Ras-related Protein Rap1b, a GTP-binding protein belonging to the proximal RAS, which affects tumor progression through regulating tumor cell proliferation, invasion and participates in the functions ...of various immune cells. However, the potential roles and mechanisms of Rap1b in tumor progression and immunology remains unclear. In this study, we systematically analyzed the pan-cancer expression and prognostic correlation of Rap1b based on GTEX, CCLE, Oncomine, PrognoScan, Kaplan-Meier plotters and TCGA databases. The potential correlations of Rap1b with immune infiltration were revealed via TIMER and TCGA database. SangerBox database was used to analyzed the correlations between Rap1b expression and immune checkpoint (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs) and DNA methylation. The results indicated that the expression level of Rap1b varies in different tumors. Meanwhile, the expression level of Rap1b strongly correlated with prognosis in patients with tumors, higher expression of Rap1b usually was linked to poor prognosis in different datasets. Rap1b was correlated closely with tumor immunity and interacted with various immune cells in different types of cancers. In addition, there were significant positive correlations between Rap1b expression and ICP, TMB, MSI, MMRs and DNA methylation. In conclusion, the results of pan-cancer analysis showed that the abnormal Rap1b expression was related to poor prognosis and tumor immune infiltration in different cancers. Furthermore, Rap1b gene may be used as a potential biomarker of clinical tumor prognosis.
Over the past decade, lithium-sulfur (Li-S) batteries have been thought of as promising alternatives for the new generation of battery systems. Although the Li-S batteries possess high-theoretical ...energy density (2600 Wh kg
) and capacity (1675 mAh g
), the problems of poor electron and ion conduction, volumetric expansion, and sulfur immobilization greatly impede the wide applicability of Li-S batteries. Herein, a defect-rich multishelled Co
O
microsphere structure doped with Fe was synthesized via a one-step hydrothermal method and subsequent thermal treatment. The unique multishelled structure provides multiple spatial confinements for lithium polysulfides trapping and buffering the volume variation during cycling. Moreover, the rich oxygen defect designed by controlled Fe doping can provide numerous catalytic sites for polysulfide redox reactions. Attributed to the synergistic effect of structural design and oxygen-defect fabrication, the sulfur composite electrode delivers a notable cycle performance, presenting a much lower capacity fading of 0.017% per cycle over 1000 cycles at 1 C and an excellent rate capability of 571.3 mAh g
at 5 C. This work proposes a potential approach for designing a transition metal oxide-based multishelled hollow structure combined with oxygen defect, which also offers a new perspective on high-performance Li-S batteries.
While the immunosuppressive function of regulatory T (Treg) cells has been extensively studied, their immune‐supportive roles have been less well investigated. Using a lymphocytic choriomeningitis ...virus (LCMV) Armstrong infection mouse model, we found that Treg cell‐derived interleukin (IL)‐15 is required for long‐term maintenance of the KLRG1+IL‐7Rα−CD62L− terminal effector memory CD8+ T (tTEM) cell subset, but dispensable for the suppressive function of Treg cells themselves. In contrast, deletion of Il15 from other sources, including myeloid cells and muscles, did not affect the composition of the memory CD8+ T cell pool. Our findings identify Treg cells as an essential IL‐15 source maintaining tTEM cells and suggest that Treg cells promote the diversity of immunological memory.
We investigated the identity of IL‐15 producing cells using several mouse strains with cell type‐specific loss of IL‐15 expression. After the resolution of acute infection, IL‐15 secreted by regulatory cells, but not skeletal muscles or myeloid cells, was required for the maintenance of a subset of memory cells referred to as terminal effector memory T cells. These KLRG1+IL‐7Rα−CD62L− similarly contracted in mice with gremline Il15 deletion. TCM: central memory T cells. TEM: effector memory T cells. tTEM: terminal effector memory T cells.
Memory CD8+ T cells mature after antigen clearance and ultimately express CD8 protein at levels higher than those detected in effector CD8+ T cells. However, it is not clear whether engagement of CD8 ...in the absence of antigenic stimulation will result in the functional activation of T cells. Here, we found that CD8 antibody‐mediated activation of memory CD8+ T cells triggered T cell receptor (TCR) downstream signaling, enhanced T cell‐mediated cytotoxicity and promoted effector cytokine production in a glucose‐ and glutamine‐dependent manner. Furthermore, pretreatment of memory CD8+ T cells with an agonistic anti‐CD8 antibody enhanced their tumoricidal activity in vitro and in vivo. From these studies, we conclude that CD8 agonism activates glucose and glutamine metabolism in memory T cells and enhances the efficacy of memory T cell‐based cancer immunotherapy.
