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1.
Curr Microbiol ; 81(6): 160, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695903

ABSTRACT

Salt stress can adversely affect plant seed germination, growth and development, and eventually lead to slow growth and even death of plants. The purpose of this study was to investigate the effects of different concentrations of NaCl and Na2SO4 stress on the physicochemical properties, enzyme activities, rhizosphere microbial community and seven active components (L-phenylalanine, Protocatechuic acid, Eleutheroside B, Chlorogenic acid, Caffeic acid, Eleutheroside E, Isofraxidin) of Acanthopanax senticosus rhizosphere soil. Statistical analysis was used to explore the correlation between the rhizosphere ecological factors of Acanthopanax senticosus and its active components. Compared with Acanthopanax senticosus under NaCl stress, Na2SO4 generally had a greater effect on Acanthopanax senticosus, which reduced the richness of fungi in rhizosphere soil and adversely affected the content of multiple active components. Pearson analysis showed that pH, organic matter, ammonium nitrogen, available phosphorus, available potassium, catalase and urease were significantly correlated with active components such as Caffeic acid and Isofraxidin. There were 11 known bacterial genera, 12 unknown bacterial genera, 9 known fungal genera and 1 unknown fungal genus significantly associated with the active ingredient. Salt stress had great changes in the physicochemical properties, enzyme activities and microorganisms of the rhizosphere soil of Acanthopanax senticosus. In conclusion, different types and concentrations of salts had different effects on Acanthopanax senticosus, and the active components of Acanthopanax senticosus were regulated by rhizosphere soil ecological factors.


Subject(s)
Bacteria , Eleutherococcus , Fungi , Rhizosphere , Salt Stress , Soil Microbiology , Bacteria/classification , Bacteria/genetics , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/metabolism , Fungi/classification , Fungi/drug effects , Fungi/genetics , Fungi/isolation & purification , Eleutherococcus/metabolism , Microbiota/drug effects , Soil/chemistry , Sodium Chloride/metabolism , Plant Roots/microbiology
2.
Mol Carcinog ; 63(5): 885-896, 2024 May.
Article in English | MEDLINE | ID: mdl-38353298

ABSTRACT

Metastasis determines clinical management decision and restricts the therapeutic efficiency in patients with squamous cell carcinoma of the head and neck (SCCHN). Epigenetic factor KDM5B serves as an oncogene in multiple cancers. However, its role in SCCHN metastasis remains unclear. Our previous study showed that KDM5B is significantly elevated in SCCHN tissue and is positively correlated with metastasis and recurrence. KDM5B overexpression predicted a poor prognosis in both disease-free survival and overall survival, which served as an independent prognostic factor in SCCHN patients. This study further investigates the exact impact of KDM5B in metastasis of SCCHN. We found that KDM5B knockdown significantly inhibits the migration and invasion of SCCHN cells both in vitro and in vivo. On the contrary, forced expression of KDM5B leads to enhanced migration and invasion, accompanied by canonical alterations of epithelial-mesenchymal transition (EMT). Mechanism investigations demonstrated that KDM5B activates Wnt/ß-catenin pathway, and inhibition of Wnt/ß-catenin pathway via a small molecule inhibitor iCRT-14 partially reverses the enhanced migratory and invasive ability caused by KDM5B in SCCHN cells. Together, our data indicate that KDM5B promotes EMT and metastasis via Wnt/ß-catenin pathway in SCCHN, suggesting that KDM5B may be a potential therapeutic target and prognosis biomarker in SCCHN.


Subject(s)
Carcinoma, Squamous Cell , Epithelial-Mesenchymal Transition , Head and Neck Neoplasms , Jumonji Domain-Containing Histone Demethylases , Squamous Cell Carcinoma of Head and Neck , Humans , beta Catenin/genetics , beta Catenin/metabolism , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Nuclear Proteins/metabolism , Repressor Proteins/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Wnt Signaling Pathway/genetics
3.
ChemSusChem ; 17(1): e202301093, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37620728

