Covalent Organic Framework with Donor1-Acceptor-Donor2 Motifs Regulating Local Charge of Intercalated Single Cobalt Sites for Photocatalytic CO2 Reduction to Syngas.

Covalent organic framework (COF) has attracted increasing interest in photocatalytic CO2 reduction, but it remains a challenge to achieve high conversion efficiency owing to the insufficient active site and fast charge recombination. Rationally optimizing the electronic structures of COF to regulate the local charge of active sites precisely is the key point to improving catalytic performance. Herein, intercalated single Co sites coordinated by imine-N motifs have been designed by using trinuclear copper-based imine-COFs with distinct electronic moieties via a molecular engineering strategy. It is confirmed that the charge delivery property and local charge distribution of these heterometallic frameworks can be profoundly influenced by electronic structures. Among these featured structures with mixed-state copper clusters, Co/Cu3-TPA-COF stands out for an exceptional photocatalytic CO2 reduction activity and tunable syngas (CO/H2) ratio by changing various bipyridines. Experimental and theoretical results indicate that interlayer Co-imine N motifs on the donor1-acceptor-donor2 structures facilitate the formation of a highly separated electron-hole state, which effectively induces the oriented electron transfer from dual electron donors to Co centers, achieving an enhanced CO2 activation and reduction. This work opens up an avenue for the design of high-performance COF-based catalysts for photocatalytic CO2 reduction.

Tumor Stimulus-Activatable Pretheranostic Agent: One Key to Three Locks.

The uncontrollable distribution of antitumor agents remains a large obstacle for specific and efficient cancer theranostics; thus, efficient construction of tumor-specific systems is highly desirable. In this work, a general design of tumor stimulus-activatable pretheranostic agents was put forward via a series of structures-tunable triphenylamine derivatives (TPA-2T-FSQ, TPA-2T-BSZ, and TPA-2T-ML) with phenothiazine, benzothiazine, and thiomorpholine as identifying groups of hypochlorite (HClO), respectively. Notably, the sulfur atom in phenothiazine of TPA-2T-FSQ was more easily oxidized to sulfoxide groups by HClO, transforming into an electron acceptor to form an excellent push-pull electronic system, which was beneficial to a large redshift of absorbance and emission wavelengths. Based on this, TPA-2T-FSQ resorted to a key of overexpressed HClO in the tumor to open "three locks", viz, NIR fluorescence, photothermal, and photoacoustic signals for multimodal diagnostic and treatment of the tumor. This study provided an elegant design to adopt tumor stimulus-triggerable pretheranostic for improving theranostic accuracy and efficiency, which was regarded as a promising candidate for precision medicine.

Engineering Single Cu Sites into Covalent Organic Framework for Selective Photocatalytic CO2 Reduction.

Photocatalytic CO2 conversion into value-added chemicals is a promising route but remains challenging due to poor product selectivity. Covalent organic frameworks (COFs) as an emerging class of porous materials are considered as promising candidates for photocatalysis. Incorporating metallic sites into COF is a successful strategy to realize high photocatalytic activities. Herein, 2,2'-bipyridine-based COF bearing non-noble single Cu sites is fabricated by chelating coordination of dipyridyl units for photocatalytic CO2 reduction. The coordinated single Cu sites not only significantly enhance light harvesting and accelerate electron-hole separation but also provide adsorption and activation sites for CO2 molecules. As a proof of concept, the Cu-Bpy-COF as a representative catalyst exhibits superior photocatalytic activity for reducing CO2 to CO and CH4 without photosensitizer, and impressively, the product selectivity of CO and CH4 can be readily modulated only by changing reaction media. Experimental and theoretical results reveal the crucial role of single Cu sites in promoting photoinduced charge separation and solvent effect in regulating product selectivity, which provides an important sight onto the design of COF photocatalysts for selective CO2 photoreduction.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

Performance Evaluation of Precise Point Positioning for BeiDou-3 B1c/B2a Signals in the Global Range.

