Synthesis of fused-pyran derivatives via a base-mediated annulation of bis-allenoates followed by auto-oxidation in air.

We introduce, for the first time, an inorganic base-mediated cyclization and auto-oxidation of bisallenones/bisalkynones. This reaction is realized under mild conditions through precise control of the base and atmosphere, providing a wide range of structurally diverse fused-pyran derivatives with moderate to excellent yields. Utilizing KOH as the initiator under a nitrogen atmosphere, a series of novel cyclohexane-fused pyran derivatives was obtained as the primary product. In contrast, under aerobic conditions with Na2S as the catalyst, oxidative cyclization predominantly occurred, yielding cyclohexanone-fused pyran derivatives. The protocol also exhibits significant regioselectivity, particularly when asymmetric bisallenones/bisalkynones are selected as substrates.

Effect of Modification Strategies on the Biological Activity of Peptides/Proteins.

Covalent attachment of biologically active peptides/proteins with functional moieties is an effective strategy to control their biodistribution, pharmacokinetics, enzymatic digestion, and toxicity. This review focuses on the characteristics of different modification strategies and their effects on the biological activity of peptides/proteins and illustrates their relevant applications and potential.

Effect of Mini-PEGs Modification on the Enzymatic Digestion of D-Amino Acid-Containing Peptides under the Action of PROK.

It was previously reported that D-amino acid-containing peptides exhibited the ability to resist enzymatic hydrolysis. This study investigated the influence of mini-PEGs modification on enzymatic hydrolysis ability of D-amino acid-containing peptides. The results showed that PEGylation promoted enzymatic hydrolysis of the D-amino acid-containing peptide, especially, the cleavage rate of the D-amino acid-containing peptide 6-w with PEG3 modification at the N-ends was up to 17 times higher in the presence of proteinase K (PROK) compared to those without PEG3 modification. Moreover, analysis of the enzymatic cleavage sites demonstrated a similar cleavage pattern of the PEGylated D-amino acid-containing peptide to that of the unmodified peptide. The computational simulations further showed that the enhanced enzymatic hydrolysis ability can be attributed to the strong interaction between PROK and the peptide after PEG3 modification and the resulting formation of a mature catalytic triad structure.

In-Situ Visualization of the Cell Formation Process of Foamed Polypropylene under Different Foaming Environments.

In this paper, the dynamic foaming process of micro-foaming polypropylene (PP) in different foaming environments in real time was obtained via a visualization device. The relationship curve between cell number (n) and foaming time (t) was plotted, and then the nucleation kinetics of foam cells was analyzed. Results showed that the formation rate of cells changed obviously with the variation of melt temperature and the content of the foaming agent. The n-t curves presented a typical "S" shape, which indicated that the appearance of the cell number increased slowly in the initial foaming period, then increased rapidly in a short time, and finally maintained a certain value. When a certain pressure was applied to the PP melt, the external force had a great influence on the n-t curve. With the increasing external force, the rate of cell formation increased rapidly, and the shape of the n-t curve changed from "S" to "semi-S" without an obvious slow increase. The investigation of the n-t relationship in the PP dynamic foaming process under different foaming environments could provide effective bases for improving the foaming quality of injection molding foaming materials.

Accelerated air-assisted in-syringe extraction and needle spray ionization coupled with miniature mass spectrometry: A streamlined platform for rapid on-site analysis.

The present study reports on a streamlined analytical platform for rapid, straightforward, and on-site sample analysis using a miniature mass spectrometer with adequate tandem mass spectrometry (MS/MS) capability. An "all-in-one" workflow is developed combining accelerated air-assisted in-syringe extraction, sorbent-packed membrane clean-up, and needle spray ionization with an in-house built syringe assembly. A custom-made metal needle with a sharp, thin, and conical tip of micrometer-scale served as an integral component of the syringe assembly. This needle was capable of both aspirating a high-speed airflow for a highly efficient in-syringe extraction and performing stable electrospray for direct miniature mass spectrometry analysis. As a proof-of-concept demonstration, the developed protocol was implemented for the identification of 40 adulterated cosmetic ingredients and validated in terms of sensitivity, linearity, matrix effect, and recovery. A custom expandable mass spectral library was established in-house for smart suspect screening. Compound search and identification were conducted following a two-stage strategy using the full-scan MS and MS/MS data. The methodology demonstrates excellent potential for outside-the-laboratory chemical analysis by reducing the high time and labor costs associated with traditional sample preparation and chromatographic separation procedures, which would meet product quality and safety inspection requirements for on-site compliance check and regulatory enforcement at the testing sites such as supermarkets, department stores, wholesale markets, and roadside stalls.