ABSTRACT

Dual-ion batteries have been considered as a competitive energy-storage device. However, owing to the lack of suitable high-capacity density and rapid-charging electrode materials, designing a cost-effective and high-performance dual-ion battery is still a great challenge. Herein, an ultrahigh-capacity dual-ion battery is constructed based on a carbon-nanotubes (CNTs) containing SnS2 -MoS2 @CNTs heterojunction anode and highly crystalline free-standing graphite paper serves as cathode. The SnS2 -MoS2 @CNTs heterojunction consisting of ultrathin nanosheets was prepared via a facile two-step hydrothermal method and shows flower-like morphology and high crystallinity. Benefiting from the unique design concept, the graphite paper/SnS2 -MoS2 @CNTs dual-ion battery delivers a high capacity of 274.2 mAh g-1 at 100 mA g-1 and has an outstanding capacity retention of 95 % after 300 cycles under 400 mA g-1 . Even at a high current density of 2 A g-1 the battery still retains a considerable capacity of 112.3 mAh g-1 . More importantly, the battery shows an extremely low self-discharge of 0.006 % h-1 after resting for 24 h. Characterization using SEM and XRD further demonstrate the excellent cycling stability and good reversibility. Consequently, this constructed dual-ion battery could be a promising energy storage device and provide new insights for the design of high-performance dual-ion batteries.

4.
Small ; 20(10): e2306140, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37875718

ABSTRACT

The shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) severely hinder the scalable application of lithium-sulfurr (Li-S) batteries. Herein, the highly dispersed α-phase molybdenum carbide nano-crystallites embedded in a porous nitrogen-doped carbon framework (α-MoC1-x @NCF) are developed via a simple metal-organic frameworks (MOFs) assisted strategy and proposed as the multifunctional separator interlayer for Li-S batteries. The inlaid MoC1-x nanocrystals and in situ doped nitrogen atoms provide a strong chemisorption and outstanding electrocatalytic conversion toward LiPSs, whereas the unique plum-like carbon framework with hierarchical porosity enables fast electron/Li+ transfer and can physically suppress LiPSs shuttling. Benefiting from the synergistic trapping-catalyzing effect of the MoC1-x @NCF interlayer toward LiPSs, the assembled Li-S battery achieves high discharge capacities (1588.1 mAh g-1 at 0.1 C), impressive rate capability (655.8 mAh g-1 at 4.0 C) and ultra-stable lifespan (a low capacity decay of 0.059% per cycle over 650 cycles at 1.0 C). Even at an elevated sulfur loading (6.0 mg cm-2 ) and lean electrolyte (E/S is ≈5.8 µL mg-1 ), the battery can still achieve a superb areal capacity of 5.2 mAh cm-2 . This work affords an effective design strategy for the construction of muti-functional interlayer in advanced Li-S batteries.

5.
ChemSusChem ; 17(8): e202301223, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38129311

ABSTRACT

Considering the extensive resources, flexible structural designability, and abundant active sites, organic electrodes have been considered as the ideal sodium storage materials. However, organic materials generally face the limitations of unstable and dissolved characteristic, leading to a poor cyclic stability. In this work, we proposed a carbon nanotube (CNT) modified polyimide as the anode for sodium-based dual-ion battery (SDIB). The polyimide remains well the structure and morphology of monomer with a stable conjugated structure and high degree of crystallinity, effectively enhancing the electrochemical performance of the SDIBs. Also, the cooperation with CNT particularly improves the ion conductivity of the anode and advances the rate performance. Combined with an ionic liquid electrolyte, the constructed dual-ion battery exhibits excellent rate capability, high specific discharge capacity and stable cycling performance. It delivers a specific discharge capacity of 119.3 mA h g-1 at 0.2 C (1 C=100 mA g-1) and still has a specific discharge capacity of 82.3 mA h g-1 even after 1000 cycles at 10 C. Besides, the system displays a low self-discharge rate and stable fast charging performance, which is expected to be applied in the large-scale electrochemical energy storage devices and inspire the future development of SDIBs.

