Self-Healable Adhesive Hydrogel with a Preserved Underwater Adhesive Ability Based on Histidine-Zinc Coordination and a Bioengineered Hybrid Mussel Protein.

Mussels are marine organisms that are capable of constructing an underwater adhesion between their bodies and rigid structures. It is well known that mussels achieve underwater adhesion through the presence of mussel adhesive proteins (MAPs) that contain high levels of 3,4-dihydroxyphenylalanine (DOPA). Although the extraordinary underwater adhesive properties of mussels are attributed to DOPA, its capacity to play a dual role in surface adhesion and internal cohesion is inherently limited. However, mussels employ a combination of chemical moieties, not just DOPA, along with anatomical components, such as plaque and byssus, in underwater adhesion. This also involves junction proteins that connect the plaque and byssus. In this study, a novel hybrid MAP was bioengineered via the fusion of the plaque protein (foot protein type 1) and the histidine-rich domain of the junction protein (foot protein type 4). To achieve direct adhesion underwater, the adhesive should maintain surface adhesion without disintegrating. Notably, the histidine-Zn-coordinated hybrid MAP hydrogel maintained a high surface adhesion ability even after cross-linking because of the preservation of its unoxidized and non-cross-linked DOPA moieties. The formulated adhesive hydrogel system based on the bioengineered hybrid MAP exhibited self-healing properties, owing to the reversible metal coordination bonds. The developed adhesive hydrogel exhibits outstanding levels of bulk adhesion in underwater environments, highlighting its potential as an effective adhesive biomaterial. Therefore, the introduction of histidine-rich domains into MAPs may be applied in various studies to formulate mussel-inspired adhesives with self-healing properties and to fully utilize the adhesive ability of DOPA.

One Carbon Ring Expansion of Bipyrrole to Bipyridine Enables Access to a π-Extended, Non-innocent, Corrole-like Ligand.

A π-extended, diaza-triphenylene embedded, mono-anionic corrole analogue and its NiII complex were synthesized from a diaza-triphenylene precursor, which was obtained from a double one-carbon insertion into a naphthobipyrrole diester. Following conversion to the corresponding activated diol and acid-catalyzed condensation with pyrrole, subsequent reaction with pentafluorobenzaldehyde afforded mono-anionic, π-extended bipyricorrole-like macrocycle. Attempted NiII insertion with Ni(OAc)2 ⋅ 4H2 O resulted an ESR active, NiII bipyricorrole radical complex, which was converted to a stable cationic NiII complex upon treatment with [(Et3 O)+ (SbCl6 )- ]. Both complexes were characterized by 1 H and 13 C NMR, UV/Vis spectroscopy and single crystal X-ray diffraction analysis. The NiII bipyricorrole radical complex is converted to a cationic NiII complex by single-electron reduction using cobaltocene. Both the cationic NiII complex and the radical NiII complex exhibited ligand-centered redox behavior, whereas the NiII remains in the +2 oxidation state.

Investigation of Minerals Extracted during Seawater Desalination Using Two-Dimensional Correlation Spectroscopy.

In this study, mineral components extracted during the desalination process were concentrated and dried, and then identified using energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), infrared (IR), and Raman spectroscopy. For detailed identification, two-dimensional correlation spectroscopy (2D-COS) was also applied to the XRD patterns, IR spectra, and Raman spectra of the minerals obtained from each desalination step. The EDS results confirm the presence of seawater minerals rich in Na+ ions in the first and second extracts, Ca2+ ions are present only in these stages, and Mg2+ ions are abundant in the third and final extracts. The presence of NaCl and MgSO4 minerals in the first to third and final extracts, respectively, was confirmed using XRD patterns. From the IR and Raman spectra, we found that the degree of hydration of SO42--related extracts decreased as seawater underwent desalination. Furthermore, 2D-COS provides information about the changes in the extracts obtained from the first to final stage. Heterospectral XRD and Raman 2D-COS provides clear assignments for Raman spectra. The use of 2D-COS helps to understand the characteristics of seawater extracts during the desalination process, and provides a better understanding of chemical and structural adaptations within the extract. As a result, this method contributes to an improved understanding of the desalination process and final products.

Molecular-Orbital Delocalization Enhances Charge Transfer in π-Conjugated Organic Semiconductors.

