An Ionic Assisted Enhancement Strategy Enabled High Performance Flexible Pressure-Temperature Dual Sensor.

Flexible pressure sensors with a broad range and high sensitivity are greatly desired yet challenging to build. Herein, we have successfully fabricated a pressure-temperature dual sensor via an ionic assisted charge enhancement strategy. Benefiting from the immobilization effect for [EMIM+] [TFSI-] ion pairs and charge transfer between ionic liquid (IL) and HFMO (H10Fe3Mo21O51), the formed IL-HFMO-TPU pressure sensor shows a high sensitivity of 25.35 kPa-1 and broad sensing range (∼10 MPa), respectively. Furthermore, the sensor device exhibits high durability and stability (5000 cycles@1 MPa). The IL-HFMO-TPU sensor also shows the merit of good temperature sensing properties. Attributed to these superior properties, the proposed sensor device could detect pressure in an ultrawide sensing range (from Pa to MPa), including breathe and biophysical signal monitoring etc. The proposed ionic assisted enhancement approach is a generic strategy for constructing high performance flexible pressure-temperature dual sensor.

The protective effect and mechanism of glycosides of cistanche deserticola on rats in middle cerebral artery occlusion (MCAO) model.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

Uncovering the Dominant Role of an Extended Asymmetric Four-Coordinated Water Network in the Hydrogen Evolution Reaction.

In situ and accurate measurement of the structure and dynamics of interfacial water in the hydrogen evolution reaction (HER) is a well-known challenge because of the coupling of water among varied structures and its dual role as reactants and solvents. Further, the interference of bulk water and intricate interfacial interactions always hinders the probing of interfacial water. Surface-enhanced infrared absorption spectroscopy is extremely sensitive for the measurement of interfacial water; herein, we develop a nanoconfinement strategy by introducing nonaqueous ionic liquids to decouple and tailor the water structure in the electric double layer and further combined with molecular dynamics simulations, successfully gaining the correlation between isolated water, water clusters, and the water network with HER activity. Our results clearly disclosed that the potential-dependent asymmetric four-coordinated water network, whose connectivity could be regulated by hydrophilic and hydrophobic cations, was positively correlated with HER activity, which provided a pioneering guidance framework for revealing the function of water in catalysis, energy, and surface science.

Enhancing Peroxidase Activity of Cytochrome c by Modulating Interfacial Interaction Forces with Graphene Oxide.

Graphene oxide (GO) has drawn worldwide attention in various biomedical fields because of its unique properties, and great progress has been made in the past years. Probing the interaction between GO and proteins, understanding and evaluating potential impact of GO on the protein structure and function, is of significant importance for design and optimization of functional interfaces and revealing the bioeffect of GO materials. Cytochrome c (cyt c), one of the key components of respiratory chain, has played important roles in energy generation/consumption and many cellular processes including growth, proliferation, differentiation, and apoptosis. In this study, by combination of solution chemistry and spectroscopy, we systematically studied the interfacial interaction between GO and cyt c. Results suggest that GO could slightly perturb the active site of cyt c, enhancing its peroxidase activity. Structure of the active site is obviously changed with elapsed time, which in turn reduces peroxidase activity. Further study suggests that adsorption of cyt c on GO and the resulted structure change is a complex process resulting from the cooperation of various interaction forces. Hydrophobic interaction and π-π stacking, as well as electrostatic attraction, only slightly perturb the microenvironment of the active site of cyt c while hydrogen-bonding interaction is the main driving force for the structural change of the active site. Furthermore, long range electrostatic attraction between GO and cyt c may facilitate the short range hydrogen-bonding interaction, which intensifies the hydrogen-bonding-induced structural change. In addition, cyt c is partially reduced by GO in an alkaline environment. Based on the understanding of interfacial interaction mechanism between GO and cyt c, stable nanocomposites with enhanced peroxidase activity are successfully constructed by modulating the interfacial interaction forces. This work not only deepens the understanding of interaction between GO and functional protein, but also is of great importance for designing and applying of GO-based biomaterials.

The Structure of Water Bonded to Phosphate Groups at the Electrified Zwitterionic Phospholipid Membranes/Aqueous Interface.

