Radiofrequency ablation (RFA) has been shown to elicit tumor-specific T-cell immune responses, but is not sufficient to prevent cancer progression. Here, we investigated immune-suppressive mechanisms ...limiting the efficacy of RFA.
We performed a retrospective case-controlled study on patients with synchronous colorectal cancer liver metastases who had received primary tumor resection with or without preoperative RFA for liver metastases. Tumor-infiltrating T cells and tumoral PD-L1 expression in human colorectal cancer tissues were analyzed by immunohistochemistry. T-cell immune responses and PD-1/PD-L1 expression were also characterized in an RFA mouse model. In addition, the combined effect of RAF and PD-1 blockade was evaluated in the mouse RFA model.
We found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary human colorectal tumors. Using mouse tumor models, we demonstrated that RFA treatment of one tumor initially enhanced a strong T-cell-mediated immune response in tumor. Nevertheless, tumor quickly overcame the immune responses by inhibiting the function of CD8(+) and CD4(+) T cells, driving a shift to higher regulatory T-cell to Teff ratio, and upregulating PD-L1/PD-1 expression. Furthermore, we established that the combined therapy of RFA and anti-PD-1 antibodies significantly enhanced T-cell immune responses, resulting in stronger antitumor immunity and prolonged survival.
The PD-L1-PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting.
Carbon based porous materials have low energy storage capacity, poor utilization rate and poor electrochemical storage performance. Therefore, this paper proposes an analytical method for ...electrochemical energy storage performance of carbon based porous materials based on high temperature decomposition. By analyzing the structure of carbon based porous materials, the parameters affecting the properties of low-carbon porous materials were obtained. The chemical properties of carbon based porous materials were studied. The carbon based porous materials were modified by high-temperature decomposition method to improve the power storage capacity of carbon based porous materials. The experimental results show that the high temperature decomposition of carbon based porous materials has strong energy storage performance, which can effectively improve the energy storage capacity of carbon based porous materials.
Study on positive and negative materials of high performance Ion batteries is presented in this manuscript. In recent years, sodium ion batteries have developed rapidly, and a number of key materials ...with electrochemical activity have emerged. Among them, the transition metal oxide as a core sodium ion battery positive electrode shows considerable sodium-embedded capacity, but the capacity decays severely during continuous cycling. This paper studies the novel findings on the mentioned issues to provide the new perspectives for assisting the future research.
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that contribute to tumorigenesis and metastasis due to their ability to degrade the extracellular matrix (ECM) and basement ...membrane. In despite of many reports in other solid tumors, the role of membrane type-2 MMP (MT2-MMP) in gastric cancer (GC) remains to be elucidated. The aim of this study was to investigate MT2-MMP expression in human GC tissue microarray (TMA) samples using immunohistochemistry (IHC). We found that MT2-MMP expression in tumor tissues was significantly higher compared to peritumoral tissues (P < 0.01). However, there were no statistically significant differences between MT2-MMP expression and clinicopathological parameters. In addition, univariate and multivariate Cox regression analysis showed GC patients with high MT2-MMP expression have poor overall survival (OS) compared to patients with low MT2-MMP expression (P = 0.013, P = 0.040, respectively). In conclusion, MT2-MMP is involved in GC invasion and metastasis and may serve as an independent prognostic factor for GC patients.
Dematiaceous Fonsecaea monophora is one of the major pathogens of chromoblastomycosis. It has been well established that melanization is catalyzed by the type I polyketide synthase (PKS) in F. ...monophora. Multidomain protein Type I PKS is encoded by six genes, in which the last enzyme thioesterase (TE) catalyzes the cyclization and releases polyketide. Two PKS genes AYO21_03016 (pks1) and AYO21_10638 have been found in F. monophora and both PKS loci have the same gene arrangement but the TE domain in AYO21_10638 is truncated at 3'- end. TE may be the key enzyme to maintain the function of pks1. To test this hypothesis, we constructed a 3'-end 500 bp deletion mutant of AYO21_03016 (Δpks1-TE-C500) and its complemented strain. We profiled metabolome of this mutant and analyzed the consequences of impaired metabolism in this mutant by fungal growth in vitro and by pathogenesis in vivo. Compared with wild-type strain, we found that the mutant repressed pks1 expression and other 5 genes expression levels were reduced by more than 50%, perhaps leading to a corresponding melanin loss. The mutant also reduced sporulation and delayed germination, became vulnerable to various environmental stresses and was less resistance to macrophage or neutrophil killings in vitro, and less virulence in mice footpad model. Metabolomic analysis indicated that many metabolites were remarkably affected in Δpks1-TE-C500, in particular, an increased nicotinamide and antioxidant glutathione. In conclusion, we confirmed the crucial role of C-terminal TE in maintaining fully function of pks1 in F. monophora. Deletion of TE negatively impacts on the synthesis of melanin and metabolites that eventually affect growth and virulence of F. monophora. Any potential inhibitor of TE then could be a novel antifungal target for drug development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two-dimensional (2D) materials, such as graphene, transition metal dichalcogenides, and black phosphorus, have attracted intense interest for applications in ultrafast pulsed laser generation, owing ...to their strong light–matter interactions and large optical nonlinearities. However, due to the mismatch of the bandgap, many of these 2D materials are not suitable for applications at near-infrared (NIR) waveband. Here, we report nonlinear optical properties of 2D α-Mo2C crystals and the usage of 2D α-Mo2C as a new broadband saturable absorber for pulsed laser generation. It was found that 2D α-Mo2C crystals have excellent saturable absorption properties in terms of largely tunable modulation depth and very low saturation intensity. In addition, ultrafast carrier dynamic results of 2D α-Mo2C reveal an ultrashort intraband carrier recovery time of 0.48 ps at 1.55 μm. By incorporating 2D α-Mo2C saturable absorber into either an Er-doped or Yb-doped fiber laser, we are able to generate ultrashort pulses with very stable operation at central wavelengths of 1602.6 and 1061.8 nm, respectively. Our experimental results demonstrate that 2D α-Mo2C can be a promising broadband nonlinear optical media for ultrafast optical applications.
Summary
Bone marrow mesenchymal stem cells (BMSCs) inhibit immune cell responsiveness, and especially of T lymphocytes. We showed that BMSCs markedly inhibited the proliferation and cytokine ...production by CD8+ T cells by a cell‐to‐cell contact phenomenon and secretion of soluble factors. BMSCs down‐regulate the expression of natural killer group 2, member D protein (NKG2D) receptors on CD8+ T cells when co‐cultured with them. Moreover, CD8+ T cells that express low levels of NKG2D had impaired proliferation after triggering by a mitogen. The major histocompatibility complex (MHC) class I chain‐related (MIC) A/B molecule, which is a typical ligand for NKG2D, was expressed on BMSCs, and caused dampening of cell proliferation. Monoclonal antibody blocking experiments targeted to MIC A/B impaired CD8+ T cell function, as evaluated by proliferation and cytokine production. In addition, the production of prostaglandin E2 (PGE2), indoleamine 2, 3‐dioxygenase (IDO) and transforming growth factor (TGF)‐β1 were increased when BMSCs were co‐cultured with CD8+ T cells. The addition of specific inhibitors against PGE2, IDO and TGF‐β partially restored the proliferation of CD8+ T cells. Our results suggest that BMSCs suppress CD8+ T cell‐mediated activation by suppressing NKG2D expression and secretion of PGE2, IDO and TGF‐β. Our observations further confirm the feasibility of BMSCs as a potential adoptive cellular therapy in immune‐mediated diseases such as graft‐versus‐host disease (GVHD).
Background: Stroke is a major contributor to disability and death worldwide. Studies have demonstrated that inflammasome/pyroptosis and its mediated inflammatory response are important factors ...aggravating brain injury after stroke. We aimed to investigate and map the knowledge structure and global trends on inflam-masome/pyroptosis in stroke.Methods: All relevant documents were obtained from the Web of Science on 5 June 2023. Bibliometric visualization diagrams were created using VOSviewer and CiteSpace. Excel was used for statistical analysis and drawing graphs.Results: A total of 1106 publications were included, with more articles published each year, especially since 2014. China (740 papers), Zhejiang University (57 papers), Wang J (25 papers), and the Journal of Neuroinflammation (45 papers) were the most productive countries, institutions, authors, and journals, respectively. The United States was the country with highest centrality (0.56) and total link strength (171), and all of the top 10 institutions were in China. China and the U.S. cooperated closely. The centralities of the top 10 authors were all lower than 0.01; no leader has yet emerged in this field. “NLRP3 inflammasome” ranked first with 447 occurrences among 2136 keywords, of which 56 terms appeared more than 10 times when categorized into four clusters: cluster 1 (inflammation), cluster 2 (pyroptosis), cluster 3 (NLRP3 inflammasome), and cluster 4 (neuroinflammation). The studies focused on the mechanisms of inflammasome/pyroptosis in stroke were mainly limited to cell and animal experiments.Conclusion: Interest in inflammasome/pyroptosis in stroke is progressively increasing. The NLRP3 inflammasome is the most extensively studied and has been a research hotspot. The mechanisms of cell death in stroke are complex and future studies are needed to strengthen the clinical research on the relationship between pyroptosis-related processes and stroke, determine at which stage NLRP3 inflammasome activation, and clarify the detailed mechanism of NLRP3 in stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report a unique phenomenon, the opposite color response of a giant polyoxometalate, (NH
)
Mo
O
(CHCOO)
(H
O)
(Mo
), to the existing states of human papillomavirus (HPV) major capsid protein, ...L1-pentamer (L1-p), and virus-like particles (VLPs). The color responses originate from the different assembly forms between Mo
and the capsid protein. The latter were inspected and separated by using CsCl gradient centrifugation, and validated in detail by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE), dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging. Furthermore, the intrinsic mechanisms were investigated in-depth by using XPS-based semi-quantitative analysis and well-designed peptides, revealing the critical points of L1 that determine the charge-transfer ratio between Mo(V) to Mo(VI), and consequently, the levels of Mo
hypochromic in different assemblies. Such a unique phenomenon is significant as it supplies a colorimetry approach to distinguish the existing states of the HPV capsid protein and would be significant in the quality assay of the HPV vaccine and existing states of other viruses in the future.
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