Carboxymethyl chitosan and dialdehyde cellulose nanocrystal based injectable self-healing emulsion gel.

The study aims to demonstrate a general method for producing emulsion gels with self-healing properties. Specifically, the self-healing emulsion gels were fabricated by crosslinking carboxymethyl chitosan (CMC) stabilized emulsion with dialdehyde cellulose nanocrystal (DACNC). The reversible imine bonds between primary amino groups from CMC and aldehyde groups from DACNC endow the emulsion gel with self-healing properties. The compressive strength of the emulsion gels was greatly increased from 37.43 kPa 83.7 kPa by encapsulating emulsion droplets (φ = 0 %-40 %.) in the gel matrix. Moreover, the emulsion gels exhibited much better self-healing and injectability ability compared to hydrogel because the emulsion droplets interacted with the 3D gel matrix, which were observed by cryo-SEM and CLSM. The emulsion droplets distributed in the gel matrix improved the mobility and interfacial contact area of CMC and DACNC. Water contact measurement confirmed that the CMC/DACNC self-healing emulsion gels showed a hydrophilic surface. The CMC/DACNC emulsion gels could maintain a good structural stability as the oil loss was <1 % after centrifugation. This research provides a method to keep the structural stability of emulsion gels by inducing self-healing ability and modified cellulose nanocrystals, which could extend the shelf life and application area of emulsion gels.

Endoplasmic reticulum stress is attenuated by glycolysis in lymphatic malformations.

BACKGROUND: This study aims to investigate the role of endoplasmic reticulum stress (ER stress) in human dermal lymphatic endothelial cells (HDLECs) and lymphatic malformations (LMs) and its relationship with aerobic glycolysis and inflammation. METHODS: The proliferation and apoptosis of HDLECs were examined with lipopolysaccharide (LPS) treatment. ER stress-associated proteins and glycolysis-related markers were detected by western blot. Glycolysis indexes were detected by seahorse analysis and lactic acid production assay kits. Immunohistochemistry was used to reveal the ER stress state of lymphatic endothelial cells (LECs) in LMs. RESULTS: LPS induced ER stress in HDLECs but did not trigger detectable apoptosis. Intriguingly, LPS-treated HDLECs also showed increased glycolysis flux. Knockdown of Hexokinase 2, a key enzyme for aerobic glycolysis, significantly inhibited the ability of HDLECs to resist ER stress-induced apoptosis. Moreover, compared to normal skin, glucose-regulated protein 78 (GRP78/BIP), and phosphorylation protein kinase R-like kinase (p-PERK), two key ER stress-associated markers, were upregulated in LECs of LMs, which was correlated with the inflected state. In addition, excessively activated ER stress inhibited the progression of LMs in rat models. CONCLUSIONS: These data indicate that glycolysis could rescue activated ER stress in HDLECs, which is required for the accelerated development of LMs. IMPACT: Inflammation enhances both ER stress and glycolysis in LECs while glycolysis is required to attenuate the pro-apoptotic effect of ER stress. Endoplasmic reticulum (ER) stress is activated in lymphatic endothelial cells (LECs) of LMs, especially in inflammatory condition. The expression of ER stress-related proteins is increased in LMs and correlated with Hexokinase 2 expression. Pharmacological activation of ER stress suppresses the formation of LM lesions in the rat model. ER stress may be a promising and effective therapeutic target for the treatment of LMs.

Effects of Connectivity Isomerization on Electron Transport Through Thiophene Heterocyclic Molecular Junction.

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

Rapid detection of trace nitrobenzene in water via SERS using a portable Raman spectrometer.

Nitrobenzene is currently the most widely used explosive substance, and is known for its high toxicity and mutagenicity. It can cause severe environmental and water pollution, posing a risk to public health. Among various explosives analysis methods, surface-enhanced Raman spectroscopy (SERS) has the advantages of fast analysis speed, low detection cost, and easy operation, and has become one of the most promising analytical detection methods. Here, we present a portable and reliable sol-based SERS method for the detection of trace amounts of 2,4,6-trinitrotoluene (TNT) in different water bodies. The Meisenheimer complex formed by nitrobenzene and hydrazine hydrate can assemble on unmodified Au nanoparticles in a sol via Au-N bonds, enabling rapid detection of TNT in seawater, lake water, and tap water using a portable Raman spectrometer. Experimental results show that this SERS method can complete the detection within a few minutes and the detection sensitivity can reach 0.01 mg L-1, which is far lower than China's national standard of no more than 0.5 mg L-1. Furthermore, this method was also successfully applied to detect trace 2,4-dinitrotoluene (2,4-DNT) and picric acid (2,4,6-trinitrophenol) in water, demonstrating its strong applicability for on-site detection of nitrobenzene explosives.

