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Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a crucial enzyme involved in phospholipid metabolism and is essential for maintaining the structure and functionality of biofilms. However, a comprehensive examination of the role of LPCAT1 across various cancer types is lacking. Multiple public databases have been utilized to examine LPCAT1 expression, genetic alterations, methylation, prognosis, biological function, and its relationship with antitumor immunity in different cancer types. The function of LPCAT1 in glioma, breast cancer and liver cancer cells was further verified using in vitro experiments. Our research indicated that LPCAT1 is upregulated in various cancers and is accompanied by a wide range of amplification mutations. Higher LPCAT1 expression was associated with poorer prognosis across multiple cancers. Further in vitro experiments demonstrated that interfering with LPCAT1 expression increased apoptosis in glioma, breast cancer and liver cancer cells and concurrently suppressed their proliferation and migration. Functional enrichment analysis revealed that LPCAT1-associated genes were primarily enriched in immune and cancer progression pathways, such as the JAK/STAT, MYC, and EMT, etc. Moreover, LPCAT1 expression was closely associated with immune cell infiltration and immune checkpoint-related gene expression. Interestingly, LPCAT1 expression levels were generally higher in patients in the immunotherapy response group. The combination of LPCAT1 and PDL1 serves as an effective predictor of immunotherapy response. In conclusion, LPCAT1 is involved in immune regulation and tumor progression and holds promise as a biomarker for predicting patient outcomes and immunotherapy efficacy.
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While supported metal nanoparticles (NPs) have shown significant promise in heterogeneous catalysis, precise control over their interaction with the support, which profoundly impacts their catalytic performance, remains a significant challenge. In this study, Pt NPs are incorporated into thioether-functionalized covalent organic frameworks (denoted COF-Sx), enabling precise control over the size and electronic state of Pt NPs by adjusting the thioether density dangling on the COF pore walls. Notably, the resulting Pt@COF-Sx demonstrate exceptional selectivity (> 99 %) in catalytic hydrogenation of p-chloronitrobenzene to p-chloroaniline, in sharp contrast to the poor selectivity of Pt NPs embedded in thioether-free COFs. Furthermore, the conversion over Pt@COF-Sx exhibits a volcano-type curve as the thioether density increases, due to the corresponding change of accessible Pt sites. This work provides an effective approach to regulating the catalysis of metal NPs via their microenvironment modulation, with the aid of rational design and precise tailoring of support structure.
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Environmental changes induced by urbanization may significantly alter plant survival strategies, thereby introducing uncertainties in their ability to withstand extreme heat. This study, centered on Jinhua City, distinguished urban, suburban, and rural areas to represent the various intensities of urbanization. It examined the leaf function properties of evergreen and deciduous trees common in these regions, focusing on leaf and branch characteristics. Employing an analysis of variance (ANOVA), principal component analysis (PCA), and path analysis (PA) of the plant functional traits and the climatic factors of each region, this study assessed the impact of urbanization on plant survival strategies. By tracking changes in plant functional traits from June to August, it explored the capacity of plants to acclimate to urban-warming-related heat stress across different urbanization gradients. The findings revealed that leaf thickness (LT) and stomatal size (SS) initially decreased and then increased, whereas specific leaf area (SLA) and leaf tissue density (LTD) first rose and then declined, from rural to urban regions. From June to August, branch wood density (WD), chlorophyll (Chl) content, LTD, and leaf dry matter content (LDMC) increased, whereas SLA and leaf water content (LWC) diminished, in all regions. PCA suggested that there was no significant change in the resource allocation strategy of plants (p > 0.05), with drought tolerance significantly reduced in the suburbs on the gradient of urbanization (p < 0.05). During the summer, with high temperature, plants were predominantly biased towards slow-return, conservative strategies, particularly among evergreen species. Compared to precipitation, PA revealed a significant urban warming effect. During summer, temperature was the main factor influencing resource investment strategy and drought resistance, with a notably stronger impact on the former. The high temperature in summer promoted a conservative survival strategy in plants, and the urbanization effect increased their tolerance to high temperatures.
