Persistent Organic Nanopores Amenable to Structural and Functional Tuning.

Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including (1)H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward-pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward-pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior.

Cinnamate-based DNA photolithography.

As demonstrated by means of DNA nanoconstructs, as well as DNA functionalization of nanoparticles and micrometre-scale colloids, complex self-assembly processes require components to associate with particular partners in a programmable fashion. In many cases the reversibility of the interactions between complementary DNA sequences is an advantage. However, permanently bonding some or all of the complementary pairs may allow for flexibility in design and construction. Here, we show that the substitution of a cinnamate group for a pair of complementary bases provides an efficient, addressable, ultraviolet light-based method to bond complementary DNA covalently. To show the potential of this approach, we wrote micrometre-scale patterns on a surface using ultraviolet light and demonstrated the reversible attachment of conjugated DNA and DNA-coated colloids. Our strategy enables both functional DNA photolithography and multistep, specific binding in self-assembly processes.

Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis.

Background: Long non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of non-protein-coding RNAs. Many miRNAs have been reported to play a key role in the progression of myocardial hypertrophy. In this study, we aimed to investigate whether lncRNA reprogramming regulators (ROR) promotes hypoxic injury in cardiomyocytes by targeting and regulating the miR-145/HS1-associated protein X-1 (HAX-1) axis. Methods: A mouse model of myocardial hypertrophy was established by conventional TAC method, and the cardiomyocytes were isolated. We transfected pcDNA3.0-ROR vector, pcDNA3.0-HAX-1 vector plasmid, and miR-145 simulant into cardiomyocytes with Lipofectamine 2000. Luciferase reporter gene was used to analyze the targeting relationship between genes. Results: The expression of ROR in hypertrophic myocardium was significantly increased after phenylephrine (PE) intervention. After transfection with si-ROR, the ROR expression in hypertrophic cardiomyocytes treated with PE decreased significantly. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) decreased and superoxide dismutase (SOD) increased. The expression of miR-145 in cardiomyocytes was significantly down-regulated after PE treatment. In hypertrophic cardiomyocytes, after up-regulating the expression of miR-145, the relative messenger ribonucleic acid (mRNA) and protein expressions of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) induced by PE decreased. Compared with the miR-NC group, wild type (WT)-ROR activity in the miR-145 group was significantly inhibited (P<0.05), and mutant (MUT)-ROR activity had no significant change (P>0.05). When cardiomyocytes were transfected with HAX-1 3'URT WT vector along with miR-145 simulant, miR-145 inhibitor, and their respective controls. Compared with the control groups, the luciferase activity of cells transfected with simulant was significantly decreased (P<0.05), and increased in inhibitor group (P<0.05). Transfection of HAX-1 3'URT mutant vector did not show this phenomenon. ROR was negatively correlated with miR-145 expression and positively correlated with HAX-1 mRNA. Conclusions: The lncRNA ROR can promote the expression of HAX-1 by competitive binding with miR-145, so as to promote the pathophysiological process of myocardial hypertrophy.

Primary hepatic neuroendocrine tumor - 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings: A case report.

BACKGROUND: Primary hepatic neuroendocrine tumors (PHNETs) are rare hepatic tumors. Their diagnosis, which is based on radiological findings, is difficult. CASE SUMMARY: We present a case of PHNET in a 79-year-old man with no clinical symptoms. Computed tomography (CT) and 2-Deoxy-2-[fluorine-18] fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) were performed for further evaluation. A hypoattenuating mass with rim-like enhancement in segment 6 of the liver was detected on contrast-enhanced CT imaging. Increased uptake was also observed on 18F-FDG PET/CT. Histopathological and immunohistochemical examinations, which revealed a grade 2 neuroendocrine tumor (NET), confirmed the diagnosis. CONCLUSION: Diagnosing PHNET is challenging, and must be distinguished from other liver tumors. Metastatic NETs should be excluded.

Facile synthesis of dual-emission fluorescent carbon nanodots for a multifunctional probe.

In this study, we developed a facile method for synthesizing dual-emission carbon nanodots (CDs) through trimesic acid and o-phenylenediamine through electrolysis for 2 h. The synthesized CDs were mainly 3-7 nm in size, with an average size of 5.17 nm. The dual-emission fluorescent property of these CDs could be observed under two different excitation wavelengths. The green emission of the CDs could be quenched after the addition of mercury ions or copper ions, and the blue emission of the CDs could be inhibited using hydroxychloroquine (HCQ). Furthermore, the quenched fluorescence of CDs/Cu2+ could be recovered through the addition of glyphosate. We developed a multifunctional chemical sensor by using these special fluorescence materials. Under optimal conditions, the detection limits of mercury ions, glyphosate, and HCQ were 0.42 µM, 1.1 mg L-1, and 0.14 µM, respectively. Moreover, this method can be used to detect mercury ions, glyphosate, and HCQ in environmental water, cereals, and urine samples, respectively.

