Macrophages phagocytize pathogens to initiate innate immunity and products from the tumor microenvironment (TME) to mediate tumor immunity. The loss of tumor-associated macrophage (TAM)-mediated immune responses results in immune suppression. To reverse this immune disorder, the regulatory mechanism of TAMs in the TME needs to be clarified. Immune molecules (cytokines and chemokines) from TAMs and the TME have been widely accepted as mutual mediators of signal transduction in the past few decades. Recently, researchers have tried to seek the intrinsic mechanism of TAM phenotypic and functional changes through metabolic connections. Numerous metabolites derived from the TME have been identified that induce the cell-cell crosstalk with TAMs. The bulk tumor cells, immune cells, and stromal cells produce metabolites in the TME that are involved in the metabolic regulation of TAMs. Meanwhile, some products from TAMs regulate the biological functions of the tumor as well. Here, we review the recent reports demonstrating the metabolic regulation between TME and TAMs.

Fe₃O₄magnetic nanoparticles (Fe₃O₄-MNPs) have been widely used in clinical diagnosis. Hemocompatibility of the nanoparticles is usually evaluated by hemolysis. However, hemolysis assessment does not measure the dysfunctional erythrocytes with pathological changes on the unbroken cellular membrane. The aim of this study is to evaluate the use of suicidal death of erythrocytes (i.e. eryptosis indices) as a novel predictive and prognostic parameter and to determine the impact of Fe₃O₄-MNPs on cellular membrane structure and the rheology properties of blood in circulation. Our results showed that phosphatidylserine externalization assessment was significantly more sensitive than classical hemolysis testing in evaluating hemocompatibility. Although no remarkable changes of histopathology, hematology and serum biochemistry indices were observedin vivo, Fe₃O₄-MNPs significantly affected hemorheology indices including erythrocyte deformation index, erythrocyte rigidity index, red blood cell aggregation index and erythrocyte electrophoresis time, which are related to the mechanical properties of the erythrocytes. Oxidative stress induced calcium influx played a critical role in the eryptotic activity of Fe₃O₄-MNPs. This study demonstrated that Fe₃O₄-MNPs cause eryptosis and changes in flow properties of blood, suggesting that phosphatidylserine externalization can serve as a predictive parameter for hemocompatibility assay.

Aim: The aim of this study was to investigate the mechanisms of Cr⁶⁺-induced red blood cells (RBCs) damage. Methods: The effect of Cr⁶⁺ exposure on RBCs was evaluated by hemolytic rate and blood gas assays. After exposure to 20 μM Cr⁶⁺, the percentage of phosphatidylserine (PS)-exposing cells, intracellular Ca²⁺, reactive oxygen species (ROS), and ATP levels were evaluated, and cell morphology was observed. RBCs were exposed to Cr⁶⁺ in different Ringer solutions to investigate the role of changes of Ca²⁺, ROS, and ATP levels in eryptosis and morphology. Results: The Cr⁶⁺-induced damage of RBCs was dose-dependent. After a 6 h incubation with Cr⁶⁺, RBCs exhibited significant Ca²⁺ influx, ROS increase, ATP depletion, and PS exposure, but displayed no obvious change in morphology at this time point. After 24 h Cr⁶⁺ exposure, the RBCs decreased in size, appeared to be spike-like, and had decreased forward scatter. Inhibition of Ca²⁺ influx attenuated PS-exposure caused by 6 h Cr⁶⁺ exposure, but did not prevent 24 h Cr⁶⁺ exposure-induced morphological change in RBCs. Inhibition of rapid ATP consumption using adenine significantly ameliorated Cr⁶⁺-caused PS-exposure at 12 h, 24 h and 48 h, and prevented 24 h Cr⁶⁺ incubation-induced morphological change in RBCs. Conclusion: Cr⁶⁺ can lead to eryptosis. Ca²⁺ influx, increased ROS levels, and rapid ATP consumption are closely related to Cr⁶⁺-induced RBCs damage. Ca²⁺ influx plays an extremely important role in Cr⁶⁺-mediated toxicity.

Increasing evidence indicates that gut microbiota may play a key role in vaccination immunity. Here, we investigate whether the human gut microbiota and metabolic function correlate with the BBIBP-CorV vaccine response. A total of 207 participants who received the BBIBP-CorV vaccine are enrolled. The gut microbiome and metabolic functions are investigated using metagenomic sequencing and metabolomic assays. We find that BBIBP-CorV vaccination is accompanied by altered microbiome composition and functional pathways, and the gut microbiome and its functional profiles correlate with the vaccine response. The levels of short-chain fatty acids (SCFAs) are much higher in the high antibody response group compared to the low response group, and several SCFAs display a positive correlation with the antibody response. Our study highlights that the gut microbiome and its function is associated with the BBIBP-CorV vaccine response, providing evidence for further exploration of microbiome modulation to improve COVID-19 vaccine efficacy.

A significant challenge associated with systemic delivery of cationic antimicrobial peptides and polymers lies in their limited hemocompatibility toward vast numbers of circulating red blood cells (RBCs). Supramolecular assembly of cationic peptides and polymers can be an effective strategy to develop an array of antimicrobial nanomaterials with tunable material structures, stability and thus optimized bioactivity to overcome some of the existing challenges associated with conventional antimicrobials. In this work, we will demonstrate the supramolecular design of self-assembling antimicrobial nanofibers (SAANs) which have tunable supramolecular nanostructures, stability, internal molecular packing and surface chemistry through self-assembly of de novo designed cationic peptides and peptide–PEG conjugates. The interaction of the SAANs with human RBCs was evaluated in a stringent biological assay (beyond a traditional hemolysis assay) where both hemolytic and eryptotic activity were examined to establish a fundamental understanding of the correlation between material structure and hemocompatibility. It was found that although the SAANs showed moderate hemolytic activities, their abilities to induce eryptosis vary significantly and are much more sensitive to the internal molecular packing, supramolecular nanostructure and stability of the nanofiber. Improved hemocompatibility requires PEGylation on stable supramolecular nanofibers composed of a highly organized β-sheet structure while PEG conjugation on weakly packed nanofibers composed of partially denatured β-sheets did not show improvement. The current study reveals the fundamental mechanism involved in the selective hemocompatibility improvement of the SAANs upon PEG conjugation. The structure–activity relationship developed in this study will provide important guidance for the future design of a broader family of peptide and polymer-based assemblies with optimized antimicrobial activity and hemocompatibility.