The first specific probe for pyrrolidine with multifunction by the interaction mechanism of atomic economic reaction.

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Fluorinated benzothiadiazole fluorescent probe based on ICT mechanism for highly selectivity and sensitive detection of fluoride ion.

Excessive fluoride ion (F-) in the environment can affect health and even endanger life when ingested by the human body. However, most fluoride probes have the disadvantages of low sensitivity and long detection time. Herein, fluorescent probe 3a is successfully synthesized by linking two acetylenyltrimethylsilyl groups at both ends of the fluorinated benzothiadiazole core. After the addition of F- to 3a, the emission at 436 nm is significantly quenched and slightly blue-shifted. It is confirmed by electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and density functional theory calculations (DFT) that these changes are due to the F- triggered Si-C bond cleavage and the subsequent inactivation of intramolecular charge transfer (ICT). The detection limit and response time of probe 3a for F- are 10-8 mol/L and 25 s, respectively. Importantly, fluorescent material 3a can be processed into portable test tools for the visual detection of fluoride ion.

Regulating donor-acceptor system toward highly efficient dual-state emission for sensitive response of nitroaromatic explosives.

Dual-state emission luminogens (DSEgens) as fluorophores emit efficiently in solution and solid forms have gained increasing concern in the field of chemical sensing. Recent efforts by our group led to the identification of DSEgens as an easy-to-visualize nitroaromatic explosives (NAEs) detection platform. However, none of the previously studied NAEs probes show effective improvement in sensitivity. Here, we designed a series of benzoxazole-based DSEgens through multiple strategies driven by theoretical calculations, revealing their improved detecting performance on NAEs. Compounds 4a-4e exhibit thermal- and photo-stability, large Stokes shift as well as sensitivity solvatochromism (except for 4a and 4b). A subtle balance between rigid conjugation and distorted conformation endows these D-A type fluorophores 4a-4e with DSE properties. Furthermore, 4d and 4e show aggregation-induced emission phenomenon caused by distorted molecular conformation and restricted intramolecular rotation. Interestingly, DSEgen 4e displays anti-interference and sensitivity towards NAEs with a detection limit of 10-8 M. It can be applied for expedient and distinct visual identification of NAEs not only in solution but also on filter paper and film, supporting this new DSEgen as reliable NAEs chemoprobe.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

Objective: To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. Methods: We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Results: Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Conclusions: Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

APOC1 predicts a worse prognosis for esophageal squamous cell carcinoma and is associated with tumor immune infiltration during tumorigenesis.

Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/TISIDB/) website, and various other analysis tools. Results: In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues (p < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan-Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) (p = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) (p = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC (p = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, Staphylococcus aureus infection, antigen processing and presentation, and graft-versus-host disease (all p < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. Conclusion: APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.

miR-181a-5p restrains non-small cell lung cancer cell invasion and migration by regulating the GTSE1/p53/NF-κB axis.

microRNAs (miRNAs) are relevant to metastasis and invasion of non-small cell lung cancer (NSCLC). This study investigated the role of miR-181a-5p in lung cancer. Expression patterns of miR-181a-5p and GTSE1 in the human NSCLC cell line A549 and normal lung epithelial cell line BASE-2B were detected. miR-181a-5p mimic was delivered into A549 cells utilizing Lipofectamine 2000 to overexpress miR-181a-5p, followed by analysis of cell viability, proliferation, apoptosis, invasion, and migration. GTSE1 (G2 and S phase-expressed-1) was predicted as the downstream target gene of miR-181a-5p using bioinformatics analysis software. Targeting relationship between miR-181a-5p and GTSE1 was validated via dual-luciferase assay, RIP assay, and RNA pull-down. Activation of the p53/NF-κB pathway was determined. miR-181a-5p was weakly-expressed in NSCLC cells relative to normal lung epithelial cells. miR-181a-5p overexpression prevented NSCLC cell proliferation, migration, and invasion. Mechanically, miR-181a-5p targeted GTSE1. GTSE1 overexpression partly annulled repression of miR-181a-5p overexpression on NSCLC cell malignant behavior. miR-181a-5p activated the p53 pathway and inhibited the NF-κB pathway by targeting GTSE1. Overall, this study for the first time validated that miR-181a-5p impeded NSCLC cell invasion and migration through activation of the p53 pathway and inhibition of the NF-κB pathway by targeting GTSE1, which may provide a potential novel insight into NSCLC treatment.

Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR.

Non-small cell lung cancer (NSCLC) is a malignant tumor. Serum exosomal miR-27b is related to tumor diagnosis. We explored the roles of serum exosomal miR-27b in NSCLC. NSCLC patients were assigned to NSCLC-early/terminal groups, with healthy subjects as controls. miR-27b expression was assessed using reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficiency was analyzed using the receiver operating characteristic curve. The correlation between serum exosomal miR-27b expression and tumor markers carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen (CEA), and cytokeratin 19-soluble fragment (CYFRA21-1) was analyzed using the Pearson analysis. The downstream target genes were predicted. Epidermal growth factor receptor (EGFR) level was assessed using enzyme-linked immunosorbent assay. Correlations of miR-27b expression with serum EGFR level and CA125, CEA, and CYFRA21-1 levels were analyzed using the Pearson analysis. Serum exosomal miR-27b was diminished in NSCLC and was further decreased in the NSCLS-terminal group. The sensitivity of miR-27b < 0.8150 for NSCLC diagnosis was 76.64%, and the specificity was 83.33%. Serum exosomal miR-27b was negatively correlated with CA125, CEA, and CYFRA21-1. miR-27b targeted EGFR. Serum EGFR was raised in NSCLC and was further elevated in the NSCLS-terminal group. miR-27b expression was negatively correlated with EGFR level. EGFR level was positively correlated with CA125, CEA, and CYFRA21-1 levels. Collectively, low expression of miR-27b assisted NSCLC diagnosis, and miR-27b exerted effects on NSCLC through EGFR.