Ratiometric G-quadruplex/hemin DNAzymes with low-dosage associative substrates.

BACKGROUND: G-quadruplex (G4)/hemin DNAzymes with conversion of substrates into colorimetric readouts are well recognized as convenient biocatalysis tools in sensor development. However, the previously developed colorimetric G4/hemin DNAzymes are diffusive substrate-based DNAzymes (DSBDs). The current colorimetric DSBDs have several drawbacks including high dosage (∼mM) of diffusive substrates (DSs), colorimetric product toxicity, and single colorimetric readout without tolerance to fluctuation of experimental factors and background. In addition, the usage of high-dosage DSs can smear the G4 foldings and their discard is more harmful to environment. Therefore, exploring alternative DNAzymes with potential to overcome these drawbacks of DSBDs is urgently needed. RESULTS: We herein developed associative substrate-based DNAzymes (ASBDs). Cyanine dyes were selected as associative substrates (ASs) due to their binding competency with G4/hemin DNAzymes. With respect to DSBDs, ASBDs needed only low dosage (∼10 µM) of ASs to be able to cause a rapid and visible substrate conversion. In addition, since cyanine dyes are NIR dyes with high extinction coefficients and their conversion products have absorption bands at shorter wavelength. Therefore, a colorimetric ratio response can be developed to follow activities of G4/hemin DNAzymes with competency to tolerate fluctuation of experimental factors and background. In particular, herein developed ASBDs can endure somewhat concentration fluctuation of H2O2. ASBDs are able to cowork with other enzymes (for example, glucose oxidase) to realize cascade sensing. SIGNIFICANCE: The developed ASBDs can operate at low dosage of substrates with a colorimetric ratio response and can overcome the drawbacks met in DSBDs. We expect that, by designing ASs with fruitful color panel in the future, our work will inspire more interesting in developing environment-benign and low-carbon G4/hemin DNAzymes and desired colorful high-performance sensors.

Polarity-Specific and Pyrimidine-over-Purine Adaptive Triplex DNA Recognition by a Near-Infrared Fluorogenic Molecular Rotor.

Triplex DNA structures have displayed a wide range of applications including nanosensing, molecule switching, and drug delivering. Therefore, it is of great importance to effectively recognize triplex DNA structures by a simple and highly selective manner. Herein, we found that a near-infrared fluorogenic probe of NIAD-4 with a molecular rotor (MR) merit can selectively recognize triplex DNA structures over G-quadruplex, i-motif, and duplex structures (Tri-over-QID selectivity), which is competent over the widely used MR probe of thioflavin T (ThT). Furthermore, NIAD-4 exhibits as well a high selectivity toward the 'pyrimidine-type' triplex structures (Y:R-Y type) with respect to the 'purine-type' triplex structures (R:R-Y type) (a Y-over-R selectivity). Interestingly, NIAD-4 recognizes the Y:R-Y triplex structures by a polarity-dependent manner. The 3' end triplet is the preferential binding field of NIAD-4 with respect to the 5' end one (a 3'-over-5' selectivity) as the 3' end triplet is more stable than the 5' end one in the Hoogsteen hydrogen bond. It is expected that the adaptive stacking interaction between NIAD-4 and the 3' end triplet favors the Tri-over-QID, Y-over-R, and 3'-over-5' selectivities since this MR probe has three rotating shafts matching well with the triplet in topology. Such a high selectivity of NIAD-4 opens a new route in designing sensors with DNA structures switching between triplex, i-motif, and G-quadruplex structures.

Local cation-tuned reversible single-molecule switch in electric double layer.

The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na+, K+, Mg2+ and Ca2+), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level.

All-or-None Selectivity in Probing Polarity-Determined Trinucleotide Repeat Foldings with a Parity Resolution by a Beyond-Size-Matching Ligand.