6.
Int J Pharm ; 648: 123583, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37940081

ABSTRACT

Irinotecan (IRT), a classic clinical chemotherapeutic agent for treating colorectal cancer, has been found to induce immunogenic cell death (ICD) while exerting cytotoxicity in tumor cells. This effect is likely to be amplified in combination with immune modulators. Unfortunately, free drugs without targeting capacity would receive poor outcomes and strong side effects. To address these issues, in this work, an acid-sensitive micelle based on an amphiphilic poly(ß-amino ester) derivative was constructed to co-deliver IRT and the immune adjuvant imiquimod (IMQ), termed PII. PII kept stable under normal physiological conditions. After internalization by tumor cells, PII dissociated in acidic lysosomes and released IRT and IMQ rapidly. In the CT26 tumor mouse model, PII increased the intra-tumoral SN38 (the active metabolite of IRT) and IMQ concentrations by up to 9.39 and 3.44 times compared with the free drug solution. The tumor inhibition rate of PII achieved 87.29%. This might profit from that IRT induced ICD, which promoted dendritic cells (DCs) maturation and intra-tumoral infiltration of CD8+ T cells. In addition, IMQ enhanced the antigen presenting ability of DCs and stimulated tumor associated macrophages to secrete tumor-killing cytokines. PII provided an effective strategy to combat colorectal cancer by synergy of chemotherapy and immunoregulation.


Subject(s)
Colorectal Neoplasms , Micelles , Animals , Mice , Imiquimod , Irinotecan , CD8-Positive T-Lymphocytes , Colorectal Neoplasms/drug therapy , Hydrogen-Ion Concentration , Cell Line, Tumor
7.
Theranostics ; 13(15): 5290-5304, 2023.
Article in English | MEDLINE | ID: mdl-37908738

ABSTRACT

Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH)2D3/VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH)2D3 in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH)2D3-VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH)2D3 restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH)2D3 plays an important role in maintaining γδ T cell homeostasis by orchestrating metabolic programs, and is a highly promising target for preventing obesity, inflammation, and insulin resistance.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Animals , Humans , Mice , Calcitriol , Diabetes Mellitus, Type 2/drug therapy , Fructose-Bisphosphatase , Inflammation , Mice, Inbred C57BL , Obesity , T-Lymphocytes
8.
ACS Nano ; 17(18): 17826-17844, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37690028

ABSTRACT

Inside the tumor microenvironment, a complicated immunosuppressive network is constituted by tumor cells and suppressive immune cells as its nodes, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells, which have mutual promotion on each other and superimposed inhibition on natural killer (NK) cells and cytotoxic T cells. Breaking the whole balance of this web is critical to tumor immunotherapy since modulation on a single node may be diluted by other factors in the network. To achieve multifaceted regulation on antitumor immunity against triple-negative breast cancer, in this work, a micelle, termed BEM, co-delivering the MDSC inhibitor, entinostat (ENT), and the immune checkpoint inhibitor, BMS-1, was constructed with pH-sensitive amphiphilic poly(ß-amino ester) derivatives. Then, BEM and the scavenger receptor A (SR-A) ligand dextran sulfate (DXS) formed a negatively charged nanoparticle (BEN). DXS detached from BEN in the weakly acidic tumor microenvironment and blocked SR-A on TAMs, reprogramming TAMs toward the M1 type. The positively charged BEM with facilitated intratumoral penetration and cellular uptake dissociated in the lysosomes, accompanied by the release of ENT and BMS-1 to suppress MDSCs and block the programmed cell death protein (PD)-1/PD-ligand 1 pathway, respectively. As a result, NK cells and CD8+ T cells in tumors were increased, as were their effector cytokines. The activated innate and adaptive antitumor immune responses suppressed the growth and metastasis of tumors and prolonged survival of 4T1 tumor-bearing mice. BEN provides a reliable approach for improving cancer immunotherapy by destroying the immunosuppression web in tumors via multinode regulation.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Animals , Mice , Ligands , Drug Delivery Systems , Immunosuppressive Agents , Tumor Microenvironment
9.
Mol Carcinog ; 62(5): 628-640, 2023 05.
Article in English | MEDLINE | ID: mdl-36727616