With the construction and development of the BeiDou navigation satellite system (BDS), the precise point positioning (PPP) performance of the BDS is worthy of research. In this study, observational data from 17 stations around the world across 20 days are used to comprehensively evaluate the PPP performance of BDS B1c/B2a signals. For greater understanding, the results are also compared with the Global Positioning System (GPS) and BDS PPP performance of different signals and system combinations. The evaluation found root mean square (RMS) values of the static PPP in the north (N), east (E), and upward (U) components, based on the B1c/B2a frequency of BDS-3, to be 6.9 mm, 4.7 mm, and 26.6 mm, respectively. Similar to the static positioning, the RMS values of kinematic PPP in the three directions of N, E, and U are 2.6 cm, 6.0 cm, and 8.5 cm, respectively. Besides this, the static PPP of BDS-3 (B1cB2a) and BDS-2 + BDS-3 (B1IB3I) have obvious system bias. Compared with static PPP, kinematic PPP is more sensitive to the number of satellites, and the coordinate accuracy in three dimensions can be increased by 27% with the combination of GPS (L1L2) and BDS. Compared with BDS-2+BDS-3 (B1IB3I), the convergence time of BDS-3 (B1CB2a) performs better in both static and kinematic modes. The antenna model does not show a significant difference in terms of the effect of the convergence speed, though the number of satellites observed has a certain influence on the convergence time.

p53 sensitizes chemoresistant non-small cell lung cancer via elevation of reactive oxygen species and suppression of EGFR/PI3K/AKT signaling.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths primarily due to chemoresistance. Somatic mutation of TP53 (36%) and epidermal growth factor receptor (EGFR; > 30%) are major contributors to cisplatin (CDDP) resistance. Substantial evidence suggests the elevated levels of reactive oxygen species (ROS) is a key determinant in cancer. The elevated ROS can affect the cellular responses to chemotherapeutic treatments. Although the role of EGFR in PI3K/Akt signaling cascade in NSCLC is extensively studied, the molecular link between EGFR and p53 and the role of ROS in pathogenesis of NSCLC are limitedly addressed. In this study, we investigated the role of p53 in regulation of ROS production and EGFR signaling, and the chemosensitivity of NSCLC. METHODS: In multiple NSCLC cell lines with varied p53 and EGFR status, we compared and examined the protein contents involved in EGFR-Akt-P53 signaling loop (EGFR, P-EGFR, Akt, P-Akt, p53, P-p53) by Western blot. Apoptosis was determined based on nuclear morphological assessment using Hoechst 33258 staining. Cellular ROS levels were measured by dichlorofluorescin diacetate (DCFDA) staining followed by flow cytometry analysis. RESULTS: We have demonstrated for the first time that activation of p53 sensitizes chemoresistant NSCLC cells to CDDP by down-regulating EGFR signaling pathway and promoting intracellular ROS production. Likewise, blocking EGFR/PI3K/AKT signaling with PI3K inhibitor elicited a similar response. Our findings suggest that CDDP-induced apoptosis in chemosensitive NSCLC cells involves p53 activation, leading to suppressed EGFR signaling and ROS production. In contrast, in chemoresistant NSCLC, activated Akt promotes EGFR signaling by the positive feedback loop and suppresses CDDP-induced ROS production and apoptosis. CONCLUSION: Collectively, our study reveals that the interaction of the p53 and Akt feedback loops determine the fate of NSCLC cells and their CDDP sensitivity.

Transcriptomic analysis of the differentiating ovary of the protogynous ricefield eel Monopterus albus.

BACKGROUND: The ricefield eel is a protogynous hermaphroditic Synbranchiform species that changes sex naturally from female to male, which offers an interesting model for studying gonadal (particularly ovarian) differentiation in vertebrates. In the present study, transcriptome sequencing of the gonad of ricefield eel larvae was performed to explore the molecular mechanisms underlying the ovarian differentiation and development. RESULTS: A total of 301,267,988 clean reads were generated from cDNA libraries of gonadal tissues of ricefield eel larvae at 6, 9, 12, and 20 days post hatching (dph), which contained undifferentiated gonads, differentiating ovaries, ovaries with oogonia, and ovaries with meiotic oocytes, respectively. De-novo assembly of all the clean reads generated a total of 265,896 unigenes with a mean size of 720 bp and a N50 of 1107 bp. RT-qPCR analysis of the developmental expression of 13 gonadal development-related functional genes indicated that RNA-seq data are reliable. Transcriptome data suggest that high expression of female development-related genes and low expression of male development-related genes in the early gonads of ricefield eel larvae participate in the cascade of sex differentiation leading to the final female phenotype. The contrasting expression patterns of genes involved in retinoid acid (RA) synthesis and degradation might result in peak production of RA at 12 dph in the gonad of ricefield eel larvae, and induce molecular events responsible for the initiation of meiosis before the meiotic signs could be observed at 20 dph. In addition, only stra6 but not stra8 could be identified in gonadal transcriptome data of ricefield eel larvae, and the expression pattern of stra6 paralleled those of genes involved in RA synthesis, suggesting that stra6 may be a downstream target of RA and play a role in RA metabolism and/or meiotic initiation in the gonad of ricefield eel larvae. CONCLUSIONS: The present study depicted the first large-scale RNA sequencing of the gonad of ricefield eel larvae, and identified many important functional genes, GO terms and KEGG pathways involved in gonadal development and germ cell meiosis. Results of the present study will facilitate future study on the ovarian differentiation of ricefield eels and other teleosts as well.

