Endoplasmic reticulum (ER) stress promotes tumor cell escape from immunosurveillance. However, the underlying mechanisms remain unknown. We hypothesized that ER stress induces hepatocellular ...carcinoma (HCC) cells to release exosomes, which attenuate antitumor immunity by modulating the expression of programmed death ligand 1 (PD‐L1) in macrophages. In this study, we demonstrated that expression of several ER stress markers (glucose‐regulated protein 78, activating transcription factor 6, protein kinase R–like ER kinase, and inositol‐requiring enzyme 1α) was up‐regulated in HCC tissues and negatively correlated with the overall survival and clinicopathological scores in patients with HCC. Expression of ER stress–related proteins positively correlated with CD68+ macrophage recruitment and PD‐L1 expression in HCC tissues. High‐throughput sequencing analysis identified miR‐23a‐3p as one of the most abundant microRNAs in exosomes derived from tunicamycin (TM)‐treated HCC cells (Exo‐TMs). miR‐23a‐3p levels in HCC tissues negatively correlated with overall survival. Treatment with Exo‐TMs up‐regulated the expression of PD‐L1 in macrophages in vitro and in vivo. Bioinformatics analysis suggests that miR‐23a‐3p regulates PD‐L1 expression through the phosphatase and tensin homolog (PTEN)–phosphatidylinositol 3‐kinase–protein kinase B (AKT) pathway. This notion was confirmed by in vitro transfection and coculture experiments, which revealed that miR‐23a‐3p inhibited PTEN expression and subsequently elevated phosphorylated AKT and PD‐L1 expression in macrophages. Finally, coculture of T cells with Exo‐TM–stimulated macrophages decreased CD8+ T‐cell ratio and interleukin‐2 production but increased T‐cell apoptosis in vitro. Conclusion: ER‐stressed HCC cells release exosomes to up‐regulate PD‐L1 expression in macrophages, which subsequently inhibits T‐cell function through an exosome miR‐23a–PTEN–AKT pathway. Our findings provide insight into the mechanism how tumor cells escape from antitumor immunity.
Microbial biofilms can be both cause and cure to a range of emerging societal problems including antimicrobial tolerance, water sanitation, water scarcity and pollution. The identities of ...extracellular polymeric substances (EPS) responsible for the establishment and function of biofilms are poorly understood. The lack of information on the chemical and physical identities of EPS limits the potential to rationally engineer biofilm processes, and impedes progress within the water and wastewater sector towards a circular economy and resource recovery. Here, a multidisciplinary roadmap for addressing this EPS identity crisis is proposed. This involves improved EPS extraction and characterization methodologies, cross-referencing between model biofilms and full-scale biofilm systems, and functional description of isolated EPS with in situ techniques (e.g. microscopy) coupled with genomics, proteomics and glycomics. The current extraction and spectrophotometric characterization methods, often based on the principle not to compromise the integrity of the microbial cells, should be critically assessed, and more comprehensive methods for recovery and characterization of EPS need to be developed.
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•Extracellular polymeric substances feature in key societal problems (clinical, environmental).•Methods and standards of EPS recovery and characterization need to be critically assessed.•More emphasis should be placed on methods that enable identification (chemical and function).•Integrated and multi-displinary analyses are required on biofilms and EPS isolates.•Will improve biofilm management and enable a more circular economy in water and waste.
•The strength of the alloy increases first and then decreases with the aging temperature increasing.•With increasing aging time, the RA of the alloy continuous decreases at 650°C.•The steady-state ...condition of RA can be reached after aging for 16h and 8h at 700°C and 750°C.•The loss of ductility is mainly attributed to the precipitation of α2 phase after aging treatment.
The effect of aging temperature between 650°C and 750°C for different aging times on the tensile properties and microstructures of Ti60 alloy were studied. The results show that the strength of the alloy increases first and then decreases with the aging temperature increases from 650°C to 750°C. The reduction of area of the alloy is more sensitive to the aging time than elongation. With increasing aging temperature and time, the volume fracture and grain size of silicides and α2 phase increase gradually. The silicides have the strengthen effect on the Ti60 alloy, but the effect weakens when the silicides grow up. The loss of ductility is mainly attributed to the precipitation of α2 phase after aging treatment.
•The CeO2–ZrO2 hollow nanospheres had strong affinity and selectivity to arsenic.•The adsorbent showed excellent ability to remove arsenic at low concentrations.•The adsorption mechanism was ...investigated by FTIR and XPS.•The adsorbent showed potential application for drinking water treatment.