Abnormal amplification of trinucleotide repeats (TNRs) is associated with neurodegenerative diseases by forming a particular hairpin bulge. It is well known that the polarity and parity of TNRs can regulate the formed hairpin structures. Therefore, there is a great challenge to efficiently discriminate the hairpin structures of TNRs with substantial selectivity. Herein, we developed a fluorescent ligand of pseudohypericin (Pse) with a beyond-size-matching (BSM) geometry to selectively sense hairpin structures of GTC and CTG TNRs. The GTC hairpin structures can bind with Pse dominantly at extreme T-T mismatches by the virtue of their most extrahelical conformations, while there is no binding event to occur with the polarity-inverted counterpart CTG hairpin structures because of the limited space provided by their intrahelical T-T mismatches. In addition, this all-or-none response with the polarity-dependent folding (PoDF) is independent of the length of these TNRs. Interestingly, the parity-dependent folding (PaDF) of GTC hairpin structures can also be resolved. Besides pure TNRs, the competency of this BSM ligand to sense the PoDF and PaDF effects was also generalized to DNAs with TNRs occurring at loop and stem end regions. To our knowledge, this is the first experimental observation with the state-of-the-art performance over the fluorescence measurement of PoDF and PaDF in TNRs. Our work provides an expedient way to elucidate the TNR folding by designing ligands having BSM features.

In situ Raman monitoring of electroreductive dehalogenation of aryl halides at an Ag/aqueous solution interface.

Electroreductive dehalogenation as an efficient and green approach has attracted much attention in pollution remediation. Herein, we have employed a shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique to in situ probe the electroreductive dehalogenation process of aryl halides with thiol groups at Ag/aqueous solution interfaces. It is found that 4-bromothiophenol (BTP) and 4-chlorothiophenol (CTP) can turn into mixed products of 4,4'-biphenyldithiol (BPDT) and thiophenol (TP) as the electrode potential decreases. The conversion ratios estimated from the Raman intensity variations of C-Cl and C-Br vibrations are 44% and 58% for CTP and BTP in neutral solution, respectively. Furthermore, the quantitative analysis of benzene ring vibrations reveals a C-C cross coupling between the benzene free radical intermediate and adjacent TP product, which results in increased selectivity for biphenyl products at negative potentials.

Selectively recognizing heptad-interfaced G-quadruplexes by a molecular rotor with an ESIPT emission.

Heptad-interfaced G-quadruplexes (G4s), formed with GGA repeats located in the nuclear proto-oncogene c-myb promoter, can be selectively targeted by a prenylated flavonol of sophoflavescenol (Sop) with restriction of molecular rotation to trigger strong excited state intramolecular proton transfer (ESIPT) emission.

Selectivity of natural isoquinoline alkaloid assembler in programming poly(dA) into parallel duplex by polyvalent synergy.

Ligand-induced assembly of disordered DNAs attracts much attention due to its potential action in transcription regulation and molecular switches-based sensors. Among natural isoquinoline alkaloids (NIAs), we screened out nitidine (NIT) as polyvalent-binding assembler to program poly(dA) into a parallel duplex assembly at neutral pH. The molecule planarity of NIAs was believed to be a determinant factor in programming the parallel poly(dA) assembly. Poly(dA) with more than six adenines can initiate the synergistic binding of NIT to generate the parallel assembly. It is expected that one A-A pair in duplex can bind one NIT molecule provided that poly(dA) is long enough, suggesting the pivotal role of the polyvalent synergy of NIT in programming the parallel poly(dA) assembly. A gold nanoparticles-based colorimetric method was also developed to screen NIT out of NIAs having the potential to construct the poly(dA) assembly. Our work will inspire more interest in developing polyadenine-based switches and sensors by concentrating NIT within the polyadenine parallel assembly.

Morphology and Anti-Corrosive Performance of Cr(III) Passivated Zn-Fe Alloy Coating on NdFeB Substrate.

In this study, low-iron Zn-Fe alloy coatings and pure Zn coatings, with or without trivalent chromium passivation treatment, were electrodeposited onto a sintered NdFeB magnet from a weak acid chloride bath. The surface morphology and structure of the coatings were then examined using the X-ray diffraction, a scanning electron microscope and 3D white-light interfering surface analysis. Meanwhile, the electrodeposition behavior and anti-corrosive properties of the coatings were investigated using cyclic voltammetry, potentiodynamic polarization, electrochemical impedance spectroscopy, and natural salt spray tests. The results indicate that a passivated Zn-Fe alloy coating with a 0.9 wt.% Fe content provided much better corrosion resistance than a pure Zn coating and could provide both anodic protection and physical barrier function in the NdFeB substrates. The Fe element in Zn-Fe alloy coating was predominantly in solid solution in η-phase and small amounts in elemental form, which was beneficial to acquire a compact coating and passivation film. Finally, the passivated Zn-Fe alloy coating withstood 210 h against a neutral 3.5 wt.% NaCl salt spray without any white rust, which was 3-4 times longer than the pure Zn coating.

