Near-Infrared Perylenecarboximide Fluorophores for Live-Cell Super-Resolution Imaging.

Organic near-infrared (NIR) photoblinking fluorophores are highly desirable for live-cell super-resolution imaging based on single-molecule localization microscopy (SMLM). Herein we introduce a novel small chromophore, PMIP, through the fusion of perylenecarboximide with 2,2-dimetheylpyrimidine. PMIP exhibits an emission maximum at 732 nm with a high fluorescence quantum yield of 60% in the wavelength range of 700-1000 nm and excellent photoblinking without any additives. With resorcinol-functionalized PMIP (PMIP-OH), NIR SMLM imaging of lysosomes is demonstrated for the first time in living mammalian cells under physiological conditions. Moreover, metabolically labeled nascent DNA is site-specifically detected using azido-functionalized PMIP (PMIP-N3) via click chemistry, thereby enabling the super-resolution imaging of nascent DNA in phosphate-buffered saline with a 9-fold improvement in spatial resolution. These results indicate the potential of PMIP-based NIR blinking fluorophores for biological applications of SMLM.

Stable π-Extended Thio[7]helicene-Based Diradical with Predominant Through-Space Spin-Spin Coupling.

In this work, a novel π-extended thio[7]helicene scaffold was synthesized, where the α-position of the thiophene unit could be functionalized with bulky phenoxy radicals after considerable synthetic attempts. This open-shell helical diradical, ET7H-R, possesses high stability in the air, nontrivial π conjugation, persistent chirality, and a high diradical character (y0 of 0.998). The key feature is a predominant through-space spin-spin coupling (TSC) between two radicals at the helical terminals. Variable-temperature continuous-wave electron spin resonance (cw-ESR) and superconducting quantum interference device (SQUID) magnetometry in the solid state reveal a singlet ground state with a nearly degenerate triplet state of ET7H-R. These results highlight the significance of a stable helical diradicaloid as a promising platform for investigating intramolecular TSCs.

High-Performance Near-Infrared Chlorinated Rylenecarboximide Fluorophores via Consecutive C-N and C-C Bond Formation.

A new class of near-infrared (NIR) fluorophores, PAI, is obtained by consecutive C-N/C-C bond formation between diphenylamines and 9,10-dibromoperylenecarboximide. Owing to the rigid structure, extended π-conjugation and pronounced push-pull substitution, these fluorophores show emission maxima up to 804 nm and large Stokes shifts. The extraordinarily high fluorescence quantum yields from 47 % to 70 % are attributed to chloro substitution in the bay positions of the perylene core. These characteristics, together with high photostability, qualify them as useful NIR emitters for applications as biomarkers and security inks.

A Terrylene-Anthraquinone Dyad as a Chromophore for Photothermal Therapy in the NIR-II Window.

A terrylenedicarboximide-anthraquinone dyad, FTQ, with absorption in the second near-infrared region (NIR-II) is obtained as a high-performance chromophore for photothermal therapy (PTT). The synthetic route proceeds by C-N coupling of amino-substituted terrylenedicarboximide (TMI) and 1,4-dichloroanthraquinone followed by alkaline-promoted dehydrocyclization. FTQ with extended π-conjugation exhibits an optical absorption band peaking at 1140 nm and extending into the 1500 nm range. Moreover, as determined by dielectric spectroscopy in dilute solutions, FTQ achieves an ultrastrong dipole moment of 14.4 ± 0.4 Debye due to intense intramolecular charge transfer. After encapsulation in a biodegradable polyethylene glycol (DSPE-mPEG2000), FTQ nanoparticles (NPs) deliver a high photothermal conversion efficiency of 49% under 1064 nm laser irradiation combined with excellent biocompatibility, photostability, and photoacoustic imaging capability. In vitro and in vivo studies reveal the great potential of FTQ NPs in photoacoustic-imaging-guided photothermal therapy for orthotopic liver cancer treatment in the NIR-II window.

Photostable NIR-II Pigments from Extended Rylenecarboximides.

A series of near-infrared (NIR) organic absorbers, named FNs and FPs, have been obtained with absorption maxima from 870 nm to 1100 nm and thus falling into the attractive second near-infrared region (NIR-II). The synthesis of their extended aromatic cores utilized an initial aryl-amination between 4-aminonaphthalene-1,8-dicarboximide (NMI-NH2 ) or 9-aminoperylene-3,4-dicarboximide (PMI-NH2 ) with chloro-substituted 9,10-anthraquinones followed by a novel base-induced cyclodehydrogenation. A NIR-II pigment, compound FPP, was obtained through de-alkylation of a soluble precursor. The synthesis of this photostable pigment is high-yielding and avoids column chromatographic purification which is important for many applications.