New insight into enzymatic hydrolysis of peptides with site-specific amino acid d-isomerization.

The isomerization of l-amino acids in peptides and proteins into d-configuration under physiological conditions would affect the physiological dysfunction and caused protein conformational diseases. The presence of d-amino acids might change the higher-order structure of proteins and triggered abnormal aggregation. In order to better understand this phenomenon and promote degradation, we systematically studied the enzymatic hydrolysis of a series of peptides obtained by replacing l-amino acids in different positions of template peptide KYNETWRSED with d-amino acids under the action of Protease K. The results showed that, compared with normal peptide, isomerization of different amino acids had different effects on the anti-enzymatic hydrolysis of the peptides, especially d-tryptophan at position 6, which significantly inhibited enzymatic hydrolysis. The analysis of the peptide cleavage site revealed that the efficiency of enzymatic hydrolysis mainly depended on the isomerization of the amino acids at a specific site of the peptide cleavage. Further studies showed that the enzymatic hydrolysis of substrates could be facilitated by optimized reaction conditions such as temperature, pH, addition of metal ions, and change of buffer. In this way the accumulation of disease-associated d-amino acid containing polypeptides/proteins could be prevented.

Selective and sensitive analysis by reactive easy ambient sonic-spray ionization: Synergistic combination of non-polar spray solvent and dicationic ionic liquid.

The present study reports the first conception to incorporate a non-polar solvent, dichloromethane, as the spray solution in easy ambient sonic-spray ionization (EASI) for mass spectrometry (MS) analysis of hydrophobic compounds. An imidazolium-based dicationic ionic liquid (DIL) at a low concentration of 20 µM was used in combination with dichloromethane. A reactive EASI strategy was implemented, by which the overall positively charged associated complexes of anionized perfluorinated compounds (PFCs) were formed in the presence of the DIL. In positive ionization mode, 19- and 6-fold enhancements in signal intensity were witnessed for the analysis of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) respectively, compared to that in negative ionization mode with no dicationic ion-pairing reagent. The limits of detection (LODs) and quantitation (LOQs) are 0.5 and 0.8 µg/m2 for PFOA and 0.4 and 0.6 µg/m2 for PFOS, respectively. The developed method allowed direct ambient analysis of samples in their native conditions and was applied to the analysis of PFCs in a variety of real textile, popcorn bucket, and oil-proof hamburger wrapping paper samples.

Influence of d-Amino Acids in Beer on Formation of Uric Acid.

Excessive intake of beer could increase serum uric acid levels, leading to high risk of gout, which was previously attributed to high purine content in beer. Recent reports that purine-rich vegetables and bean products do not cause higher uric acid levels do not support this theory. Why excessive intake of beer could increase a high risk of gout has been unclear. Other factors affecting the accumulation of uric acid in the blood have been explored. Beer contains relatively high levels of d-amino acids due to the racemization of l-amino acids induced by food processing. d-amino acid was catalyzed by d-amino acid oxidase to produce H2O2, which is further oxidized in the presence of Fe2+ to produce hydroxyl radicals, resulting in DNA damage and formation of a large amount of purine bases, which are oxidized to uric acid by a series of enzymes. Some food ingredients, such as vitamins and I-, prompt d-amino acids to form uric acid. d-amino acids in beer are one of the key factors responsible for the increase in uric acid levels. The biological response of d-amino acids could explain gout occurrence in beer drinkers.

Preparation and Comparison of Properties of Three Phase Change Energy Storage Materials with Hollow Fiber Membrane as the Supporting Carrier.