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Currently, therapeutic modalities such as surgery, chemotherapy, radiotherapy, and immunotherapy are being used to treat HNSCC. However, the treatment outcomes of most patients are dismal because they are already in middle or advanced stage by the time of diagnosis and poorly responsive to treatments. It is therefore of great interest to clarify mechanisms that contribute to the metastasis of cells to identify possible targets for therapy. In this study, we identified the Na+ -coupled bicarbonate transporter, SLC4A7, play essential roles in the metastasis of HNSCC. Our results showed that the relative expression of SLC4A7 messenger RNA was highly expressed in HNSCCs samples from TCGA, and compared with precancerous cells of human oral mucosa (DOK), SLC4A7 was highly expressed in HNSCC cell lines. In vitro and in vivo experiments showed that dysregulation of SLC4A7 had minor influence on the proliferation of HNSCC but impacted HNSCC's migration and invasion. Meanwhile, SLC4A7 could promote epithelial-mesenchymal transition (EMT) in HNSCC. RNA-seq, KEGG pathway enrichment analysis and Western blot further revealed that downregulation of SLC4A7 in HNSCC cells inhibited the PI3K/AKT pathway. These findings were further validated via rescue experiments using a small molecule inhibitor of PI3K/mTOR (GDC-0980). Our findings suggest that SLC4A7 promotes EMT and metastasis of HNSCC through the PI3K/AKT/mTOR signaling pathway, which may be a valuable predictive biomarker and potential therapeutic target in HNSCC.


Subject(s)
Head and Neck Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Bicarbonates/metabolism , Epithelial-Mesenchymal Transition/genetics , Head and Neck Neoplasms/genetics , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Movement/genetics , Sodium-Bicarbonate Symporters/genetics , Sodium-Bicarbonate Symporters/metabolism
10.
Article in English | MEDLINE | ID: mdl-36300925

ABSTRACT

Sodium-based dual-ion batteries have shown great promise for large-scale energy storage applications due to their wide operating voltages, environmental friendliness, abundant sodium resources, and low cost, which are widely investigated by researchers. However, the development of high-performance anode materials is a key requirement for the realization of such electrochemical energy storage systems at the practical application level. Carbonaceous anode materials based on intercalation/deintercalation mechanisms typically exhibit low discharge capacities, while metal-based materials based on conversion or alloying reactions show unsatisfactory stability in performance. On the contrary, organic materials display high theoretical capacities due to their flexible molecular structure designability and stable cyclic performance with fast reaction kinetics based on the unique enolization reaction. Herein, we report an organic polymer anode material of polyimide (PNTO), combined with a high-concentration electrolyte; the sodium-based dual-ion battery system constructed exhibits outstanding electrochemical performance. The full battery shows an ultra-high specific discharge capacity of 293.2 mAh g-1 and can be cycled stably for 3200/5600/4100 cycles at ultra-high rates of 60/120/150 C without degradation. Furthermore, the dual-ion battery system demonstrates an extremely low self-discharge rate of 0.03% h-1 and superior fast-charging-slow-discharging performance. It is one of the best performances reported up to now for a dual-ion full battery based on an organic polymer anode. This novel battery system design strategy will facilitate the advancement of high-performance organic-based dual-ion batteries and is expected to be a promising candidate for large-scale energy storage applications.

11.
Acta Pharmacol Sin ; 43(12): 3045-3054, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36050519

ABSTRACT

Immunotherapy that activates immune systems for combating cancer has yielded considerable clinical benefits recently. However, the immunosuppressive tumor microenvironment (ITME) is a major hurdle to immunotherapy as it supports tumor to evade immune surveillance. Reversing ITME facilitates the recruitment and activation of antitumor immune cells, thereby promoting immunotherapy. Our group has developed various nanosized drug delivery systems (NDDSs) to modulate ITME with enhanced efficacy and safety. In the review we introduce the ITME-remodeling strategies for improving immunotherapy based on NDDSs including triggering tumor cells to undergo immunogenetic cell death (ICD), applying tumor vaccine, and directly regulating intratumoral immune components (immune cells or cytokines). In order to guide the design of NDDSs for amplified effects of antitumor immunotherapy, the contributions and future directions of this field are also discussed.


