Tumor-Associated Monocytes Reprogram CD8+ T Cells into Central Memory-Like Cells with Potent Antitumor Effects.

CD8+ T cells are critical for host antitumor responses, whereas persistent antigenic stimulation and excessive inflammatory signals lead to T cell dysfunction or exhaustion. Increasing early memory T cells can improve T cell persistence and empower T cell-mediated tumor eradication, especially for adoptive cancer immunotherapy. Here, it is reported that tumor-associated monocytes (TAMos) are highly correlated with the accumulation of CD8+ memory T cells in human cancers. Further analysis identifies that TAMos selectively reprogram CD8+ T cells into T central memory-like (TCM-like) cells with enhanced recall responses. L-NMMA, a pan nitric oxide synthase inhibitor, can mitigate TAMo-mediated inhibition of T cell proliferation without affecting TCM-like cell generation. Moreover, the modified T cells by TAMo exposure and L-NMMA treatment exhibit long-term persistence and elicit superior antitumor effects in vivo. Mechanistically, the transmembrane protein CD300LG is involved in TAMo-mediated TCM-like cell polarization in a cell-cell contact-dependent manner. Thus, the terminally differentiated TAMo subset (CD300LGhighACElow) mainly contributes to TCM-like cell development. Taken together, these findings establish the significance of TAMos in boosting T-cell antitumor immunity.

Advancements in Performance Optimization of Electrospun Polyethylene Oxide-Based Solid-State Electrolytes for Lithium-Ion Batteries.

Polyethylene oxide (PEO)-based solid-state electrolytes for lithium-ion batteries have garnered significant interest due to their enhanced potential window, high energy density, and improved safety features. However, the issues such as low ionic conductivity at ambient temperature, substantial ionic conductivity fluctuations with temperature changes, and inadequate electrolyte interfacial compatibility hinder their widespread applications. Electrospinning is a popular approach for fabricating solid-state electrolytes owing to its superior advantages of adjustable component constitution and the unique internal fiber structure of the resultant electrolytes. Thus, this technique has been extensively adopted in related studies. This review provides an overview of recent advancements in optimizing the performance of PEO solid-state electrolytes via electrospinning technology. Initially, the impacts of different lithium salts and their concentrations on the performance of electrospun PEO-based solid-state electrolytes were compared. Subsequently, research pertaining to the effects of various additives on these electrolytes was reviewed. Furthermore, investigations concerning the enhancement of electrospun solid-state electrolytes via modifications of PEO molecular chains are herein detailed, and lastly, the prevalent challenges and future directions of PEO-based solid-state electrolytes for lithium-ion batteries are summarized.

Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect.

Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK.

Genetic distinction between functional tissue-resident and conventional natural killer cells.

Tissue-residential natural killer (trNK) cells act as pioneering responders during infectious challenges. However, their discrimination with conventional NK (cNK) cells is still an issue. Through an integrative transcriptome comparison of the two NK subgroups from different tissues, we have defined two genesets capable of efficiently distinguishing them. Based on the two genesets, a fundamental difference between the activation of trNK and cNK is identified and further confirmed. Mechanistically, we have discovered a particular role of chromatin landscape in regulating the trNK activation. In addition, IL-21R and IL-18R are respectively highly expressed by trNK and cNK, indicating a role of cytokine milieu in determining their differential activation. Indeed, IL-21 is particularly critical in accessorily promoting trNK activation using a bunch of bifunctional transcription factors. Together, this study sheds light on the bona fide difference between trNK and cNK, which will further expand our knowledge about their distinct functionalities during immune responses.

PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation.

Anti-programmed death-1 (PD-1) immunotherapy that aims to restore T cell activity in cancer patients frequently leads to immune-related adverse events such as colitis. However, the underlying mechanism is still elusive. Here, we find that Pdcd1-deficient mice exhibit disrupted gut microbiota and aggravated dextran sulfate sodium (DSS)-induced colitis. In addition to T cells, PD-1 is also substantially expressed in colonic lymphoid tissue inducer (LTi) cells. During DSS-induced colitis, LTi cell activation is accompanied by increased PD-1 expression, whereas PD-1 deficiency results in reduced interleukin-22 (IL-22) production by LTi cells and exacerbated inflammation. Mechanistically, activated LTi cells reprogram their metabolism toward carbohydrate metabolism and fatty acid synthesis, while fatty acid oxidation (FAO) is unchanged. However, PD-1 deficiency leads to significantly elevated FAO in LTi cells, which in turn attenuates their activation and IL-22 production. Consistently, FAO suppression efficiently restores IL-22 production in Pdcd1-/- LTi cells. Thus, our study provides unforeseen mechanistic insight into colitis occurrence during anti-PD-1 immunotherapy through LTi cell metabolic reconfiguration.

Recycling and Reutilizing Polymer Waste via Electrospun Micro/Nanofibers: A Review.

The accumulation of plastic waste resulting from the increasing demand for non-degradable plastics has led to a global environmental crisis. The severe environmental and economic drawbacks of inefficient, expensive, and impractical traditional waste disposal methods, such as landfills, incineration, plastic recycling, and energy production, limit the expansion of their applications to solving the plastic waste problem. Finding novel ways to manage the large amount of disposed plastic waste is urgent. Until now, one of the most valuable strategies for the handling of plastic waste has been to reutilize the waste as raw material for the preparation of functional and high-value products. Electrospun micro/nanofibers have drawn much attention in recent years due to their advantages of small diameter, large specific area, and excellent physicochemical features. Thus, electrospinning recycled plastic waste into micro/nanofibers creates diverse opportunities to deal with the environmental issue caused by the growing accumulation of plastic waste. This paper presents a review of recycling and reutilizing polymer waste via electrospinning. Firstly, the advantages of the electrospinning approach to recycling plastic waste are summarized. Then, the studies of electrospun recycled plastic waste are concluded. Finally, the challenges and future perspectives of electrospun recycled plastic waste are provided. In conclusion, this paper aims to provide a comprehensive overview of electrospun recycled plastic waste for researchers to develop further studies.