Herein, we have used a hollow fiber membrane as a support layer material to encapsulate paraffin in order to prepare a phase change energy storage material. The phase change energy storage materials with three different support layers were successfully prepared and various properties were systematically characterized. There are also few reports on the use of hollow fiber membranes as the support carrier for the preparation of phase change energy storage materials. The significance of this work is in exploring the use of hollow fiber membranes as a support layer to prepare phase change energy storage materials. In addition, the choice of support carriers for phase change energy storage materials was enriched. Both the hollow fiber membrane columnar hollow portion and the pore structure of the membrane wall could be used to encapsulate paraffin, which makes it more advantageous than the other support materials. The SEM characterization confirmed that paraffin was successfully encapsulated on the membrane wall and columnar hollow part of the membranes. The TGA results indicate that the introduction of the membrane as an encapsulation carrier delayed the decomposition of the composite phase change energy storage materials. The activation energy during the decomposition in the three different phase change energy storage materials was calculated by the decomposition kinetics. Among the three fiber membranes explored in this work, the polypropylene (PP) encapsulation membrane performed better than the other two encapsulation membranes in terms of encapsulation content of paraffin, porosity, latent heats, thermal stability, and activation energy.

Synthesis of Negatively Charged Polyol-Functional PSF Membranes with Good Hydrophilic and Efficient Boron Removal Properties.

Boron removal remains a major barrier to water purification, it is important to develop a specialized adsorption membrane for boron removal. By means of a simple and effective method, a hydrophilic membrane for boron removal with a polyhydroxy functional group on the surface was prepared. Firstly, a polysulfone (PSF) membrane was modified by co-depositing polyethyleneimine (PEI) with dopamine (DA) in one-step to produce amine-rich surfaces, then the DA/PEI-functionalized membranes were reacted with glycidol, with the prepared membranes corresponding to PSF-PDA/PEI membranes and PSF-diol membranes. The prepared membranes were characterized by water-uptake, FTIR, (X-ray photoelectron spectroscopy) XPS, (Field emission scanning electron microscope) FESEM, and zeta potential measurements. The hydrophilicity of the membrane was characterized by the static water contact angle (WCA) test. In addition, we systematically studied the impact of initial boron concentration, chelating time, and pH value on boron removal performance. The results showed that the PSF-diol membrane had strong hydrophilicity with a WCA of about 38°. The maximum adsorption capacity of boron appeared to be 1.61 mmol/g within 10 min at a boron concentration of 300 mg/L. Adsorption kinetics showed that saturation adsorption can be achieved in minutes at the initial concentration of 5 mg/L, which is beneficial to a rapid filtration process.

Direct Mass Spectrometry Analysis Using In-Capillary Dicationic Ionic Liquid-Based in Situ Dispersive Liquid-Liquid Microextraction and Sonic-Spray Ionization.

The current study reports on a direct mass spectrometry (MS) analysis method using in-capillary dicationic ionic liquid (DIL)-based in situ dispersive liquid-liquid microextraction (DLLME) and sonic-spray ionization (SSI). The developed method merged extraction, enrichment, ionization, and detection of perfluorinated compounds (PFCs) in environmental water into a single step. A microliter-scale ternary fluidic system was designed and integrated into a disposable pulled capillary, in which an imidazolium-based germinal DIL reagent activated an in situ metathesis reaction. A penetrating slug-flow microextraction (SFME) process was subsequently initiated with significantly enhanced interfacial areas and mass transfer rates for the analytes of interest, the mechanism of which was revealed by simulations. An SSI assembly was in-house built, and it enabled a Venturi self-pumping using a stream of nitrogen gas flow coaxial to the capillary under atmospheric pressure to automatically spray at the tip of the capillary. The in situ formed DIL could bind with anionic PFC analytes to generate a positively charged complex, which benefits a signal increase of 1 to 2 orders in magnitude in the positive ion mode than in the negative ion mode for most analytes. The high sensitivity allowed the measure of sub-ppb (parts per billion) levels of PFCs in the environmental water samples. The developed method is a promising protocol for MS analysis because of unprecedented ease, significantly enhanced sensitivity, and potentially high sample throughput.

Dielectric Relaxation and Beyond Limiting Behavior of Alternating-Current Conductivity in a Supermolecular Ferroelectric.