Arsenic contaminated natural water is commonly used as drinking water source in some districts of Asia. To meet the increasingly strict drinking water standards, exploration of efficient arsenic removal methods is highly desired. In this study, hierarchically porous CeO2–ZrO2 nanospheres were synthesized, and their suitability as arsenic sorbents was examined. The CeO2–ZrO2 hollow nanospheres showed an adsorption capacity of 27.1 and 9.2mgg−1 for As(V) and As(III), respectively, at an equilibrium arsenic concentration of 0.01mgL−1 (the standard for drinking water) under neutral conditions, indicating a high arsenic removal performance of the adsorbent at low arsenic concentrations. Such a great arsenic adsorption capacity was attributed to the high surface hydroxyl density and presence of hierarchically porous network in the hollow nanospheres. The analysis of Fourier transformed infrared spectra and X-ray photoelectron spectroscopy demonstrated that the adsorption of arsenic on the CeO2–ZrO2 nanospheres was completed through the formation of a surface complex by substituting hydroxyl with arsenic species. In addition, the CeO2–ZrO2 nanospheres were able to remove over 97% arsenic in real underground water with initial arsenic concentration of 0.376mgL−1 to meet the guideline limit of arsenic in drinking water regulated by the World Health Organization without any pre-treatment and/or pH adjustment.
Isothermal compression testing of as-cast Ti60 titanium alloy is carried out at the deformation temperature range of 970–1120°C with 50°C intervals, strain rate range of 0.01–10s−1 and height ...reduction of 75%. The hot deformation behavior of as-cast Ti60 titanium alloy is characterized based on the analysis of the stress–strain behavior, kinetics and the processing map. The constitutive equation of as-cast Ti60 titanium alloy is established, which describes the flow stress as a function of the strain rate and deformation temperature. The apparent activation energies are calculated to be 574.8kJ/mol in the α+β two-phase field and 194.0kJ/mol in the β single-phase field, respectively. Based on the dynamic material model and the Prasad's instability criterion, the processing maps for the alloy are constructed at strains of 0.4 and 0.7. The maps exhibit a stable domain in the temperature range of 970–1120°C and strain rate range of 0.01–0.1s−1 with two peaks in power dissipation of 70% and 70%, occurring at 970°C/0.01s−1 and 1120°C/0.01s−1, respectively. The high efficiency values of power dissipation indicate dynamic recrystallization in these fields, and dynamic recrystallization fraction increases with increasing deformation temperature. Therefore, the optimal processing condition for cogging procedure of as-cast Ti60 titanium alloy is 1120°C/0.01s−1. Moreover, the material also undergoes flow instabilities domain occurring at strain rates higher than 1s−1. This instability domain exhibits flow localization and cracking which should be avoided during hot processing in order to obtain the satisfactory properties.
Aims: The lipid reference intervals (RIs) that are currently used for children in China are not based on studies of the local population and normally do not consider age or gender differences. This ...study aimed to establish age- and sex-specific RIs for the fasting serum lipid levels in the pediatric population aged 0 – 15 years in Nanjing, China.Methods: 5,866 children aged 3 days to ＜15 years were recruited to establish serum lipid RIs, and the triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed using the Roche cobas702 automatic biochemical analyzer. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nHDL-C) levels were calculated (LDL-C=TC−HDL-C−TG/5, and nHDL-C=TC−HDL-C). Smoothed percentile curves for the boys and girls were generated using the LMS method. Age- and sex-specific RIs were the determined according to the methods recommended by the Clinical and Laboratory Standards Institute EP28-A3c guidelines.Results: This study showed that the serum lipid levels varied considerably throughout childhood and adolescence, with sex differences, especially in infants aged less than 2 years and puberty. Based on the Harris-Boyd method, sex partitions were required for ages ＜6 months in the TC indicator and for ages ≤ 28 days in LDL-C and nHDL-C. Age partitions were also required for all serum lipid parameters.Conclusions: We established age- and sex-specific RIs for TG, TC, HDL-C, LDL-C, and nHDL-C parameters in children aged 0 days to ＜15 years in Nanjing, China. These data are thus considered to be useful for the screening of dyslipidemia in children and adolescents.