N-alkylation briefly constructs tunable multifunctional sensor materials: Multianalyte detection and reversible adsorption.

A series of N-alkyl-substituted polybenzimidazoles (SPBIs), synthesized by simple condensation and N-alkylation, act as functional materials with tunable microstructures and sensing performance. For their controllable morphologies, the formation of nano-/microspheres is observed at the n(RBr)/n(PBI) feed ratio of 5:1. Products with different degrees of alkylation can recognize metal ions and nitroaromatic compounds (NACs). For example, SPBI-c, obtained at the feed ratio of 1:1, can selectively detect Cu2+, Fe3+, and NACs. By contrast, SPBI-a, obtained at the feed ratio of 0.1:1, can exclusively detect Cu2+ with high sensitivity. Their sensing mechanisms have been studied by FT-IR spectroscopy, SEM, XPS, and DFT calculations. Interestingly, the SPBIs can adsorb Cu2+ in solution and show good recyclability. These results demonstrate that polymeric materials with both sensing and adsorption applications can be realized by regulating the alkylation extent of the main chain, thus providing a new approach for the facile synthesis of multifunctional materials.

Preparation of Large Conjugated Polybenzimidazole Fluorescent Materials and Their Application in Metal Ion Detection.

A new type of conjugated polybenzimidazole (CPBI) was synthesized through a simple polycondensation reaction without metal catalysis, and N-alkylation modification was carried out to solve the problems of solubility and fluorescence properties. A series of nano-microsphere polymers CPBIn with large conjugation, good solubility, and strong fluorescence has been successfully used as "turn-off" fluorescent probes for the first time. The results show that, under suitable N-alkylation conditions, the obtained CPBIn can be used as a highly sensitive and selective fluorescent probe for the detection of Cu2+ and Zn2+ at the same time, and their detection limits are both nM levels. In addition, CPBI2 can be designed as an ultra-sensitive IMPLICATION logic gate at the molecular level, cyclically detecting Cu2+. With the test paper containing CPBI2, easy and quick on-site detection can be achieved. This research provides a new idea for the brief synthesis of multifunctional materials.

Simple inorganic base promoted C-N and C-C formation: synthesis of benzo[4,5]imidazo[1,2-a]pyridines as functional AIEgens used for detecting picric acid.

Metal-free catalyzed intermolecular tandem Michael addition/cyclization has been developed for the synthesis of benzo[4,5]imidazo[1,2-a]pyridines from α-bromocinnamaldehyde and 2-substituted benzimidazoles. The reaction promoted by a simple inorganic base displays moderate to good yields and good functional group tolerance. The optical properties of some typical products have been investigated. We found that, due to the presence of the benzene ring at the C1-position of benzo[4,5]imidazo[1,2-a]pyridines which restricts intramolecular motion, as a new type of aggregation-induced emission (AIE) luminogen (AIEgen), they show very good solid-state fluorescence with quantum yields up to 88.80%. Importantly, the AIE performance of compound 3b can be useful to detect the nitroaromatic explosive picric acid (PA) with a detection limit and quenching constant of 42.5 nM and 7.27 × 104 M-M, respectively.

Controllable preparation and performance of bio-based poly(lactic acid-iminodiacetic acid) as sustained-release Pb2+ chelating agent.

The bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

Original Research: Establishment of an early embolus-related cerebral injury model after cardiopulmonary bypass in miniature pigs.

Embolus-related cerebral injury is still a serious adverse event after cardiopulmonary bypass (CPB). But there is no stable animal model for basic and clinical research purposes. We chose miniature pig to establish a stable animal model of embolus-related cerebral injury after CPB and verified the validity of results by correlating the histopathological findings with those of diffusion-weighted magnetic resonance imaging (DW-MRI). Based on different treatment regimens, 24 male miniature pigs were randomly assigned into four groups: Control, CPB, embolus, and CPB-embolus groups. DW-MRI was performed before and after surgery to diagnose and locate the brain lesions. Histopathological changes in brain tissues were examined using H&E and Nissl staining. All surgical procedures were uneventful with 100% postoperative survival of pigs. Two animals in the Embolus group and six animals in the CPB-embolus group showed signs of ischemic penumbra on DW-MRI performed 6 h after surgery. Consistent with the results of DW-MRI, histopathological examination showed necrosis and ischemic lesions. In this paper, we demonstrate the feasibility and validity of a pig model of embolus-related cerebral injury associated with CPB. This model may be used in the future for basic and translational research.