A cyclen-based hybrid supermolecule crystal, [(FeCl2 )(cyclen)]Cl (1), where cyclen=1,4,7,10-tetraazacyclododecane, was prepared using a liquid-liquid diffusion approach. The variable crystal structures exhibit that compound 1 belongs to an orthorhombic crystal system, Pna21 space group (point group C2V ) in the temperature range of 150-400 K. This hybrid supermolecule shows a dielectric relaxation behavior around room temperature, and the ferroelectric nature of 1 has been directly verified by hysteresis measurements. In addition, the AC (alternating current) conductivity study reveals that the 1 displays a beyond limiting behavior. These interesting findings are for the first time reported in the field of supermolecular ferroelectrics. This study may open a new way to construct supermolecular ferroelectrics and give insights into their conductor behavior.

[(18-Crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 : A Multifunctional Molecular Switch of Dielectric, Conductivity and Magnetic Properties.

Multifunctional materials that exhibit different physical properties in a single phase have potential for use in multifunctional devices. Herein, we reported an organic-inorganic hybrid compound [(18-crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 (1) by incorporating KCl and FeCl3 into a 18-crown-6 molecule, which acts as a host of the six O atoms providing a lone pair of electrons to anchor the guest potassium cation, and [FeCl4 ]- as a counterion for charge balance to construct a complex salt. This salt exhibited a one-step reversible structural transformation giving two separate high and low temperature phases at 373 K, which was confirmed by systematic characterizations including differential scanning calorimetry (DSC) measurements, variable-temperature structural analyses, and dielectric, impedance, variable-temperature magnetic susceptibility measurements. Interestingly, the structural transformation was coupled to both hysteretic dielectric phase transition, conductivity switch and magnetic-phase transition at 373 K. This result gives an idea for designing a new type of phase-transition materials harboring technologically important magnetic, conductivity and dielectric properties.

Positioned substituent effect on self-assembly behaviors of perylene diimide derivatives on graphite.

Three kinds of π-conjugated perylenetetracarboxylic diimide (PTCDI)-based organic functional derivatives, i.e., N,N'-di(2-ethylhexyl)-3,4,9,10-perylene diimide (molecule 1), N,N'-di(2-ethylhexyl)-1,7-dithien-2-yl-3,4,9,10-perylene diimide (molecule 2), N,N'-di(2-ethylhexyl)-1,7-di(2-bromothien-5-yl)-perylene-3,4,9,10-perylene diimide (molecule 3), have been prepared and investigated by using a scanning tunneling microscopy under ambient conditions. All of them can form long-ranged ordered self-assembled monolayer (SAM) with two different phase structures on highly oriented pyrolitic graphite (HOPG) surface. Coexistence of the two phases in the formed SAMs depends strongly on cooperation of various interactions including the molecule-substrate and molecule-molecule. Orientation of the molecular perylene cores primarily governs the molecular orientation in the SAMs by π-π interaction of the molecule-substrate through uttermost matching the graphite surface lattice. At the same time, the branched alkyl-chain substituents at N-sites can adjust intermolecular distances through conformation change while cyclic π-conjugated substituents at bay-positions lead to molecular rotation movement on HOPG, driven by the decreased molecule-substrate interaction caused by distortion of the perylene cores and the intermolecular interaction among the adjacent bay-substituents with rotation conformation change. In addition, the lateral forces from rotation conformation change of the bay-position substituents can also be strong enough to keep the orientation of the perylene cores unchanged. DFT calculation results further reveal the formation mechanisms for the three molecular self-assembly systems. These findings distinctly show that the SAM structures based on the π-conjugated PTCDI-based organic functional derivative molecules can be precisely modulated through introducing suitable substituents at both N- and bay-positions on the PTCDI core.

Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

BACKGROUND: Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). METHOD: We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. RESULTS: All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P < 0.01). CONCLUSION: Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas.

Effectiveness and safety of CT-guided (125)I seed brachytherapy for postoperative locoregional recurrence in patients with non-small cell lung cancer.