Signal-3L 2.0: A Hierarchical Mixture Model for Enhancing Protein Signal Peptide Prediction by Incorporating Residue-Domain Cross-Level Features.

Signal peptides play key roles in targeting and translocation of integral membrane proteins and secretory proteins. However, signal peptides present several challenges for automatic prediction methods. One challenge is that it is difficult to discriminate signal peptides from transmembrane helices, as both the H-region of the peptides and the transmembrane helices are hydrophobic. Another is that it is difficult to identify the cleavage site between signal peptides and mature proteins, as cleavage motifs or patterns are still unclear for most proteins. To solve these problems and further enhance automatic signal peptide recognition, we report a new Signal-3L 2.0 predictor. Our new model is constructed with a hierarchical protocol, where it first determines the existence of a signal peptide. For this, we propose a new residue-domain cross-level feature-driven approach, and we demonstrate that protein functional domain information is particularly useful for discriminating between the transmembrane helices and signal peptides as they perform different functions. Next, in order to accurately identify the unique signal peptide cleavage sites along the sequence, we designed a top-down approach where a subset of potential cleavage sites are screened using statistical learning rules, and then a final unique site is selected according to its evolution conservation score. Because this mixed approach utilizes both statistical learning and evolution analysis, it shows a strong capacity for recognizing cleavage sites. Signal-3L 2.0 has been benchmarked on multiple data sets, and the experimental results have demonstrated its accuracy. The online server is available at www.csbio.sjtu.edu.cn/bioinf/Signal-3L/ .

Modeling and Assessment of GPS/BDS Combined Precise Point Positioning.

Precise Point Positioning (PPP) technique enables stand-alone receivers to obtain cm-level positioning accuracy. Observations from multi-GNSS systems can augment users with improved positioning accuracy, reliability and availability. In this paper, we present and evaluate the GPS/BDS combined PPP models, including the traditional model and a simplified model, where the inter-system bias (ISB) is treated in different way. To evaluate the performance of combined GPS/BDS PPP, kinematic and static PPP positions are compared to the IGS daily estimates, where 1 month GPS/BDS data of 11 IGS Multi-GNSS Experiment (MGEX) stations are used. The results indicate apparent improvement of GPS/BDS combined PPP solutions in both static and kinematic cases, where much smaller standard deviations are presented in the magnitude distribution of coordinates RMS statistics. Comparisons between the traditional and simplified combined PPP models show no difference in coordinate estimations, and the inter system biases between the GPS/BDS system are assimilated into receiver clock, ambiguities and pseudo-range residuals accordingly.

Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation.

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 µM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

Scp3 expression in relation to the ovarian differentiation in the protogynous hermaphroditic ricefield eel Monopterus albus.

Synaptonemal complex protein 3 (Scp3), which is encoded by scp3, is a meiotic marker commonly used to trace the timing of gonadal differentiation in vertebrates. In the present study, the ricefield eel scp3 cDNA was cloned, and a fragment encoding amino acids 49 to 244 was overexpressed. The recombinant Scp3 polypeptide was purified and used to generate a rabbit anti-Scp3 polyclonal antiserum. In adult ricefield eels, scp3 mRNA was predominantly detected in the gonads and faintly detected in discrete brain areas. In the gonads, Scp3 immunoreactivities were shown to be localized to the germ cells, including meiotic primary growth oocytes, spermatocytes, and pre-meiotic spermatogonia. During early ovarian differentiation, immunoreactive Scp3 was not detected in the gonads of ricefield eels at 6 days post-hatching (dph) but was found to be abundantly localized in the cytoplasm of some oogonia at 7 dph, coinciding with the appearance of the ovarian cavity and ovarian differentiation. At 14 dph, strong Scp3 immunostaining was detected on one side of the nucleus with a distinct polarity in some germ cells, presumably at the leptotene stage. Consistent with these results, the expression of scp3 mRNA was faintly detected in the gonads of ricefield eels at 6 dph, increased at 8 dph, and then remained relatively high thereafter. Taken together, these results suggest that the appearance of immunoreactive Scp3 in oogonia could be a marker for early ovarian differentiation in ricefield eels. The translocation of the Scp3 protein from the cytoplasm to the nucleus in the oogonium of ricefield eels appears to be a controlled process that warrants further study.