Subject(s)
Cancer Vaccines , Neoplasms , Humans , Immunotherapy , Drug Delivery Systems , Tumor Microenvironment , Neoplasms/therapy , Cancer Vaccines/therapeutic use , Immunologic Factors/pharmacology
12.
Front Cardiovasc Med ; 9: 930000, 2022.
Article in English | MEDLINE | ID: mdl-36035915

ABSTRACT

The associations between sleep duration and cardiovascular diseases (CVDs) have been explored in many observational studies. However, the causality of sleep duration and many CVDs, such as coronary artery disease (CAD), heart failure (HF), and stroke, remains unclear. In this study, we conducted a systematic meta-review and meta-analysis of the results of observational and Mendelian randomization (MR) studies to examine how sleep duration impacts the risk of CVDs. We searched articles published in English and before 10 September 2021 in PubMed, Web of Science, and Embase. The articles were screened independently by two reviewers to minimize potential bias. We combined the meta-analyses of observational studies and 11 MR studies and summarized evidence of the effect of sleep duration on the risk of CAD, HF, stroke, and cardiovascular and all-cause mortality. Results showed that (a) evidence is accumulating that short sleep duration is a causal risk factor for CAD and HF; (b) abundant evidence from observational studies supports that long sleep duration is associated with the risk of CAD, stroke, and mortality, and long sleep duration has no causal associations with stroke and CAD in the MR studies; the causation of long sleep duration and other CVDs should be further studied; and (c) emerging evidence indicates that an increase in hours of sleep is associated with a decreased risk of CAD. Finally, we discussed the underlying pathophysiological mechanisms underlying short sleep duration and CVDs and suggested that increasing sleep duration benefits cardiovascular health.

13.
Front Oncol ; 12: 917400, 2022.
Article in English | MEDLINE | ID: mdl-35880165

ABSTRACT

Endocrine therapy is considered as an effective strategy for estrogen and progestogen receptor (ER and PR)-positive breast cancer (BRCA) patients, whereas resistance to these agents is the major cause of BRCA mortality in women. Immune checkpoint receptor (ICR) blockade is another approach to treat BRCA, but the response rate of this approach for non-triple-negative breast cancer (non-TNBC) is relatively low. Recently, the androgen receptor (AR) has been identified as a tumor suppressor in ER-positive BRCA; however, the relationship between the levels of androgens and ICRs on T cells in BRCA is unclear. We observed that testosterone and dihydrotestosterone (DHT) in patients with HER2 and Luminal B were significantly lower than those in healthy controls, and the expression of AR has significant correlation with overall survival (OS) advantage for Luminal B patients. Moreover, testosterone and DHT were positively correlated with the PD-1 expression on Vδ1+ T cells in HER2 and Luminal B patients. These results suggest a potential approach of combining androgens with PD-1 blockade for treating HER2 and Luminal B breast cancer.

14.
ACS Omega ; 7(9): 7616-7624, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35284716

ABSTRACT

Energy issues have attracted great concern worldwide. Developing new energy has been the main choice, and the exploitation of the electrochemical energy storage devices plays an important role. Herein, a high-performance dual-ion battery system is proposed, which consists of a graphite cathode and SnS2 anode, with a high-concentration lithium salt electrolyte (4 M LiTFSI). The benefits from the typical sandwich-like layer structure of SnS2 are as follows: the highest discharge specific capacity of the battery could reach 130.0 mA h g-1 at a current density of 100 mA g-1, and even under an ultra-high current density of 2000 mA g-1, the highest capacity of 66.3 mA h g-1 is still achieved, with an outstanding capacity retention over 100% after 1000 cycles. Inspiringly, this system delivers an excellent low self-discharge of 1.19%/h, surpassing most of the reported dual-ion batteries. In addition, the working mechanism and structural stability are also investigated by X-ray diffraction and Raman spectra, indicating a good reversibility. These results reveal that this graphite/SnS2 dual-ion battery system could provide a promising alternative for a future high-performance energy storage device.

