Benzoselenadiazole-Functionalized H-Bonded Arylamide Foldamers: Solvent-Responsive Properties and Helix Self-Assembly Directed by Chalcogen Bonding in Solid State.

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state.

Quantitative detection of urinary bladder cancer antigen via peptide-immobilized magnetic bead-based SERS probe.

Antibody pairing is a difficult step in developing all immune-sandwich assay for antigen detection. Urinary bladder cancer (UBC) antigen is a typical bladder cancer biomarker for the early diagnosis of bladder cancer. Based on peptide-antibody pairing, a surface-enhanced Raman scattering platform for the ultrasensitive detection of UBC is presented. The phage display tech was used to screen and obtain a 12-peptide ligand against UBC (KD = 4.84 × 10-7 M). Twelve-peptide-conjugate magnetic beads (MNs@12-peptide) and antibody-conjugate silver nanoparticles (AgNPs@Ab) were prepared for SERS measurements. AgNPs@Ab can be linked onto the surface of MNs@12-peptide through ligand/antibody recognition to assess a sandwich-shape complex, which turns on the SERS signal of 4-ABP. Furthermore, the second SERS signal amplification is from the magnetic field-induced spontaneous collection effect. The above design enhances the SERS signal to achieve the limit of detection as 6.25 ng/mL, the clinical threshold of 10 ng/mL. Six clinical urine samples from bladder cancer patients and healthy volunteers were also successfully detected using the dual enhancement SERS measurement. The proposed method provides the future direction of fully automated and ultrasensitive assays.

Effect of docetaxel on mechanical properties of ovarian cancer cells.

Docetaxel could inhibit the proliferation of tumor cells by targeting microtubules. The extension of cellular microtubules plays an important role in the invasion and metastasis of tumor cells. This paper aims to study the distribution and mechanical properties of cytoskeletal proteins with low concentration of docetaxel. MTT assay was used to detect the minimum drug activity concentration of docetaxel on SKOV-3 cells, fluorescence staining was used to analyze the distribution of cytoskeleton proteins, scanning electron microscopy(SEM) was used to observe the morphology of single cells, and atomic force microscopy(AFM) was used to determine the microstructure and mechanical properties of cells. The results showed that the IC10 of docetaxel was 1 ng/ml. Docetaxel can effectively inhibit the formation of cell pseudopodia, hinder the indirectness between cells, reduce the cell extension area, and make the cells malformed. In addition, when AFM analyzes the effects of drugs on cell microstructure and mechanical properties, the average cell surface roughness and cell height are positively correlated with the concentration of docetaxel. Especially when the concentration was 100 ng/ml, the adhesion decreased by 37.04% and Young's modulus increased by 1.57 times compared with the control group. This may be because docetaxel leads to microtubule remodeling and membrane protein aggregation, which affects cell microstructure and increases cell strength, leading to significant changes in the mechanical properties of ovarian cells. This is of great significance to the study of the formation mechanism of tumor cell invasion and migration activities mediated by actin.

Halogen Bonding Directed Supramolecular Quadruple and Double Helices from Hydrogen-Bonded Arylamide Foldamers.

Halogen bonding has been used to glue together hydrogen-bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF2 I or fluorinated iodobenzene group at the other end, engage in head-to-tail N⋅⋅⋅I halogen bonds to form one-component supramolecular P and M helices, which stack to afford supramolecular double-stranded helices. One of the double helices can dimerize to form a G-quadruplex-like supramolecular quadruple helix. Another symmetric compound, which bears a pyridine at each end, binds to ICF2 CF2 I through N⋅⋅⋅I halogen bonds to form two-component supramolecular P and M helices, with one turn consisting of four (2+2) molecules. Half of the pyridine-bearing molecules in two P helices and two M helices stack alternatingly to form another supramolecular quadruple helix. Another half of the pyridine-bearing molecules in such quadruple helices stack alternatingly with counterparts from neighboring quadruple helices, leading to unique quadruple helical arrays in two-dimensional space.

Ordered hexagonal mesoporous aluminosilicates with low Si/Al ratio: synthesis, characterization, and catalytic application.