Gaining insight into the water structure at the electrified phospholipid membranes/aqueous interface is vital and essential for elucidating the mechanism of many biochemical reactions, but still remains a formidable challenge. Herein, based on the superiority of surface enhanced infrared absorption (SEIRA) spectroscopy combined with electrochemistry in interfacial analysis, the evolution of local water structure at the zwitterionic phospholipid membranes/aqueous interface with an external electric field is revealed by means of ion perturbation. The strongly hydrogen-bonded water directly bonded to the phosphate groups (PO2- ) has a strong mechanical strength to resist potential perturbations, and that portion of water greatly affects the electrostatic properties of the phospholipid membranes. This study innovates the basic understanding of electric double layer (EDL) at the membranes/aqueous interface.

Understanding the Synergic Mechanism of Weak Interactions between Graphene Oxide and Lipid Membrane Leading to the Extraction of Lipids.

Revealing how weak forces interact synergistically to induce differences in nanobio effects is critical to understanding the nature of the nanobio interface. Herein, graphene oxide (GO) and a lipid membrane are selected as a nanobio model, and interaction forces at the GO-biomembrane interface are modulated by varying the amounts and species of oxygenated functional groups on the surface of GO. A synergic mechanism of interfacial interaction forces is investigated by a combination of surface-enhanced infrared absorption (SEIRA) spectroscopy, confocal laser scanning microscopy (CLSM), and electrochemical impedance spectroscopy (EIS). The results reveal that after balancing with electrostatic repulsion, the moderate attraction between GO and lipid headgroups (such as electrostatic and/or hydrophobic interactions) is most favorable for lipid extraction, whereas lipid extraction is inhibited under an attraction that is too strong or too weak. Under moderate attraction between GO and the headgroups of lipids, the appropriate degree of rotation freedom is maintained for GO, which is beneficial to the hydrogen-bonding interaction between the C═O group in the phosphatide hydrophobic region and GO, thus triggering the insertion of GO into the lipid alkyl chain region, resulting in the rapid and significant extraction of lipids. Our results have important guiding significance for how to reveal the synergistic mechanism of weak interactions at the nanobio interface.

Proton Transfer at the Interaction Interface of Graphene Oxide.

Proton transfer plays a crucial role in a variety of biological phenomena. The transformation of nanomaterials in the environment and biology makes probing the potential proton transfer between nanomaterials and biomolecules a crucial issue, but it still remains a significant challenge. Here, we report proton transfer at the interface of graphene oxide (GO) by studying the GO-induced vibrational changes of interfacial water and carboxyl-terminated self-assembled monolayer (SAM) with surface-enhanced infrared absorption spectroscopy. In addition to simply acting as a macromolecular buffer in solution, the GO sheet behaves as a two-dimensional hydrogen-bonded exchangeable proton pool to dissociate and transfer protons at the interface with a suitable Brønsted base pair, which may bear a significant potential toxic origin for biological systems with proton-coupled reactions.

In Situ Surface-Enhanced Infrared Absorption Spectroscopy of Aqueous Molecules with Facile-Prepared Large-Area Reduced Graphene Oxide Island Film.

Midinfrared plasmons in patterned graphene could advance the development of surface-enhanced infrared absorption spectroscopy (SEIRAS). However, limitation in measuring the extinction spectra with transmission and external reflection configurations greatly restricts the analyses of aqueous samples. In addition, complicated, time- and cost-consuming preparation of patterned graphene also limits its progress. Here we demonstrate a facile-prepared large-scale reduced graphene oxide island film on a total internal reflection silicon prism, which not only shows a prominent enhancement effect in mid-infrared region but also effectively eliminates the contribution of bulk solution by optical near-field effect. As a result, the entire vibrational fingerprints of methylene blue monolayer in aqueous solution can be acquired with high sensitivity in real time. Our work extends the application of graphene-based SEIRAS to aqueous environment, breaking through previously unattainable technology.

Lanthanide-Coordinated Black Phosphorus.

Black phosphorus (BP) possesses unique physical properties and, owing to its intrinsic instability, the proper surface and chemical coordination is the key point in many applications. Herein, a facile and efficient surface lanthanide-coordination strategy based on lanthanide (Ln) sulfonate complexes is designed to passivate and functionalize different BP-based nanostructures including quantum dots, nanosheets, and microflakes. By means of Ln-P coordination, the lone-pair electrons of phosphorus are occupied, thus preventing oxidation of BP, and the LnL3 @BP exhibits excellent stability in both air and water. Furthermore, accompanied by the original photothermal performance of BP nanostructures, the Gd-coordinated BP has high R1 relativities in magnetic resonance (MR) imaging, and other Ln (Tb, Eu, and Nd) coordinated BP structures exhibit fluorescence spanning the visible to near-infrared regions. Not only is LnL3 surface passivation an efficient method to enhance the stability of BP, but also the MR or fluorescence derived from lanthanide ions extends the application of BP to optoelectronics and biomedical engineering.

