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Rechargeable Mn-metal batteries (MMBs) can attract considerable attention because Mn has the intrinsic merits including high energy density (976 mAh g-1), high air stability, and low toxicity. However, the application of Mn in rechargeable batteries is limited by the lack of proper cathodes for reversible Mn2+ intercalation/de-intercalation, thus leading to low working voltage (<1.8 V) and poor cycling stability (≤200 cycles). Herein, a high-voltage and durable MMB with graphite as the cathode is successfully constructed using a LiPF6-Mn(TFSI)2 hybrid electrolyte, which shows a high discharge voltage of 2.34 V and long-term stability of up to 1000 cycles. Mn(TFSI)2 can reduce the plating/stripping overpotential of Mn ions, while LiPF6 can efficiently improve the conductivity of the electrolyte. Electrochemical in-situ characterization implies the dual-anions intercalation/de-intercalation at the cathode and Mn2+ plating/stripping reaction at the anode. Theoretical calculations unveil the top site of graphite is the energetically favorable for anions intercalation and TFSI- shows the low migration barrier. This work paves an avenue for designing high-performance rechargeable MMBs towards electricity storage.
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Although the blockade of immune checkpoint PD-1/PD-L1 has achieved great success, the lack of tumor-infiltrating immune cells and PD-L1 expression in the tumor microenvironment results in a limited response in certain tumor types. Thus, rational and optimal combination strategies were urgently needed. The combination of PD-1/PD-L1 blockade and anti-angiogenic therapy has been reported to have great potential. Here, a chimeric peptide OGS was designed by conjugating the peptides OPBP-1 (8-12) and DA7R targeting PD-L1 and VEGFR2, respectively. OGS could bind to both human and mouse PD-L1 with high affinity and block the PD-1/PD-L1 interaction, and also inhibit the migration and tube formation of HUVEC cells in wound healing and tube formation assays. To further prolong the half-life of OGS, it was modified by coupling with peptide DSP which has a high binding affinity to both human serum albumin (HSA) and mouse serum albumin (MSA) to form the peptide DSPOGS. DSPOGS could not directly affect the viability, apoptosis, and cell cycle of tumor cells in vitro, while significantly inhibiting the tumor growth in the MC38 mouse model. DSPOGS could elicit a potent anti-tumor immune response and inhibit tumor angiogenesis, with the enhancement of tumor infiltrating CD8+ T cells and the IFN-γ secreting CD8+ T cells in the spleen and tumor-draining lymph node. Further, the combination of radiotherapy with DSPOGS could dramatically improve the therapeutic efficacy. Our study could provide a promising paradigm for the combination of immune checkpoint blockade, anti-angiogenesis, and radiotherapy.
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Antígeno B7-H1 , Neoplasias , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Humanos , Imunoterapia/métodos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Microambiente TumoralRESUMO
In recent years solid Li+ conductors with competitive ionic conductivity to those of liquid electrolytes have been reported. However, the incorporation of highly conductive solid electrolytes into the lithium-ion batteries is still very challenging mainly due to the high resistance existing at the solid-solid interfaces throughout the battery structure. Here, we demonstrated a universal interfacial modification strategy through coating a curable polymer-based glue electrolyte between the electrolyte and electrodes, aiming to address the poor solid-solid contact and thus decrease high interfacial resistance. The liquid glue exhibits both great wettability as well as chemical/electrochemical stability to most of the electrodes, and it can be easily solidified into a polymer electrolyte layer through a "post-curing" treatment. As a result, symmetric Li batteries with the glue modification exhibit much smaller impedance and enhanced stability upon plating/stripping cycles compared to the batteries without glue modification. The all-solid-state Li-S batteries with glue modification show significantly enhanced performances. The strategy of developing glue electrolytes to improve the electrode-electrolyte interface contact provides an alternative option for improving many other solid-state batteries.
