ABSTRACT
Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of cytotoxic T lymphocytes (CTL) and dendritic cells (DC). Here, we report the development and application of a machine-learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD-1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells (GSC) and non-GSC GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.
ABSTRACT
Brain tumors, particularly glioblastoma (GBM), are devastating and challenging to treat, with a low 5-year survival rate of only 6.6%. Mouse models are established to understand tumorigenesis and develop new therapeutic strategies. Large-scale genomic studies have facilitated the identification of genetic alterations driving human brain tumor development and progression. Genetically engineered mouse models (GEMMs) with clinically relevant genetic alterations are widely used to investigate tumor origin. Additionally, syngeneic implantation models, utilizing cell lines derived from GEMMs or other sources, are popular for their consistent and relatively short latency period, addressing various brain cancer research questions. In recent years, the success of immunotherapy in specific cancer types has led to a surge in cancer immunology-related research which specifically necessitates the utilization of immunocompetent mouse models. In this review, we provide a comprehensive summary of GEMMs and syngeneic mouse models for adult brain tumors, emphasizing key features such as model origin, genetic alteration background, oncogenic mechanisms, and immune-related characteristics. Our review serves as a valuable resource for the brain tumor research community, aiding in the selection of appropriate models to study cancer immunology.
ABSTRACT
All-solid-state batteries (ASSBs) based on inorganic solid electrolytes fascinate a large body of researchers in terms of overcoming the inferior energy density and safety issues of existing lithium-ion batteries. To date, the cathode designs in the ASSBs achieve remarkable achievements, adding the urgency of scaling up the battery system toward inorganic solid-state pouch cell configuration for the application market. Herein, the recent developments of cathode materials and the design considerations for their application in the pouch cell format are reviewed to straighten out the roadmap of ASSBs. Specifically, the intercalation compounds and the conversion materials with conversion chemistries are highlighted and discussed as two potentially valuable material types. This review focuses on the basic electrochemical mechanisms, mechanical contact issues, and sheet-type structure in inorganic solid-state pouch cells with corresponding perspectives, thus guiding the future research direction. Finally, the benchmarks for manufacturing inorganic solid-state pouch cells to meet practical high energy density targets are provided in this review for the development of commercially viable products.
ABSTRACT
While layered metal oxides remain the dominant cathode materials for the state-of-the-art lithium-ion batteries, conversion-type cathodes such as sulfur present unique opportunities in developing cheaper, safer, and more energy-dense next-generation battery technologies. There has been remarkable progress in advancing the laboratory scale lithium-sulfur (Li-S) coin cells to a high level of performance. However, the relevant strategies cannot be readily translated to practical cell formats such as pouch cells and even battery pack. Here these key technical challenges are addressed by molecular engineering of the Li metal for hydrophobicization, fluorination and thus favorable anode chemistry. The introduced tris(2,4-di-tert-butylphenyl) phosphite (TBP) and tetrabutylammonium fluoride (TBA+F-) as well as cellulose membrane by rolling enables the formation of a functional thin layer that eliminates the vulnerability of Li metal towards the already demanding environment required (1.55% relative humidity) for cell production and gives rise to LiF-rich solid electrolyte interphase (SEI) to suppress dendrite growth. As a result, Li-S pouch cells assembled at a pilot production line survive 400 full charge/discharge cycles with an average Coulombic efficiency of 99.55% and impressive rate performance of 1.5 C. A cell-level energy density of 417 Wh kg-1 and power density of 2766 W kg-1 are also delivered via multilayer Li-S pouch cell. The Li-S battery pack can even power an unmanned aerial vehicle of 3 kg for a fairly long flight time. This work represents a big step forward acceleration in Li-S battery marketization for future energy storage featuring improved safety, sustainability, higher energy density as well as reduced cost.
ABSTRACT
Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neuro-oncology, and the survival status of patients after relapse usually means rapid deterioration, thus becoming the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulating the body's immune system to recognize and attack cancer cells, which could be used in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma. This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and especially focus on rGBM.