Revealing the Effect of Protein Weak Adsorption to Nanoparticles on the Interaction between the Desorbed Protein and its Binding Partner by Surface-Enhanced Infrared Spectroelectrochemistry.

In recent years, the properties of protein corona have attracted intense interest in the field of nanobio interface, but a long-ignored research issue is how the desorbed proteins suffering from conformational change upon weak association with nanoparticles affect their functional properties when further interacting with their downstream protein partners. In this Article, surface-enhanced infrared absorption spectroscopy (SEIRAS) and electrochemical cyclic voltammetry were used to study the adsorption and redox properties of the soluble cytochrome c (cyt c) on 11-mercaptoundecanoic acid (MUA) self-assembled monolayer (SAM) after weakly binding to and then desorbed from nano-TiO2. For the first time, our study reveals that the weak interaction between cyt c and nano-TiO2 induces the protein to undergo a heterogeneous conformational change. More importantly, the cyt c with a largely unfolded conformation exhibits a weaker interaction with its binding partner mimics than the native-like cyt c but a faster adsorption rate even at a concentration that is much lower than that of native-like cyt c. Correspondingly, the cyt c with a large unfolding shows a greatly positive-shifted formal potential (Ef) relative to the native-like protein possibly due to the disruption of the pocket structure of heme in the vicinity of Met80. These properties could enable the largely unfolded cyt c to undergo a favorable binding but an unavailable electron transfer to cytochrome c oxidase even in the presence of high-concentration native cyt c, probably causing the disruption of electron flow.

The Role of Water Distribution Controlled by Transmembrane Potentials in the Cytochrome†c-Cardiolipin Interaction: Revealing from Surface-Enhanced Infrared Absorption Spectroscopy.

The interaction of cytochrome c (cyt c) with cardiolipin (CL) plays a crucial role in apoptotic functions, however, the changes of the transmembrane potential in governing the protein behavior at the membrane-water interface have not been studied due to the difficulties in simultaneously monitoring the interaction and regulating the electric field. Herein, surface-enhanced infrared absorption (SEIRA) spectroelectrochemistry is employed to study the mechanism of how the transmembrane potentials control the interaction of cyt c with CL membranes by regulating the electrode potentials of an Au film. When the transmembrane potential decreases, the water content at the interface of the membranes can be increased to slow down protein adsorption through decreasing the hydrogen-bond and hydrophobic interactions, but regulates the redox behavior of CL-bound cyt c through a possible water-facilitated proton-coupled electron transfer process. Our results suggest that the potential drop-induced restructure of the CL conformation and the hydration state could modify the structure and function of CL-bound cyt c on the lipid membrane.

Analyzing Structural Properties of Heterogeneous Cardiolipin-Bound Cytochrome C and Their Regulation by Surface-Enhanced Infrared Absorption Spectroscopy.

Apoptotic mechanisms are not fully understood due to limitations in present analytical methods. Such understanding may be advanced by unravelling the structural properties of heterogeneous cardiolipin (CL)-bound cytochrome c (cyt c) and the factors or events that regulate them. In this study, surface-enhanced infrared absorption spectroscopy (SEIRAS) was employed to probe the adsorption of cyt c on CL membranes in biomimetic conditions. The results clearly show that pure electrostatic interactions result in the unfolding of partial α-helices, while the synergy between hydrogen bonding and electrostatic interactions governs orientation homogeneity of adsorbed protein, and conformational transition between α-helices and ß-sheet. Hydrogen bonding plays a dual role; along with hydrophobic interactions, it may disturb the microenvironment of some secondary structures such as the ß-turn type III, while it also triggers structural changes in lipid molecules likely resulting from the extension of CL acyl chains to the hydrophobic channels of cyt c. These findings provide the details of protein transitions in early apoptosis at the molecular level.

Self-assembly of nitrogen-doped carbon nanoparticles: a new ratiometric UV-vis optical sensor for the highly sensitive and selective detection of Hg(2+) in aqueous solution.