Ordered hexagonal mesoporous aluminosilicates with lower Si/Al ratio below 5 have been successfully synthesized via the co-assembly of preformed aluminosilicate precursors with Gemini surfactant [C12H25N+(CH3)2(CH2)6N+(CH3)2C12H25] x 2Br(-) as the template. Powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, N2 adsorption-desorption isotherm measurements, Fourier transform infrared spectroscopy, 27Al nuclear magnetic resonance, thermogravimetric analysis, and temperature-programmed desorption of cyclohexylamine are employed to characterize the resulting samples. The phenol alkylation reaction is carried out to evaluate their catalytic performances. These studies indicate that the sample with a low Si/Al ratio of 3 still retains a highly ordered hexagonal mesoporous structure. And it also possesses the highest acidity of 0.96 mmol among the samples with lower Si/Al ratios below 5 due to its higher specific surface area together with more content of tetrahedrally coordinated Al in the framework. The catalytic tests confirm that the acidity of the samples plays a key role in determining their catalytic performances.

Mechanical Field Guiding Structure Design Strategy for Meta-Fiber Reinforced Hydrogel Composites by Deep Learning.

Fiber-reinforced hydrogel composites are widely employed in many engineering applications, such as drug release, and flexible electronics, with more flexible mechanical properties than pure hydrogel materials. Comparing to the hydrogel strengthened by continuous fiber, the meta-fiber reinforced hydrogel provides stronger individualized design ability of deformation patterns and tunable stiffness, especially for the elaborate applications in joint, cartilage, and organ. In this paper, a novel structure design strategy based on deep learning algorithm is proposed for hydrogel reinforced by meta-fiber to achieve targeted mechanical properties, such as stress and displacement fields. A solid mechanic model for meta-fiber reinforced hydrogel is first developed to construct the dataset of fiber distribution and the corresponding mechanical properties of the composite. Generative adversarial network (GAN) is then trained to characterize the relationship between stress or displacement field, and meta-fiber distribution. The well-trained GAN is implemented to design meta-fiber reinforced hydrogel composite structure under specific operation conditions. The results show that the deep learning method may efficiently predict the structure of the hydrogel composite with satisfied confidence, and has great potential for applications in drug delivery and flexible electronics.

Multiple non-covalent-interaction-directed supramolecular double helices: the orthogonality of hydrogen, halogen and chalcogen bonding.

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

Mechanical properties of CTCs in patients with diagnosed ovarian cancer.

The incidence and mortality of gynecologic cancers have been constantly increasing in China over the last 2 decades, which become a major health concern for women. Survival rates of gynecologic cancers are generally not satisfactory and decrease along with the advancing stage, this is mainly due to the lack of a clear prognostic evaluation during the treatment, which brings difficulties to the treatment. Therefore, more accurate prognostic evaluation methods are urgently needed. To solve this problem, this article explores the changes in the biomechanical properties of cells. Changes in the biomechanical properties of circulating tumor cells (CTCs) were explored by nano detection technology. The reference criteria for clinical evaluation of ovarian cancer (Age, FIGO stage, Histologic type, CA-125, Ascites, Single/Double, Residual lesion, and Chemotherapy) were compared and analyzed. The results showed that the average cell height of CTCs was 4.12 ± 0.83 µm before chemotherapy and 4.87 ± 0.71 µm after chemotherapy, with an average increase of 18.203 %. The apparent Young's modulus (E) was 3.884 ± 0.045 kPa before chemotherapy and 4.514 ± 0.025 kPa after chemotherapy, which increased by 0.63 kPa. The ROC analysis of FIGO stage of ovarian cancer patients showed that Young's modulus of cells could better reflect the accuracy of the evaluation of FIGO stage of patients, with the accuracy reaching 76.7 %, which was higher than the detection accuracy of CA-125 (72.6 %). In conclusion, the mechanical properties of CTCs can indicate the FIGO stage and diagnosis of patients and predict the prognostic risk of patients.

Two and three-dimensional halogen-bonded frameworks: self-assembly influenced by crystallization solvents.

In this paper, two types of solid phase 2D and 3D XBOFs were selectively constructed from identical building blocks of tetraphenylmethane tetrapyridine derivative and 1,4-diiodotetrafluorobenzene by changing the crystallization solvent. This 3D XBOF is a novel hybrid supramolecular organic framework with the synergistic control of hydrogen and halogen bonds.

Quantitative detection of Ganodermati lucidum immunomodulatory protein-8 by a peptide-antigen-antibody sandwich ELISA.