Immunosuppression is a significant factor in the progression of tumor invasion and metastasis. Melatonin, a well-known hormone, has certain cytotoxic and immune regulatory effects to inhibit tumor ...function. Exosomes are small membrane vesicles released by many kinds of cells, which contain different macromolecules, such as mRNAs and microRNAs (miRNAs), and proteins that can mediate communications between cells. Tumor-derived exosomes may cause immunosuppression, however, it is unknown whether melatonin can attenuate an immunosuppressive status by altering the function of tumor-derived exosomes. In the present study, we evaluated the effects of hepatocellularcarcinoma-derived exosomes (Exo-con) and exosomes derived from hepatocellularcarcinoma cells treated with 0.1 mM melatonin (Exo-MT), on the expression of inflammatory factors and programmed death ligand 1(PD-L1) by co-culturing Exo-con and Exo-MT, respectively, with macrophages differentiated from THP-1 cells or RAW264.7 cells. Our
results indicate that Exo-MT can downregulate the expression of PD-L1 on macrophages while Exo-con can upregulate the expression of PD-L1 through flow cytometry and immunofluorescence analysis. In addition, Exo-con upregulates the secretion of cytokines, such as IL-6, IL-10, IL-1β, and TNF-α in macrophages. Accordingly, Exo-MT could attenuate the high expression of these inflammatory cytokines. Furthermore,
experiments confirmed the results found
. PD-L1 expression and cytokine secretion were lower in the Exo-MT group compared with those in the Exo-con group. Working to identify a specific mechanism, our research shows that Exo-MT decreases STAT3 activation compared to the Exo-con group. In summary, we found exosomes from melatonin treated hepatocellularcarcinoma cells alters the immunosupression status through STAT3 pathway in macrophages. Our study may provide a new avenue to investigate the mechanisms of melatonin in regulating an immunosuppressive status.
Extracellular polymeric substances（EPS） are organic metabolic compounds excreted by microorganisms. They largely impact microbial aggregate structures and functions.Extracellular polysaccharides（EP） ...in EPS are responsible for the formation of microbial aggregates. In this work, we successfully separated and characterized EP from EPS of the bacterium Bacillus megaterium TF10. Extraction of EP from EPS was optimized using Sevag＇s reagent. Chemical characteristics, functional groups, and molecular weight（MW） distribution of EP were compared with the harvested EPS and soluble microbial products（SMP）. We found that the polymers of lower MW and free proteins were successfully removed by Sevag＇s reagent. The higher MW components of EPS were predominantly polysaccharides,while the polymers of lower MW tended to secrete to the supernatant and were described as SMP. A part of the proteins in the EP was polysaccharide-bonded. Our results can be further used in elucidating the complex flocculation mechanisms in which EP play a major role.
As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA ...sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increased HLA-DQA1high classic monocytes and PTGS2high monocytes in advanced gout and overactivated CD8+ T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.
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•Systemic inflammation in remission gout with MSU crystal deposition is observed•HLA-DQA1high CD14+ monocytes boost immune responses and bone erosion in advanced gout•CD8+ T cells are overactivated in remission gout at intercritical and advanced stage•Upregulation of PTGS2 in monocyte subtypes promotes AA metabolism in advanced gout
Gu et al. find systemic inflammation and immune responses in remission gout with MSU crystal deposition by scRNA-seq analysis of PBMCs from gout patients and healthy volunteers. The findings reveal MSU crystal-related immune cell expression changes, which provide potential anti-inflammatory therapeutic targets in remission gout.
Global efforts to restore the world’s degraded croplands require knowledge on the degree and extent of accelerated soil organic carbon (SOC) loss induced by soil erosion. However, the methods for ...assessing where and to what extent erosion takes place are still inadequate for precise detection of erosion hotspots at high spatial resolution. Drawing on recent advances in multitemporal Sentinel-2 remote sensing to create a bare soil composite that reflects erosion-induced variations in soil spectral signatures, this study attempted to develop a spectra-based soil erosion mapping approach to pinpoint eroded hotspots in a typical catchment located in the black soil region of northeast China as characterized by undulating landscapes. We built a ground-truth dataset consisting of three classes of soils representing Severe, Moderate and Low erosion intensity because of their inter-class contrasts in estimated erosion rates from 137Cs tracing. The spectral separability of different erosion classes was first tested by a combined principal component and linear discriminant analysis (PCA-LDA) against laboratory hyperspectral data and then validated against Sentinel-2-derived broadband spectra. The results show that PCA-LDA produced excellent classification accuracy (Kappa coefficient > 0.9) for both data sources and even more so for Sentinel-2 spectra, highlighting the effectiveness of the multitemporal approach to extract bare soil pixels. Further investigations into the spectral curves enabled identification of distinctive spectral features representative of shifting soil albedo and biochemical composition due to erosion-induced SOC mobilization. A classification scheme comprising the spectral features was applied to the Sentinel-2 bare soil composite for pixel-wise soil erosion mapping, in which 15.9% of the cropland area was detected as erosion hotspots, while the Moderate class occupied 65.4%. Comparing the erosion map to a NDVI map demonstrated the negative impact of soil erosion on crop growth from a spatial perspective, highlighting the potential of the proposed approach to aid targeted cropland management for food security and climate.
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