS/RGOnanocomposites showed excellent photocatalytic activity against standard textile dye solutions.•CdS/RGO nanocomposites showed good reusability after 4 cycles.
Quantum dots (QDs) sized sub-10 nanometer (nm) cadmium sulfide (CdS) nanoparticles (NPs) embedded graphene sheets photocatalyst expected significant interest owing to their tunable band gap and high surface to volume ratio. Here demonstrate a single source precursor cadmium diethyldithiocarbamate (CdDTC2) used in presence of reduced graphene oxide (RGO) as template to synthesis sub-10 nm CdS NPs embedded graphene sheet by thermal decomposition method under optimized experimental conditions. The resulting CdS sub-10 NPs modified RGO was characterized with various analytical methods including XRD, HRTEM, UV, FTIR, Raman, XPS, SEM and EDX with mapping. The incorporation of sub-10 CdS NPs uniformly loaded on both sides of RGO was observed by HRTEM micrographs. The photocatalytic performance of the CdS/RGO was studied using a standard textile dye methylene blue (MB) under direct sun light exposure. The results proved that CdS/RGO catalyst exhibit an enhanced degradation rate than the pure CdS NPs. Electrochemical impedance spectroscopic method was employed to examine the prepared CdS/RGO nanocomposites. Results illustrate to CdS species on the surface of RGO can efficiently hasten the separation and postponed the recombination rate in transfer of photo-excited charge carriers. Also, sub-10 CdS/RGO nanocomposites have high surface area and the present method can be used for the preparation of CdS/RGO in large scale.
Background : Chemosensitivity tests have been a widely discussed research topic for many years. Our group performed the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) in ...patients with advanced gastric cancer over the period from December 2012 to December 2017. By considering how the sensitivities to cisplatin (CDDP), docetaxel (DOC), paclitaxel (PTX), and CPT11 correlated with the clinical outcome, we sought mainly to verify how the CD-DST should be used.Methods : Patients with advanced gastric cancer underwent gastrectomy with lymph node dissection, and the surgical samples were retrospectively examined by the CD-DST to assess chemosensitivity in Nippon Medical School Tama Nagayama hospital. The patients went on to receive postoperative adjuvant chemotherapies either as standard adjuvant therapies or chemotherapies.CD-DST test was not performed for S1 because S-1 is a key drug commonly used in chemotherapy for gastric cancer. While oxaliplatin has also become a key drug for advanced gastric cancer recently, it was still not adopted for gastric cancer in 2012 so CD-DST test was not performed.The χ2 test was used for all statistical analyses. A p-value of <0.05 was assumed to indicate statistical significance. 3-year survival rates were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the obtained curves.Results : Seventy-seven percent (77/115) of the tumors derived from gastric cancer patients could be cultured in this study. The rate of sensitivity was 41% (30/73) for CDDP, 83% (57/69) for DOC, 83% (58/70) for PTX, and 49% (33/67) for CPT11. No correlation between CDDP sensitivity and outcome was observed in patients who underwent the CDDP. Likewise, the sensitivities to CDDP, DOC, PTX, and CPT11 were not found to be correlated with the various patient characteristics. Patients with poorly differentiated adenocarcinoma tended to be sensitive to the CDDP (P=0.051).Conclusions : No difference between CDDP sensitivity or outcome was observed in the patients administered CDDP. The CD-DST demonstrated a high rate of sensitivity to DOC and PTX in the patients studied.
Small-sized fluorescent carbon dots (CDs) are gaining increasing attention in the field of biomedical applications. The environmental and biological compatibility of positively charged CDs has been ...extensively investigated; however, the potential cytotoxicity caused by negatively and particularly neutrally charged small CDs has been significantly overlooked. In this study, we conducted a comprehensive investigation into the cellular membrane disruption effect of weakly negatively charged 3-nm CDs using a combination of various biophysical techniques. Our findings demonstrate that even at a low concentration of 0.5 μg mL−1, these CDs induce significant perturbations on the cellular membrane, resulting in increased membrane permeability due to asymmetric disruption of the bilayer structure. Furthermore, CDs exhibit distinct mechanisms at different concentrations, including prompt insertion into the bilayer at low concentrations (<20 μg mL−1) and a synergistic effect after a threshold time at high concentrations (e.g., 25–200 μg mL−1). Moreover, these CDs possess specific antibacterial properties against Acinetobacter baumannii (with a minimum inhibitory concentration of 50 μg mL−1) while showing minimal hemolytic or cytotoxic effects on mammalian cells. This study provides comprehensive insights into the biophysical aspects of cellular membrane toxicity caused by small weakly negatively charged CDs and contributes to assessing their potential biomedical applications.