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Background: The nectin adhesion molecule CD112, an important component of tumor progression, belongs to the nectin family. However, a comprehensive evaluation of its clinical relevance and mechanism in various cancers is yet to be conducted. Methods: This investigation fully examined the relationship between prognosis and CD112 expression. We clarified the function of CD112 in tumor immunity by employing The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. This involved examining its connections to tumor mutation burden (TMB), DNA methylation, tumor immune invasion, mismatch repair (MMR), microsatellite instability (MSI), and common immune checkpoint inhibitors (ICIs). Additionally, the impact of CD112 knockdown on cell function was examined in colorectal cancer (CRC) cell lines. Results: In the current study, we found malignant tissues express high levels of CD112, which was related to TMB, MMR, MSI, and DNA methylation. Survival analysis indicated that patients with high CD112 expression had an unfavorable prognosis more frequently. In addition, CD112 expression was negatively associated with infiltration levels of CD4 positive (CD4+) T cells, CD8 positive (CD8+) T cells, and T cells. Western blotting and pathway enrichment analysis showed that CD112 is significantly linked to epithelial-to-mesenchymal transition (EMT). Additionally, CRC cells migrate and proliferate less when CD112 was knocked down. CD112 expression was found to be negatively associated with anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) treatment outcomes in patients. Conclusions: CD112 may act as a possible prognostic marker in immune therapy and may stimulate tumor growth by upregulating the EMT pathway.
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Synthesizing the best material globally is challenging; it needs to know what and how much the best ingredient composition should be for satisfying multiple figures of merit simultaneously. Traditional one-variable-at-a-time methods are inefficient; the design-build-test-learn (DBTL) method could achieve the optimal composition from only a handful of ingredients. A vast design space needs to be explored to discover the possible global optimal composition for on-demand materials synthesis. This research developed a hypothesis-guided DBTL (H-DBTL) method combined with robots to expand the dimensions of the search space, thereby achieving a better global optimal performance. First, this study engineered the search space with knowledge-aware chemical descriptors and customized multiobjective functions to fulfill on-demand research objectives. To verify this concept, this novel method was used to optimize colorimetric ammonia sensors across a vast design space of as high as 19 variables, achieving two remarkable optimization goals within 1 week: first, a sensing array was developed for ammonia quantification of a wide dynamic range, from 0.5 to 500 ppm; second, a new state-of-the-art detection limit of 50 ppb was reached. This work demonstrates that the H-DBTL approach, combined with a robot, develops a novel paradigm for the on-demand optimization of functional materials.
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Procedimentos Cirúrgicos Robóticos , Robótica , Amônia , Colorimetria , AlgoritmosRESUMO
SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial-mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration.
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Proliferação de Células , Neoplasias Colorretais , Família de Moléculas de Sinalização da Ativação Linfocitária , Animais , Feminino , Humanos , Camundongos , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Instabilidade de Microssatélites , Prognóstico , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/genéticaRESUMO
Niobium pentoxides (Nb2O5) present great potential as next-generation anode candidates due to exceptional lithium-ion intercalation kinetics, considerably high capacity, and reasonable redox potential. Although four phases of Nb2O5 including hexagonal, orthorhombic, tetragonal, and monoclinic polymorphs show diverse characteristics in electrochemical performance, stable lifetime, high specific capacity, and fast intercalation properties cannot be delivered simultaneously with a single phase. Herein, this issue is addressed by generating a homogeneous mixture of orthorhombic and monoclinic crystals at the nanoscale. Reversible lithium-ion intercalation/deintercalation of the monoclinic phase is achieved, and exceptional lithium storage sites are created at the interface of the two phases. As a result, electrochemical features of stable lifetime from the orthorhombic phase and high specific performance from the monoclinic phase are harmoniously combined. This dual-phase Nb2O5/C nanohybrids deliver as high as 380 mA h g-1 (0.01-3.0 V) and 184 mA h g-1 (1.0-3.0 V) after 200 cycles. The essential principle of property enhancement is further confirmed through in situ XRD measurements and DFT calculations. The dual-phase concept can be further applied on electrodes with multiphases to achieve high electrochemical performance.
