Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a complex immune evasion mechanism posing a challenge to treatment. The role of the S100A10 gene in various cancers has garnered significant attention. This study aims to elucidate the impact of S100A10 on CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, thereby elucidating its role in immune evasion in HCC. By analyzing the HCC-related data from the GEO and TCGA databases, we identified differentially expressed genes associated with lipid metabolism and developed a prognostic risk model. Subsequently, through RNA-seq and PPI analyses, we determined vital lipid metabolism genes and downstream factors S100A10, ACOT7, and SMS, which were significantly correlated with CD8+ T cell infiltration. Given the most significant expression differences, we selected S100A10 for further investigation. Both in vitro and in vivo experiments were conducted, including co-culture experiments of CD8+ T cells with MHCC97-L cells, Co-IP experiments, and validation in an HCC mouse model. S100A10 was significantly overexpressed in HCC tissues and potentially regulates CD8+ T cell exhaustion and lipid metabolism reprogramming through the cPLA2 and 5-LOX axis. Silencing S100A10 could inhibit CD8+ T cell exhaustion, further suppressing immune evasion in HCC. S100A10 may activate the cPLA2 and 5-LOX axis, initiating lipid metabolism reprogramming and upregulating LTB4 levels, thus promoting CD8+ T cell exhaustion in HCC tissues, facilitating immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells. This research highlights the critical role of S100A10 via the cPLA2 and 5-LOX axis in immune evasion in HCC, providing new theoretical foundations and potential targets for diagnosing and treating HCC.

Selectively "size-excluding" water molecules to enable a highly reversible zinc metal anode.

Significant water-related side reactions hinder the development of highly safe, low-cost aqueous zinc metal batteries (AZMBs) for grid-scale energy storage. Herein, by regulating the length of alkyl chains, we successfully adjust interstitial voids between the polymer chains of a metal soap interface between 1.48 Å (size of a zinc ion) and 4.0 Å (size of a water molecule). Therefore, water molecules are selectively "size-excluded," while smaller zinc ions are permitted to pass through. Consequently, water-related side reactions (including hydrogen evolution and corrosion) could be effectively inhibited. Furthermore, abundant zinc ion tunnels accompanied with zincophilic components facilitate the homogenization of the Zn2+ flux, thus preventing dendrite growth. Therefore, the Zn symmetric cell shows a lifespan of approximately 10 000 cycles at 20 mA cm-2 and 1 mA h cm-2, and the Zn//Na5V12O32 (NVO) full cell delivers much better cycling stability with much higher capacity retention of around 93% after 2000 cycles at 2 A g-1 compared to its bare Zn counterpart (19%). This work provides valuable insights for the utilization of metal soap interfaces and regulation of their channel size between perpendicular alkyl chains to realize precise water shielding, which is not only applicable in ZMBs but also in other aqueous batteries.

Assessing the particulate matter emission reduction characteristics of small turbofan engine fueled with 100 % HEFA sustainable aviation fuel.

With the continuous increase in global air transportation, the impact of ultrafine particulate matter (PM) emissions from aviation on human health and environmental pollution is becoming increasingly severe. In addition to carbon reduction throughout the lifecycle, Sustainable Aviation Fuels (SAF) also represent a significant pathway for reducing PM emissions. However, due to issues such as airworthiness safety and adaptability, existing research has mostly focused on the emission performance of SAF when blended with traditional fuels at <50 %, leaving the emission characteristics of higher blending ratios to be explored. In this study, using measurement methods recommended by the International Civil Aviation Organization (ICAO), the PM emission reduction characteristics of small turbofan engines fueled with 100 % Hydroprocessed Esters and Fatty Acids (HEFA)-SAF were experimentally evaluated and compared with traditional fuels RP-3 and Diesel, while avoiding the interference of lubricant blending combustion. The results showed that the peak number concentration of particle size distribution (PSD), PM total number, as well as the number and mass concentration of non-volatile particulate matter (nvPM) decreased initially and then increased with rising thrust conditions. HEFA-SAF exhibits PSD with smaller diameters, and the Geometric Mean Diameter (GMD) ranges from 7.7 nm to 20.3 nm under all conditions. Both volatile particulates (vPM) and nvPM from HEFA-SAF are significantly reduced, with nvPM number emission index (EIn) being 92 % and 71 % lower than Diesel and RP-3, respectively. The nvPM mass emission index (EIm) also shows reductions of 96 % and 89 % compared to Diesel and RP-3. Microscopic characterization also indicated that using HEFA-SAF emitted fewer and smaller PMs. This study establishes a foundation for evaluating the effectiveness of 100 % SAF in reducing PM emissions within the aviation sector, and contributes to the airworthiness regulations development related to the use of SAF in a variety of application environments, alongside enhancing environmental protection measures.

Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione.

BACKGROUND: Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood. This study examined the role of mitoGSH in regulating NET-induced ferroptosis of smooth muscle cells (SMCs) during AAA formation. METHODS: Concentrations of NET markers were tested in plasma samples. Western blotting and immunofluorescent staining were performed to detect the expression and localization of NET and ferroptosis markers in tissue samples. The role of NETs and SMC ferroptosis during AAA formation was investigated using peptidyl arginine deiminase 4 gene (Padi4) knockout or treatment with a PAD4 inhibitor, ferroptosis inhibitor or activator in an angiotensin II-induced AAA mouse model. The regulatory effect of SLC25A11, a mitochondrial glutathione transporter, on mitoGSH and NET-induced ferroptosis of SMCs was investigated using in vitro and in vivo experiments. Transmission electron microscopy was used to detect mitochondrial damage. Blue native polyacrylamide gel electrophoresis was used to analyze the dimeric and monomeric forms of the protein. RESULTS: Significantly elevated levels of NETosis and ferroptosis markers in aortic tissue samples were observed during AAA formation. Specifically, NETs promoted AAA formation by inducing ferroptosis of SMCs. Subsequently, SLC25A11 was identified as a potential biomarker for evaluating the clinical prognosis of patients with AAA. Furthermore, NETs decreased the stability and dimerization of SLC25A11, leading to the depletion of mitoGSH. This depletion induced the ferroptosis of SMCs and promoted AAA formation. CONCLUSION: During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11, leading to the depletion of mitoGSH and subsequent activation of NET-induced ferroptosis of SMCs. Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA.

The requirement of the mitochondrial protein NDUFS8 for angiogenesis.

Mitochondria are important for the activation of endothelial cells and the process of angiogenesis. NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I. We aimed to investigate the potential involvement of NDUFS8 in angiogenesis. In human umbilical vein endothelial cells (HUVECs) and other endothelial cell types, we employed viral shRNA to silence NDUFS8 or employed the CRISPR/Cas9 method to knockout (KO) it, resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation. Significantly, NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. In addition, there was a moderate increase in apoptosis within NDUFS8-depleted endothelial cells. Conversely, ectopic overexpression of NDUFS8 demonstrated a pro-angiogenic impact, enhancing cell proliferation, migration, and capillary tube formation in HUVECs and other endothelial cells. NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. Conversely, NDUFS8 overexpression boosted Akt-mTOR activation. Furthermore, the inhibitory effects of NDUFS8 knockdown on cell proliferation, migration, and capillary tube formation were rescued by Akt re-activation via a constitutively-active Akt1. In vivo experiments using an endothelial-specific NDUFS8 shRNA adeno-associated virus (AAV), administered via intravitreous injection, revealed that endothelial knockdown of NDUFS8 inhibited retinal angiogenesis. ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8. Lastly, we observed an increase in NDUFS8 expression in retinal proliferative membrane tissues obtained from human patients with proliferative diabetic retinopathy. Our findings underscore the essential role of the mitochondrial protein NDUFS8 in regulating endothelial cell activation and angiogenesis.

Dilemma of Low-Cost Filter Paper as Separator: Toughen Its Wet Strength for Robust Aqueous Zinc-Ion Batteries.

The industrialization of aqueous zinc-ion batteries (AZIBs) is hampered by poor-performance separators. Filter paper (FP), with mature production processes and low prices, has potential as a separator. However, its swelling and decline of mechanical durability in aqueous environments make it easily punctured by dendrites. In response, wet strength promotion is proposed to toughen FP for robust AZIBs, termed wet-strengthened FP (WSFP). Due to the self-cross-linking network formed on cellulose fibers, water molecules are prevented from easily permeating and disrupting the hydrogen bonds between cellulose molecules. Moreover, the positively charged network can anchor SO42-, thus increasing the Zn2+ transference number and facilitating uniform zinc deposition. Surprisingly, the half and full cells with the WSFP separator present much more stable cycling than untreated FP and glass fiber (GF) separators. These results suggest that robust and low-cost WSFP separators provide a new avenue for the development of high-performance AZIBs with potential for commercialization.