Ultrathin Covalent Organic Framework Nanosheets/Ti3C2Tx-Based Photoelectrochemical Biosensor for Efficient Detection of Prostate-Specific Antigen.

Designable and ultrathin covalent organic framework nanosheets (CONs) with good photoelectric activity are promising candidates for the construction of photoelectrochemical (PEC) biosensors for the detection of low-abundance biological substrates. However, achieving highly sensitive PEC properties by using emerging covalent organic framework nanosheets (CONs) remains a great challenge due to the polymeric nature and poor photoelectric activity of CONs. Herein, we report for the first time the preparation of novel composites and their PEC sensing properties by electrostatic self-assembly of ultrathin CONs (called TTPA-CONs) with Ti3C2Tx. The prepared TTPA-CONs/Ti3C2Tx composites can be used as photocathodes for PEC detection of prostate-specific antigen (PSA) with high sensitivity, low detection limit, and good stability. This work not only expands the application of CONs but also opens new avenues for the development of efficient PEC sensing platforms.

Synthesis and Visualization of Entangled 3D Covalent Organic Frameworks with High-Valency Stereoscopic Molecular Nodes for Gas Separation.

The structural diversity of three-dimensional (3D) covalent organic frameworks (COFs) are limited as there are only a few choices of building units with multiple symmetrically distributed connection sites. To date, 4 and 6-connected stereoscopic nodes with Td , D3h , D3d and C3 symmetries have been mostly reported, delivering limited 3D topologies. We propose an efficient approach to expand the 3D COF repertoire by introducing a high-valency quadrangular prism (D4h ) stereoscopic node with a connectivity of eight, based on which two isoreticular 3D imine-linked COFs can be created. Low-dose electron microscopy allows the direct visualization of their 2-fold interpenetrated bcu networks. These 3D COFs are endowed with unique pore architectures and strong molecular binding sites, and exhibit excellent performance in separating C2 H2 /CO2 and C2 H2 /CH4 gas pairs. The introduction of high-valency stereoscopic nodes would lead to an outburst of new topologies for 3D COFs.

Multi-omics analysis reveals prognostic value of tumor mutation burden in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure. METHOD: The mutation data was analyzed by employing "maftools" package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package "limma". Gene ontology (GO) enrichment analysis was implemented with "clusterProfiler", "enrichplot" and "ggplot2" packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS algorithm were employed. Additionally, the potential role of risk score on immune checkpoint blockade (ICB) immunotherapy was further explored. The quantitative real-time polymerase chain reaction was performed to detect expression of HTRA3. RESULTS: TMB value was positively correlated with older age, male gender and early T status. A total of 75 intersection genes between TMB-related genes and differentially expressed genes (DEGs) were screened and enriched in extracellular matrix-relevant pathways. Risk score based on three hub genes significantly affected overall survival (OS) time, infiltration of immune cells, and ICB-related hub targets. The prognostic performance of risks score was validated in the external testing group. Risk-clinical nomogram was constructed for clinical application. HTRA3 was demonstrated to be a prognostic factor in HCC in further exploration. Finally, mutation of TP53 was correlated with risk score and do not interfere with risk score-based prognostic prediction. CONCLUSION: Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.

Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. This study aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC. METHODS: Univariate Cox regression analysis was performed to determine the prognosis-related AS events and gene set enrichment analysis (GSEA) was employed for functional annotation, followed by the development of prognostic signatures using univariate Cox, LASSO and multivariate Cox regression. K-M survival analysis, proportional hazards model, and ROC curves were conducted to validate prognostic value. ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed to uncover the context of TIME in HCC. Quantitative real-time polymerase chain reaction was implemented to detect ZDHHC16 mRNA expression. Cytoscape software 3.8.0 were employed to visualize AS-splicing factors (SFs) regulatory networks. RESULTS: A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, eight AS prognostic signature with robust prognostic predictive accuracy were constructed. Furthermore, quantitative prognostic nomogram was developed and exhibited robust validity in prognostic prediction. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. ZDHHC16 presented promising prospect as prognostic factor in HCC. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs). CONCLUSION: Herein, exploration of AS patterns may provide novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.,) for prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And pivotal players of AS events in context of TIME and immunotherapy efficiency were revealed, contributing to clinical decision-making and personalized prognosis monitoring of HCC.