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Aside from antibodies, peptides show great potential as immune checkpoint inhibitors (ICIs) due to several advantages, such as better tumor penetration and lower cost. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Here, we found that LAG-3 expression was higher than programmed cell death protein 1 (PD-1) in multiple human cancers by TCGA databases, and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning, which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II. Subsequently, d-amino acids were introduced to substitute the N- and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1, which restores T cell function in vitro and inhibits tumor growth in vivo. Further, a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1 blocking peptide OPBP-1(8-12), which activates T cell with enhanced proliferation and IFN-γ production. More importantly, LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response. In conclusion, we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function, and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.
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The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8+ T cell-mediated cytotoxicity. Immune checkpoint blockade (ICB) could induce tumor ferroptosis through IFN-γ released by immune cells, indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth. However, the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet. In this study, the small molecule Hemin that could bind with TIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay. Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells. Hemin reinvigorated the function of CD8+ T cells to secrete IFN-γ and the elevated IFN-γ could synergize with Hemin to induce ferroptosis in tumor cells. Hemin inhibited tumor growth by boosting CD8+ T cell immune response and inducing ferroptosis in CT26 tumor model. More importantly, Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model. In summary, our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis, which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.
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Ferroptose , Hemina , Imunoterapia , Receptores Imunológicos , Hemina/farmacologia , Receptores Imunológicos/metabolismo , Animais , Humanos , Ferroptose/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Simulação de Acoplamento Molecular , Células Jurkat , Camundongos Endogâmicos C57BL , Inibidores de Checkpoint Imunológico/farmacologia , Sinergismo Farmacológico , Interferon gama/metabolismo , Interferon gama/imunologia , Receptores Virais/metabolismo , Camundongos Endogâmicos BALB CRESUMO
Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis, and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in future.
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Ácidos Ftálicos , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo , Ésteres/química , Hidrólise , Cristalografia por Raios X , Catálise , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/genéticaRESUMO
Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of biosulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.
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Alteromonas , Genoma Bacteriano , Compostos de Sulfônio , Compostos de Sulfônio/metabolismo , Alteromonas/genética , Água do Mar/microbiologia , SulfetosRESUMO
Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.
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Filogenia , Compostos de Sulfônio , Compostos de Sulfônio/metabolismo , Cianobactérias/genética , Cianobactérias/metabolismo , Cianobactérias/enzimologia , Metiltransferases/metabolismo , Metiltransferases/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Vias Biossintéticas/genéticaRESUMO
BACKGROUND: Macrophage receptor with collagenous structure (MARCO), a novel immune checkpoint expressed on tumor-associated macrophages, has antitumor therapeutic properties. However, the association between MARCO and patient prognosis, immune infiltration, and ICI immunotherapy needs to be studied urgently. METHODS: MARCO distribution in cancer tissues was investigated using the TCGA and GTEx databases. The PrognoScan and KM Plotter databases was used to assess the MARCO prognosis. TIMER2.0, GEPIA, cBioPortal, and GSEA all confirmed the link between MARCO and immune infiltration, mutation profile, and enrichment pathway analysis. Data visualization was implemented by R language. RESULTS: In general, MARCO had a substantial impact on the prognosis of cancer patients and was expressed differently in cancer and adjacent normal tissues. High expression of MARCO was associated with poorer OS in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), colon adenocarcinoma (COAD), and prostate adenocarcinoma (PRAD). However, high expression of MARCO had a better PFI in brain lower-grade glioma (LGG) and skin cutaneous melanoma (SKCM). We discovered that MARCO expression was lowest in pancreatic adenocarcinoma (PAAD) and rectum adenocarcinoma (READ) stage 1, BLCA stage 2, LUSC and stomach adenocarcinoma (STAD) stage 3, and liver hepatocellular carcinoma (LIHC) stage 4. Subsequently, we analyzed the correlation between MARCO and 47 immune checkpoints and observed that MARCO was positively connected with CD80, CD86, and leukocyte-associated immunoglobulin-like receptor 1(LAIR1) in most cancers. In COAD, MARCO has the most microsatellite instability (MSI). In addition, we discovered that high expression of MARCO patients had a better prognosis after immune checkpoint inhibitor (ICI) treatment in SKCM. Finally, GSEA revealed a significant correlation between MARCO and TNF/NFκB signaling, KRAS signaling, PI3K/AKT/mTOR pathway, IL-6-STAT3 signaling, TGFß pathway, and p53 pathway. CONCLUSION: This study comprehensively investigated the relationship between MARCO and clinical prognosis, immune infiltration, and ICI immunotherapy in various cancers. We demonstrated the potential of MARCO as an emerging biomarker, exploring new avenues for future tumor immunotherapy.