Nomogram for predicting pathological complete response and tumor downstaging in patients with locally advanced rectal cancer on the basis of a randomized clinical trial.

BACKGROUND: Preoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer (LARC). The model for predicting pCR in LARC patients was based on standard treatment only. This study aimed to establish a nomogram with pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response (pCR) and tumor downstaging or good response (ypT0-2N0M0) after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial. METHODS: Between January 2011 and February 2015, 309 patients with rectal cancer were enrolled from a prospective randomized study (NCT01211210). All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (C-index) and calibration plots. RESULTS: Of the 309 patients, 53 (17.2%) achieved pCR and 132 (42.7%) patients were classified as tumor downstaging with ypT0-2N0M0. Based on the logistic-regression analysis and clinical consideration, tumor length (P = 0.005), tumor circumferential extent (P = 0.036), distance from the anal verge (P = 0.019), and neoadjuvant treatment regimen (P < 0.001) showed independent association with pCR following neoadjuvant treatment. The tumor length (P = 0.015), tumor circumferential extent (P = 0.001), distance from the anal verge (P = 0.032), clinical T category (P = 0.012), and neoadjuvant treatment regimen (P = 0.001) were significantly associated with good tumor downstaging (ypT0-2N0M0). Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802 (95% confidential interval [CI], 0.736-0.867) and 0.730 (95% CI, 0.672-0.784). Internal validation revealed good performance of the calibration plots. CONCLUSIONS: The nomogram provided individual prediction responses to different preoperative treatment for patients with rectal cancer. This model might help physicians in selecting an optimized treatment, but warrants further external validation.

Rational modification of tricarboxylic acid cycle for improving L-lysine production in Corynebacterium glutamicum.

BACKGROUND: Oxaloacetate (OAA) and L-glutamate are essential precursors for the biosynthesis of L-lysine. Reasonable control of all potentially rate-limiting steps, including the precursors supply rate, is of vital importance to maximize the efficiency of L-lysine fermentation process. RESULTS: In this paper, we have rationally engineered the tricarboxylic acid (TCA) cycle that increased the carbon yield (from 36.18 to 59.65%), final titer (from 14.47 ± 0.41 to 23.86 ± 2.16 g L-1) and productivity (from 0.30 to 0.50 g L-1 h-1) of L-lysine by Corynebacterium glutamicum in shake-flask fermentation because of improving the OAA and L-glutamate availability. To do this, the phosphoenolpyruvate-pyruvate-oxaloacetate (PEP-pyruvate-OAA) node's genes ppc and pyc were inserted in the genes pck and odx loci, the P1 promoter of the TCA cycle's gene gltA was deleted, and the nature promoter of glutamate dehydrogenase-coding gene gdh was replaced by Ptac-M promoter that resulted in the final engineered strain C. glutamicum JL-69Ptac-M gdh. Furthermore, the suitable addition of biotin accelerates the L-lysine production in strain JL-69Ptac-M gdh because it elastically adjusts the carbon flux for cell growth and precursor supply. The final strain JL-69Ptac-M gdh could produce 181.5 ± 11.74 g L-1 of L-lysine with a productivity of 3.78 g L-1 h-1 and maximal specific production rate (qLys, max.) of 0.73 ± 0.16 g g-1 h-1 in fed-batch culture during adding 2.4 mg L-1 biotin with four times. CONCLUSIONS: Our results reveal that sufficient biomass, OAA and L-glutamate are equally important in the development of L-lysine high-yielding strain, and it is the first time to verify that fed-batch biotin plays a positive role in improving L-lysine production.

4,5,9,10-Pyrene Diimides: A Family of Aromatic Diimides Exhibiting High Electron Mobility and Two-Photon Excited Emission.

The design and synthesis of high-performance n-type organic semiconductors are important for the development of future organic optoelectronics. Facile synthetic routes to reach the K-region of pyrene and produce 4,5,9,10-pyrene diimide (PyDI) derivatives are reported. The PyDI derivatives exhibited efficient electron transport properties, with the highest electron mobility of up to 3.08 cm2 V-1 s-1 . The tert-butyl-substituted compounds (t-PyDI) also showed good one- and two-photon excited fluorescence properties. The PyDI derivatives are a new family of aromatic diimides that may exhibit both high electron mobility and good light-emitting properties, thus making them excellent candidates for future optoelectronics.

Identification and determination of myriocin in Isaria cicadae and its allies by LTQ-Orbitrap-HRMS.