What's new?
Memory CD8+ T cells mature after antigen clearance and ultimately express high levels of CD8 protein. However, it is unclear whether engagement of CD8 in the absence of antigenic stimulation could result in the functional activation of T cells. Our study shows that CD8 agonists can activate memory T‐cell glucose and glutamine metabolism in the absence of T‐cell receptor stimulation. Furthermore, CD8 agonists can enhance the efficacy of memory T cell‐based cancer immunotherapy. The authors propose targeting CD8 as a potentially useful, intrinsically specific and importantly, tumor‐agnostic approach to antitumor immunotherapy.
In article number 2001165, Xin Wang, Zhongwei Chen, and co‐workers develop a hierarchical Fe3−xC@C hollow microsphere consisting of Fe‐deficient Fe3−xC subunits with a mesoporous carbon coating that ...serves as an excellent lithium polysulfide adsorbent to immobilize the sulfur species against their shuttling behaviors, as well as an efficient catalyst to promote the sulfur conversion reaction kinetics. The cation‐deficient design holds great promise in the development of high‐performance Li‐S batteries.
Abstract
Lithium–sulfur (Li–S) batteries present one of the most promising energy storage systems owing to their high energy density and low cost. However, the commercialization of Li–S batteries is ...still hindered by several technical issues; the notorious polysulfide shuttling and sluggish sulfur conversion kinetics. In this work, unique hierarchical Fe
3‐
x
C@C hollow microspheres as an advanced sulfur immobilizer and promoter for enabling high‐efficiency Li–S batteries is developed. The porous hollow architecture not only accommodates the volume variation upon the lithiation–delithiation processes, but also exposes vast active interfaces for facilitated sulfur redox reactions. Meanwhile, the mesoporous carbon coating establishes a highly conductive network for fast electron transportation. More importantly, the defective Fe
3‐
x
C nanosized subunits impose strong LiPS adsorption and catalyzation, enabling fast and durable sulfur electrochemistry. Attributed to these structural superiorities, the obtained sulfur electrodes exhibit excellent electrochemical performance, i.e., high areal capacity of 5.6 mAh cm
−2
, rate capability up to 5 C, and stable cycling over 1000 cycles with a low capacity fading rate of 0.04% per cycle at 1 C, demonstrating great promise in the development of practical Li–S batteries.
The malate shuttle is traditionally understood to maintain NAD
/NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions is unclear. Here we show that ...chronic viral infections induce CD8
T cell expression of GOT1, a central enzyme in the malate shuttle. Got1 deficiency decreased the NAD
/NADH ratio and limited antiviral CD8
T cell responses to chronic infection; however, increasing the NAD
/NADH ratio did not restore T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis and led to a toxic accumulation of ammonia in CD8
T cells. Supplementation with 2-KG assimilated and detoxified ammonia in Got1-deficient T cells and restored antiviral responses. These data indicate that the major function of the malate shuttle in CD8
T cells is not to maintain the NAD
/NADH balance but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8
T cells during chronic infection.
Lipid metabolism is important in various cancers. However, the association between lipid metabolism and uterine corpus endometrial carcinoma (UCEC) is still unclear. In this study, we collected ...clinicopathologic parameters and the expression of lipid metabolism-related genes (LMRGs) from the Cancer Genome Atlas (TCGA). A lipid metabolism-related risk model was built and verified. The risk score was developed based on 11 selected LMRGs. The expression of 11 LMRGs was confirmed by qRT-PCR in clinical samples. We found that the model was an independent prediction factor of UCEC in terms of multivariate analysis. The overall survival (OS) of low-risk group was higher than that in the high-risk group. GSEA revealed that MAPK signaling pathway, ERBB signaling pathway, ECM receptor interaction, WNT pathway, and TGF-β signaling pathway were enriched in the high-risk group. Low-risk group was characterized by high tumor mutation burden (TMB) and showed sensitive response to immunotherapy and chemotherapy. In brief, we built a lipid metabolism gene expression-based risk signature which can reflect the prognosis of UCEC patients and their response to chemotherapeutics and immune therapy.
A tensile‐strained MXene/CNT porous microsphere was developed by Xin Wang, Zhongwei Chen, and co‐workers in their Research Article on page 2371 as an electrocatalyst for high‐performance ...lithium–sulfur batteries. A unique O‐Ti‐C interface was constructed on the MXene surface through a spray‐drying process and heat treatment to produce internal stress, inducing lattice distortion and expansion of the Ti−Ti bonds.
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