In order to rapidly determine the concentration of recombinant Ganoderma lucidum immunomodulatory protein-8 (rLZ-8) at a lower cost, a peptide-antigen-antibody sandwich ELISA method was developed based on a dodecapeptide LTPHKHHKHLHA with higher affinity for rLZ-8, which was identified from phage display after four rounds of screening. The binding mode between rLZ-8 and the peptide ligand was further simulated and revealed by molecular docking. Standard addition and repetitive testing were carried out to evaluate the accuracy, reproducibility and feasibility of the developed ELISA detection method. The method based on this peptide ligand was then successfully applied in the quantitative determination of rLZ-8 concentrations in fermentation broth. In summary, the peptide-antigen-antibody sandwich ELISA method developed here could be conveniently applied in the detection of rLZ-8 during fermentation and might provide new insights for the detection of other specific proteins.

Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy.

Despite that photodynamic therapy (PDT) has been applied for the treatment of cancer and skin diseases for more than two decades, all clinically used photodynamic agents (PDAs) suffer the drawback of skin phototoxicity of PDAs, which requires patients to avoid exposure to natural light for weeks after treatment, but has so far lacked effective suppression methods. Here, we report that three-dimensional diamondoid supramolecular organic frameworks (SOFs), that possess well-defined 2.1-nm porosity, can be used to suppress the skin phototoxicity of Photofrin, HiPorfin and Talaporfin, three porphyrin-based PDAs which clinically receive the most wide applications by injecting SOF after PDT, via an adsorption and retention mechanism. Fluorescence and dynamic light scattering experiments confirm that the SOFs have strong interaction with PDAs, and can adsorb PDAs at a micromolar concentration, whereas dialysis experiments support that the adsorption leads to an important retention effect. In vitro and in vivo experiments reveal that SOFs have high biocompatibility. Studies with healthy and tumor-bearing mouse models demonstrate that, when the PDAs are administrated at a dose comparable with the clinical one, SOF can remarkably suppress sunlight-induced skin phototoxicity, whereas the PDT efficacy of mice treated with SOF post-PDT is maintained. This work provides an efficient strategy for the improvement of the safety of clinically used PDAs.

Supramolecular Organic Frameworks as Adsorbents for Efficient Removal of Excess Bilirubin in Hemoperfusion.

Excess bilirubin accumulates in the bodies of patients suffering from acute liver failure (ALF) to cause much irreversible damage and bring about serious clinical symptoms such as kernicterus, hepatic coma, or even death. Hemoperfusion is a widely used method for removing bilirubin from the blood, but clinically used adsorbents have unsatisfactory adsorption capacity and kinetics. In this study, we prepared four supramolecular organic framework microcrystals SOF-1-4 via slow evaporation of their aqueous solutions under infrared light. SOF-1-4 possess good regularity and excellent stability. We demonstrate that all the four SOFs could serve as adsorbents for bilirubin with fast adsorption kinetics within 20 min and ultrahigh adsorption capacity of 609.1 mg g-1, driven by electrostatic interaction and hydrophobicity. The superior adsorption performance of the SOFs outperformed most of the reported bilirubin adsorbents. Remarkably, SOF-3 could remove about 90% of bilirubin in the presence of 40 g L-1 BSA with a minimal loss of albumin and was thus further processed to a bead-shaped composite with a diameter of 2 mm with poly(ether sulfone) (PES). This PES-loaded SOF could efficiently adsorb bilirubin to the normal level from human plasma with an adsorption equilibrium concentration of 7.8 mg L-1 in 6 h through a dynamic hemoperfusion process. This work provides a new vitality for the development of novel bilirubin adsorbents for hemoperfusion therapy.

Porous Polymers as Universal Reversal Agents for Heparin Anticoagulants through an Inclusion-Sequestration Mechanism.

