A triphenylamine-based fluorescence probe for detection of hypochlorite in mitochondria.

The level of HClO/ClO- in mitochondria is essential to keep the normal function of mitochondria. Therefore, it is meaningful to accurately and quickly monitor ClO- in mitochondria. In this work, a new triphenylamine-based fluorescence probe PDTPA was designed and synthesized, in which pyridinium salt and dicyano-vinyl group were introduced as mitochondria targeting site and reaction site for ClO-. The probe showed high sensitivity and fast fluorescence response (<10 s) in the detection of ClO-. Moreover, the probe PDTPA had good linearity in a wide concentration range of ClO- and its detection limit was calculated as 10.5 µM. Confocal fluorescence images demonstrated that the probe could target mitochondria and track the fluctuations of endogenous/exogenous ClO- levels in the mitochondria of living cells.

Highly selective and sensitive benzopyran-based fluorescent probes for imaging exogenous and endogenous peroxynitrite.

Peroxynitrite is widely present in organisms and closely related to many pathophysiological functions. Therefore, it is of great physiological significance to develop capable probes for detecting ONOO-. In this work, a novel fluorescent probe B-Ch was designed based on the intramolecular charge transfer (ICT) effect. By means of molecular engineering, the replacement from diethylamine group to hydroxyl group has improved the detection sensitivity of the probe. After the addition of ONOO-, the solution color and fluorescence showed noticeable changes, which were visible to the naked eye. The probe showed excellent advantages: visualization, good selectivity, low sensitivity (22.4 nM), good stability and biocompatibility, exogenous and endogenous imaging of ONOO- in HeLa cells.

Coumarin-cyanine hybrid: A ratiometric fluorescent probe for accurate detection of peroxynitrite in mitochondria.

There is an urgent need to develop highly sensitive and selective fluorescence probes for ONOO- in mitochondria. Herein, we reported a ratiometric fluorescent probe COUS with coumarin-cyanine hybrid as fluorophore and C = C bonds as reaction sites of ONOO-. The probe COUS was sensitive and selective to ONOO-, and had a large fluorescence emission shift (239 nm) as well as a low detection limit (41.88 nM). Moreover, COUS showed the mitochondrial targeting ability, and the targeting moiety could dissociate from the probe when reacting with ONOO-, which enabled COUS to accurately detect ONOO- in mitochondria.

Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients.

BACKGROUND: Many biomarkers have predictive value for overall survival (OS) and disease-free survival (DFS) in tumor patients. However, the role of indirect bilirubin (IBIL) in local advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) has not been studied. AIM: To explore the predictive value of IBIL before nCRT (pre-IBIL) for the OS and DFS of LARC patients treated with nCRT. METHODS: A total of 324 LARC patients undergoing nCRT with total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. Cox regression analysis was performed, and a Cox-based nomogram was developed to predict OS and DFS. We also assessed the predictive performance of the nomogram with calibration plots and receiver operating characteristic (ROC) curves. RESULTS: Among 324 patients, the median pre-IBIL was 6.2 µmol/L (interquartile range: 4.6 µmol/L-8.4 µmol/L). In the Cox multivariate regression analysis, we found that pre-IBIL, smoking history, tumor regression grade (TRG), vascular invasion, and carbohydrate antigen 19-9 before nCRT (pre-CA19-9) were predictors of OS. Additionally, pre-IBIL, body mass index (BMI), nCRT with surgery interval, TRG, and vascular invasion were predictors of DFS. Predictive nomograms were developed to predict 5-year OS and 5-year DFS with area under the ROC curve values of 0.7518 and 0.7355, respectively. Good statistical performance on internal validation was shown by calibration plots and ROC curves. CONCLUSION: This study demonstrated that pre-IBIL was an independent prognostic factor for OS and DFS in LARC patients treated with nCRT followed by TME. Nomograms incorporating pre-IBIL, BMI, smoking history, nCRT with surgery interval, TRG, vascular invasion, and pre-CA19-9 could be helpful to predict OS and DFS.

Large-Scale Production of Rectorite Nanosheets and Their Co-Assembly with Aramid Nanofibers for High-Performance Electrical Insulating Nanopapers.

Compared with raw rectorite microplatelets (RMs), rectorite nanosheets (RNs) have considerably greater application prospects in the preparation of advanced composite materials because of their larger aspect ratio, higher surface reactivity, and intrinsically superior mechanical and physical properties. However, the difficulty in the efficient preparation of RNs significantly limits their large-scale applications. Here, a scalable poly(vinylpyrrolidone)-assisted stirring approach is developed to prepare ultrathin RNs from the abundant natural RMs. A higher production rate (≈0.675 g h-1 ) is achieved compared with that of most other nanosheets. Additionally, instead of using conventional time- and energy-consuming high-speed centrifugation, an efficient poly(dienedimethylammonium chloride)-assisted sedimentation strategy is proposed here to rapidly separate the exfoliated RNs from the RN dispersion. Then, the RNs are co-assembled with aramid nanofibers (ANFs) into large-scale nacre-mimetic ANF-RN nanopapers with considerably enhanced mechanical, electrical insulating, and high-temperature-resistant properties compared with pure ANF nanopapers and ANF-RM micropapers. Moreover, these properties are superior to those of previously reported ANF-based nanopapers and commercial insulating micropapers.

Diabetes and Colorectal Cancer Risk: Clinical and Therapeutic Implications.

Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association include hyperinsulinemia, insulin-like growth factor (IGF) axis, hyperglycemia, inflammation induced by adipose tissue dysfunction, gastrointestinal motility disorder, and impaired immunological surveillance. Several studies have shown that underlying diabetes adversely affects the prognosis of patients with CRC. This review explores the novel anticancer agents targeting IGF-1R and receptor for advanced glycation end products (RAGE), both of which play a vital role in diabetes-induced colorectal tumorigenesis. Inhibitors of IGF-1R and RAGE are expected to become promising therapeutic choices, particularly for CRC patients with diabetes. Furthermore, hypoglycemic therapy is associated with the incidence of CRC. Selection of appropriate hypoglycemic agents, which can reduce the risk of CRC in diabetic patients, is an unmet issue. Therefore, this review mainly summarizes the current studies concerning the connections among diabetes, hypoglycemic therapy, and CRC as well as provides a synthesis of the underlying pathophysiological mechanisms. Our synthesis provides a theoretical basis for rational use of hypoglycemic therapies and early diagnosis and treatment of diabetes-related CRC.