ABSTRACT
The safe operation of rechargeable batteries is crucial because of numerous instances of fire and explosion mishaps. However, battery chemistry involving metallic lithium (Li) as the anode is prone to thermal runaway in flammable organic electrolytes under abusive conditions. Herein, an in situ encapsulation strategy is proposed to construct nonflammable quasi-solid electrolytes through the radical polymerization of a hexafluorobutyl acrylate (HFBA) monomer and a pentaerythritol tetraacrylate (PETEA) crosslinker. The quasi-solid system eliminates the inherent flammability of ether electrolytes with zero self-extinguishing time owing to the gas-phase radical capturing ability of HFBA. Additionally, the graphitized carbon layer generated during the decomposition of PETEA at high temperatures obstructs the heat and oxygen required for combustion. When coupled with Au-modified reduced graphene oxide anodic current collectors and lithium sulfide cathodes, the assembled anode-free Li-metal cell based on the quasi-solid electrolyte exhibits no signs of cell expansion or gas generation during cycling, and thermal runaway is eliminated under multiple mechanical, electrical, and thermal abuse scenarios and even rigorous strikes. This nonflammable quasi-solid configuration with gas- and condensed-phase flame-retardant mechanisms can drive a technological leap in anode-free Li-metal pouch cells and secure the practical applications necessary to power this society in a safe manner.
ABSTRACT
Utilizing catalysts to accelerate polysulfides conversion are of paramount importance to eliminate the shuttling effect and improve the practical performance of lithium-sulfur (Li-S) batteries. The amorphism, attributes to the abundant unsaturated surface active sites, has recently been recognized as a contribution to increase the activity of catalysts. However, the investigation on amorphous catalysts has received limited interest in lithium-sulfur batteries due to lack of understanding of their composition structure activity. Herein, a amorphous Fe-Phytate structure is proposed to enhance polysulfide conversion and suppress polysulfide shuttling by modifying polypropylene separator (C-Fe-Phytate@PP). The polar Fe-Phytate with distorted VI coordination Fe active centers strongly intake polysulfide electron by forming FeS bond to accelerate the polysulfide conversion. The surface mediated polysulfides redox gives rise to a higher exchange current in comparison with carbon. Furthermore, Fe-Phytate owns robust adsorption to polysulfide and effectively reduce the shuttling effect. With the C-Fe-Phytate@PP separator, the Li-S batteries exhibit an outstanding rate capability of 690 mAh g-1 at 5 C and an ultrahigh areal capacity of 7.8 mAh cm-2 even at a high sulfur loading of 7.3 mg cm-2 . The work provides a novel separator for facilitating the actual applications of Li-S batteries.
ABSTRACT
The practical application of lithium metal batteries is considered to be one of the most promising successors for lithium-ion batteries due to their ability to meet the high-energy storage demands of modern society. However, their application is still hindered by the unstable solid electrolyte interphase (SEI) and uncontrollable dendrite growth. In this study, we propose a robust composite SEI (C-SEI) that consists of a fluorine doped boron nitride (F-BN) inner layer and an organic polyvinyl alcohol (PVA) outer layer. Both theoretical calculations and experimental results demonstrate that the F-BN inner layer induces the formation of favourable components (LiF and Li3N) at the interface, promoting rapid ionic transport and inhibiting electrolyte decomposition. The PVA outer layer acts as a flexible buffer in the C-SEI, ensuring the structural integrity of the inorganic inner layer during lithium plating and stripping. The C-SEI modified lithium anode shows a dendrite-free performance and stable cycle over 1200 h, with an ultralow overpotential (15 mV) at 1 mA cm-2 in this study. This novel approach also enhances the stability of capacity retention rate by 62.3% after 100 cycles even in anode-free full cells (C-SEI@Cu||LFP). Our findings suggest a feasible strategy for addressing the instability inherent in SEI, showing great prospects for the practical application of lithium metal batteries.
ABSTRACT
Without excess Li, anode-free Li-metal batteries (AFLMBs) have been proposed as the most likely solution to realizing highly-safe and cost-effective Li-metal batteries. Nevertheless, short cyclic life puzzles conventional AFLMBs due to anodic dead Li accumulation with a local current concentration induced by irreversible electrolyte depletion, insufficient active Li reservoir and slow Li+ transfer at the solid electrolyte interphase (SEI). Herein, SrI2 is introduced into carbon paper (CP) current collector to effectively suppress dead Li through synergistic mechanisms including reversible I- /I3 - redox reaction to reactivate dead Li, dielectric SEI surface with SrF2 and LiF to prevent electrolyte decomposition and highly ionic conductive (3.488â mS cm-1 ) inner layer of SEI with abundant LiI to enable efficient Li+ transfer inside. With the SrI2 -modified current collector, the NCM532/CP cell delivers unprecedented cyclic performances with a capacity of 129.2â mAh g-1 after 200â cycles.