Heparins are widely used anticoagulants for surgical procedures and extracorporeal therapies. However, all of them have bleeding risks. Protamine sulfate, the only clinically approved antidote for unfractionated heparin (UFH), has adverse effects. Moreover, protamine can only partially neutralize low-molecular-weight heparins (LMWHs) and is not effective for fondaparinux. Here, an inclusion-sequestration strategy for efficient neutralization of heparin anticoagulants by cationic porous supramolecular organic frameworks (SOFs) and porous organic polymers (POPs) is reported. Isothermal titration calorimetric and fluorescence experiments show strong binding affinities of these porous polymers toward heparins, whereas dynamic light scattering and zeta potential analysis confirm that the heparin sequences are adsorbed into the interior of the porous hosts. Activated partial thromboplastin time, anti-FXa, and thromboelastography assays indicate that their neutralization efficacies are higher than or as high as that of protamine for UFH and generally superior to protamine for LMWHs and fondaparinux, which is further confirmed by tail-transection model in mice and ex vivo aPTT or anti-FXa analysis in rats. Acute toxicity evaluations reveal that one of the SOFs displays outstanding biocompatibility. This work suggests that porous polymers can supply safe and rapid reversal of clinically used heparins, as protamine surrogates, providing an improved approach for their neutralization.

Discovery and mechanistic studies of a general air-promoted metal-catalyzed aerobic N-alkylation reaction of amides and amines with alcohols.

The thermodynamically unfavorable anaerobic dehydrogenative alcohol activation to aldehydes and hydridometal species is found to be the bottleneck in metal-catalyzed N-alkylations due to a general and unnoticed catalyst deactivation by amines/amides. Thus, different from the anaerobic dehydrogenation process in borrowing hydrogen or hydrogen autotransfer reactions that require noble metal complexes or addition of capricious ligands for catalyst activation, the water-producing, exothermic, metal-catalyzed aerobic alcohol oxidation is thermodynamically more favorable and the most effective and advantageous aldehyde generation protocol. This leads to a general and advantageous air-promoted metal-catalyzed aerobic N-alkylation methodology that effectively uses many simpler, less expensive, more available, and ligand-free metal catalysts that were inactive under typical anaerobic borrowing hydrogen conditions, avoiding the use of preformed metal complexes and activating ligands and the exclusive requirement of inert atmosphere protection. This aerobic method is quite general in substrate scope and tolerates various amides, amines, and alcohols, revealing its potentially broad utilities and interests in academy and industry. In contrast to the commonly accepted borrowing hydrogen mechanism, based on a thorough mechanistic study and supported by the related literature background, a new mechanism analogous to the relay race game that has never been proposed in metal-catalyzed N-alkylation reactions is presented.

The characterization of a short chain dehydrogenase/reductase (SDRx) in Comamonas testosteroni.

C. testosteroni is a research topic that can degrade steroid hormones into water and carbon dioxide through a series of enzymes in the body. Short-chain dehydrogenase (SDR) are a class of NAD (P) H-dependent oxidoreductases in C. testosteroni. Its main function is catalyzing the redox of the hydroxyl/ketone group of the hormone. In this paper, a SDR gene(SDRx) is cloned from C. testosteroni ATCC11996 and expressed. The polyclonal antibody was prepared and the SDRx gene knocked out by homologous recombination. Wild type and mutant C. testosteroni induced by testosterone, estradiol, estrone and estriol. The growth curves of the bacteria were measured by spectrophotometer. ELISA established the expression of SDRx protein, and high-performance liquid chromatography(HPLC) detected the contents of various hormones. The results show that the growth of wild type was faster than mutant type induced by testosterone. The concentration of SDRx is 0.318 mg/ml under testosterone induction. It has a great change in steroid hormones residue in culture medium measured by HPLC: Testosterone residue in the mutant type group was 42.4 % more than the wild type in culture medium. The same thing happens with induced by estrone. In summary, this SDRx gene involved in the degradation of testosterone and estradiol, and effects the growth of C. testosteroni.

Dynamic mechanics of HK-2 cell reaction to HG stimulation studied by atomic force microscopy.

Renal tubular cell injury by exposure to high glucose (HG) stimulation mainly accounts for diabetic nephropathy (DN). To understand the mechanism of injury by HG, quantitative characterization has commonly focused on the cells that are already impaired, which ignores the signals for the process of being injured. In this study, the architecture and morphology of HK-2 cells were observed dynamically by multiple imaging methods. AFM (atomic force microscopy)-based single-cell force spectroscopy was employed to investigate the dynamic mechanics quantitatively. The results showed that the Young's modulus increased continuously from 2.44 kPa up to 4.15 kPa for the whole period of injury by HG, while the surface adhesion decreased from 2.43 nN to 1.63 nN between 12 h and 72 h. In addition, the actin filaments of HK-2 cells exposed to HG depolymerized and then nucleated with increasing Young's modulus. The absence of cell pseudopodia coincided with the reduced cell adhesion, strongly suggesting close relationships between the cell architecture, morphology and mechanical properties. Furthermore, the stages of cell reactions were identified and assessed. Overall, the dynamic mechanics of the cells facilitate the identification of injured cells and the assessment of the degree of injury for accurate diagnoses and treatments.