Loading Mode-Induced Enhancement in Friction for Microscale Graphite/Hexagonal Boron Nitride Heterojunction.

Classical friction laws traditionally assume that the friction between solid pairs remains constant with a given normal load. However, our study has unveiled a remarkable deviation from conventional wisdom. In this paper, we discovered that altering the loading mode of micro graphite flakes led to significant changes in the lateral friction under identical normal loads. By adding a cap onto a single graphite flake to disperse the normal load applied by an atomic force microscope (AFM) tip, we were able to distribute the concentrated force. Astonishingly, our results demonstrated a notable 4-7 times increase in friction as a consequence of load dispersion. Finite element analysis (FEA) further confirmed that the increase in compressive stress at the edges of the graphite flake, resulting from load dispersion, led to a significant increase in friction. This study underscores the critical role of the loading mode in microscale friction dynamics, challenging the prevailing notion that friction remains static with a given normal force. Importantly, our research sheds light on the potential for achieving macroscale structural superlubricity (SSL) by assembling microscale SSL graphite flakes by using a larger cap.

Unveiling the Pharmacological Role of Human Deubiquitinating Enzymes in Temozolomide Response of Glioblastoma Cells.

Temozolomide (TMZ) stands as the primary chemotherapeutic drug utilized in clinical glioma treatment, particularly for high-grade glioblastoma (GBM). However, the emergence of TMZ resistance in GBM poses a significant hurdle to its clinical efficacy. Our objective was to elucidate the role of deubiquitinating enzymes (DUBs) in GBM cell resistance to TMZ. We employed the broad-spectrum DUBs inhibitor G5 to investigate the function of DUBs in TMZ cytotoxicity against GBM cells. Eighty-two GBM cell lines with specified DUBs knockout were generated and subjected to CCK-8 assays to assess cell proliferation and TMZ resistance. Furthermore, the association between DUBs and TMZ resistance in GBM cells, along with the modulation of autophagic flux, was examined. The pan-DUBs inhibitor G5 demonstrated the ability to induce cell death and enhance TMZ toxicity in GBM cells. Subsequently, we identified potential DUBs involved in regulating GBM cell proliferation and TMZ resistance. The impact of DUBs knockout on TMZ cytotoxicity was found to be associated with their regulation of TMZ-induced autophagy. In summary, our study provides primary insights into the role of DUBs in GBM cell proliferation and TMZ resistance, and contributes to a deeper understanding of the complex function of DUBs genes underlying TMZ resistance in GBM cells.

Epigenetic Dynamics in Meniscus Cell Migration and its Zonal Dependency in Response to Inflammatory Conditions: Implications for Regeneration Strategies.

Meniscus injuries pose significant challenges in clinical settings, primarily due to the intrinsic heterogeneity of the tissue and the limited efficacy of current treatments. Endogenous cell migration is crucial for the healing process, yet the regulatory mechanisms of meniscus cell migration and its zonal dependency within the meniscus are not fully understood. Thus, this study investigates the role of epigenetic mechanisms in governing meniscus cell migration under inflammatory conditions, with a focus on their implications for injury healing and regeneration. Here, we discovered that a proinflammatory cytokine, TNF-α treatment significantly impedes the migration speed of inner meniscus cells, while outer meniscus cells are unaffected, underscoring a zonal-dependent response within the meniscus. Our analysis identified distinct histone modification patterns and chromatin dynamics between inner and outer meniscus cells during migration, highlighting the necessity to consider these zonal-dependent properties in devising repair strategies. Specifically, we found that TNF-α differentially influences histone modifications, particularly H3K27me3, between the two cell types. Transcriptome analysis further revealed that TNF-α treatment induces substantial gene expression changes, with inner meniscus cells exhibiting more pronounced alterations than outer cells. Gene cluster analysis pointed to distinct responses in chromatin remodeling, extracellular matrix assembly, and wound healing processes between the zonal cell populations. Moreover, we identified potential therapeutic targets by employing existing epigenetic drugs, GSKJ4 (a histone demethylase inhibitor) and C646 (a histone acetyltransferase inhibitor), to successfully restore the migration speed of inner meniscus cells under inflammatory conditions. This highlights their potential utility in treating meniscus tear injuries. Overall, our findings elucidate the intricate interplay between epigenetic mechanisms and meniscus cell migration, along with its meniscus zonal dependency. This study provides insights into potential targets for enhancing meniscus repair and regeneration, which may lead to improved clinical outcomes for patients with meniscus injuries and osteoarthritis.

YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C­Dependent SMOX mRNA Stabilization.

The modification and recognition of 5-methylcytosine (m5C) are involved in the initiation and progression of various tumor types. However, the precise role and potential mechanism of Y-box-binding protein 1 (YBX1) in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, it is found that YBX1 is frequently upregulated in ESCC compared with matched nontumor tissues. Gain- and loss-of-function assays show that YBX1 promoted the proliferation and metastasis of ESCC cells both in vitro and in vivo. Functional studies revealed that NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a critical RNA methyltransferase that facilitates YBX1-mediated ESCC progression. Mechanistically, integrated analysis based on RNA immunoprecipitation sequencing (RIP-seq) and m5C methylated RNA immunoprecipitation and sequencing (MeRIP-seq) assays identified spermine oxidase (SMOX) as a target gene containing an m5C site in its coding sequence (CDS) region, which coincided well with the binding site of YBX1. Overexpression of SMOX-WT but not SMOX-Mut partially restored the proliferation and invasion ability of ESCC cells curbed by YBX1 knockdown. Moreover, YBX1 activated the mTORC1 signaling pathway by stabilizing SMOX mRNA. The study reveals that YBX1 promotes ESCC development by stabilizing SMOX mRNA in an m5C-dependent manner, thus providing a valuable therapeutic target for ESCC.

Classification molecular subtypes of hepatocellular carcinoma based on PRMT-related genes.

Background: Recent studies highlighted the functional role of protein arginine methyltransferases (PRMTs) catalyzing the methylation of protein arginine in malignant progression of various tumors. Stratification the subtypes of hepatocellular carcinoma (HCC) is fundamental for exploring effective treatment strategies. Here, we aim to conduct a comprehensive analysis of PRMTs with bioinformatic tools to identify novel biomarkers for HCC subtypes classification and prognosis prediction, which may be potential ideal targets for therapeutic intervention. Methods: The expression profiling of PRMTs in HCC tissues was evaluated based on the data of TCGA-LIHC cohort, and further validated in HCC TMA cohort and HCC cell lines. HCC was systematically classified based on PRMT family related genes. Subsequently, the differentially expressed genes (DEGs) between molecular subtypes were identified, and prognostic risk model were constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression analysis to evaluate the prognosis, gene mutation, clinical features, immunophenotype, immunotherapeutic effect and antineoplastic drug sensitivity of HCC. Results: PRMTs expression was markedly altered both in HCC tissues and HCC cell lines. Three molecular subtypes with distinct immunophenotype were generated. 11 PRMT-related genes were enrolled to establish prognostic model, which presented with high accuracy in predicting the prognosis of two risk groups in the training, validation, and immunotherapy cohort, respectively. Additionally, the two risk groups showed significant difference in immunotherapeutic efficacy. Further, the sensitivity of 72 anticancer drugs was identified using prognostic risk model. Conclusion: In summary, our findings stratified HCC into three subtypes based on the PRMT-related genes. The prognostic model established in this work provide novel insights into the exploration of related therapeutic approaches in treating HCC.

Comprehensive analysis of HOX family genes in endometrial cancer.

Background: Endometrial cancer (EC) is one of the most prevalent malignancies in the female population. Homeoboxes (HOXs) are a large family of transcription factors that have a variety of functions in biological processes (BPs), including developmental differentiation, and their dysregulated expression has been implicated in tumorigenesis. However, the involvement of HOXs in EC has received little attention. Thus, we aimed to identify the potential role of HOXs in EC from a multi-omics perspective through bioinformatics analysis. Methods: We obtained transcriptome, mutation, and methylation data and the corresponding clinical data for normal and tumor tissues from The Cancer Genome Atlas (TCGA) database. Abnormal expression of HOXs in EC was identified via differential analysis, and the diagnostic value of HOXs in EC was assessed with the receiver operating characteristic (ROC) method. Univariate and multivariate Cox regression models were employed to evaluate the predictive efficacy of HOXs in EC. Methylation and mutation analyses revealed epigenetic and genetic sequence alterations in HOXs. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the altered immune microenvironment in EC. Moreover, the gene activity and pathway enrichment of downstream key HOX genes were revealed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis in EC. Results: HOXs were found to be linked to the growth of EC and potentially playing a role in establishing the tumor immune microenvironment in patients with EC. HOXB9 was found to be a vital prognostic molecule in patients with EC and is expected to contribute to a novel treatment approach. Conclusions: We used bioinformatics techniques to clarify the potential role of HOXs from a multi-omics perspective, and our findings provide a foundation for future investigations into the molecular mechanisms of HOXs in EC.