15.
J Immunother Cancer ; 10(3)2022 03.
Article in English | MEDLINE | ID: mdl-35318258

ABSTRACT

BACKGROUND: Epidemiological surveys have revealed that low serum vitamin D level was correlated with increased risk of tumors. Dysfunctional T cells in patients with tumor are characterized as exhausted with high levels of immune checkpoint receptors (ICRs). However, whether the reduced level of vitamin D in patients with cancer correlates with cytotoxic T-cell exhaustion is unknown. METHODS: Periphery blood samples from 172 patients with non-small cell lung cancer (NSCLC) were prospectively collected. Patients with NSCLC received one course of intravenous docetaxel (75 mg/m2) followed by treatment with or without rocaltrol at a dose of 0.5-2.0 µg/day for total of 3 weeks. We performed phenotypical and functional analysis of T-cell through flow cytometry. Vitamin D receptor (VDR) knockout and overexpression CD8+ and Vδ2+ T cells were constructed using Cas9-gRNA targeted and overexpressing approaches to identify 1α,25(OH)2D3/VDR-mediated transcription regulation for ICRs or antitumor activity in T cells. RESULTS: We show that serum level of vitamin D is negatively correlated with expression of programmed cell death-1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), but positively correlated with CD28 expression on CD8+ and Vγ9Vδ2+ T cells in patients with NSCLC. 1α,25(OH)2D3, the active form of vitamin D, promotes the nuclear translocation of VDR, which binds to the promoter region of Pdcd1, Tim3, and Tigit genes and inhibits their expression. Besides, 1α,25(OH)2D3 pretreatment also promotes the methylation of CpG island in the promoter region of the Pdcd1 gene and increases H3K27 acetylation at the promoter region of the Cd28 gene, which leads to surface PD-1 downregulation and CD28 upregulation, respectively. We further reveal that VDR-mediated Ca2+ influx enhanced expression of Th1 cytokines via T-cell receptor activation. Functionally, 1α,25(OH)2D3 pretreated CD8+ T cells or Vγ9Vδ2+ T cells showed increased Th1 cytokine production and enhanced antitumor immunity. Finally, oral 1α,25(OH)2D3 could also decrease expression of PD-1, Tim-3, TIGIT and increase expression of CD28, resulting in cytokine production (associated with antitumor immunity) by cytotoxic T cells of patients with NSCLC. CONCLUSIONS: Our findings uncover the pleiotropic effects of 1α,25(OH)2D3 in rescuing the exhausted phenotype of human cytotoxic T cells in patients with tumor and in promoting their antitumor immunity. TRIAL REGISTRATION NUMBER: ChiCTR2100051135.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , CD28 Antigens , CD8-Positive T-Lymphocytes , Cytokines , Hepatitis A Virus Cellular Receptor 2/genetics , Humans , Programmed Cell Death 1 Receptor , Vitamin D/pharmacology
16.
J Cancer ; 12(21): 6519-6530, 2021.
Article in English | MEDLINE | ID: mdl-34659543

ABSTRACT

Migration and invasion are the initial step in the metastatic process, while metastasis is responsible for the poor prognosis of head and neck squamous cell carcinoma (HNSCC). Since miRNA has been found as an important regulator of gene expression at the post-transcriptional level in various diseases including carcinoma, exploring the role of miRNA in cancer metastasis will facilitate the target therapy of advanced HNSCC. MiR-328-3p has been reported to be an onco-miRNA or a tumor suppressor in several cancers. However, the role of miR-328-3p in HNSCC migration and invasion remains undefined. In this study, we first demonstrated that miR-328-3p enhanced migration and invasion of HNSCC in vitro, accompanying with a promotion of epithelial-mesenchymal transition (EMT) and mTOR activity. Meanwhile, we confirmed that miR-328-3p directly targeted the 3'UTR of H2A histone family, member X (H2AFX), which served as a tumor suppressor in migration and invasion of HNSCC. Moreover, H2AFX could partially reverse the migration and invasion of HNSCC caused by miR-328-3p. Overall, our results indicated that miR-328-3p enhanced migration and invasion of HNSCC through targeting H2AFX and activated the mTOR pathway.

17.
ACS Omega ; 6(39): 25329-25337, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34632191

ABSTRACT

Based on the advantages of intrinsic safety, flexibility, and good interfacial contact with electrodes, a gel polymer electrolyte (GPE) is a promising electrolyte for lithium-ion batteries, compared with the conventional liquid electrolyte. However, the unstable electrochemical performance and the liquid state in a microscale limit the commercial application of GPE. Herein, we developed a novel gel polymer electrolyte for lithium-ion batteries by blending methyl methacrylate (MMA), N-butyl-N-methyl-piperidinium (Pyr14TFSI), and lithium salts in a solvent-free procedure, with SiO2 and Li0.33La0.56TiO3 (LLTO) additives. The prepared MMA-Pyr14TFSI-3 wt % LLTO electrolyte shows the best electrochemical performance and obtains a high ion conductivity of 4.51 × 10-3 S cm-1 at a temperature of 60 °C. Notably, the electrochemical window could be stable up to 5.0 V vs Li+/Li. Moreover, the batteries with the GPE also show excellent electrochemical performance. In the LiFePO4/MMA-Pyr14TFSI-3 wt % LLTO/Li cell, a high initial discharge capacity was achieved 150 mA h g-1 at 0.5C with a Coulombic efficiency over 99% and maintaining a good capacity retention of 90.7% after 100 cycles at 0.5C under 60 °C. In addition, the physical properties of the GPE have been investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD) measurements, Fourier transform infrared (FTIR) spectroscopy, and thermogravimetry (TG).

