A concise approach to 2-pyrrolin-5-one scaffold construction from α-halohydroxamates and ß-keto compounds.

A concise approach to the construction of the 2-pyrrolin-5-one scaffold was developed via a one-pot reaction with formal [3 + 2] annulation/elimination between ß-keto nitrile/ß-keto ester and unsubstituted α-halohydroxamates. This reaction features mild conditions, easy handling, broad substrate scope and good yields. Remarkably, the products could be readily converted into potentially bioactive alkylidenepyrrolinones, pyrroles, pyran-fused pyrrole heterocycles and other useful compounds, exhibiting versatile synthetic potential.

Comparison of toxicity of Ti3 C2 and Nb2 C Mxene quantum dots (QDs) to human umbilical vein endothelial cells.

Recently, we developed highly fluorescent Ti3 C2 and Nb2 C Mxene quantum dots (QDs) for labeling of in vitro models. However, the mechanism of the toxicity of the prepared QDs was not explored before. In this study, we addressed the possible mechanism associated with cytotoxicity of the QDs to human umbilical vein endothelial cells (HUVECs). Exposure to up to 100 µg/ml Ti3 C2 but not Nb2 C QDs for 24 h significantly induced cytotoxicity. The exposure also increased intracellular Ti and Nb elements, indicating the internalization of both types of QDs. None of the QDs promoted interleukin 6 (IL-6) and IL-8 releases. Rather, Ti3 C2 QDs significantly reduced IL-6 and IL-8 release, indicating that the toxicity of Ti3 C2 QDs was not due to elevated inflammatory responses. Exposure to Ti3 C2 but not Nb2 C QDs resulted in increased LC3B-II/I ratio and beclin-1 proteins, biomarkers of autophagy, as well as the accumulation of autophagic substance p62. Ti3 C2 QDs also more effectively promoted pro-caspase 3 but not pro-caspase 8 compared with Nb2 C QDs. Furthermore, pre-treatment with autophagic modulators altered the cytotoxicity of Ti3 C2 QDs, which further confirmed the role of autophagic dysfunction in Ti3 C2 QD-induced toxicity to HUVECs. In conclusion, the results from this study suggested that high levels of Ti3 C2 QDs could induce cytotoxicity to HUVECs by inducing the dysfunction of autophagy. Nb2 C QDs appeared to be more biocompatible to HUVECs compared with Ti3 C2 QDs at the same mass concentrations, which suggested a role of composition of Mxene QDs to determine their toxicity to human endothelial cells.

Voltage-Rectified Current and Fluid Flow in Conical Nanopores.

Ion current rectification (ICR) refers to the asymmetric potential-dependent rate of the passage of solution ions through a nanopore, giving rise to electrical current-voltage characteristics that mimic those of a solid-state electrical diode. Since the discovery of ICR in quartz nanopipettes two decades ago, synthetic nanopores and nanochannels of various geometries, fabricated in membranes and on wafers, have been extensively investigated to understand fundamental aspects of ion transport in highly confined geometries. It is now generally accepted that ICR requires an asymmetric electrical double layer within the nanopore, producing an accumulation or depletion of charge-carrying ions at opposite voltage polarities. Our research groups have recently explored how the voltage-dependent ion distributions and ICR within nanopores can induce novel nanoscale flow phenomena that have applications in understanding ionics in porous materials used in energy storage devices, chemical sensing, and low-cost electrical pumping of fluids. In this Account, we review our most recent investigations on this topic, based on experiments using conical nanopores (10-300 nm tip opening) fabricated in thin glass, mica, and polymer membranes. Measurable fluid flow in nanopores can be induced either using external pressure forces, electrically via electroosmotic forces, or by a combination of these two forces. We demonstrate that pressure-driven flow can greatly alter the electrical properties of nanopores and, vice versa, that the nonlinear electrical properties of conical nanopores can impart novel and useful flow phenomena. Electroosmotic flow (EOF), which depends on the magnitude of the ion fluxes within the double layer of the nanopore, is strongly coupled to the accumulation/depletion of ions. Thus, the same underlying cause of ICR also leads to EOF rectification, i.e., unequal flows occurring for the same voltage but opposite polarities. EOF rectification can be used to electrically pump fluids with very precise control across membranes containing conical pores via the application of a symmetric sinusoidal voltage. The combination of pressure and asymmetric EOF can also provide a means to generate new nanopore electrical behaviors, including negative differential resistance (NDR), in which the current through a conical pore decreases with increasing driving force (applied voltage), similar to solid-state tunnel diodes. NDR results from a positive feedback mechanism between the ion distributions and EOF, yielding a true bistability in both fluid flow and electrical current at a critical applied voltage. Nanopore-based NDR is extremely sensitive to the surface charge near the nanopore opening, suggesting possible applications in chemical sensing.