Sequence-specific, dynamic covalent crosslinking in aqueous media.

This article describes an associating system that integrates the specificity of multiple hydrogen bonding and the strength of dynamic covalent interactions. Linear oligoamides that sequence-specifically pair into H-bonded duplexes in nonpolar solvents were modified with S-trityl groups, allowing the reversible formation of disulfide bonds. The disulfide-crosslinking reactions of oligoamides capable of pairing via two, four, and six intermolecular H-bonds, along with several control strands, were examined using ESI, MALDI-TOF, reverse phase HPLC, and two-dimensional NMR. Results from these studies demonstrate that this system possesses both the high fidelity of multiply H-bonded assemblies and the high stability of covalent interaction, leading to the sequence-specific crosslinking of complementary oligoamides in not only nonpolar (methylene chloride) solutions but also highly competitive (aqueous) media. Experiments were designed to systematically probe the mechanism behind the specific formation of the sequence-matched products, which revealed a thermodymically controlled process. Multiple pairs in the same solution were crosslinked in a sequence-specific fashion. In addition, a length-dependent selectivity was also observed. Thus, oligoamides with different lengths or sequences did not crosslink into mismatched products. As few as two H-bonds is sufficient to bias the specific formation of the crosslinked product in aqueous media, suggesting that associating units with tunable sizes, high stability, and high specificity can be conveniently designed. The combination of H-bonding and dynamic covalent interactions represents a new, generalizable strategy for developing highly specific molecular associating units that are stable in a wide variety of media. These associating units will greatly facilitate the construction of various structures with many applications.

Preliminary mechanistic information on disulfide-bond formation and the role of hydrogen bonds by nanoelectrospray mass spectrometry.

The formation of disulfide-bonds is vital for the proper folding of most secreted proteins and the stabilization of the final protein structure, including many of medical importance. The determination of disulfide-bonds is an important aspect of gaining a comprehensive understanding of the chemical structure of a protein. A long-term goal of ours is to examine the mechanism of disulfide-bond formation in aqueous solution and the potential role hydrogen bonds play in this process. Here, we report preliminary results from a method that utilizes the oxidizing power of iodine to generate disulfide bonds from synthesized model compounds, which is followed by nanoelectrospray ionization (nanoESI)- mass spectrometry (MS). By continuously monitoring the reaction mixture during disulfide formation, this nanoESI approach provides insight on the sequence of intermediate species formed, and how hydrogen-bonding donor/acceptor pairs may promote disulfide bond formation.

Amphiphilic diblock copolymer of hydrophilic-functionalized lactone and lactide via switchable organocatalytic polymerization.

Main-chain degradable amphiphilic diblock copolymers composed of a hydrophilic-functionalized polyester and PLA were facilely prepared by one-pot ring-opening polymerization (ROP) via actively manipulating the catalytic states of an acid-base catalytic system. The resultant block copolymers showed low critical micelle concentration (CMC) in water and were capable of forming stable micelles with optimal hydrodynamic particle size (average diameter 83 nm) and narrow particle distribution.

Bioinspired interconnected hydrogel capsules for enhanced catalysis.

Polysaccharide-based hydrogel capsules with interconnected inner membranes have been prepared. The obtained capsules have a multi-layer internal structure composed of many invaginations of interconnected hydrogel membranes as mimics of the cristae in mitochondria. These cristae-like internal membranes endow the capsules with high specific area, which makes the capsules ideal supporting materials for catalytic species such as metal nanoparticles and enzymes.

Everolimus (RAD001) inhibits the proliferation of rat vascular smooth muscle cells by up-regulating the activity of the p27/kip1 gene promoter.

OBJECTIVE: We investigated whether the inhibitory effect of the immunosuppressant everolimus (RAD001) on vascular smooth muscle cell (VSMC) proliferation is mediated by p27/kip1 gene promoter activity. METHODS: In this experimental study, cultured rat VSMCs were transiently transfected with a recombinant plasmid (pXp27) containing p27/kip1 gene promoter sequence and a chloramphenicol acetyltransferase (CAT) reporter gene. After stimulation with the mitogen platelet-derived growth factor (PDGF-BB, 10 ng/mL) in the presence or absence of RAD001 (10 nM), the promoter activity, mRNA expression, and protein expression of p27/kip1 were examined by CAT assay, RT-PCR, and immunoblotting, respectively. Cell cycle-related changes were detected by flow cytometry. DNA synthesis was determined using 3H-TdR incorporation. RESULTS: Compared with the non-stimulation group, PDGF-BB stimulation induced a significant proliferative response in the VSMCs as indicated by decreased p27/kip1 gene promoter activity, decreased p27/kip1 mRNA and protein expression, increased S-phase and G2/M-phase cells, and increased DNA synthesis. RAD001 intervention increased p27/kip1 gene promoter activity 3.5-fold, promoted p27/kip1 mRNA and protein expression, increased G0-phase cells, reduced DNA synthesis, and, overall, inhibited PDGF-BB-stimulated cell proliferation. CONCLUSION: RAD001 inhibits PDGF-BB-stimulated proliferation of cultured VSMCs by upregulating p27/kip1 gene promoter activity and increasing p27/kip1 mRNA and protein expression.