Water-soluble nitrogen-doped carbon nanoparticles (N-CNPs) prepared by the one-step hydrothermal treatment of uric acid were found to show ratiometric changes in their UV-vis spectra due to Hg(2+)-mediated self-assembly. For the first time, such a property was developed into a UV-vis optical sensor for detecting Hg(2+) in aqueous solutions with high sensitively and selectively (detection limit = 1.4 nM). More importantly, this novel sensor exhibits a higher linear sensitivity over a wider concentration range compared with the fluorescence sensor based on the same N-CNPs. This work opens an exciting new avenue to explore the use of carbon nanoparticles in constructing UV-vis optical sensors for the detection of metal ions and the use of carbon nanoparticles as a new building block to self-assemble into superlattices.

Recent developments in methodology employed to study the interactions between nanomaterials and model lipid membranes.

With the boom of nanotechnology, nanomaterials (NMs) have been widely utilized in diverse applications, especially in biological and biomedical fields. Understanding how NMs interact with biomolecules, including proteins, DNA, and lipids, is of great importance for revealing the limitations posed and opportunities offered. Model lipid membrane, as a simplified cell membrane model, has been widely used to study the nanomaterial-lipid membrane interactions. In this article, current and emerging techniques, both experimental and theoretical, to investigate the interactions between NMs and model lipid membrane are summarized with each tool's capacities and limitations, along with future directions and challenges in this exciting area. This critical information will provide methodological guidance for researchers in this field.

Revealing the Nature of Interaction between Graphene Oxide and Lipid Membrane by Surface-Enhanced Infrared Absorption Spectroscopy.

Revealing the nature of interaction between graphene oxide (GO) and lipid membrane is a crucial issue but still remains challenging. Here, we describe our recent effort toward this direction by studying the GO-induced vibrational changes of interfacial water and lipid membrane with surface-enhanced infrared absorption (SEIRA) spectroscopy. The experimental results provide evidence that overcoming the electrostatic repulsion of phosphate group, its hydrogen bonding attraction as well as the electrostatic and hydrophobic interaction of choline group are the driving forces for the effective adsorption of GO on lipid membrane. This work will open exciting new avenues to explore the use of SEIRA spectroscopy technique in probing nanobio interface.

Comprehensive characterization of sphingolipid ceramide N-deacylase for the synthesis and fatty acid remodeling of glycosphingolipids.

Sphingolipid ceramide N-deacylase (SCDase) catalyzes reversible reactions in which the amide linkage in glycosphingolipids is hydrolyzed or synthesized. While SCDases show great value for the enzymatic synthesis of glycosphingolipids, they are relatively poorly characterized enzymes. In this work, the enzymatic properties of SCDase from Shewanella alga G8 (SA_SCD) were systematically characterized and compared with the commercially available SCDase from Pseudomonas sp. TK4 (PS_SCD). The optimal pH values for the hydrolytic and synthetic activity of SA_SCD were pH 6.0 and pH 7.5, respectively. Both activities were strongly inhibited by Zn(2+) and Cu(2+), while Fe(2+), Co(2+), Ni(2+), Mn(2+), Ca(2+), and Mg(2+) promoted the hydrolytic activity but inhibited the synthetic activity. SA_SCD showed very broad substrate specificity both in hydrolysis and synthesis. Importantly, SA_SCD has a broader specificity for acyl donor acceptance than does PS_SCD, especially for unsaturated fatty acids and fatty acids with very short or long acyl chains. Further kinetic analysis revealed that the k cat/K M value for the hydrolytic activity of SA_SCD was 8.9-fold higher than that of PS_SCD for GM1a, while the values for the synthetic activity were 38-fold higher for stearic acid and 23-fold higher for lyso-GM1a (d18:1) than those of PS_SCD, respectively. The broad fatty acid specificity and high catalytic efficiency, together with the ease of expression of SA_SCD in Escherichia coli, make it a better biocatalyst than is PS_SCD for the synthesis and structural remodeling of glycosphingolipids.

Transformation of Black Phosphorus through Lattice Reconstruction for NIR-II-Responsive Cancer Therapy.

The photothermal performance of black phosphorus (BP) in the near infrared (NIR)-II bio-window (1000-1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2 P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2 P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2 P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2 P QDs-based liposomal nano-platform (Ni2 P-DOX@Lipo-cRGD) is designed by incorporation of Ni2 P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064-nm laser irradiation owing to the photothermal effect of Ni2 P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2 P-DOX@Lipo-cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR-II transformation of nano-materials and may shed light on the construction of multifunctional nano-platforms for cancer treatment.