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Although single-atom Cu sites exhibit high efficiency in CO2 hydrogenation to methanol, they are prone to forming Cu nanoparticles due to reduction and aggregation under reaction conditions, especially at high temperatures. Herein, single-atom Cu sites stabilized by adjacent Na+ ions have been successfully constructed within a metal-organic framework (MOF)-based catalyst, namely MOF-808-NaCu. It is found that the electrostatic interaction between the Na+ and Hδ- species plays a pivotal role in upholding the atomic dispersion of Cu in MOF-808-NaCu during CO2 hydrogenation, even at temperatures of up to 275°C. This exceptional stabilization effect endows the catalyst with excellent activity (306 g·kgcat-1·h-1), high selectivity to methanol (93%) and long-term stability at elevated reaction temperatures, far surpassing the counterpart in the absence of Na+ (denoted as MOF-808-Cu). This work develops an effective strategy for the fabrication of stable single-atom sites for advanced catalysis by creating an alkali-decorated microenvironment in close proximity.
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Breast cancer (BC) stands out as the cancer with the highest incidence of morbidity and mortality among women worldwide, and its incidence rate is currently trending upwards. Improving the efficiency of breast cancer diagnosis and treatment is crucial, as it can effectively reduce the disease burden. Circulating tumor DNA (ctDNA) originates from the release of tumor cells and plays a pivotal role in the occurrence, development, and metastasis of breast cancer. In recent years, the widespread application of high-throughput analytical technology has made ctDNA a promising biomarker for early cancer detection, monitoring minimal residual disease, early recurrence monitoring, and predicting treatment outcomes. ctDNA-based approaches can effectively compensate for the shortcomings of traditional screening and monitoring methods, which fail to provide real-time information and prospective guidance for breast cancer diagnosis and treatment. This review summarizes the applications of ctDNA in various aspects of breast cancer, including screening, diagnosis, prognosis, treatment, and follow-up. It highlights the current research status in this field and emphasizes the potential for future large-scale clinical applications of ctDNA-based approaches.
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Biomarcadores Tumorais , Neoplasias da Mama , DNA Tumoral Circulante , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/sangue , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Feminino , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , PrognósticoRESUMO
A novel class of crystalline porous materials has been developed utilizing multilevel dynamic linkages, including covalent B-O, dative BâN and hydrogen bonds. Typically, boronic acids undergo in situ condensation to afford B3O3-based units, which further extend to molecular complexes or chains via BâN bonds. The obtained superstructures are subsequently interconnected via hydrogen bonds and π-π interactions, producing crystalline porous organic frameworks (CPOFs). The CPOFs display excellent solution processability, allowing dissolution and subsequent crystallization to their original structures, independent of recrystallization conditions, possibly due to the diverse bond energies of the involved interactions. Significantly, the CPOFs can be synthesized on a gram-scale using cost-effective monomers. In addition, the numerous acidic sites endow the CPOFs with high NH3 capacity, surpassing most porous organic materials and commercial materials.
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BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.
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Antígeno B7-H1 , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Relevância Clínica , Linfócitos B , Linfócitos T CD4-PositivosRESUMO
BACKGROUND: Gait model consists of a marker set and a segment pose estimation algorithm. Plugin marker set and inverse kinematic algorithm (IK.) are prevalent in gait analysis, especially musculoskeletal motion analysis. Adding extra markers for the plugin marker set could increase the robustness to marker misplacement, motion artifacts, and even markers occlusion. However, how the different marker sets affect the gait analysis's kinematic output is unclear. Therefore, this study aims to investigate the effect of marker sets on the kinematic output during level walking in different populations. RESULTS: In all three planes, there are significant differences (P < 0.05) between marker sets in some kinematic variables at the hip, knee, and ankle. In different populations, the kinematic variables that show significant differences varied. When comparing the kinematic differences between populations using the two marker sets separately, the range of motion (ROM) of hip flexion was only found to be a significant difference using the redundant marker set, while the peak internal rotation at the knee was only found a significant difference using plugin marker set. In addition, the redundant marker set shows less intra-subject variation than the plugin marker set. CONCLUSION: The findings in this study demonstrate the importance of marker set selection since it could change the result when comparing the kinematic differences between populations. Therefore, it is essential to increase the caution in explaining the result when using different marker sets. It is crucial to use the same marker set, and the redundant marker set might be a better choice for gait analysis.
