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CD8+ T cell activation leads to the rapid proliferation and differentiation of effector T cells (Teffs), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8+ Teffs, the mechanisms that regulate CD8+ T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8+ T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8+ T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8+ T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8+ T cells by directly binding to GLUT10's intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8+ T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti–programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8+ T cells and identify that TME accumulated lactic acid inhibits CD8+ T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8+ T cell–mediated antitumor effects. Editor's summary: CD8+ T cells are a critical part of antitumor immunity and depend on metabolites including glucose to maintain their function. Here, Liu et al. have evaluated targeting glucose transport 10 (GLUT10) as a way to increase CD8+ T cell function by disrupting the competitive binding of lactic acid that increased glucose uptake, thereby increasing proliferation and antitumor capacity. Authors developed a mimic peptide, PG10.3, to treat mouse models alone or in combination with anti–programmed cell death 1 to improve antitumor effects. This represents a new potential therapeutic option to improve outcomes for patients undergoing immunotherapy that will require further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Many regions of the world have experienced dramatic changes in occurrence of heat waves. Investigating changes in their spatial patterns is of great importance for understanding the causes of heat waves and their related processes. This paper, based on observation data collected from 611 meteorological stations, used the weighted mean center tool in ArcGIS to calculate China’s heat wave center of gravity and to trace its migration over the past five decades. The results show an association between its north-south movements and the change of Arctic Oscillation Index, especially for the period after the mid-1980s, during which substantial north-south displacements took place. This study also revealed a close relationship between its west-east movements and the change in annual number of heat wave days before the 1990s, after which it was replaced by a time-dependent relationship that showed increasing heat wave trend only. [ABSTRACT FROM AUTHOR]

The dibromomaleimide derivative, N-(4-bromobutyl)-dibromomaleimide (dBMIB), is found to be a highly efficient coupling agent to dimerize thiol-terminated hydrophilic polymers by substituent reaction. When mono-thiol poly(ethylene oxide) (PEO45-SH) is mixed with dBMIB in an equivalent molar feed in water, a dimer of PEO45 with a maleimide unit located at the chain center, (PEO45)2MIB, is obtained quantitatively. The dBMIB is also used to dimerize thiol- terminated poly( N-(2-acryloyloxyethyl) pyrrolidone) and poly( N, N-dimethyl acrylamide). Moreover, the butylene bromide of (PEO45)2MIB is transferred into a butylene azide, which is allowed to react with alkynyl-terminated polystyrene to give a A2B miktoarm star polymer via a copper-catalyzed azide-alkyne cycloaddition coupling reaction. [ABSTRACT FROM AUTHOR]

Abstract: A smart poly(ethylene oxide) polymer containing two thermally reversible groups located at the chain center (F2-PEO) was synthesized by a maleimide–furan (MF) [4+2] Diels–Alder (DA) reaction between one bis[(furan-2-yl)methyl] terephthalate (F2) and two maleimide-terminated poly(ethylene glycol) methyl ethers (MI-PEOs). MF adducts underwent retro-DA (rDA) addition at a higher temperature, and the maleimide–anthracene (MA) addition reaction could occur simultaneously. Therefore, when F2-PEO and bis((anthracen-10-yl)methyl) succinate (AN2) were refluxed in toluene for 48h, the cores of F2-PEOs were replaced with the MA adducts in situ to give new polymers AN2-PEOs. Moreover, when F2-PEOs were mixed with the molecules containing four anthracene units (AN4), the rDA reaction of the MF adducts and the MA addition reactions occurred simultaneously, generating four-arm star PEOs. The core reorganization of polymers has been confirmed by SEC, UV, 1H NMR, and MALDI-TOF mass spectra. [Copyright &y& Elsevier]

Obesity is a major risk factor for poor breast cancer outcomes, but the impact of obesity-induced tumor microenvironment (TME) metabolites on breast cancer growth and metastasis remains unclear. Here, we performed TME metabolomic analysis in high-fat diet (HFD) mouse models and found that glutathione (GSH) levels were elevated in the TME of obesity-accelerated breast cancer. The deletion of glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in GSH biosynthesis, in adipocytes but not tumor cells reduced obesity-related tumor progression. Mechanistically, we identified that GSH entered tumor cells and directly bound to lysosomal integral membrane protein-2 (scavenger receptor class B, member 2 [SCARB2]), interfering with the interaction between its N and C termini. This, in turn, recruited mTORC1 to lysosomes through ARF1, leading to the activation of mTOR signaling. Overall, we demonstrated that GSH links obesity and breast cancer progression by acting as an activator of mTOR signaling. Targeting the GSH/SCARB2/mTOR axis could benefit breast cancer patients with obesity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

CD8 + T cell activation leads to the rapid proliferation and differentiation of effector T cells (T effs ), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8 + T effs , the mechanisms that regulate CD8 + T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8 + T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8 + T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8 + T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8 + T cells by directly binding to GLUT10's intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8 + T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti-programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8 + T cells and identify that TME accumulated lactic acid inhibits CD8 + T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8 + T cell-mediated antitumor effects.

Background: Osteoprotegerin (OPG) is a secretory glycoprotein and participates in the progression of atherosclerotic lesions. We aim to explore the relationship between OPG and the prognosis of coronary artery disease (CAD)., Methods: Plasma OPG concentrations were measured in 3,766 patients with stable CAD enrolled in the PEACE trial. The PEACE trial (NCT00000558) group followed up the patients and examined their future clinical outcomes., Results: In summary, 208 (5.5%) primary outcomes occurred, 295 patients (7.8%) died from all-cause death, 128 (3.4%) died from cardiovascular causes, and 94 (2.5%) experienced heart failure during a median follow-up of 1,892 days. In addition, we found that higher plasma levels of OPG were associated with a higher incidence of all-cause death, cardiovascular death, and heart failure, even after adjusting clinical cofounders., Conclusion: It was demonstrated that elevated plasma OPG levels were associated with an increased incidence of all-cause death, cardiovascular death, and heart failure in patients with stable CAD., Systematic Review Registration: https://clinicaltrials.gov/ct2/show/NCT00000558?term=NCT00000558&draw=2&rank=1, identifier: NCT00000558., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SB declared a past co-authorship with the author MT., (© 2023 Ma, Zhao, Yan, Liu, Zang, Zhang, Ruan, Xu and He.)

Three new organic-inorganic hybrid complexes based on 3d-transition metal monosubstituted Keggin polyoxometalates (POMs) with imidazole (Im) as pendant ligands, formulated as (HIm)(6-)[SiW11O39NiIm]0.8[SiW11O39Ni(H2O)]0.2.7H2O (1), (Im)4Na6[SiW11O39MnIm]0.69[SiW11O39Mn(H2O)]0.31.7.5H2O (2) and (HIm)6[SiW11O39CoIm]0.63[SiW11O39Co(H2O)]0.37.7H2O (3), have been synthesized and characterized by IR spectroscopy, UV-visible spectroscopy, elemental analysis, TG analysis, cyclic voltammetry, magnetic properties, EPR and single-crystal/powder X-ray diffraction. The structural analyses indicate that the 3d metal atoms are incorporated into the vacancy of the alpha-[SiW11O39](8-) (SiW11). Complexes 1-3 are the first examples of crystallographically characterized 3d-transition metal mono-substituted POMs with an antenna organic ligand synthesized under normal bench conditions.