Water-Soluble 3D Covalent Organic Framework that Displays an Enhanced Enrichment Effect of Photosensitizers and Catalysts for the Reduction of Protons to H2.

Covalent organic frameworks (COFs) are emerging porous polymers that have 2D or 3D long-range ordering. Currently available COFs are typically insoluble or decompose upon dissolution, which remarkably restricts their practical implementations. For 3D COFs, the achievement of noninterpenetration, which maximizes their porosity-derived applications, also remains a challenge synthetically. Here, we report the synthesis of the first highly water-soluble 3D COF (sCOF-101) from irreversible polymerization of a preorganized supramolecular organic framework through cucurbit[8]uril (CB[8])-controlled [2 + 2] photodimerization. Synchrotron X-ray scattering and diffraction analyses confirm that sCOF-101 exhibits porosity periodicity, with a channel diameter of 2.3 nm, in both water and the solid state and retains the periodicity under both strongly acidic and basic conditions. As an ordered 3D polymer, sCOF-101 can enrich [Ru(bpy)3]2+ photosensitizers and redox-active polyoxometalates in water, which leads to remarkable increase of their photocatalytic activity for proton reduction to produce H2.

The effects of dexamethasone on 17ß-HSD1 levels at the rat optic nerve.

Dexamethasone (DEX) is associated with many inflammation and metabolic diseases. We analyzed the effects of DEX on the expression of estrogen metabolism enzyme 17ß-HSD1 at the optic nerve. Rats were treated with different concentrations of intraperitoneal DEX. Western Blot analysis showed that 17ß-HSD protein was expressed in the optic nerve tissue. The enzyme was detected by immunohistochemistry on the terminal foot of Muller cells from the ganglion cell layer of rat retina. ELISA analysis showed that the 17ß-HSD1 protein expression of DEX-treated group is 2.4 fold comparing to the control group. The results indicated that DMXS sodium phosphate might modulate the expression of 17ß-HSD1 protein in optic tissue. This study sheds light on understanding of the relationship among DEX, 17ß-HSD presence and distribution of visual neural systems. At the same time, DEX treatment affects the athletic ability and memory of the animals. Compared with the control group, the experimental group showed slow response to stimulation, inertia, depression, cowardice and lack of appetite. The results of ethology experiments showed that all the parameters decreased by 15-30%.

Self-repair behaviour of the neuronal cell membrane by conductive atomic force indentation.

Conductive atomic force indentation (CAFI) was proposed to study the self-repair behaviour of the neuronal cell membrane here. CAFI was used to detect the changes of membrane potentials by performing the mechanical indentation on neurons with a conductive atomic force microscope. In the experiment, a special insulation treatment was made on the conductive probe, which turned out to be a conductive nanoelectrode, to implement the CAFI function. The mechanical properties of the neuronal cell membrane surface were tested and the membrane potential changes of neurons cultured in vitro were detected. The self-repair behaviour of the neuronal cell membrane after being punctured was investigated. The experiment results show that CAFI provides a new way for the study of self-repair behaviours of neuronal cell membranes and mechanical and electrical properties of living cells.

[Detection of procalcitonin based on fluorescence immune chromatography].

Procalcitonin (PCT) is the precursor of calcitonin related to the severity of human bacterial infection. We made a test strip by coupling anti-PCT to quantum dot, in order to develop a highly sensitive and convenient PCT testing product. The anti-PCT titer had reached 107 because of the stability by coupling anti-PCT with quantum dot. The detecting linear range of the experiment was 0.15 to 120 µg/L, the sensitivity was 0.007 µg/L, the recovery range was 91% to 113%, and the intra- and inter-assay coefficient of variation was less than 8%. Comparing the homemade fluorescence-detected test strip with PCT ELISA kit on sale, we got accurate results which could mostly accomplish the test of clinical samples.