A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate.

This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer-a device that is more available than the combination BHB/glucometer. Strategies that use a "3D pop-up"-that is, large-scale changes in 3D structure and fluidic paths-by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.

Paper-based potentiometric ion sensing.

This paper describes the design and fabrication of ion-sensing electrochemical paper-based analytical devices (EPADs) in which a miniaturized paper reference electrode is integrated with a small ion-selective paper electrode (ISPE) for potentiometric measurements. Ion-sensing EPADs use printed wax barriers to define electrochemical sample and reference zones. Single-layer EPADs for sensing of chloride ions include wax-defined sample and reference zones that each incorporate a Ag/AgCl electrode. In EPADs developed for other electrolytes (potassium, sodium, and calcium ions), a PVC-based ion-selective membrane is added to separate the sample zone from a paper indicator electrode. After the addition of a small volume (less than 10 µL) of sample and reference solutions to different zones, ion-sensing EPADs exhibit a linear response, over 3 orders of magnitude, in ranges of electrolyte concentrations that are relevant to a variety of applications, with a slope close to the theoretical value (59.2/z mV). Ion-selective EPADs provide a portable, inexpensive, and disposable way of measuring concentrations of electrolyte ions in aqueous solutions.

Determination of dynamic interactions of droplets in continuous fluids using droplet probe.

HYPOTHESIS: Interactions between droplets are of fundamental importance for understanding phenomena involving droplet collision and coalescence that determine multiphase flow behavior. The quantitative understanding of these interactions is essential for the manipulation and control of emulsions or complex fluids. The existing methods for interaction force determination are typically based on expensive mechanical probes and fine distance control. Therefore, further development of new techniques for interaction force determination is expected to be beneficial for research on surface force. EXPERIMENTS: In this study, droplet deformation during the interaction between two droplets was captured and analyzed to determine the interaction force. The approach speed of the two droplets was controlled by the injection rate of the fluid. The dynamic interaction force between two tetradecane droplets in various aqueous solutions was determined using the newly developed method, and the effects of two-phase physical properties and operating conditions on the measurement errors were investigated. FINDINGS: The droplet profile deformation was first applied as a probe to detect the interaction force. The measurement results were in good agreement with those obtained using the precise weighing sensor of a commercial interfacial tensiometer (K100, Kruss, Germany). The newly developed method was reliable, simple, and did not require the use of expensive devices. Furthermore, droplet deformability was found to be the key parameter in determining the total interaction force between the droplets.

Energy Saving and Energy Generation Smart Window with Active Control and Antifreezing Functions.

Windows are the least energy efficient part of the buildings, as building accounts for 40% of global energy consumption. Traditional smart windows can only regulate solar transmission, while all the solar energy on the window is wasted. Here, for the first time, the authors demonstrate an energy saving and energy generation integrated smart window (ESEG smart window) in a simple way by combining louver structure solar cell, thermotropic hydrogel, and indium tin oxides (ITO) glass. The ESEG smart window can achieve excellent optical properties with ≈90% luminous transmission and ≈54% solar modulation, which endows excellent energy saving performance. The outstanding photoelectric conversion efficiency (18.24%) of silicon solar cells with louver structure gives the smart window excellent energy generation ability, which is more than 100% higher than previously reported energy generation smart window. In addition, the solar cell can provide electricity to for ITO glass to turn the transmittance of hydrogel actively, as well as the effect of antifreezing. This work offers an insight into the design and preparation together with a disruptive strategy of easy fabrication, good uniformity, and scalability, which opens a new avenue to realize energy storage, energy saving, active control, and antifreezing integration in one device.

