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Ideal solid electrolytes for lithium (Li) metal batteries should conduct Li+ rapidly with low activation energy, exhibit a high Li+ transference number, form a stable interface with the Li anode, and be electrochemically stable. However, the lack of solid electrolytes that meet all of these criteria has remained a considerable bottleneck in the advancement of lithium metal batteries. In this study, we present a design strategy combining all of those requirements in a balanced manner to realize quasi-solid-state electrolyte-enabled Li metal batteries (LMBs). We prepared Li+-coordinated triptycene-based ionic porous organic polymers (Li+@iPOPs). The Li+@iPOPs with imidazolates and phenoxides exhibited a high conductivity of 4.38 mS cm-1 at room temperature, a low activation energy of 0.627 eV, a high Li+ transference number of 0.95, a stable electrochemical window of up to 4.4 V, excellent compatibility with Li metal electrodes, and high stability during Li deposition/stripping cycles. The high performance is attributed to charge delocalization in the backbone, mimicking the concept of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), which facilitates the diffusion of coordinated Li+ through the porous space of the triptycene-based iPOPs. In addition, Li metal batteries assembled using Li+@Trp-Im-O-POPs as quasi-solid-state electrolytes and a LiFePO4 cathode showed an initial capacity of 114 mAh g-1 and 86.7% retention up to 200 cycles.
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Anion exchange membrane fuel cell (AEMFC) is an emerging and promising technology that can help realize a carbon-neutral, sustainable economy. Also, compared to the proton exchange membrane counterpart, AEMFC can achieve comparable cell outputs with lower costs due to the applicability of non-platinum group metal electrocatalysts for the reaction on the electrodes' surfaces. However, the wide application of the AEMFCs has been impeded by the unsatisfactory stability and performance of the hydroxide-conductive membranes in the past. Recently researchers have made breakthroughs using polyarylene (PA)-based AEMs. This article summarizes the recent advances of a class of AEMs with aromatic backbone without ether bonds, mainly synthesized by Friedel-Crafts polycondensation. Such PA-based AEMs showed high chemical/mechanical stabilities and ionic conductivity, and even the fuel cell with those AEMs showed impressive peak power density of up to 2.58â W cm-2. In this concept article, we classify major strategies for making PA-based AEMs to show the recent trends, highlight synthesis, characterization, and properties, and provide a brief outlook.
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Chiral nanomaterials with unique chiral configurations and biocompatible ligands have been booming over the past decade for their interesting chiroptical effect, unique catalytical activity, and related bioapplications. The catalytic activity and selectivity of chiral nanomaterials have emerged as important topics, that can be potentially controlled and optimized by the rational biochemical design of nanomaterials. In this review, chiral nanomaterials synthesis, composition, and catalytic performances of different biohybrid chiral nanomaterials are discussed. The construction of chiral nanomaterials with multiscale chiral geometries along with the underlying principles for enhancing chiroptical responses are highlighted. Various biochemical approaches to regulate the selectivity and catalytic activity of chiral nanomaterials for biocatalysis are also summarized. Furthermore, attention is paid to specific chiral ligands, materials compositions, structure characteristics, and so on for introducing selective catalytic activities of representative chiral nanomaterials, with emphasis on substrates including small molecules, biological macromolecule, and in-site catalysis in living systems. Promising progress has also been emphasized in chiral nanomaterials featuring structural versatility and improved chiral responses that gave rise to unprecedented chances to utilize light for biocatalytic applications. In summary, the challenges, future trends, and prospects associated with chiral nanomaterials for catalysis are comprehensively proposed.