Classification of Signature-Based Phenotypes of Aging-Related Genes to Identify Prognostic and Immune Characteristics in HCC.

Hepatocellular carcinoma (HCC), which has become one of the most significant malignancies causing cancer-related mortality, presents genetic and phenotypic heterogeneity that makes predicting prognosis challenging. Aging-related genes have been increasingly reported as significant risk factors for many kinds of malignancies, including HCC. In this study, we comprehensively dissected the features of transcriptional aging-relevant genes in HCC from multiple perspectives. We applied public databases and self-consistent clustering analysis to classify patients into C1, C2, and C3 clusters. The C1 cluster had the shortest overall survival time and advanced pathological features. Least absolute shrinkage and selection operator (LASSO) regression analysis was adopted to build the prognostic prediction model based on six aging-related genes (HMMR, S100A9, SPP1, CYP2C9, CFHR3, and RAMP3). These genes were differently expressed in HepG2 cell lines compared with LO2 cell lines measured by the mRNA expression level. The high-risk score group had significantly more immune checkpoint genes, higher tumor immune dysfunction and exclusion score, and stronger chemotherapy response. The results indicated that the age-related genes have a close correlation with HCC prognosis and immune characteristics. Overall, the model based on six aging-associated genes demonstrated great prognostic prediction ability.

Boric acid group-functional Tb-MOF as a fluorescent and captured probe for the highly sensitive and selective determination of propyl gallate in edible oils.

This study reports the development of a Tb-metal-organic framework (Tb-MOF)-based fluorescent platform for the detection of propyl gallate (PG). The Tb-MOF using 5-boronoisophthalic acid (5-bop) as the ligand exhibited multiple emissions at 490, 543, 585, and 622 nm under an excitation wavelength of 256 nm. The fluorescence of Tb-MOF was selectively and significantly weakened in the presence of PG due to the special nucleophilic reaction between the boric acid of Tb-MOF and o-diphenol hydroxyl of PG, and the combined effect of static quenching and internal filtering. Furthermore, this sensor enabled the determination of PG within seconds in a wide linear range of 1-150 µg/mL, and with a low detection limit of 0.098 µg/mL, and high specificity against other phenolic antioxidants. This work provided a new route for the sensitive and selective determination of PG in soybean oil, thus was perspective to monitor and reduce the risk of PG overuse.

NSUN2 stimulates tumor progression via enhancing TIAM2 mRNA stability in pancreatic cancer.

NSUN2 is a nuclear RNA methyltransferase which catalyzes 5-methylcytosine (m5C), a posttranscriptional RNA modification. Aberrant m5C modification has been implicated in the development of multiple malignancies. However, its function in pancreatic cancer (PC) needs to be elucidated. Herein, we determined that NSUN2 was overexpressed in PC tissues and related to aggressive clinical features. Silence of NSUN2 by lentivirus weakened the capability of proliferation, migration and invasion of PC cells in vitro and inhibited the growth and metastasis of xenograft tumors in vivo. Contrarily, overexpression of NSUN2 stimulated PC growth and metastasis. Mechanistically, m5C-sequencing (m5C-seq) and RNA-sequencing (RNA-seq) were carried out to identify downstream targets of NSUN2 and results showed that loss of NSUN2 led to decreased m5C modification level concomitant with reduced TIAM2 mRNA expression. Further validation experiments proved that NSUN2 silence accelerated the decay of TIAM2 mRNA in a YBX1-dependent manner. Additionally, NSUN2 exerted its oncogenic function partially through enhancing TIAM2 transcription. More importantly, disruption of the NSUN2/TIAM2 axis repressed the malignant phenotype of PC cells through blocking epithelial-mesenchymal transition (EMT). Collectively, our study highlighted the critical function of NSUN2 in PC and provided novel mechanistic insights into NSUN2/TIAM2 axis as promising therapeutic targets against PC.