Selectively Identifying Exposed-over-Unexposed C-C+ Pairs in Human Telomeric i-Motif Structures with Length-Dependent Polymorphism.

The i-motif structure (iM) has attracted much attention, because of its in vivo bioactivity and wide in vitro applications such as DNA-based switches. Herein, the length-dependent folding of cytosine-rich repeats of the human telomeric 5'-(CCCTAA)n-1CCC-3' (iM-n, where n = 2-8) was fully explored. We found that iM-4, iM-5, and iM-8 mainly form the intramolecular monomer iM structures, while a tetramolecular structure populates only for iM-3. However, iM-6 and iM-7 have the potential to fold as well into the dimeric iM structures besides the monomer ones. The natural hypericin (Hyp) was used as the polymorphism-selective probe to recognize the iM structures. Interestingly, only iM-3, iM-6, and iM-7 can efficiently switch on the Hyp fluorescence by specifically binding with the outmost C-C+ base pairs that are exposed directly to solution. However, other iM structures that fold in a way with a coverage of the outmost C-C+ pairs by loop sequences are totally unavailable for the Hyp binding. Theoretical modeling indicates that adaptive π-π and cation-π interactions contribute to the Hyp recognition toward the exposed C-C+ pairs. This specific iM recognition can be boosted by a photocatalytic DNAzyme construct. Our work provides a reliable fluorescence method to selectively explore the polymorphism of iM structures.

Switching G-quadruplex to parallel duplex by molecular rotor clustering.

Switching of G-quadruplex (G4) structures between variant types of folding has been proved to be a versatile tool for regulation of genomic expression and development of nucleic acid-based constructs. Various specific ligands have been developed to target G4s in K+ solution with therapeutic prospects. Although G4 structures have been reported to be converted by sequence modification or a unimolecular ligand binding event in K+-deficient conditions, switching G4s towards non-G4 folding continues to be a great challenge due to the stability of G4 in physiological K+ conditions. Herein, we first observed the G4 switching towards parallel-stranded duplex (psDNA) by multimolecular ligand binding (namely ligand clustering) to overcome the switching barrier in K+. Purine-rich sequences (e.g. those from the KRAS promoter region) can be converted from G4 structures to dimeric psDNAs using molecular rotors (e.g. thioflavin T and thiazole orange) as initiators. The formed psDNAs provided multiple binding sites for molecular rotor clustering to favor subsequent structures with stability higher than the corresponding G4 folding. Our finding provides a clue to designing ligands with the competency of molecular rotor clustering to implement an efficient G4 switching.

Recent Advances in Single-Molecule Sensors Based on STM Break Junction Measurements.

Single-molecule recognition and detection with the highest resolution measurement has been one of the ultimate goals in science and engineering. Break junction techniques, originally developed to measure single-molecule conductance, recently have also been proven to have the capacity for the label-free exploration of single-molecule physics and chemistry, which paves a new way for single-molecule detection with high temporal resolution. In this review, we outline the primary advances and potential of the STM break junction technique for qualitative identification and quantitative detection at a single-molecule level. The principles of operation of these single-molecule electrical sensing mainly in three regimes, ion, environmental pH and genetic material detection, are summarized. It clearly proves that the single-molecule electrical measurements with break junction techniques show a promising perspective for designing a simple, label-free and nondestructive electrical sensor with ultrahigh sensitivity and excellent selectivity.

In Situ Raman Monitoring of Potential-Dependent Adlayer Structures on the Au(111)/Ionic Liquid Interface.

Probing the adlayer structures on an electrode/electrolyte interface is one of the most important tasks in modern electrochemistry for clarifying the electrochemical processes. Herein, we have combined cyclic voltammetry and electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy techniques to explore the potential-dependent adlayer structures on Au(111) in a room-temperature ionic liquid of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF6) without or with pyridine (Py). It is clearly found that the BMI+ cations strongly adsorb on the negatively charged surface with a flat-lying orientation, leaving a little space for Py adsorption. Upon increasing the potentials of the electrode, the variations of Raman band intensities and frequencies reveal that the interaction between the BMI+ cations and the Au surface becomes weak; meanwhile, the Py adsorption becomes strong, and its geometry turns from flat, tilted to vertical. Finally, BMI+ cations desorb and leave plenty of surface sites for Py adsorption in bulk solution, and a N-bonded compact Py adlayer is formed on the very positively charged surface. This causes obvious anodic peaks in cyclic voltammograms, and the peak currents increase with the square root of the scanning rate. The present work provides a fair molecular-level understanding of electrochemical interfaces and molecular adsorption of Py in ionic liquids.