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Nanoestruturas , Nanoestruturas/química , Catálise , Estereoisomerismo , Materiais Biomiméticos/química , Biomimética/métodos , BiocatáliseAssuntos
Vacinas contra Papillomavirus , Verrugas , Humanos , Verrugas/virologia , Verrugas/diagnóstico , Feminino , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Dermatoses do Pé/virologia , Dermatoses Faciais/virologia , Dermatoses Faciais/diagnósticoRESUMO
BACKGROUND: Although PD-1 blockade is effective for treating several types of cancer, the efficacy of this agent in glioblastoma is largely limited. To overcome non-responders and the immunosuppressive tumor microenvironment, combinational immunotherapeutic strategies with anti-PD-1 need to be considered. Here, we developed IL-12-secreting mesenchymal stem cells (MSC_IL-12) with glioblastoma tropism and evaluated the therapeutic effects of anti-PD-1, MSC_IL-12, and their combination against glioblastoma. METHODS: Therapeutic responses were evaluated using an immunocompetent mouse orthotopic model. Tumor-infiltrating lymphocytes (TILs) were analyzed using immunofluorescent imaging. Single-cell transcriptome was obtained from mouse brains after treatments. RESULTS: Anti-PD-1 and MSC_IL-12 showed complete tumor remission in 25.0% (4/16) and 23.1% (3/13) of glioblastoma-implanted mice, respectively, and their combination yielded synergistic antitumor efficacy indicated by 50.0% (6/12) of complete tumor remission. Analyses of TILs revealed that anti-PD-1 increased CD8+ T cells, while MSC_IL-12 led to infiltration of CD4+ T cells and NK cells. Both therapies reduced frequencies of Tregs. All these aspects observed in each monotherapy group were superimposed in the combination group. Notably, no tumor growth was observed upon rechallenge in cured mice, indicating long-term immunity against glioblastoma provoked by the therapies. Single-cell RNA-seq data confirmed these results and revealed that the combined treatment led to immune-favorable tumor microenvironment-CD4+, CD8+ T cells, effector memory T cells, and activated microglia were increased, whereas exhausted T cells, Tregs, and M2 polarized microglia were reduced. CONCLUSION: Anti-PD-1 and MSC_IL-12 monotherapies show long-term therapeutic responses, and their combination further enhances antitumor efficacy against glioblastoma via inducing immune-favorable tumor microenvironment.
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Glioblastoma , Células-Tronco Mesenquimais , Animais , Camundongos , Glioblastoma/patologia , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1 , Imunoterapia/métodos , Interleucina-12 , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células-Tronco Mesenquimais/patologia , Microambiente TumoralRESUMO
Poly(ethylene oxide) (PEO)-based electrolytes are often used for Li+ conduction as they can dissociate the Li salts efficiently. However, high entanglement of the chains and lack of pathways for rapid ion diffusion limit their applications in advanced batteries. Recent developments in ionic covalent organic frameworks (iCOFs) showed that their highly ordered structures provide efficient pathways for Li+ transport, solving the limitations of traditional PEO-based electrolytes. Here, we present imidazolate COFs, PI-TMEFB-COFs, having methoxyethoxy chains, synthesized by Debus-Radziszewski multicomponent reactions and their ionized form, Li+@PI-TMEFB-COFs, showing a high Li+ conductivity of 8.81â mS cm-1 and a transference number of 0.974. The mechanism for such excellent electrochemical properties is that methoxyethoxy chains dissociate LiClO4, making free Li+, then those Li+ are transported through the imidazolate COFs' pores. The synthesized Li+@PI-TMEFB-COFs formed a stable interface with Li metal. Thus, employing Li+@PI-TMEFB-COFs as the solid electrolyte to assemble LiFePO4 batteries showed an initial discharge capacity of 119.2â mAh g-1 at 0.5â C, and 82.0 % capacity and 99.9 % Coulombic efficiency were maintained after 400â cycles. These results show that iCOFs with ether chains synthesized via multicomponent reactions can create a new chapter for making solid electrolytes for advanced rechargeable batteries.
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Rechargeable Li metal batteries have the potential to meet the demands of high-energy density batteries for electric vehicles and grid-energy storage system applications. Achieving this goal, however, requires resolving not only safety concerns and a shortened battery cycle life arising from a combination of undesirable lithium dendrite and solid-electrolyte interphase formations. Here, a series of microcrack-free anionic network polymer membranes formed by a facile one-step click reaction are reported, displaying a high cation conductivity of 3.1 × 10-5 S cm-1 at high temperature, a wide electrochemical stability window up to 5 V, a remarkable resistance to dendrite growth, and outstanding non-flammability. These enhanced properties are attributed to the presence of tethered borate anions in microcrack-free membranes, which benefits the acceleration of selective Li+ cations transport as well as suppression of dendrite growth. Ultimately, the microcrack-free anionic network polymer membranes render Li metal batteries a safe and long-cyclable energy storage device at high temperatures with a capacity retention of 92.7% and an average coulombic efficiency of 99.867% at 450 cycles.