Salt-Assisted Fabrication of a Water-Based Covalent Organic Framework Ink and Its Hybrid Films for Photothermal Actuators.

The exceptional properties of two-dimensional covalent organic framework materials (2D-COFs), including their large π-conjugated structure at the molecular level and π-π multilayer stacking, have attracted interest for soft photothermal actuator applications. However, the conventional synthesis of COFs as microcrystalline powders limits their processing in water due to their limited dispersibility. Herein, we present a simple and environmentally friendly method to fabricate water-suspended COF inks by adjusting the surface potential of COF powders through adsorption of ionic species such as Na+ and Cl-. This technique effectively prevents the accumulation and aggregation of COF powder, resulting in an aqueous COF ink that can be easily cast into homogeneous hybrid COF films by Mayer-rod coating. In addition, the resulting photothermal actuator exhibited a fast response time within 3 s at a curvature of 2.35 cm-1 in the near-infrared light. This facile and practical approach to fabricating water-based COFs ink represents a promising strategy for the development of practical applications of COFs in photothermal actuators.

Ultrathin MOF nanosheet-based resistive sensors for highly sensitive detection of methanol.

Sensors with high-sensitivity for resistive methanol gas detection are highly desirable. Herein, we report newly designed ultrathin anionic metal-organic framework (MOF) nanosheets (NSs), with an average thickness of 10 nm and an electrical conductivity of 3.77 × 10-4 S cm-1. The ultrathin MOF NSs can be used as the active material in an electronic methanol gas sensor, which exhibits high sensitivity toward methanol gas at room temperature, i.e., high Rair/Rgas (363.2 at 100 ppm), fast gas response/recovery speed (6 s/2 s at 20 ppm), long-term stability, and superior cross-selectivity against other interfering gases.

Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function.

In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the "LN chain" system is not fully understood. To explore the mechanistic and histo-anatomical significance of LNs as lymph fluid filters, we subcutaneously injected fluorescent tracers into mice and examined the details of lymphatic transport to the LNs qualitatively and quantitatively. Lymph-borne tracers were selectively accumulated in the MARCO+ subcapsular-medullary sinus border (SMB) region of the LN, in which reticular lymphatic endothelial cells and CD169+F4/80+ medullary sinus macrophages construct a dense meshwork of the physical barrier, forming the main body to capture the tracers. We also demonstrated stepwise filtration via the LN chain in the lymphatic basin, which prevented tracer leakage into the blood. Furthermore, inflammatory responses that induce the remodeling of LN tissue as well as the lymphatic pathway reinforce the overall filtering capacity of the lymphatic basin. Taken together, specialized tissue infrastructure in the LNs and their systematic orchestration constitute an integrated filtering system for lymphatic recirculation.

Landscape of Prognostic m6A RNA Methylation Regulators in Hepatocellular Carcinoma to Aid Immunotherapy.

Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy with a high mortality worldwide. N6-methyladenosine (m6A) may participate extensively in tumor progression. Methods: To reveal the landscape of tumor immune microenvironment (TIME), ESTIMATE analysis, ssGSEA algorithm, and the CIBERSORT method were used. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering results with TIME and immunotherapy. Then, we yielded a risk signature by systematical bioinformatics analyses. Immunophenoscore (IPS) was implemented to estimate the immunotherapeutic significance of risk signature. Results: The m6A-based clusters were significantly correlated with overall survival (OS), immune score, immunological signature, immune infiltrating, and ICB-associated genes. Risk signature possessed robust prognostic validity and significantly correlated with TIME context. IPS was employed as a surrogate of immunotherapeutic outcome, and patients with low-risk scores showed significantly higher immunophenoscores. Conclusion: Collectively, m6A-based clustering subtype and signature was a robust prognostic indicator and correlated with TIME and immunotherapy, providing novel insight into antitumor management and prognostic prediction in HCC.