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•3-nm CDs at 0.5 μg mL−1 can induce cell membrane permeabilization.•Low- and high-concentration CDs induce distinct membrane permeabilization processes.•The CDs asymmetrically disturb lipid packing in both leaflets of the membrane.•The incorporation of CDs into a membrane disrupts its electrical properties.•The CDs exhibit antibacterial ability with minimal hemolytic or cytotoxic effects.
Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE(-/-) mice ...with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)-targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E- and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI.
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•Succinic acid (>80%) was achieved from ultrasonic oxidation of furfural.•The statistical design provided the optimum conditions.•SO3H-CD-carbon showed well activity and ...recyclability.
The selective transformation of furfural (FF) into bio-based succinic acid (SA) promoted by co-existence of H2O2 and SO3H-CD-carbon catalyst was investigated using an ultrasonic system. This research was proposed on the novel catalytic system with the environmental friendly for SA production. A new SO3H-CD-carbon catalyst was synthesized via in-situ hydrothermal carbonization with sulfonation using β-cyclodextrin (CD) as a carbon source and hydroxyethylsulfonic acid as a sulfonating agent. The results showed that the synergistic effects of SO3H-CD-carbon catalyst and H2O2 on the FF oxidation had a significant importance for improving the SA yield. A highest SA yield of 81.2% was successfully achieved through the optimum conditions obtained from 2k factorial and Box-Behnken designs. The SO3H-CD-carbon catalyst also exhibited the better catalytic performance when compared with various commercial sulfonic acid catalysts such as Amberlyst-35, Nafion SAC-13 and SiO2-Tosic acid. Moreover, the spent catalyst was be easily regenerated recovering its initial density of acid sites which resulted in the well recyclability up to 13 cycles.
Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. In addition, PD-L1 has been shown to interact with B7-1 costimulatory ...molecule to inhibit T-cell responses. Extensive studies have shown that PD-1/PD-L blockade restores exhausted T cells during chronic viral infections and tumors. In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. Coadministration of sPD-1 DNA with human papilloma virus-16 E7 DNA vaccine significantly enhanced E7-specific CD8(+) T-cell responses, resulting in potent antitumor effects against E7-expressing tumors. We also found that sPD-1, codelivered with adenovirus-based vaccine, could increase antigen-specific CD8(+) T-cell responses, indicating vaccine type-independent adjuvant effect of sPD-1. In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. Codelivery of sPD-1 DNA also enhanced maturation of dendritic cells (DCs) in vivo which was accompanied by upregulation of DC maturation markers such as major histocompatibility complex class II. Taken together, our findings show that sPD-1 potently enhances codelivered antigen-specific CD8(+) T-cell responses and in vivo maturation of DCs during activation of naive CD8(+) T cells, suggesting that an immunization strategy with sPD-1 as an adjuvant can be used to increase antigen-specific T-cell immunity elicited by vaccination.
A crop rotation system combining agricultural production with phytoremediation is an economical and sustainable method of remediation of cadmium (Cd)-contaminated farmland. This study focuses on ...migration and transformation of Cd in rotation systems and the influencing factors. In a two-year field experiment, four rotation systems were evaluated: traditional rice and oilseed rape (TRO), low-Cd rice and oilseed rape (LRO), maize and oilseed rape (MO), and soybean and oilseed rape (SO). Oilseed rape is a remediation plant in rotation systems. Compared to 2020, the grain Cd concentrations of traditional rice, low-Cd rice, and maize in 2021 decreased by 73.8%, 65.7%, and 24.0% (below the safety limits), respectively. However, soybean increased by 71.4%. The LRO system featured the highest oil content of rapeseed (about 50%) and economic output/input ratio (1.34). Removal efficiency of total Cd in soil was 10.03% (TRO) > 8.3% (LRO) > 5.32% (SO) > 3.21% (MO). Crop uptake of Cd was influenced by bioavailability of soil Cd, and soil environmental factors regulated the bioavailable Cd. Redundancy analysis (RDA) indicated that soil nitrate‑nitrogen (NO3−-N) had a dominant impact on bioavailable Cd in soil, with variance contributions of 56.7% for paddy-upland (TRO and LRO) and 53.5% for dryland (MO and SO) rotation systems. The difference reflected that ammonium N (NH4+-N) was a secondary factor in paddy-upland rotations, while it was the available phosphorus (P) in dryland rotations, with variance contributions of 10.4% and 24.3%, respectively. The comprehensive evaluation of crop safety, production, economic benefits, and remediation efficiency revealed that the LRO system was efficient and more acceptable to local farmers, providing a new direction for the utilization and remediation of Cd-contaminated farmland.