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Single-atom catalysts (SACs) have been investigated and applied to energy conversion devices. However, issues of metal agglomeration, low metal loading, and substrate stability have hindered realization of the SACs' full potential. Recently, covalent organic framework (COF)-based SACs have emerged as promising materials to enable highly efficient catalytic reactions. Here, we summarize the representative COF-based SACs and their wide application in clean energy devices and conversion reactions, such as hydrogen evolution reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, oxygen reduction reaction, and oxygen evolution reaction. Based on their catalysis conditions, these reactions are categorized into photocatalyzed and electrocatalyzed reactions. We also summarize their design strategies, including heteroatom inclusion, donor-acceptor pairs, pore engineering, interface engineering, etc. Although COF-based SACs are promising, more efforts, such as linkage engineering, functional groups, ionization, multifunctional sites for cocatalyzed systems, etc., could improve them to be the ideal SAC materials. At the end, we provide our perspectives on where the field will proceed in the next 5 years.
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Chemically inert organic networks exhibiting electrical conductivity comparable to metals can advance organic electronics, catalysis, and energy storage systems. Covalent-organic frameworks (COFs) have emerged as promising materials for those applications due to their high crystallinity, porosity, and tunable functionality. However, their low conductivity has limited their practical utilization. In this study, copper-coordinated-fluorinated-phthalocyanine and 2,3,6,7-tetrahydroxy-9,10-anthraquinone-based COF (CuPc-AQ-COF) films with ultrahigh conductivity are developed. The COF films exhibit an electrical conductivity of 1.53 × 103 S m-1 and a Hall mobility of 6.02 × 102 cm2 V-1 s-1 at 298 K, reaching the level of metals. The films are constructed by linking phthalocyanines and anthraquinones through vapor-assisted synthesis. The high conductivity properties of the films are attributed to the molecular design of the CuPc-AQ-COFs and the generation of high-quality crystals via the vapor-assisted method. Density functional theory analysis reveals that an efficient donor-acceptor system between the copper-coordinated phthalocyanines and anthraquinones significantly promotes charge transfer. Overall, the CuPc-AQ-COF films set new records of COF conductivity and mobility and represent a significant step forward in the development of COFs for electronic, catalytic, and electrochemical applications.
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Lithium (Li)-metal batteries (LMBs) possess the highest theoretical energy density among current battery designs and thus have enormous potential for use in energy storage. However, the development of LMBs has been severely hindered by safety concerns arising from dendrite growth and unstable interphases on the Li anode. Covalent organic frameworks (COFs) incorporating either redox-active or anionic moieties on their backbones have high Li-ion (Li+) conductivities and mechanical/chemical stabilities, so are promising for solid electrolyte interphases (SEIs) in LMBs. Here, we synthesized anthraquinone-based silicate COFs (AQ-Si-COFs) that contained both redox-active and anionic sites via condensation of tetrahydroxyanthraquinone with silicon dioxide. The nine Li+-mediated charge/discharge processes enabled the AQ-Si-COF to demonstrate an ionic conductivity of 9.8 mS cm-1 at room temperature and a single-ion-conductive transference number of 0.92. Computational studies also supported the nine Li+ mechanism. We used AQ-Si-COF as the solid electrolyte interphase on the Li anode. The LMB cells with a LiCoO2 cathode attained a maximum reversible capacity of 188 mAh g-1 at 0.25 C during high-voltage operation. Moreover, this LMB cell demonstrated suppressed dendrite growth and stable cyclability, with its capacity decreasing by less than 3% up to 100 cycles. These findings demonstrate the effectiveness of our redox-active and anionic COFs and their practical utility as SEI in LMB.