Highly Fluorescent Collagen-Based Quantum Dots as an Efficient Interlinkage in the 2D Perovskite Bulk for Improved Solar Cells.

A design-inexpensive, effective, and easy-to-prepare additive in the large-scale preparation of perovskite solar cells (PSCs) is urgently desired to alleviate the future energy crisis. Carbon-based quantum dots have demonstrated novel nanomaterials with excellent chemical stability and high electrical conductivity, which exhibit great potential as additives for perovskite optoelectronics. Herein, we designed novel highly fluorescent collagen-based quantum dots (Col-QDs) and thoroughly studied the micromorphological characteristics, photoluminescence properties, and the states of surface-functionalized groups on the Col-QDs. It is found that the introduction of Col-QDs in the two-dimensional (2D) perovskite precursor can be further confirmed as an efficient interlinkage via Col-Pb bands in the pure 2D perovskite heterojunction, which significantly improves the crystallinity, orientation, and interlayer coupling of perovskite crystal plates, as observed by grazing incidence X-ray diffraction (GIWAXS) and X-ray photoelectron spectroscopy (XPS). Finally, the champion Col-QD additive can efficiently modulate the photovoltaic performance of pure 2D PSCs with a significant increase of photoelectric conversion efficiency (PCE) from 8.18% up to 10.45%, which ranks among the best efficiencies of highly pure 2D PSCs. These results provide a facile and feasible approach to modulate the interlayer interaction of pure 2D perovskites and further improve their output of PSCs, which would further facilitate the burgeoning applications of the Col-QDs in various perovskite-based optical-related fields.

Pressure-dependent ion current rectification in conical-shaped glass nanopores.

Ion current rectification that occurs in conical-shaped glass nanopores in low ionic strength solutions is shown to be dependent on the rate of pressure-driven electrolyte flow through the nanopore, decreasing with increasing flow rate. The dependence of the i-V response on pressure is due to the disruption of cation and anion distributions at equilibrium within the nanopore. Because the flow rate is proportional to the third power of the nanopore orifice radius, the pressure-driven flow can eliminate rectification in nanopores with radii of ∼200 nm but has a negligible influence on rectification in a smaller nanopore with a radius of ∼30 nm. The experimental results are in qualitative agreement with predictions based on finite-element simulations used to solve simultaneously the Nernst-Planck, Poisson, and Navier-Stokes equations for ion fluxes in a moving electrolyte within a conical nanopore.

Designed post-self-assembly structural and functional modifications of a truncated tetrahedron.

Post-self-assembly modifications of a discrete metal-organic supramolecular structure have been developed. Such modifications allow the properties of the self-assembled supramolecular species to be changed in a simple and efficient manner (>90% yield). Initiated by the application of chemical stimuli, the post-self-assembly modifications described herein result in three distinct changes to the supramolecular system: an individual building-block component change, an overall structural modification, and a functional evolution of a [6+4] metal-organic supramolecular structure. The three modifications have been carefully examined by a range of characterization methods, including NMR and UV-vis spectroscopy, electrospray ionization mass spectrometry, pulsed field gradient spin echo NMR measurements, electrochemical analysis, and computational simulations.

Post-self-assembly covalent chemistry of discrete multicomponent metallosupramolecular hexagonal prisms.

The multicomponent coordination-driven self-assembly of hexakis[4-(4-pyridyl)phenyl]benzene, cis-(PEt(3))(2)Pt(II)(OTf)(2), and amine- or maleimide-functionalized isophthalate forms discrete hexagonal prisms as single reaction products. The amino or maleimide groups decorating the isophthalate pillars of the prisms provide reactive sites for post-self-asssembly modifications. In this communication, we demonstrate that the hexagonal prisms can be functionalized without disrupting the prismatic cores, enabling the incorporation of new functionalities under mild conditions.