A hybrid linear ion trap-quadrupole-Orbitrap high-resolution mass spectrometry (LTQ-Orbitrap-HRMS) was used to qualitatively and quantitatively analyse the myriocin in Isaria cicadae and its allies. The samples were prepared with 95% methanol for 30 min by ultrasonic-assisted extraction. The target compound was purified by ODS solid-phase extraction (SPE) column. The enriched samples were identified by mass spectrometry. The results showed that the contents of myriocin in both wild and artificial Isaria cicadae were below the detection limit, while a strain of Ophiocordyceps longissima and Cordyceps cicadae Shing (Dujiaolong), both closely related to the Isaria cicadae, and its asexual mycelia are rich in myriocin. It suggests that it may be wrong to consider C. cicadae as I. cicadae's teleomorph in Genbank or Mycobank in many published reports based on chemical classification, and the species rich in myriocin is probably not Isaria cicadae.

Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer.

Colon cancer is one of the most frequently diagnosed cancer and the third most fatal malignancy worldwide. HOTAIR, a cancer-associated long non-coding RNA (lncRNA), is a powerful biomarker of metastasis and poor prognosis in a diverse group of cancers. Nevertheless, an understanding of how HOTAIR is involved in colon cancer progression is limited. In the present study, we hypothesized that HOTAIR plays a crucial role in colon cancer development. We evaluated the expression of HOTAIR in 120 colon cancer samples, matched adjacent non-tumor mucosa and 32 lymph node metastasis tissues by real-time PCR. Increased HOTAIR expression was significantly correlated with the depth of tumor invasion, lymph node metastasis, organ metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with high HOTAIR expression had higher recurrence rates and reduced metastasis-free and overall survival than patients with low HOTAIR expression. Moreover, our findings revealed that HOTAIR had a limited effect on cell proliferation but significantly promoted colon cancer cell migration and invasion in vitro. Depletion of HOTAIR increased the expression of E-cadherin while concomitantly decreasing expression of vimentin and MMP9. Hence, HOTAIR may be another pleiotropic modulator participating in epithelial-mesenchymal transition (EMT). These results indicate that HOTAIR may also be a valuable predictor for colon cancer management; furthermore, this lncRNA may be a potential target for cancer prevention and treatment.

Comparison of three mathematical prediction models in patients with a solitary pulmonary nodule.

BACKGROUND: Effective methods for managing patients with solitary pulmonary nodules (SPNs) depend critically on the predictive probability of malignancy. METHODS: Between July 2009 and June 2011, data on gender, age, cancer history, tumor familial history, smoking status, tumor location, nodule size, spiculation, calcification, the tumor border, and the final pathological diagnosis were collected retrospectively from 154 surgical patients with an SPN measuring 3-30 mm. Each final diagnosis was compared with the probability calculated by three predicted models-the Mayo, VA, and Peking University (PU) models. The accuracy of each model was assessed using area under the receiver operating characteristics (ROC) and calibration curves. RESULTS: The area under the ROC curve of the PU model [0.800; 95% confidence interval (CI): 0.708-0.891] was higher than that of the Mayo model (0.753; 95% CI: 0.650-0.857) or VA model (0.728; 95% CI: 0.623-0.833); however, this finding was not statistically significant. To varying degrees, calibration curves showed that all three models overestimated malignancy. CONCLUSIONS: The three predicted models have similar accuracy for prediction of SPN malignancy, although the accuracy is not sufficient. For Chinese patients, the PU model may has greater predictive power.

Cullin 4B is a novel prognostic marker that correlates with colon cancer progression and pathogenesis.

Cullin 4B (CUL4B), a scaffold protein of the Cullin4B-RING E3 ligase complex, functions in proteolysis. The present study aims to investigate its expression pattern and evaluate whether CUL4B expression was associated with histopathological and prognosis in the patients with colon cancer. Real-time PCR and western blot were used to identify CUL4B expression in tumor tissue and the paired adjacent normal mucosa from patients with colon cancer. Immunohistochemistry on a tissue microarray containing 203 cases of colon cancer was performed to analyze the association between CUL4B expression and clinicopathological features. Results indicated that CUL4B mRNA and protein levels in tumor tissues were both higher than that in normal mucosae (P < 0.001). Immunohistochemical study displayed that high CUL4B expression was significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, and advanced tumor stage. Patients with CUL4B-positive tumors had a higher recurrence rate and poorer survival than patients with CUL4B-negative tumors. In multivariate analyses, CUL4B expression was an independent factor for determining colon cancer prognosis after surgery. In conclusion, CUL4B might promote the progression of colon cancer and can be served as a novel independent prognostic marker for the prediction of recurrence in colon cancer.