Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

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.

In-depth Profiling and Quantification of the Lysine Acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer.

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.

Crystalline Porous Organic Frameworks Based on Multiple Dynamic Linkages.

A novel class of crystalline porous materials has been developed utilizing multilevel dynamic linkages, including covalent B-O, dative B←N and hydrogen bonds. Typically, boronic acids undergo in situ condensation to afford B3O3-based units, which further extend to molecular complexes or chains via B←N 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.

Three-Dimensional Covalent Organic Frameworks with Ultra-Large Pores for Highly Efficient Photocatalysis.

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.

Functional Regulation and Stability Engineering of Three-Dimensional Covalent Organic Frameworks.

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.

Quantitative Assessment of Crystallinity and Stability in ß-Ketoenamine-Based Covalent Organic Frameworks.

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.

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.

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.

Comparison of plugin and redundant marker sets to analyze gait kinematics between different populations.

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.

An Integrated Transcriptomics and Proteomics Analysis Implicates lncRNA MALAT1 in the Regulation of Lipid Metabolism.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in various cancers, and its overexpression is associated with tumor growth and metastasis. MALAT1 has been recognized as a key player in the regulation of RNA splicing and transcription; however, the landscape of gene expression regulated by MALAT1 remains unclear. In this study, we employed an integrated transcriptomics and proteomics strategy to characterize the alterations in gene expression induced by MALAT1 knockdown in hepatocellular carcinoma (HCC) cells and identified 2662 differentially expressed transcripts and 1149 differentially expressed proteins. Interestingly, downregulation of MALAT1 reduced the abundances of multiple genes in the AMP-activated protein kinase (AMPK) signaling and biosynthesis of unsaturated fatty acids pathways. Further investigation showed that MALAT1 knockdown inhibited glucose uptake and lipogenesis by reducing the expression levels of these lipid metabolism related genes, which contributes to the oncogenic role of MALAT1 in tumor cell proliferation and invasion. This study uncovers the function of MALAT1 in the modulation of cancer lipid metabolism, reveals the underlying molecular mechanism, and further supports the potential therapeutic opportunities for targeting MALAT1 in HCC treatment.

Three-Dimensional Covalent Organic Frameworks: From Synthesis to Applications.

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.

Enaminone-Linked Covalent Organic Frameworks for Boosting Photocatalytic Hydrogen Production.

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 1078 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 (3-107 times). The facile synthesis, excellent activity, and high chemical stability demonstrate that En-COFs are a promising platform for photocatalysis.

Five-Direction Occlusion Filling with Five Layer Parallel Two-Stage Pipeline for Stereo Matching with Sub-Pixel Disparity Map Estimation.

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.

Three-Dimensional Triptycene-Functionalized Covalent Organic Frameworks with hea Net for Hydrogen Adsorption.

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 305 cm3 g-1 (or 2.72 wt%) at 77 K and 1 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.

Gating Effects for Ion Transport in Three-Dimensional Functionalized Covalent Organic Frameworks.

The development of bioinspired nano/subnano-sized (<2 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.

Three-Dimensional Triptycene-Based Covalent Organic Frameworks with ceq or acs Topology.

The growth of three-dimensional covalent organic frameworks (3D COFs) with new topologies is still considered as a great challenge due to limited availability of high-connectivity building units. Here we report the design and synthesis of 3D triptycene-based COFs, termed JUC-568 and JUC-569, following the deliberate symmetry-guided design principle. By combining a triangular prism (6-connected) node with a planar triangle (3-connected) or another triangular prism node, the targeted COFs adopt non-interpenetrated ceq or acs topology, respectively. Both materials show permanent porosity and impressive performance in the adsorption of CO2 (∼98 cm3/g at 273 K and 1 bar), CH4 (∼48 cm3/g at 273 K and 1 bar), and especially H2 (up to 274 cm3/g or 2.45 wt % at 77 K and 1 bar), which is highest among porous organic materials reported to date. This research thus provides a promising strategy for diversifying 3D COFs based on complex building blocks and promotes their potential applications in energy storage and environment-related fields.

3D Thioether-Based Covalent Organic Frameworks for Selective and Efficient Mercury Removal.