ABSTRACT
Incorporation of ceramic materials into separators has been frequently applied in both research and industry to improve the overall high-temperature performances of lithium ion batteries. However, inorganic ceramic particles tend to form aggregation in separators and even fall off in the separator matrix due to the inferior combination between ceramic particles and polymer matrix, giving rise to a decrease in separator porosity and thus the degradation of battery performances. Herein, a single-layer core-shell architecture is designed to reinforce the polymer matrix through encircling Al2 O3 particles by poly(vinylidene fluoride) with strong inter-molecular interaction. The 3D-reinforced microstructure effectively improves pore distribution and thermal stability to resist the dimensional deformation at high temperatures, thus giving rise to a high Coulombic efficiency of 99.16% and 87.5% capacity retention after 500 cycles at 80 °C for LiFePO4 /Li batteries. In particular, the excellent performances of the proposed separator microstructure are confirmed with a thickness value of commercial separators. This work provides a promising strategy to fabricate a core-shell structural composite separator for stable lithium ion batteries at high temperatures.
ABSTRACT
Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors - cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) - and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.
Subject(s)
DNA-Binding Proteins , Glioblastoma , Melanoma , Membrane Proteins , Animals , DNA-Binding Proteins/genetics , Glioblastoma/pathology , Glioblastoma/therapy , Humans , Inflammasomes , Leukocytes, Mononuclear/pathology , Membrane Proteins/genetics , Mice , Nucleotidyltransferases/geneticsABSTRACT
Background: Ankyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted to explore its function in prognosis and immune microenvironment. Method: In this study, mRNA expression data were downloaded from TCGA and GTEx database. Next generation sequencing data from 14 glioblastoma multiforme (GBM) samples by neurosurgical resection were used as validation dataset. Multiple bioinformatics methods (ssGSEA, Kaplan-Meier, Cox regression analysis, GSEA and online tools) were applied to explore ASB3 expression, gene activity, prognosis of patients in various cancers, and its correlation with clinical information, immune microenvironment and pertinent signal pathways in GBM. The biological function of ASB3 in tumor-infiltrating lymphocytes (TILs) was verified using an animal model. Results: We found that ASB3 was aberrant expressed in a variety of tumors, especially in GBM, and significantly correlated with the prognosis of cancer patients. The level of ASB3 was related to the TMB, MSI and immune cell infiltration in some cancer types. ASB3 had a negative association with immune infiltration and TME, including regulatory T cells (Tregs), cancer-associated fibroblasts, immunosuppressors and related signaling pathways in GBM. ASB3 overexpression reduced the proportion of Tregs in TILs. GSEA and PPI analysis also showed negative correlation between ASB3 expression and oncogenetic signaling pathways in GBM. Conclusion: A comprehensive pan-cancer analysis of ASB3 showed its potential function as a biomarker of cancer prognosis and effective prediction of immunotherapy response. This study not only enriches the understanding of the biological function of ASB3 in pan-cancer, especially in GBM immunity, but also provides a new reference for the personalized immunotherapy of GBM.
Subject(s)
Cancer-Associated Fibroblasts , Glioblastoma , Animals , Glioblastoma/genetics , Carcinogenesis , Cell Transformation, Neoplastic , Computational Biology , Tumor Microenvironment/geneticsABSTRACT
OBJECTIVE: The aim of the objective was to present our initial experience and evaluate the feasibility of the novel comprehensive modified laparoscopic pyeloplasty (CMLP) technique based on membrane anatomy. MATERIALS AND METHODS: Forty-eight patients underwent CMLP from February 2016 to October 2020. CMLP involves the following: dissection of the ureter was based on the fascia or fusion fascia formed by embryonic development. The ureter was separated from the ureteral sheath, and the pelvis and ureter were incised with incomplete amputation. The first stitch was placed between the lower point of the spatulated ureter and the lowest corner of the renal pelvis to ensure correct orientation of the anastomosis; anastomosis of the renal pelvis and ureter was performed using the touchless technique. RESULTS: All CMLPs were completed successfully without conversion. The mean overall operating time was 230.96 min. The median estimated blood loss was 50.00 (interquartile range 20.00-57.50) mL. The average postoperative hospital stay was 9.31 days. The average follow-up time was 24.73 months. No major complications occurred. In 1 case, revision laparoscopic pyeloplasty was performed, but the obstruction persisted after double J stent removal, so ultimately, the double J stent required regular replacement. Another asymptomatic patient with hydronephrosis experienced failed treatment and is still under follow-up. The overall success rate was 95.83% (46/48). The success rate in patients with recurrent ureteropelvic junction obstruction (UPJO) was 87.5% (7/8). CONCLUSIONS: CMLP is a practical and effective treatment option for UPJO with a high success rate. An advantage of CMLP is the clear surgical field.