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Marcha , Joelho , Humanos , Fenômenos Biomecânicos , Caminhada , Articulação do Joelho , Amplitude de Movimento Articular , RotaçãoRESUMO
The design and synthesis of covalent organic frameworks (COFs) with high chemical stability pose significant challenges for practical applications. Although a growing number of robust COFs have been developed and employed for a broad scope of applications, the assessment of COF stability has primarily relied on qualitative descriptions, lacking a rational and quantitative assessment. Herein, a novel assessment method is presented that enables visual and quantitative depiction of COF stability. By analyzing the PXRD patterns of chemically stable ß-ketoenamine-based COFs (KEA-COFs), two crystallinity-dependent parameters are identified, the relative intensity (I2θrel ) and the relative area (A2θrel ) of the main peak (2θ), which are expected to establish a standardized criterion for assessing COF crystallinity. Based on these parameters, the crystalline changes after stability tests can be visually presented, which provides a rational and quantitative assessment of their stability. This study not only demonstrates the remarkable chemical stability of KEA-COFs, but also provides valuable insights into the quantitative evaluation of COFs' crystallinity and stability.
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To explore the clinical role of QPRT in breast cancer. The gene expression, methylation levels and prognostic value of QPRT in breast cancer was analyzed using TCGA data. Validation was performed using the data from GEO dataset and TNMPLOT database. Meta analysis method was used to pool the survival data for QPRT. The predictive values of QPRT for different drugs were retrieved from the ROC plot. The expression differences of QPRT in acquired drug-resistant and sensitive cell lines were analyzed using GEO datasets. GO and KEGG enrichment analysis were conducted for those genes which were highly co-expressed with QPRT in tissue based on TCGA data and which changed after QPRT knockdown. Timer2.0 was utilized to explore the correlation between QPRT and immune cells infiltration, and the Human Protein Atlas was used to analyse QPRT's single-cell sequencing data across different human tissues. The expression of QPRT in different types of macrophages, and the expression of QPRT were analysed after coculturing HER2+ breast cancer cells with macrophages. Additionally, TargetScan, Comparative Toxicogenomics and the connectivity map were used to research miRNAs and drugs that could regulate QPRT expression. Cytoscape was used to map the interaction networks between QPRT and other proteins. QPRT was highly expressed in breast cancer tissue and highly expressed in HER2+ breast cancer patients (P < 0.01). High QPRT expression levels were associated with worse OS, DMFS, and RFS (P < 0.01). Two sites (cg02640602 and cg06453916) were found to be potential regulators of breast cancer (P < 0.01). QPRT might predict survival benefits in breast cancer patients who received taxane or anthracycline. QPRT was associated with tumour immunity, especially in macrophages. QPRT may influence the occurrence and progression of breast cancer through the PI3K-AKT signalling pathway, Wnt signalling pathway, and cell cycle-related molecules.
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Neoplasias da Mama , MicroRNAs , Pentosiltransferases , Feminino , Humanos , Antraciclinas , Neoplasias da Mama/genética , Fosfatidilinositol 3-Quinases , Pentosiltransferases/genéticaRESUMO
Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract.
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Telomerase , Humanos , Domínio Catalítico , Transformação Celular Neoplásica , Epigênese Genética , Genoma HumanoRESUMO
Covalent organic frameworks (COFs), possessing pre-designable structures and tailorable functionalities, are promising candidates for photocatalysis. Nevertheless, the most studied imine-linked COFs (Im-COFs) usually suffer from unsatisfactory stability and photocatalytic performance. To meet this challenge, a series of highly stable enaminone-linked COFs (En-COFs) have been synthesized and afford much improved visible-light-driven hydrogen production activities, ranging from 44 to 1078â times that of isoreticular Im-COFs, with the only difference being the linkages (enaminone vs. imine) in their structures. The enhanced light-harvesting ability, facilitated exciton dissociation and improved chemical stability account for the superior activity. Furthermore, quinoline-linked COFs (Qu-COFs) have been further obtained via the post-modification of Im-COFs. Compared with Im-COFs, the photocatalytic activities of Qu-COFs are significantly improved after modification, but still below those of the corresponding En-COFs (3-107â times). The facile synthesis, excellent activity, and high chemical stability demonstrate that En-COFs are a promising platform for photocatalysis.