Nanoparticle transport in conical-shaped nanopores.

This report presents a fundamental study of nanoparticle transport phenomena in conical-shaped pores contained within glass membranes. The electrophoretic translocation of charged polystyrene (PS) nanoparticles (80- and 160-nm-radius) was investigated using the Coulter counter principle (or "resistive-pulse" method) in which the time-dependent nanopore current is recorded as the nanoparticle is driven across the membrane. Particle translocation through the conical-shaped nanopore results in a direction-dependent and asymmetric triangular-shaped resistive pulse. Because the sensing zone of conical-shaped nanopores is localized at the orifice, the translocation of nanoparticles through this zone is very rapid, resulting in pulse widths of ~200 µs for the nanopores used in this study. A linear dependence between translocation rate and nanoparticle concentration was observed from 10(7) to 10(11) particles/mL for both 80- and 160-nm-radius particles, and the magnitude of the resistive pulse scaled approximately in proportion to the particle volume. A finite-element simulation based on continuum theory to compute ion fluxes was combined with a dynamic electric force-based nanoparticle trajectory calculation to compute the position- and time-dependent nanoparticle velocity as the nanoparticle translocates through the conical-shaped nanopore. The computational results were used to compute the resistive pulse current-time response for conical-shaped pores, allowing comparison between experimental and simulated pulse heights and translocation times. The simulation and experimental results indicate that nanoparticle size can be differentiated based on pulse height, and to a lesser extent based on translocation time.

Synthesis of titania-silica core-shell microspheres via a controlled interface reaction in a microfluidic device.

In this work, we describe a novel, simple microfluidic method for fabricating titania-silica core-shell microspheres. Uniform droplets of silica sol were dispersed into an oil phase containing tetrabutyl titanate via a coaxial microfluidic device. The titanium alkoxide hydrolyzed at the water-oil interface after the formation of the aqueous droplets. A gel shell containing the titanium hydroxide formed around the droplets, and the titania-silica core-shell microspheres were obtained after calcinations. The X-ray diffraction results show that titania coatings crystallized into a pure anatase structure. The scanning electron microscopy and energy-dispersive spectrometry characterization shows that the microspheres are monodispersed with uniform titania coating on the surface. The dispersity and size of the microspheres could easily be controlled by changing the microfluidic flow parameters. The titania content on the surface could be adjusted in the large range of 1.0-98.0 mol % by varying the continuous phase composition and the reaction time, and the structures of the core-shell microshperes could also be controlled.

Quartz nanopore membranes for suspended bilayer ion channel recordings.

A method is described for fabricating 25-75 mum thick fused quartz membranes containing a single conical shaped nanopore (orifice radius ranging from 10 to 1000 nm). The quartz nanopore membrane (QNM) provides an excellent solid support structure for lipid bilayers in ion channel recordings due to the large electrical resistivity of fused quartz. Electrical measurements demonstrate that the leakage current through 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers suspended across a 500-1000 nm radius QNM orifice is immeasurably small, corresponding to a bilayer resistance greater than 10(12) ohms. Translocation of single-stranded DNA oligomers (poly dA 50-mer and poly dA 20-mer) through a protein ion channel (alpha-hemolysin) reconstituted in a DPhPC bilayer suspended across the QNM orifice is demonstrated.

One-step synthesis of chitosan-silica hybrid microspheres in a microfluidic device.

This article describes a simple microfluidic method to fabricate chitosan-silica hybrid microspheres in one step. We dissolved tetraethoxysilane (TEOS) into a chitosan/acetic acid aqueous solution to form a chitosan-silica sol, and then emulsified it in an organic phase mainly containing n-octanol and an organic base triotylamine (TOA) via a co-axial microfluidic device. The formed aqueous droplets were solidified because of the extraction of acetic acid and water to the organic phase. The simple method presented has the advantages of controllable sphere diameter, narrow size distribution and good sphericity. The porous structures of the microspheres were displayed by SEM images. It is found that the inner and surface structures can be controlled by adjusting the solidification reagent component. Furthermore, we chemically grafted bovine serum albumin (BSA) on the microspheres. The existence of silica in the chitosan spheres can enhance both of mechanical intensity and protein loading capacity of the microspheres.