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Circular RNA (circRNA) is a non-coding RNA with a covalently closed loop structure and usually more stable than messenger RNA (mRNA). However, coding sequences (CDSs) following an internal ribosome entry site (IRES) in circRNAs can be translated, and this property has been recently utilized to produce proteins as novel therapeutic tools. However, it is difficult to produce large proteins from circRNAs because of the low circularization efficiency of lengthy RNAs. In this study, we report that we successfully synthesized circRNAs with the splint DNA ligation method using RNA ligase 1 and the splint DNAs, which contain complementary sequences to both ends of precursor linear RNAs. This method results in more efficient circularization than the conventional enzymatic method that does not use the splint DNAs, easily generating circRNAs that express relatively large proteins, including IgG heavy and light chains. Longer splint DNA (42 nucleotide) is more effective in circularization. Also, the use of splint DNAs with an adenine analog, 2,6-diaminopurine (DAP), increase the circularization efficiency presumably by strengthening the interaction between the splint DNAs and the precursor RNAs. The splint DNA ligation method requires 5 times more splint DNA than the precursor RNA to efficiently produce circRNAs, but our modified splint DNA ligation method can produce circRNAs using the amount of splint DNA which is equal to that of the precursor RNA. Our modified splint DNA ligation method will help develop novel therapeutic tools using circRNAs, to treat various diseases and to develop human and veterinary vaccines.
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The molecular mechanisms underlying melanoma metastasis remain poorly understood. In this study, we aimed to delineate the mechanisms underlying gene expression alterations during metastatic potential acquisition and characterize the metastatic subclones within primary cell lines. We performed single-cell RNA sequencing of a poorly metastatic melanoma cell line (WM239A) and its subclones with high metastatic potential to the lung (113/6-4L) and the brain (131/4-5B1 and 131/4-5B2). Unsupervised clustering of 8173 melanoma cells identified three distinct clusters according to cell type ('Primary', 'Lung' and 'Brain' clusters) with differential expression of MITF and AXL pathways and putative cancer and cell cycle drivers, with the lung cluster expressing intermediate but distinct gene profiles between primary and brain clusters. Principal component (PC) analysis revealed that PC2 (the second PC), which was positively associated with MITF expression and negatively with AXL pathways, primarily segregated cell types, in addition to PC1 of the cell cycle pathway. Pseudotime trajectory and RNA velocity analyses suggested the existence of cellular subsets with metastatic potential in the Primary cluster and an association between PC2 signature alteration and metastasis potential acquisition. Analysis of The Cancer Genome Atlas melanoma samples by clustering into PC2-high and -low clusters by quartiles of PC2 signature expression revealed that the PC2-high cluster was an independent significant factor for poor prognosis (p-value = 0.003) with distinct genomic and transcriptomic characteristics, compared to the PC2-low cluster. In conclusion, we identified signatures of melanoma metastasis with prognostic significance and putative pro-metastatic subclones within a primary cell line.
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The lack of anion exchange membranes (AEMs) that possess both high hydroxide conductivity and stable mechanical and chemical properties poses a major challenge to the development of high-performance fuel cells. Improving one side of the balance between conductivity and stability usually means sacrificing the other. Herein, we used facile, high-yield chemical reactions to design and synthesize a piperidinium polymer with a polyethylene backbone for AEM fuel cell applications. To improve the performance, we introduced ionic crosslinking into high-cationic-ratio AEMs to suppress high water uptake and swelling while further improving the hydroxide conductivity. Remarkably, PEP80-20PS achieved a hydroxide conductivity of 354.3â mS cm-1 at 80 °C while remaining mechanically stable. Compared with the base polymer PEP80, the water uptake of PEP80-20PS decreased by 69 % from 813 % to 350 %, and the swelling decreased substantially by 85 % from 350.0 % to 50.2 % at 80 °C. PEP80-20PS also showed excellent alkaline stability, 84.7 % remained after 35â days of treatment with an aqueous KOH solution. The chemical design in this study represents a significant advancement toward the development of simultaneously highly stable and conductive AEMs for fuel cell applications.