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Benefiting from their unique structural merits, three-dimensional (3D) large-pore COF materials demonstrate high surface areas and interconnected large channels, which makes these materials promising in practical applications. Unfortunately, functionalization strategies and application research are still absent in these structures. To this end, a series of functional 3D stp-topologized COFs are designed based on porphyrin or metalloporphyrin moieties, named JUC-640-M (M = Co, Ni, or H). Interestingly, JUC-640-H exhibits a record-breaking low crystal density (0.106 cm3 g-1) among all crystalline materials, along with the largest interconnected pore size (4.6 nm) in 3D COFs, high surface area (2204 m2 g-1), and abundant exposed porphyrin moieties (0.845 mmol g-1). Inspired by the unique structural characteristics and photoelectrical performance, JUC-640-Co is utilized for the photoreduction of CO2 to CO and demonstrates a high CO production rate (15.1 mmol g-1 h-1), selectivity (94.4%), and stability. It should be noted that the CO production rate of JUC-640-Co has exceeded those of all reported COF-based materials. This work not only produces a series of novel 3D COFs with large channels but also provides a new guidance for the functionalization and applications of COFs.
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Three-dimensional covalent organic frameworks (3D COFs) with spatially periodic networks demonstrate significant advantages over their 2D counterparts, including enhanced specific surface areas, interconnected channels, and more sufficiently exposed active sites. Nevertheless, research on these materials has met an impasse due to serious problems in crystallization and stability, which must be solved for practical applications. In this Minireview, we first summarize some strategies for preparing functional 3D COFs, including crystallization techniques and functionalization methods. Hereafter, applications of these functional materials are presented, covering adsorption, separation, catalysis, fluorescence, sensing, and batteries. Finally, the future challenges and perspectives for the development of 3D COFs are discussed.
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Binocular stereoscopic matching is an essential method in computer vision, imitating human binocular technology to obtain distance information. Among plentiful stereo matching algorithms, Semi-Global Matching (SGM) is recognized as one of the most popular vision algorithms due to its relatively low power consumption and high accuracy, resulting in many excellent SGM-based hardware accelerators. However, vision algorithms, including SGM, are still somewhat inaccurate in actual long-range applications. Therefore, this paper proposes a disparity improvement strategy based on subpixel interpolation and disparity optimization post-processing using an area optimization strategy, hardware-friendly divider, split look-up table, and the clock alignment multi-directional disparity occlusion filling, and depth acquisition based on floating-point operations. The hardware architecture based on optimization algorithms is on the Stratix-IV platform. It consumes about 5.6 K LUTs, 12.8 K registers, and 2.5 M bits of on-chip memory. Meanwhile, the non-occlusion error rate of only 4.61% is about 1% better than the state-of-the-art works in the KITTI2015 dataset. The maximum working frequency can reach up to 98.28 MHz for the 640 × 480 resolution video and 128 disparity range with the power dissipation of 1.459 W and 320 frames per second processing speed.
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Covalent organic frameworks (COFs) have attracted extensive interest due to their unique structures and various applications. However, structural diversities are still limited, which greatly restricts the development of COF materials. Herein, we report two unusual cubic (8-connected) building units and their derived 3D imine-linked COFs with bcu nets, JUC-588 and JUC-589. Owing to these unique building blocks with different sizes, the obtained COFs can be tuned to be microporous or mesoporous structures with high surface areas (2728 m2 g-1 for JUC-588 and 2482 m2 g-1 for JUC-589) and promising thermal and chemical stabilities. Furthermore, the high selectivity of CO2/N2 and CO2/CH4, excellent H2 uptakes, and efficient dye adsorption are observed. This research thus provides a general strategy for constructing stable 3D COF architectures with adjustable pores via improving the valency of rigid building blocks.