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Neoplasias , Receptores Imunológicos , Humanos , Biomarcadores , Imunoterapia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: Aside from immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), intervention of CD47/Sirpα mediated 'don't eat me' signal between macrophage and tumor cell is considered as a promising therapeutic approach for cancer immunotherapy. Compared with CD47, the novel immune checkpoint CD24/Siglec-10 can also deliver 'don't eat me' signal and CD24 shows much lower expression level in normal tissue which might avoid unwanted side effects. METHODS: Cell-based phage display biopanning and D-amino acid modification strategy were used to identify the CD24/Siglec-10 blocking peptide. Cell-based blocking assay and microscale thermophoresis assay were used to validate the blocking and binding activities of the peptide. Phagocytosis and co-culture assays were used to explore the in vitro function of the peptide. Flow cytometry was performed to assess the immune microenvironment after the peptide treatment in vivo. RESULTS: A CD24/Siglec-10 blocking peptide (CSBP) with hydrolysis-resistant property was identified. Surprisingly, we found that CSBP could not only block the interaction of CD24/Siglec-10 but also PD-1/PD-L1. CSBP could induce the phagocytosis of tumor cell by both the macrophages and monocytic myeloid-derived suppressor cells (M-MDSCs), which can further activate CD8+ T cells. Besides, combination of radiotherapy and CSBP synergistically reduced tumor growth and altered the tumor microenvironment in both anti-PD-1-responsive MC38 and anti-PD-1-resistant 4T1 tumor models. CONCLUSIONS: In summary, this is the first CD24/Siglec-10 blocking peptide which blocked PD-1/PD-L1 interaction as well, functioned via enhancing the phagocytosis of tumor cells by macrophages and M-MDSCs, and elevating the activity of CD8+ T cells for cancer immunotherapy.
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Antígeno CD47 , Neoplasias , Humanos , Antígeno B7-H1 , Antígeno CD24/metabolismo , Antígeno CD47/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Imunoterapia , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/uso terapêutico , Microambiente TumoralRESUMO
Solid polymer electrolytes (SPEs), which are favorable to form intimate interfacial contacts with electrodes, are promising electrolyte of choice for long-cycling lithium metal batteries (LMBs). However, typical SPEs with easily oxidized oxygen-bearing polar groups exhibit narrow electrochemical stability window (ESW), making it impractical to increase specific capacity and energy density of SPE based LMBs with charging cut-off voltage of 4.5 V or higher. Here, we apply a polyfluorinated crosslinker to enhance oxidation resistance of SPEs. The crosslinked network facilitates transmission of the inductive electron-withdrawing effect of polyfluorinated segments. As a result, polyfluorinated crosslinked SPE exhibits a wide ESW, and the Li|SPE|LiNi0.5Co0.2Mn0.3O2 cell with a cutoff voltage of 4.5 V delivers a high discharge specific capacity of ~164.19 mAh g-1 at 0.5 C and capacity retention of ~90% after 200 cycles. This work opens a direction in developing SPEs for long-cycling high-voltage LMBs by using polyfluorinated crosslinking strategy.
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PD-1/PD-L1 blockade has achieved substantial clinical results in cancer treatment. However, the expression of other immune checkpoints leads to resistance and hinders the efficacy of PD-1/PD-L1 blockade. T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Development of small molecules targeting TIM-3 is a promising strategy for cancer immunotherapy. Here, to identify small molecule inhibitors targeting TIM-3, the docking pocket in TIM-3 was analyzed by Molecular Operating Environment (MOE) and the Chemdiv compound database was screened. The small molecule SMI402 could bind to TIM-3 with high affinity and prevent the ligation of PtdSer, HMGB1, and CEACAM1. SMI402 reinvigorated T cell function in vitro. In the MC38-bearing mouse model, SMI402 inhibited tumor growth by increasing CD8+ T and natural killing (NK) cells infiltration at the tumor site, as well as restoring the function of CD8+ T and NK cells. In conclusions, the small molecule SMI402 shows promise as a leading compound which targets TIM-3 for cancer immunotherapy.