Revealing the Nanoarchitectonics of Amyloid ß-Aggregation on Two-Dimensional Biomimetic Membranes by Surface-Enhanced Infrared Absorption Spectroscopy.

The in vivo folding of amyloid ß (Aß) is influenced by many factors among which biomembrane interfaces play an important role. Here, using surface-enhanced infrared absorption (SEIRA) spectroscopy and atomic force microscopy (AFM), the adsorption, structure, and morphology of Aß42 aggregating on different two-dimensional interfaces were investigated. Results show that interfaces facilitate the aggregation of Aß42 and are conducive to the formation of homogeneous aggregates, while the aggregates vary on different interfaces. On hydrophobic interfaces, strong hydrophobic interactions with the C-terminus of Aß42 result in the formation of small oligomers with a small proportion of the ß-sheet structure. On hydrophilic interfaces, hydrogen-bonding interactions and electrostatic interactions promote the formation of large aggregate particles with ß-sheet structure. The hydration repulsion plays an important role in the interaction of Aß42 with interfaces. These findings help to understand the nature of Aß42 adsorption and aggregation on the biomembrane interface and the origin of heterogeneity and polymorphism of Aß42 aggregates.

Combined chemotherapy based on bioactive black phosphorus for pancreatic cancer therapy.

Pancreatic cancer is the most aggressive malignant tumor with difficulty in early diagnosis, very short survival time in advanced stage, and lack of effective treatment options. In this work, a novel combination chemotherapy strategy based on bioactive black phosphorus (BP) and gemcitabine (GEM) is developed for efficient treatment of pancreatic cancer. The combined cell cycle blockage in G2/M phase induced by BP and G0/G1 phase by GEM results in synergistic killing of pancreatic cancer cells with the combination index (CI) < 1. The iRGD modified zein nanoparticles co-loaded with BP quantum dots (BPQDs) and GEM are designed and prepared as a targeted nanoplatform (BP-GEM@NPs). After intravenous injection, the in vivo distribution and pharmacokinetics results demonstrate that BP-GEM@NPs shows excellent tumor targeting capability and significantly prolonged blood circulation time. The targeted co-delivery of BPQDs and GEM induces much more pancreatic tumor cell apoptosis and synergistically inhibits tumor growth in both subcutaneous xenograft and orthotopic models. Meanwhile, BP-GEM@NPs exhibit good biocompatibility without bring adverse effects. This work indicates the great potential of BP-GEM@NPs as a combination chemotherapy for pancreatic cancer and provides insights into development of biomedicine by exploring the intrinsic bioactivities of nanomaterials.

Colorimetric immunosensing using liposome encapsulated MnO2 nanozymes for SARS-CoV-2 antigen detection.

Development of specific signal reporters with signal amplification effect are highly needed for sensitive and accurate detection of pathogen. Herein, we design a colorimetric immunosensing nanosystem based on liposome encapsulated quantum dots-sized MnO2 nanozyme (MnO2QDs@Lip) as a signal reporter for ultrasensitive and fast detection of SARS-CoV-2 antigen. The pathogenic antigens captured and separated by antibody-conjugated magnetic beads (MBs) are further connected with antibody-modified MnO2QDs@Lip to form a sandwich-like immunocomplex structure. After triggered release, MnO2 QDs efficiently catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB, which can be qualitatively observed by naked eyes and quantitatively analyzed by UV-Vis spectra or smartphone platforms. By taking advantages of immuno-magnetic separation, excellent peroxidase-like catalytic activity of MnO2 QDs, and high encapsulation efficiency of MnO2QDs@Lip, ultrasensitive detection of SARS-CoV-2 antigen ranging from 0.1 pg/mL to 100 ng/mL is achieved within 20 min. The limit of detection (LOD) is calculated to be 65 fg/mL in PBS buffer. Furthermore, real clinical samples of SARS-CoV-2 antigens can be effectively identified by this immunosensing nanosystem with excellent accuracy. This proposed detection nanosystem provides a strategy for simple, rapid and ultrasensitive detection of pathogens and may shed light on the development of new POCT detection platforms for early diagnosis of pathogens and surveillance in public health.