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BACKGROUND: Although cytoreductive surgery followed by adjuvant chemotherapy is effective as a standard treatment for early-stage ovarian cancer, the majority of ovarian cancer cases are diagnosed at the advanced stages with dissemination to the peritoneal cavity, leading to a poor prognosis. Therefore, it is crucial to understand the cellular and molecular mechanisms underlying metastasis and identify novel therapeutic targets. OBJECTIVE: In this study, we aimed to elucidate the mechanisms underlying gene expression alterations during the acquisition of metastatic potential and characterize the metastatic subpopulations within ovarian cancer cells. METHODS: We conducted single-cell RNA sequencing of two human ovarian cancer cell lines: SKOV-3 and SKOV-3-13, a highly metastatic subclone of SKOV-3. Suppression of NFE2L1 expression was performed through siRNA-mediated knockdown and CRISPR-Cas9-mediated knockout. RESULTS: Clustering and pseudotime trajectory analysis revealed pro-metastatic subpopulation within these cells. Furthermore, gene set enrichment analysis and prognosis analysis indicated that NFE2L1 could be a key transcription factor in the acquisition of metastasis potential. Inhibition of NFE2L1 significantly reduced migration and viability of both cells. In addition, NFE2L1 knockout cells exhibited significantly reduced tumor growth in a mouse xenograft model, recapitulating in silico and in vitro results. CONCLUSION: The results presented in this study deepen our understanding of the molecular pathogenesis of ovarian cancer metastasis with the ultimate goal of developing treatments targeting pro-metastatic subclones prior to metastasis.
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Neoplasias Ovarianas , Fatores de Transcrição , Humanos , Animais , Camundongos , Feminino , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Análise de Sequência de RNA , Fator 1 Relacionado a NF-E2/genéticaRESUMO
Water purification is becoming increasingly important due to the scarcity and industrial contamination of water. Although traditional adsorbents such as activated carbon and zeolites can remove heavy metal ions from water, they have slow kinetics and low uptake. To address these problems, metal-organic framework (MOF) adsorbents have been developed, which are characterized by facile synthesis, high porosity, designability, and stability. Water-stable MOFs, such as MIL-101, UiO-66, NU-1000, and MOF-808, have attracted considerable research interest. Thus, in this review, we summarize the developments of these MOFs and highlight their adsorption performance characteristics. Moreover, we discuss functionalization methods that are typically used to improve these MOFs' adsorption performance. This minireview is timely and will help readers understand the design principles and working phenomena of next-generation MOF-based adsorbents.
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Estruturas Metalorgânicas , Metais Pesados , Compostos Organometálicos , Purificação da Água , Água , Íons , Adsorção , Purificação da Água/métodosRESUMO
Recent advances in adsorbents have improved the removal of mercury ions from wastewater. Metal-organic frameworks (MOFs) have been increasingly used as adsorbents due to their high adsorption capacity and ability to adsorb various heavy metal ions. UiO-66 (Zr) MOFs are mainly used because they are highly stable in aqueous solutions. However, most functionalized UiO-66 materials are unable to achieve a high adsorption capacity because of the undesired reactions that occur during post-functionalization. Herein, we report a facile post-functionalization method to synthesize a MOF adsorbent with fully active amide- and thiol-functionalized chelating groups, termed UiO-66-A.T. UiO-66-A.T. was synthesized via a two-step reaction by crosslinking with a monomer containing a disulfide moiety, followed by disulfide cleavage to activate the thiol groups. UiO-66-A.T. removed Hg2+ from water with a maximum adsorption capacity of 691 mg g-1 and a rate constant of 0.28 g mg-1 min-1 at pH 1. In a mixed solution containing 10 different heavy metal ions, UiO-66-A.T. has a Hg2+ selectivity of 99.4%, which is the highest reported to date. These results demonstrate the effectiveness of our design strategy for synthesizing purely defined MOFs to achieve the best Hg2+ removal performance to date among post-functionalized UiO-66-type MOF adsorbents.