Subject(s)
Laparoscopy , Ureter , Ureteral Obstruction , Female , Humans , Kidney Pelvis/surgery , Laparoscopy/methods , Male , Ureter/surgery , Ureteral Obstruction/complications , Ureteral Obstruction/surgery , Urologic Surgical Procedures/methodsABSTRACT
Lithium metal batteries (LMBs) have aroused extensive interest in the field of energy storage owing to the ultrahigh anode capacity. However, strong solvation of Li+ and slow interfacial ion transfer associated with conventional electrolytes limit their long-cycle and high-rate capabilities. Herein an electrolyte system based on fluoroalkyl ether 2,2,2-trifluoroethyl-1,1,2,3,3,3-hexafluoropropyl ether (THE) and ether electrolytes is designed to effectively upgrade the long-cycle and high-rate performances of LMBs. THE owns large adsorption energy with ether-based solvents, thus reducing Li+ interaction and solvation in ether electrolytes. With THE rich in fluoroalkyl groups adjacent to oxygen atoms, the electrolyte owns ultrahigh polarity, enabling solvation-free Li+ transfer with a substantially decreased energy barrier and ten times enhancement in Li+ transference at the electrolyte/anode interface. In addition, the uniform adsorption of fluorine-rich THE on the anode and subsequent LiF formation suppress dendrite formation and stabilize the solid electrolyte interphase layer. With the electrolyte, the lithium metal battery with a LiFePO4 cathode delivers unprecedented cyclic performances with only 0.0012% capacity loss per cycle over 5000 cycles at 10 C. Such enhancement is consistently observed for LMBs with other mainstream electrodes including LiCoO2 and LiNi0.5 Mn0.3 Co0.2 O2 , suggesting the generality of the electrolyte design for battery applications.
ABSTRACT
Developing advanced electrode materials with enhanced charge-transfer kinetics is the key to realizing fast energy storage technologies. Commonly used modification strategies, such as nanoengineering and carbon coating, are mainly focused on electron transfer and bulk Li+ diffusion. Nonetheless, the desolvation behavior, which is considered as the rate-limiting process for charge-storage, is rarely studied. Herein, we designed a nitridation layer on the surface of Wadsley-Roth phase FeNb11O29 (FNO-x@N) to act as a desolvation promoter. Theoretical calculations demonstrate that the adsorption and desolvation of solvated Li+ is efficiently improved at FNO-x@N/electrolyte interphase, leading to the reduced desolvation energy barrier. Moreover, the nitridation layer can also help to prevent solvent cointercalation during Li+ insertion, leading to advantageous shrinkage of block area and reduced volume change of lattice cell during cycling. Consequently, FNO-x@N exhibits a high-rate capacity of 129.7 mAh g-1 with negligible capacity decay for 10â¯000 cycles.
ABSTRACT
It is still challenging to develop sulfur electrodes for Li-S batteries with high electrical conductivity and fast kinetics, as well as efficient suppression of the shuttling effect of lithium polysulfides. To address such issues, herein, polar MoTe2 with different phases (2H, 1T, and 1T') were deeply investigated by density functional theory calculations, suggesting that the 1T'-MoTe2 displays concentrated density of states (DOS) near the Fermi level with high conductivity. By optimization of the synthesis, 1T'-MoTe2 quantum dots decorated three-dimensional graphene (MTQ@3DG) was prepared to overcome these issues, and it accomplished exceptional performance in Li-S batteries. Owing to the chemisorption and high catalytic effect of 1T'-MoTe2 quantum dots, MTQ@3DG/S exhibits highly reversible discharge capacity of 1310.1 mAh g-1 at 0.2 C with 0.026% capacity fade rate per cycle over 600 cycles. The adsorption calculation demonstrates that the conversion of Li2S2 to Li2S is the rate-limiting step where the Gibbs free energies are 1.07 eV for graphene and 0.97 eV for 1T'-MoTe2, revealing the importance of 1T'-MoTe2. Furthermore, in situ Raman spectroscopy investigation proved the suppression of the shuttle effect of LiPSs in MTQ@3DG/S cells during the cycle.