Tuning the binding configurations of single-molecule junctions by molecular co-assembly.

Significant variability issues in metal-molecule contacts, such as adsorption geometry, lead to characteristic variability in the electrical responses of individual molecules. Herein, co-assembling 1-ethylimidazole (EIM) on Au(111) has been shown to be a feasible and effective strategy for tuning the binding configurations of pyridine-linked molecular junctions in the most common aqueous environments and atmospheric environments. The single-molecule conductance measurements clearly show a transition from multiple conductance peaks to a single conductance peak with increasing EIM concentration. Raman spectroscopy and DFT calculations suggest that the thermodynamically favorable EIM adsorbate results in the vertical orientation of the bipyridine.

Electrochemically activated carbon-halogen bond cleavage and C-C coupling monitored by in situ shell-isolated nanoparticle-enhanced Raman spectroscopy.

The electroreductive cleavage of carbon-halogen bonds has attracted increasing attention in both electrosynthesis and pollution remediation. Herein, by employing the in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique, we have successfully investigated the electroreductive dehalogenation process of aryl halides with the thiol group on a smooth Au electrode in aqueous solution at different pH values. The obtained potential-dependent Raman spectra directly reveal a mixture of the reduction products 4,4'-biphenyldithiol (BPDT) and thiophenol (TP). The conversion ratios of the C-Cl and C-Br bonds at pH = 7 are 37% and 55%, respectively. Furthermore, quantitative analysis of the intensity variations of ν(C-Cl), ν(C-Br) and aromatic ν(CC) stretching modes suggests electroreductive dehalogenation via both direct electron transfer reduction and electrocatalytic hydrodehalogenation. Molecular evidence for the C-C cross coupling process through TP reaction with benzene free radical intermediates is found at negative potentials, which leads to the increasing selectivity of biphenyl products.

Visualizing an Electrochemically Induced Radical Cation of Bipyridine at Au(111)/Ionic Liquid Interfaces toward a Single-Molecule Switch.

Room-temperature ionic liquids (RTILs) emerged as ideal solvents, and bipyridine as one of the most used ligands have been widely employed in surface science, catalysis, and molecular electronics. Herein, in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and STM break junction (STM-BJ) technique has been employed to probe the electrochemical process of bipyridine at Au(111)/IL interfaces. It is interestingly found that these molecules undertake a redox process with a pair of well-defined reversible peaks in cyclic voltammograms (CVs). The spectroscopic evidence shows a radical cation generated with rising new Raman peaks related to parallel CC stretching of a positively charged pyridyl ring. Furthermore, these electrochemically charged bipyridine is also confirmed by electrochemical STM-BJ at the single-molecule level, which displays a binary conductance switch ratio of about 400% at the redox potentials. This present work offers a molecular-level insight into the pyridine-mediated reaction process and electron transport in RTILs.

Visible light-driven i-motif-based DNAzymes.

DNA foldings provide variant possibilities to develop DNAzymes with remarkable catalytic performance. In spite of fruitful reports on G-quadruplex DNAzymes, four-stranded cytosine-rich i-motifs have not been explored as the potential skeletons of DNAzymes. In this work, we developed a visible light-driven DNAzyme based on human telomeric i-motifs using a natural photosensitizer of hypericin (Hyp) as the cofactor and dissolved oxygen as the oxidant source. The i-motif folding in acidic solution caused the distal thymine overhangs at the 3' and 5' ends to approach each other to provide a favorable binding site for Hyp via an interaction of fully complementary hydrogen bonding. However, the i-motifs without the distal overhangs or with the inappropriate overhang length and the base identity exhibited no binding with Hyp. The binding event converted Hyp from the fully dark state to the emissive state under visible light illumination. Subsequently, the excited Hyp had an opportunity to transfer energy to dissolved oxygen. Resultantly, singlet oxygen (1O2) was generated to initiate the substrate oxidation. The catalytic performance of the DNAzyme can be improved using a long-lived mediator. Our developed i-motif-based DNAzyme can be driven by almost the whole range of visible lights, suggesting broad applications in the photocatalytic fields, for example, as an alternative strategy in developing biodevices.