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Mercúrio , Metais Pesados , Poluentes Químicos da Água , Cinética , Água , AdsorçãoRESUMO
Nevus sebaceous (NS) is a congenital hamartoma associated with an increased risk of secondary neoplasms in approximately 10%-20% of patients. However, additional genomic alterations underlying tumorigenesis in NS lesions have not been clarified. We performed whole-exome sequencing of archived tumor tissues (n = 8; six basal cell carcinomas and two trichoepitheliomas) and matched germline tissues (n = 7) with from seven patients with secondary tumors arising from NS. We also analyzed NS lesions without secondary tumors (n = 8). Somatic mutations and copy number alterations (CNAs) were analyzed. We identified a median of 129 somatic mutations (corresponding to 2.6/Mb in target regions, range 26-336) for eight tumors, while a median of 118 somatic mutations (2.3/Mb, range 1-196) for eight NS lesions. Known RAS hotspot mutations were found in seven of the eight tumors (six for HRAS p.G13R and one for HRAS p.Q61R) and in six of the eight NS lesions (four for HRAS p.G13R, one for KRAS p.G12C, and one KRAS p.G12D). Except RAS mutations, several putative driver mutations were detected in tumors: TP53 p.F134L/p.R213*, MYCN p.P59L, OR2Z1 p.P167S, PTPN14 p.Q768*, and SMO p.W535L. As for CNAs, two tumors harbored copy-loss in regions encompassing PTCH1 gene. However, eight NS lesions did not harbor both putative driver mutations and CNAs. In conclusion, our study revealed that secondary tumors arising from NS harbor known RAS hotspot mutations and additional genomic alterations, including putative driver mutations and PTCH1 copy-loss. These results could help to define the high-risk group for tumor development in patients with NS and provide evidence for prophylactic resection.
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Nevo , Neoplasias Cutâneas , Humanos , Sequenciamento do Exoma , Proteínas Proto-Oncogênicas p21(ras)/genética , Mutação , Nevo/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Genômica , Proteínas Tirosina Fosfatases não Receptoras/genéticaRESUMO
Macrocycles with well-defined cavities and the ability to undergo supramolecular interactions are classical materials that have played an essential role in materials science. However, one of the most substantial barriers limiting the utilization of macrocycles is their aggregation, which blocks the active regions. Among many attempted strategies to prevent such aggregation, installing macrocycles into covalent organic frameworks (COFs), which are porous and stable reticular networks, has emerged as an ideal solution. The resulting macrocycle-based COFs (M-COFs) preserve the macrocycles' unique activities, enabling applications in various fields such as single-atom catalysis, adsorption/separation, optoelectronics, phototherapy, and structural design of forming single-layered or mechanically interlocked COFs. The resulting properties are unmatchable by any combination of macrocycles with other substrates, opening a new chapter in advanced materials. This review focuses on the latest progress in the concepts, synthesis, properties, and applications of M-COFs, and presents an in-depth outlook on the challenges and opportunities in this emerging field.
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Traditionally, diagnostic pathology uses histology representing structural alterations in a disease's cells and tissues. In many cases, however, it is supplemented by other morphology-based methods such as immunohistochemistry and fluorescent in situ hybridization. Single-cell RNA sequencing (scRNA-seq) is one of the strategies that may help tackle the heterogeneous cells in a disease, but it does not usually provide histologic information. Spatial sequencing is designed to assign cell types, subtypes, or states according to the mRNA expression on a histological section by RNA sequencing. It can provide mRNA expressions not only of diseased cells, such as cancer cells but also of stromal cells, such as immune cells, fibroblasts, and vascular cells. In this review, we studied current methods of spatial transcriptome sequencing based on their technical backgrounds, tissue preparation, and analytic procedures. With the pathology examples, useful recommendations for pathologists who are just getting started to use spatial sequencing analysis in research are provided here. In addition, leveraging spatial sequencing by integration with scRNA-seq is reviewed. With the advantages of simultaneous histologic and single-cell information, spatial sequencing may give a molecular basis for pathological diagnosis, improve our understanding of diseases, and have potential clinical applications in prognostics and diagnostic pathology.