18.
ACS Appl Mater Interfaces ; 13(37): 44254-44265, 2021 Sep 22.
Article in English | MEDLINE | ID: mdl-34519196

ABSTRACT

Combining the advantages of dual-ion batteries (DIBs) and sodium-ion batteries (SIBs), we herein develop a superior sodium-based dual-ion battery (Na-DIB) based on the PTCDA organic anode and ionic liquid (IL) electrolyte. The system shows the highest specific discharge capacity of 177 mAh g-1 at 0.5C and excellent capacity retention over 100% at 2C after 200 cycles. Notably, even at an ultrahigh rate of 20C, the battery still maintains a considerable capacity of 60 mAh g-1 with a coulombic efficiency (CE) close to 100 and 94% capacity retention after 1000 cycles. Moreover, the self-discharge of the system has been investigated and shown to have an extremely low value of 0.18% h-1. Consequently, this work presents an excellent Na-DIB system, which could be a promising candidate for large-scale applications.

19.
Front Oncol ; 11: 679517, 2021.
Article in English | MEDLINE | ID: mdl-34381711

ABSTRACT

Triple-negative breast cancer (TNBC) escape from immune-mediated destruction was associated with immunosuppressive responses that dampened the activation of tumor-infiltrating CD8 and γδ T cells. TNBC had a higher level of programmed cell death 1-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO), compared with other breast cancer subtypes. But, clinical studies have revealed that the response rate of PD-1/PD-L1 antibody for TNBC treatment was relatively low. However, the antitumor responses of human Vγ9Vδ2 T cells or IDO inhibitor in TNBC treatment are unknown. In this study, we found that IDO1 and PD-L1 were highly expressed in TNBC patients. Analysis of the clinical samples demonstrated that Vγ9Vδ2 T cells became exhausted in triple-negative breast cancer patients. And Vγ9Vδ2 T cells combined with αPD-L1 could not further enhance their antitumor responses in vitro and in vivo. However, Vγ9Vδ2 T cells combined with IDO1 inhibitor 1-Methyl-L-tryptophan (1-MT) or Lindrostat showed substantial inhibitory effects on MDA-MB-231 tumor cells. Finally, we found that IDO1 inhibitor promoted T cell's cytotoxicity by enhancing perforin production. These results converged to suggest the potential application of Vγ9Vδ2 T cells treated with IDO1 inhibitor for TNBC therapy.

20.
ACS Omega ; 5(22): 13185-13195, 2020 Jun 09.
Article in English | MEDLINE | ID: mdl-32548505

ABSTRACT

Photocatalytic technology aiming to eliminate organic pollutants in water has been rapidly developed. In this work, we successfully synthesized CuWO4/ZnO photocatalysts with different weight ratios of CuWO4 through facile hydrothermal treatment. Crystal structures, forms, and optical properties of these as-prepared materials were investigated and analyzed. 3% CuWO4/ZnO showed the optimum photodegradation efficiency toward methylene blue under the irradiation of simulated sunlight for 120 min, the degradation rate of which was 98.9%. The pseudo-first-order rate constant of 3% CuWO4/ZnO was ∼11.3 and ∼3.5 times bigger than that of pristine CuWO4 and ZnO, respectively. Furthermore, the material exhibited high stability and reusability after five consecutive photocatalytic tests. In addition, free radical capture experiments were conducted and the possible mechanism proposed explained that the synergistic effect between CuWO4 and ZnO accelerates the photodegradation reaction. This work provides a feasible technical background for the efficient and sustainable utilization of photocatalysts in wastewater control.

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