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Receptor Celular 2 do Vírus da Hepatite A , Neoplasias , Animais , Camundongos , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Microambiente TumoralRESUMO
The presence of trace amounts of moisture in the electrolyte can cause hydrolysis of LiPF6 and deteriorate the stability of lithium metal batteries. Herein, we propose a multifunctional ionic liquid-type additive constituting a 1-methyl-1-butyl pyrrolidium cation (Py14+) and an acetate anion (CH3COO-) (denoted as IL-AC in this study), which can effectively adsorb the trace moisture and thus prevent the hydrolysis of LiPF6 via intermolecular interactions. The prepared IL-AC can also remove HF to suppress the dissolution of transition metal ions from cathode materials through the reaction CH3COO- + HF â CH3COOH + F-. Compared with the baseline electrolyte, the contents of HF and transition metal ions are significantly lower in the electrolyte with 0.5% IL-AC. Upon the addition of 0.5% IL-AC additive and 2500 ppm H2O, the Li||NCM811 battery shows a capacity of 153.7 mAh g-1 after 300 cycles, while the Li||LNMO battery possesses stable capacity retention of 93.22% after 500 cycles at 1C and a Coulombic efficiency greater than 99%. Thus, this work provides a convenient and effective method to absorb trace amounts of water and remove HF in the electrolyte and provides a new path for the expensive and tedious process of water removal from the electrolyte in industry.
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As a promising alternative as lithium-ion anode, niobium dioxide appeals to researchers due to high theoretical capacity and good electron conductivity. However, rarely work about NbO2 based high performance anode is reported. Here, NbO2 nanoparticles emcoated in continuous carbon matrix is constructed through CO2 /H2 coupling treatment. CO2 activation introduces unique carbon emcoating structure, which builds interconnected electron conductive network with low carbon content. Furthermore, crystallographic phase of NbO2 is enhanced during H2 treatment, which increases the lithium storage ability. Electrochemical performance of NbO2 anodes is significantly improved based on the carbon emcoating structure. A high reversible capacity of 391â mAh g-1 is retained after 350â cycles at 0.2â C. Additionally, at a current density of 1â A g-1 , the reversible capacity reaches 139â mAh g-1 . Compared with conventional NbO2 /C nanohybrids, the lithium diffusion coefficient of carbon-emcoated sample shows improvement of three orders of magnitude. Moreover, the inâ situ XRD investigation shows a reversible lithium insertion behaviour with a limited volume change.
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PURPOSE: To observe the short-term dynamic change in serum CXC chemokine ligand-10 (CXCL10) levels in patients with Graves' disease (GD) before and after iodine therapy and to analyze the relationship between CXCL10 levels and clinical disease indices. METHODS: ELISA was used to determine serum levels of CXCL10 in 43 patients with GD shortly before radioiodine therapy and on days six, 14, and 60, post-therapy. RESULTS: Patients with newly diagnosed GD showed significantly higher levels of serum CXCL10 compared with the control group (P < 0.01). The serum CXCL10 level increased slightly on day six after treatment of radioactive iodine (P < 0.01). There was no significant statistical difference in serum CXCL10 levels pre-treatment and on day 14 post-treatment. A significant reduction in serum CXCL10 level was observed on day 60 (P < 0.01). GD patients with exophthalmia showed higher serum CXCL10 level than GD patients without exophthalmia. No correlation was found between levels of CXCL10 and FT3, FT4 or TSH at any time point, but significant positive correlation was shown between thyroid peroxidase antibodies (TPOAb) and CXCL10 (r=0.50, P < 0.01). CONCLUSION: CXCL10 participates in the early inflammatory response after radioactive iodine therapy in patients with Graves' disease and shows a strong association with the autoimmune process.
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Quimiocina CXCL10/sangue , Doença de Graves/sangue , Doença de Graves/radioterapia , Radioisótopos do Iodo/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy.