Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. Here, we compared the single-cell and spatial landscapes of 20 CTL-rich HCCs with distinct prognoses using multiplexed in situ staining and validated the prognostic value of myeloid spatial patterns in a cohort of 386 patients.
View Article and Find Full Text PDFBackground: The potential of preoperative CT in the assessment of myeloid immune response and its application in predicting prognosis and immune-checkpoint therapy outcomes in hepatocellular carcinoma (HCC) has not been explored.
Methods: A total of 165 patients with pathological slides and multi-phase CT images were included to develop a radiomics signature for predicting the imaging-based myeloid response score (iMRS). Overall survival (OS) and recurrence-free survival (RFS) were assessed according to the iMRS risk group and validated in a surgical resection cohort ( = 98).
Background: Sex hormones and their related receptors have been reported to impact the development and progression of tumors. However, their influence on the composition and function of the tumor microenvironment is not well understood. We aimed to investigate the influence of sex disparities on the proliferation and accumulation of macrophages, one of the major components of the tumor microenvironment, in hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2024
The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis.
View Article and Find Full Text PDFThe spleen is an important site of hematopoietic stem/progenitor cell (HSPC) preconditioning and tumor-promoting myeloid cell generation in cancer, but the regulatory mechanism remains unclear. Here, we found that PKR-like endoplasmic reticulum kinase (PERK) mediated HSPC reprogramming into committed MDSC precursors in the spleen via PERK-ATF4-C/EBPβ signaling. Pharmacological and genetic inhibition of this pathway in murine and human HSPCs prevented their myeloid descendant cells from becoming MDSCs even with subsequent exposure to tumor microenvironment (TME) factors.
View Article and Find Full Text PDFBACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC.
View Article and Find Full Text PDFBackground: Biodegradation of toxic organic dye using nanomaterial-based microbial biocatalyst is an ecofriendly and promising technique.
Materials And Methods: Here, we have investigated the novel properties of functionalized Au-Ag bimetallic nanoparticles using extremophilic proteins (Drp-Au-AgNPs) and their degradation efficiency on the toxic triphenylmethane dye malachite green (MG).
Results And Discussion: The prepared Drp-Au-AgNPs with an average particle size of 149.
Understanding the synthetic mechanisms and cell-nanoparticle interactions of biosynthesized and functionalized gold nanoparticles (AuNPs) using natural products is of great importance for developing their applications in nanomedicine. In this study, we detailed the biotransformation mechanism of Au(III) into AuNPs using a hydroxylated tetraterpenoid deinoxanthin (DX) from the extremophile Deinococcus radiodurans. During the process, Au(III) was rapidly reduced to Au(I) and subsequently reduced to Au(0) by deprotonation of the hydroxyl head groups of the tetraterpenoid.
View Article and Find Full Text PDFIron acquisition by bacteria is well studied, but iron export from bacteria is less understood. Herein, we identified dr1440 with a P-type ATPase motif as a potential exporter of iron from Deinococcus radiodurans, a bacterium known for its extreme resistance to radiation and oxidants. The DR1440 was located in cell membrane as demonstrated by fluorescence labelling analysis.
View Article and Find Full Text PDFBackground: Biosynthesis of noble metallic nanoparticles (NPs) has attracted significant interest due to their environmental friendly and biocompatible properties.
Methods: In this study, we investigated syntheses of Au, Ag and Au-Ag bimetallic NPs using protein extracts of , which demonstrated powerful metal-reducing ability. The obtained NPs were characterized and analyzed by various spectroscopy techniques.
Here we identified a functional MazEF-dr system in the exceptionally stress-resistant bacterium . We showed that overexpression of the toxin MazF-dr inhibited the growth of . The toxic effect of MazF-dr was due to its sequence-specific endoribonuclease activity on RNAs containing a consensus 5'ACA3', and it could be neutralized by MazE-dr.
View Article and Find Full Text PDFThe translocation and assembly module (TAM) in bacteria consists of TamA and TamB that form a complex to control the transport and secretion of outer membrane proteins. Herein, we demonstrated that the DR_1462-DR_1461-DR_1460 gene loci on chromosome 1 of Deinococcus radiodurans, which lacks tamA homologs, is a tamB homolog (DR_146T) with two tamB motifs and a DUF490 motif. Mutation of DR_146T resulted in cell envelope peeling and a decrease in resistance to shear stress and osmotic pressure, as well as an increase in oxidative stress resistance, consistent with the phenotype of a surface layer (S-layer) protein SlpA (DR_2577) mutant, demonstrating the involvement of DR_146T in maintenance of cell envelope integrity.
View Article and Find Full Text PDFis an extreme bacterium known for its high resistance to stresses including radiation and oxidants. The ability of to reduce Au(III) and biosynthesize gold nanoparticles (AuNPs) was investigated in aqueous solution by ultraviolet and visible (UV/Vis) absorption spectroscopy, electron microscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). efficiently synthesized AuNPs from 1 mM Au(III) solution in 8 h.
View Article and Find Full Text PDFMater Sci Eng C Mater Biol Appl
June 2016
Uncontrolled bleeding frequently occurs in some emergencies which can result in severe injury and even death. Keratin hydrogel has been found that it had good ahemostatic efficacy in the previous studies. However, an ideal hemostatic agent should not require mixing or preparation in advance, and hydrogel is not easy to store and carry.
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