Distinguish cancer cells based on targeting turn-on fluorescence imaging by folate functionalized green emitting carbon dots.

Developing efficient methods for visual detection of cancer cells has the potential to contribute greatly to basic biological research and early diagnosis of cancer. Here, we report facile and one-step synthesis of green fluorescence carbon dots (CDs) with the help of a new passivating agent--poly(acrylate sodium) (PAAS). Based on the as-prepared CDs, a novel turn-on fluorescence probe was designed for targeting imaging of cancer cells via hydrogen-bond interaction between folic acid and CDs (FA-CDs). Intracellular experiments indicated that FA-CDs probe could accurately distinguish folate receptor (FR)-positive cancer cells in different cell mixtures with turn-on mode. In particular, combining the targeting of FA-CDs probe with the excellent photostability of CDs has inestimable meaning for fluorescence-assisted surgical resection and acquisition real-time information about tumor cells. Obviously, the as-prepared FA-CDs probe may have great potential as a high-performance platform for accurately recognizing special cancer cells, which may provide new tools for cancer prognosis and therapy.

The rational design of a highly sensitive and selective fluorogenic probe for detecting nitric oxide.

A rationally designed small-molecule fluorogenic probe for nitric oxide (NO) detection based on a new switching mechanism has been developed. Attaching a NO-responsive dihydropyridine pendant group to a fluorophore led to a probe that displays a very high sensitivity to NO concentrations down to the low nM range and a very high specificity to NO while being insensitive to other oxidative oxygen/nitrogen species that often interfere with the sensing of NO.

Site-selective metal-coordination-based patterning of silane monolayers.

Herein, we report a method to pattern a derivatized nifedipine silane monolayer that aromatizes under UV irradiation. Using a functionalized SCS-Pd(II) pincer complex, we demonstrate that a strong metal-coordination complex between the aromatized nifedipine derivative and the pincer complex is formed. This methodology integrates SAM photolithography (top-down) and molecular recognition directed self-assembly (bottom-up) strategies to create simple and rapid synthesizable functional patterned surfaces.

Sequence-specific association in aqueous media by integrating hydrogen bonding and dynamic covalent interactions.

Oligoamide strands that associate in a sequence-specific fashion into hydrogen-bonded duplexes in nonpolar solvents were converted into disulfide cross-linked duplexes in aqueous media. Thus, by incorporating trityl-protected thiol groups, which allows the reversible formation of disulfide bonds, into the oligoamide strands, only duplexes consisting of complementary hydrogen-bonding sequences were formed in aqueous solution as well as in methanol. The sequence-specific cross-linking of oligoamide strands was confirmed by MALDI-TOF, reverse-phase HPLC, and by isolating a cross-linked duplex. This study demonstrates that the sequence-specificity characteristic of multiply hydrogen-bonded systems can be extended into competitive media through the interplay of H-bonding and reversible covalent interactions, based on which a new class of molecular associating and ligating units that are compatible with both polar and nonpolar environments can be conveniently obtained.

Shape-persistent macrocyclic aromatic tetrasulfonamides: Molecules with nanosized cavities and their nanotubular assemblies in solid state.

Alkoxy side-chain-flanked diarylsulfonamide serves as a reliable structural motif for constructing macrocyclic aromatic tetrasulfonamides. This 90 degrees structural motif is persistent both in solution and in the solid state, which allows the one-step formation of tetrasulfonamide macrocycles. These macrocycles adopt a cone-shaped conformation in solution and in the solid state. For each molecule, an interior cavity surrounded by the aromatic residues is formed. The cavity sizes of the macrocycles can be tuned by incorporating aromatic residues of proper sizes. Guest (solvent) molecules are found in the cavities and bound by side chains. In solution, 1H NMR shows that the cone conformations undergo rapid interconversion at room temperature. The alkoxy side chains are found to be indispensable for maintaining the cone conformation. In addition, these porous molecules self-assemble into hollow tubular structures in the solid state. A variety of host molecules and building blocks for constructing nanoporous solid-state structures can be expected from these molecules.

Synthesis of crescent aromatic oligoamides.

[structures: see text] This article describes the synthetic procedures for the preparation of crescent (and helical) aromatic oligoamides developed in recent years in our laboratory. The large-scale preparation of a variety of monomers derived from various tetrasubstituted benzenes is presented. Three different strategies for constructing various oligomers consisting of meta- and meta/para-linked benzene residues are discussed. Factors affecting coupling efficiency and yields are analyzed. The developed synthetic methods have provided the basis for the preparation of longer oligomers and for the development of solid-phase synthesis.