PURPOSE: To retrospectively evaluate the effectiveness and safety of CT-guided (125)I seed brachytherapy (CTISB) in 38 non-small cell lung cancer (NSCLC) patients with locoregional recurrence (LRR). METHODS AND MATERIALS: In total, we analyzed 38 NSCLC patients with LRR treated with percutaneous CTISB in our hospital between 2001 and 2008; among them, 15 also received combined chemotherapy: 1-6 cycles (median, 2) of platinum-based regimens. The change in tumor volume was evaluated based on followup contrast material-enhanced CT or positron emission tomography scans. RESULTS: The median Day 0 dosimetry was as follows: The volume treated with the prescription dose (V100) was 96.3% (90.1-123.5%), and the minimum dose received by at least 90% of the tumor volume (D90) was 124.8 Gy (116.0-130.7 Gy). The median duration of the followup period calculated from the first CTISB treatment was 22.5 months (range, 8-98 months). Two months after CTISB, complete response, partial response, and progressive disease were observed in 50%, 37%, and 8% of patients, respectively. Median overall survival (OS) after CTISB was 21 months (95% confidence interval, 7.4-34.6), and the rates of 2-year OS, progression-free survival, and local control were 47.4%, 39.5%, and 83.5%, respectively. Both univariate and multivariate analysis indicated that D90 was significant prognostic factors for OS and progression-free survival. CONCLUSION: For selected NSCLC patients with limited LRR, CTISB is effective and can provide a high rate of local cancer control with minimal trauma.

Antibody-Free Colorimetric Detection of Total Aflatoxins in Rice Based on a Simple Two-Step Chromogenic Reaction.

The prevalently used immunoassays for fast screening of aftatoxins (AFs) usually cannot meet the requirement for simultaneous determination of total AFs (aflatoxin B1 + aflatoxin B2 + aflatoxin G1 + aflatoxin G2) due to the deficiency of highly group-specific antibodies. This paper describes a two-step chromogenic reaction based method to quantitatively detect total AFs in rice using colorimetric measurement without antibody. In the method, colorless AFs transform into green-colored indophenol products through the reaction with sodium hydroxide and 2,6-dibromoquinone-4-chloroimide (DBQC) successively, allowing selectively determining total AFs up to 3.9 µg/kg over other competitive mycotoxins under optimal conditions by a UV-vis spectrophotometer. In addition, the colorimetric measurement results of the rice samples agree well with that of a standard HPLC method, demonstrating the good reliability and applicability of the method. Uniquely, the method has potential for on-site detection of total AFs in rice when using a nylon membrane-based device.

Calibration ruler for CW-EPR distance measurement using diradical molecule of rigid structure.

Many experimental factors and uncontrollable factors may introduce errors in the distance measurement by continuous wave electron paramagnetic resonance. To deal with this problem, several C60 nitroxide diradical adducts with rigid structure and definite molecular dimension were used as distance calibration rulers. Based on the improvement of distance calculation program via adding simulation programs of experimental spectra and dipolar broadening function, respectively, the distance calibration method was developed under different conditions such as different solvent, solution concentration, measuring temperature, and microwave power. As a result, stable distance calibration rulers were established within the range of 8-13 Å. The distance calibration effect was evaluated resulting in a corresponding distance measurement precision of 0.84 Å. The results suggested that the influence of non-dipolar spectral broadening factors could be overcome, and the established experimental and calculation methods were suitable to a wide range of situations. The developed method will ensure more accurate and objective distance measurement in biomacromolecular analysis.

CT-guided 125I brachytherapy on pulmonary metastases after resection of colorectal cancer: A report of six cases.

Colorectal cancer (CRC) is one of the most common malignancies in the world and distant metastasis is the main cause of cancer-related mortality. Percutaneous computed tomography (CT) guided radioactive 125I seed implantation (CTRISI) is a minimally invasive technique used to treat pulmonary metastases in CRC patients. In the present study, following colorectal cancer resection, six patients with pulmonary metastases were treated with computed tomography (CT)-guided percutaneous implantation of radioactive 125I seeds. At six months following seed implantation, CT examination was performed and compared with the images captured prior to the treatment. Of the total 13 lesions, four had disappeared, eight were reduced by >50% and one was enlarged, indicating that the local control rate was 92.3% (12/13). Overall, two patients developed intraoperative pneumothorax and one experienced hemoptysis subsequent to the procedure. Following a median follow-up period of 31 months, no local recurrence was observed in 12 of the metastatic lesions. The mean survival time was 32.7 months and the median survival time was 31 months.

2-Benzyl-3-hy-droxy-3-methyl-2,3-dihydro-1H-isoindol-1-one.

In the title compound, C(16)H(15)NO(2), the isoindoline ring system is approximately planar (mean deviation = 0.0186 Å) and makes a dihedral angle of 61.91 (4)° with the phenyl ring. In the crystal, mol-ecules form inversion dimers via pairs of O-H⋯O hydrogen bonds.