ABSTRACT
The slow redox kinetics during cycling process and the serious shuttle effect caused by the solubility of lithium polysulfides (LiPSs) dramatically hinder the practical application of Li-S batteries. Herein, a facile and scalable spray-drying strategy is presented to construct conductive polar Mo2 C quantum dots-decorated carbon nanotube (CNT) networks (MCN) as an efficient absorbent and electrocatalyst for Li-S batteries. The results reveal that the MCN/S electrode exhibits a high specific capacity of 1303.3 mAh g-1 at 0.2 C, and ultrastable cycling stability with decay of 0.019% per cycle even at 1 C. Theoretical simulation uncovers that Mo2 C exhibits much stronger binding energies for S8 and Li2 Sn . The energy barrier for the conversion between Li2 S4 and Li2 S2 decreases from 1.02 to 0.72 eV when hybriding with Mo2 C. Furthermore, in situ discharge/charge-dependent Raman spectroscopy shows that long-chain Li2 S8 configuration is generated via S8 ring opening near the first plateaus at ≈2.36 V versus Li/Li+ and the S6 2- configuration in CNT/S electrode is maintained below the potential of ≈2.30 V versus Li/Li+ , indicating that the shuttle of soluble LiPSs happens during the whole discharge process. This work provides deep insights into the polar nanoarchitecture design and scalable fabrication for advanced Li-S batteries.
ABSTRACT
Although Li-metal anodes are extremely attractive owing to the ultrahigh theoretical specific capacity, the low Coulombic efficiency and severe safety hazards resulting from uncontrollable Li dendrites growth hinder their widespread implementation. Herein, we propose a novel design of Ni macropore arrays for the functional Li deposition host. Benefiting from the regulated electric field distribution, Li nucleation and growth can be well confined within conductive Ni macropores. Consequently, the Ni macropore array electrode exhibits stable Li deposition behavior, i.e., high Coulombic efficiency of above 97% over 400 cycles for 1.0 mAh cm-2. Most importantly, the LiFePO4 || Li-Ni macropore arrays full cell also shows greatly enhanced cycling stability (90.3 mAh g-1 at 1 C after 700 cycles), holding great promise for high-performance rechargeable Li metal batteries.
ABSTRACT
Lithium metal represents an ultimate anode material of lithium batteries for its high energy density. However, its large negative redox potential and reactive nature can trigger electrolyte decomposition and dendrite formation, causing unstable cycling and short circuit of batteries. Herein, we engineer a resilient solid electrolyte interphase on the Li anode by compositing the battery separator with organosulfur compounds and inorganic salts from garlic. These compounds take part in battery reactions to suppress dendrite growth through reversible electrochemistry and attenuate ionic concentration gradient. When the Li anode and the separator are paired with the LiFePO4 cathode, one obtains a battery delivering long-term cycling stability of 3000 cycles, a rate capacity of 100 mAh g-1 at 10 C (2.5 mA cm-2), a Coulombic efficiency of 99.9%, and a low battery polarization. Additionally, with high-loading 20 mg cm-2 LiFePO4 cathodes, an areal capacity of 3.4 mAh cm-2 is achieved at 0.3 C (1 mA cm-2).
ABSTRACT
The lithium sulfur battery is regarded as a potential next-generation high-energy battery system. However, polysulfides dissolve and shuttle through the electrolytes, causing rapid capacity decay, serious self-discharge, and poor high-temperature performances. Here, we demonstrate that by directly introducing glutamate into commercial electrolytes, these issues can be tackled simultaneously. With abundant negatively charged hydroxyl groups, the glutamate additive electrolyte effectively suppresses the shuttling of negatively charged polysulfide ions through strong repulsive interaction up to 1.54 eV. With glutamate additive electrolyte, the lithium sulfur battery has a capacity retention of 60% after 1000 cycles at 5.95 mA/cm2, a self-discharge rate on the order of one-third that of commercial electrolytes, and stable operation at 60 °C.