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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Acetilação , Humanos , Lisina , Espectrometria de Massas , Processamento de Proteína Pós-Traducional , Proteoma , Sirtuína 2RESUMO
ConspectusAs one of the most attractive members in the porous materials family, covalent organic frameworks (COFs) have been reported thousands of times since their first discovery in 2005, covering their design, synthesis, and applications. However, an overwhelming majority of these COFs are based on two-dimensional (2D) topologies while three-dimensional (3D) COFs are numbered fewer than 100 up to date. In fact, baring enhanced specific surface area, interconnected channels, well-exposed functional moieties, and highly adjustable structures, 3D COFs are often more competitive in various application fields like adsorption, separation, chemical sensing, and heterogeneous catalysis compared with their 2D counterparts. However, significant crystallization problems and poor chemical stabilities, which might be attributed to the highly void frameworks and the absence of π-π stacking, have raised severe limitations over the research and application of 3D COFs. To solve these problems, more elaborate synthesis regulations or more moderate functionalization conditions are required. More importantly, the strategies for enhancing chemical stabilities of 3D COFs are of vital importance for their further development and practical applications.In this Account, we review the design principles, functional approaches, and stability regulation methods toward functional 3D COFs. We begin the discussion with some essential elements in the construction of 3D COF structures, including topologies, interpenetrations, linkages, and synthetic methods. After that, we focus on several strategies for the functionalization of 3D COFs, including in situ approaches (utilizing in situ generated COF linkages as the active sites), bottom-up synthesis (embedding functional moieties from predesigned building blocks), and postsynthesis modification (covalent modification or metalation of pristine frameworks). At last, we highlight some approaches toward the durable amplification of 3D COFs, which is highly important for framework functionalization and practical application. This target could be achieved through not only the introduction of some extra strengthening force, such as hydrophobic effects, coulomb repulsion, and steric hindrance effects, but also the utilization of robust linkages, which could enhance the stability from material nature.Due to their high surface area, various interpenetrated channels, multifarious functionalities, and promising stabilities, 3D COFs demonstrated excellent performance and have great potential in a wide range of application fields including adsorption and separation, heterogeneous catalysis, energy storage, and so on. Although the development of these materials has been limited by serious crystallization problems and stability restriction, great efforts have been devoted by researchers in the past decade, and a mass of strategies have been developed in synthesis control, functionalization regulation, and stability enhancement for 3D COFs. We expect 3D COFs to be practically utilized in the future with further advances in the design, preparation, and functionalization of these materials.
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Owing to the finite building blocks and difficulty in structural identification, it remains a tremendous challenge to elaborately design and synthesize three-dimensional covalent organic frameworks (3D COFs) with predetermined topologies. Herein, we report the first two cases of 3D COFs with the non-interpenetrated hea net, termed JUC-596 and JUC-597, by using the combination of tetrahedral and triangular prism building units. Due to the presence of triptycene functional groups and fluorine atoms, JUC-596 exhibits an exceptional performance in the H2 adsorption up to 305â cm3 g-1 (or 2.72â wt%) at 77â K and 1â bar, which is higher than previous benchmarks from porous organic materials reported so far. Furthermore, the strong interaction between H2 and COF materials is verified through the DFT theoretical calculations. This work represents a captivating example of rational design of functional COFs based on a reticular chemistry guide and demonstrates its promising application in clean energy storage.
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The development of bioinspired nano/subnano-sized (<2â nm) ion channels is still considered a great challenge due to the difficulty in precisely controlling pore's internal structure and chemistry. Herein, for the first time, we report that three-dimensional functionalized covalent organic frameworks (COFs) can act as an effective nanofluidic platform for intelligent modulation of the ion transport. By strategic attachment of 12-crown-4 groups to the monomers as ion-driver door locks, we demonstrate that gating effects of functionalized COFs can be activated by lithium ions. The obtained materials exhibit an outstanding selective ion transmission performance with a high gating ratio (up to 23.6 for JUC-590), which is among the highest values in metal ion-activated solid-state nanochannels reported so far. Furthermore, JUC-590 offers high tunability, selectivity, and recyclability of ion transport proved by the experimental and simulated studies.