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•Rotation with oilseed rape ensures food security for succeeding rice crops.•LRO had the highest economic value, oil content, and ideal Cd removal efficiency.•Soybean and oilseed rape rotation mutually promoted Cd uptake.•Soil NO3−-N is the dominant factor influencing Cd bioavailability.•Soil Cd bioavailability is decreased by increasing available P in the dryland.
The rapid increase in soil acidity coupled with the deleterious effects of cadmium (Cd) toxicity had led to a decline in worldwide agricultural production. Rice absorbs and accumulates Cd(II) from ...polluted paddy soils, increasing human health risks throughout the food chain. A 35-day hydroponic experiment with four
japonica
and four
indica
(two each of them tolerant and sensitive cultivars) was conducted in this study to investigate the adsorption and absorption of Cd(II) by rice roots as related with surface chemical properties of the roots. The results showed that the three chemical forms of exchangeable, complexed, and precipitated Cd(II) increased with the increase in Cd(II) concentration for all rice cultivars. The roots of
indica
rice cultivars carried more negative charges and had greater functional groups and thus adsorbed more exchangeable and complexed Cd(II) than those of
japonica
rice cultivars. This led to more absorption of Cd(II) by the roots and greater toxicity of Cd(II) to the roots of
indica
rice cultivars and more inhibition of Cd(II) stress on the growth of the roots and whole plants of
indica
rice cultivars compared with
japonica
rice cultivars, which was one of the main reasons for more declines in the biomass and length of
indica
rice roots and shoots than
japonica
rice cultivars. Cd(II) stress showed more toxicity to the sensitive rice cultivars and thus greater inhibition on the growth of the cultivars due to more exchangeable and complexed Cd(II) adsorbed by their roots induced by more negative charges and functional groups on the roots compared with tolerant rice cultivar for both
indica
and
japonica
, which resulted in greater decreases in the biomass and length of roots and shoots as well as chlorophyll contents of the sensitive cultivars than the tolerant cultivars. The roots of sensitive rice cultivars also absorbed more Cd(II) than tolerant rice cultivars due to the same reasons as above. These findings will provide useful references for the safe utilization and health risk prevention of Cd-contaminated paddy fields.
Summary
Fc receptors (FcR) are expressed on immune cells and bind to the Fc tail of antibodies. This interaction is essential for FcR‐mediated signaling and triggering of cellular effector functions. ...FcR activation is tightly regulated to prevent immune responses by non‐antigen bound antibodies or in the absence of ‘danger signals’. FcR activity may be modulated at the plasma membrane via cross‐talk with integrins. In addition, cytokines at the site of infection/inflammation can increase FcR avidity, a process referred to as inside‐out signaling. This regulatory mechanism has been described for FcγRI (CD64), FcγRIIa (CD32a), and FcαRI (CD89) and is also well‐known for integrins. Key cellular events during inside‐out signaling are (de)phosphorylation, clustering, cytoskeleton rearrangements, and conformational changes. The latter can be studied with antibodies that specifically recognize epitopes exposed by the active (high affinity) or inactive (low affinity) state of the FcR. These antibodies are important tools to investigate the role of FcR activation in disease settings. Research on FcR has gained momentum with the rise of monoclonal antibodies (mAb) entering the clinic for the treatment of cancer and other diseases. The clinical outcome of mAb therapy may be improved by increasing FcR avidity by cytokine stimulation.
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