Enantioselective one-pot synthesis of 4H-chromene derivatives catalyzed by a chiral Ni(ii) complex.

A Ni(ii)-bis(oxazoline) complex and p-TSOH are used to form enantioenriched 4H-chromenes from ortho-quinone methides (o-QMs) and dicarbonyls, providing the desired products in up to 95% ee. The method is compatible with various ß-ketoester substrates, and the products obtained could be converted into biologically active 4H-chromene derivatives.

Biomimicry Surface-Coated Proppant with Self-Suspending and Targeted Adsorption Ability.

Proppant is a key material, which can increase the production of unconventional petroleum and gas. Excellent proppants with a long migration distance are required in the fracture network. Resin-coated proppants have been confirmed as a good choice because of the long migration and the self-suspending ability in fracturing fluids. However, the distribution of the resin-coated proppants in fracture networks is random. The design of proppants with targeted adsorption is urgently needed. In this study, a novel proppant coated with a phenolic resin shell doped with Fe3O4 nanoparticles on ceramic (coated proppant) was designed and investigated. Based on the results, the coated proppant was adsorbed on the magnetic component's parts of the fracture network surface, which helps in enhancing the uniform distribution of the proppant in the fracture rock cracks. Meanwhile, the self-suspending ability of the coated proppant is five times higher than that of the uncoated proppant and can migrate a longer distance in the fracture network. Moreover, the liquid conductivity of the coated proppant is 30% higher than that of the uncoated ones at a closure pressure of 6.9 MPa. In summary, new insights into the design of functional proppants and further guidelines on the production of unconventional petroleum and gas have been provided in this study.

Novel Stable DNA Nanoscale Material and Its Application on Specific Enrichment of DNA.

DNA nanostructures are a new type of technology for constructing nanomaterials that has been developed in recent years. By relying on the complementary pairing of DNA molecules to form a double-stranded property, DNA molecules can construct a variety of nanoscale structures of 2D and 3D shapes. However, most of the previously reported DNA nanostructures rely solely on hydrogen bonds to maintain structural stability, resulting in DNA structures that can be maintained only at low temperature and in the presence of Mg2+, which greatly limits the application of DNA nanostructures. This study designed a DNA nanonetwork structure (nanonet) and changed its topological structure to DNA nanomesh by using DNA topoisomerase to make it thermally stable, while escaping the dependence on Mg2+, and the stability of the structure can be maintained in a nonsolution state. Moreover, the nanomesh also has a large amount of ssDNA (about 50%), providing active sites capable of exerting biological functions. Using the above characteristics, we prepared the nanomesh into a device capable of adsorbing specific DNA molecules, and used the device to enrich DNA. We also tried to mount antibodies using DNA probes. Preliminary results show that the DNA nanomesh also has the ability to enrich specific proteins.

Controllable preparation of microscale tubes with multiphase co-laminar flow in a double co-axial microdevice.

This article describes a simple method for the fabrication of microscale polymer tubes. A double co-axial microchannel device was designed and fabricated. Liquid/liquid/liquid multiphase co-laminar flows were realized in a microchannel by choosing working systems. Three kinds of polymeric solutions were selected as the middle phase while a polyethyleneglycol aqueous solution was used as the inner and outer phases in the microfluidic process. The outer and inner phases acted as extractants of the polymer solvent. A stable double core-annular flow was formed by optimizing the composition of the outer and inner phases, and highly uniform tubes were successfully fabricated by the solvent extraction method. Both the outer diameter of the tubes and the wall thickness could be adjusted from 300 microm to 900 microm and from 40 microm to 150 microm by varying the flux of the fluids and the rolling velocity of the collection roller. In addition, titanium dioxide (TiO2) nanoparticles were successfully encapsulated into the polymer tubes with this technique. This technology has the potential to generate hollow fiber membranes for applications in separation and reaction processes.

Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis.

BACKGROUND: It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival. METHODS: Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis. RESULTS: The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34-47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01). CONCLUSIONS: TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.