Developing functionalized 3D covalent organic frameworks (3D COFs) is critical to broaden their potential applications. However, the introduction of specific functionality in 3D COFs remains a great challenge because most of the functional groups are not compatible with the synthesis conditions. Herein, for the first time 3D thioether-based COFs (JUC-570 and JUC-571) for mercury (Hg2+ ) removal from aqueous solution is reported. These 3D thioether-based COFs prepared by the bottom-up approach display high Hg2+ uptakes (972 mg g-1 for JUC-570 and 970 mg g-1 for JUC-571 at pH = 5), fast adsorption kinetics (distribution coefficient Kd value of 2.29 × 107  mL g-1 for JUC-570 and 2.07 × 107  mL g-1 for JUC-571), and favorable selectivity. In particular, JUC-570 is periodically decorated with isopropyl groups around imine bonds that markedly improve its chemical stability and effectively prevent the pore collapse, and thus endows high Hg2+ adsorption capacity (619 mg g-1 ) and excellent cycle performance even at pH = 1. This study not only puts forward a new route to construct stable functionalized 3D COFs, but also promotes their potential applications in areas related to the environment.

3D Hydrazone-Functionalized Covalent Organic Frameworks as pH-Triggered Rotary Switches.

The property expansion of 3D functionalized covalent organic frameworks (COFs) is important for developing their potential applications. Herein, the first case of 3D hydrazone-decorated COFs as pH-triggered molecular switches is reported, and their application in the stimuli-responsive drug delivery system is explored. These functionalized COFs with hydrazone groups on the channel walls are obtained via a multi-component bottom-up synthesis strategy. They exhibit a reversible E/Z isomerization at various pH values, confirmed by UV-vis absorption spectroscopy and proton conduction. Remarkably, after loading cytarabine (Ara-C) as a model drug molecule, these pH-responsive COFs show an excellent and intelligent sustained-release effect with an almost fourfold increase in the Ara-C release at pH = 4.8 than at pH = 7.4, which will effectively improve drug-targeting. Thus, these results open a way toward designing 3D stimuli-responsive functionalized COF materials and promote their potential application as drug carriers in the field of disease treatment.

Design and applications of three dimensional covalent organic frameworks.

Covalent organic frameworks (COFs), as an emerging class of crystalline porous polymers connected by dynamic covalent bonds, have been well studied over the past decade. Recently, three dimensional (3D) COFs have attracted extensive interest for the synthesis and applications of novel COFs. The principal reason for this rising trend is based on their unique porous features and excellent performances compared to previously reported two dimensional (2D) frameworks with the layered AA-stacking mode. This critical review describes the current state-of-the-art development of 3D COFs in the design principles, synthetic methods, functionalization strategies, and potential applications. Some major challenges associated with future perspectives are further discussed, inspiring the development of 3D COFs.

Three-Dimensional Radical Covalent Organic Frameworks as Highly Efficient and Stable Catalysts for Selective Oxidation of Alcohols.

With excellent designability, large accessible inner surface, and high chemical stability, covalent organic frameworks (COFs) are promising candidates as metal-free heterogeneous catalysts. Here, we report two 3D radical-based COFs (JUC-565 and JUC-566) in which radical moieties (TEMPO) are uniformly decorated on the channel walls via a bottom-up approach. Based on grafted functional groups and suitable regular channels, these materials open up the application of COFs as highly efficient and selective metal-free redox catalysts in aerobic oxidation of alcohols to relevant aldehydes or ketones with outstanding turn over frequency (TOF) up to 132 h-1 , which has exceeded other TEMPO-modified catalytic materials tested under similar conditions. These stable COF-based catalysts could be easily recovered and reused for multiple runs. This study promotes potential applications of 3D functional COFs anchored with stable radicals in organic synthesis and material science.

Three-Dimensional Mesoporous Covalent Organic Frameworks through Steric Hindrance Engineering.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with large pores and high surface areas is of great importance for various applications. However, it remains a major challenge due to the frequent structural interpenetration and pore collapse after the removal of guest species situated in the pores. Herein, we report for the first time a series of 3D mesoporous COFs through a general method of steric hindrance engineering. By placing methoxy and methyl groups strategically on the monomers, we can obtain non-interpenetrated 3D COFs of diamondoid structures with permanent mesopores (up to 26.5 Å) and high surface areas (>3000 m2 g-1), which are far superior to those of reported conventional COFs with the same topology. This work thus opens a new avenue to create 3D large-pore COFs for potential applications in adsorption and separation of large inorganic, organic, and biological molecules.