π-Conjugated organic semiconductors are promising materials for surface-enhanced Raman scattering (SERS)-active substrates based on the tunability of electronic structures and molecular orbitals. Herein, we investigate the effect of the temperature-mediated resonance-structure transitions of poly(3,4-ethylenedioxythiophene) (PEDOT) in poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT : PSS) films on the interactions between substrate and probe molecules, thereby affecting the SERS activity. Absorption spectroscopy and density functional theory calculations show that this effect occurs mainly due to delocalization of the electron distribution in molecular orbitals, effectively promoting the charge transfer between the semiconductor and probe molecules. In this work, we investigate for the first time the effect of electron delocalization in molecular orbitals on SERS activity, which will provide new design ideas for the development of highly sensitive SERS substrates.

Probe-Free Identification of RNA Virus Variants with Point Mutations by Surface-Enhanced Raman Spectroscopy.

As observed in the COVID-19 pandemic, RNA viruses continue to rapidly evolve through mutations. In the absence of effective therapeutics, early detection of new severely pathogenic viruses and quarantine of infected people are critical for reducing the spread of the viral infections. However, conventional detection methods require a substantial amount of time to develop probes specific to new viruses, thereby impeding immediate response to the emergence of viral pathogens. In this study, we identified multiple types of viruses by obtaining the spectral fingerprint of their surface proteins with probe-free surface-enhanced Raman scattering (SERS). In addition, the SERS-based method can remarkably distinguish influenza virus variants with several surface protein point mutations from their parental strain. Principal component analysis (PCA) of the SERS spectra systematically captured the key Raman bands to distinguish the variants. Our results show that the combination of SERS and PCA can be a promising tool for rapid detection of newly emerging mutant viruses without a virus-specific probe.

Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Post Synthetic Modification of Planar Antiaromatic Hexaphyrin (1.0.1.0.1.0) by Regio-Selective, Sequential SNAr.

In spite of unique structural, spectroscopic and redox properties, the synthetic variants of the planar, antiaromatic hexaphyrin (1.0.1.0.1.0) derivatives 2, has been limited due to the low yields and difficulty in access to the starting material. A chemical modification of the meso-substituents could be good alternative overcoming the synthetic barrier. Herein, we report a regio-selective nucleophilic aromatic substitution (SNAr) of meso-pentafluorophenyl group in rosarrin 2 with catechol. The reaction afforded benzodioxane fused rosarrin 3 as single product with high yield. The intrinsic antiaromatic character of the starting rosarrin 2 retained throughout the reactions. Clean, two electron reduction was achieved by treatment of 3 with SnCl2•2H2O affording 26π-electron aromatic rosarrin 4. The synthesized compounds exhibited noticeable changes in photophysical and redox properties compared with starting rosarrin 2.

Direct Dynamic Evidence of Charge Separation in a Dye-Sensitized Solar Cell Obtained under Operando Conditions by Raman Spectroscopy.

Interfaces play an important role in enhancing the energy conversion performance of dye-sensitized solar cells (DSCs). The interface effects have been studied by many techniques, but most of the studies only focused on one part of a DSC, rather than on a complete solar cell. Hence, monitoring the interface evolution of a DSC is still very challenging. Here, in situ/operando resonance Raman (RR) spectroscopic analyses were carried out to monitor the dynamics of the photovoltaic conversion processes in a DSC. We observed the creation of new species (i.e., polyiodide and iodine aggregates) in the photosensitization process. We also obtained molecular-scale dynamic evidence that the bands from the C=C and C=N bonds of 2,2'-bipyridyl (bpy), the S=C=N bonds of the NCS ligand, and photochemical products undergo reasonably strong intensity and frequency changes, which clearly demonstrates that they are involved in charge separation. Furthermore, RR spectroscopy can also be used to quickly evaluate the performance of DSCs.

Different Molecular Interaction between Collagen and α- or ß-Chitin in Mechanically Improved Electrospun Composite.

Although collagens from vertebrates are mainly used in regenerative medicine, the most elusive issue in the collagen-based biomedical scaffolds is its insufficient mechanical strength. To solve this problem, electrospun collagen composites with chitins were prepared and molecular interactions which are the cause of the mechanical improvement in the composites were investigated by two-dimensional correlation spectroscopy (2DCOS). The electrospun collagen is composed of two kinds of polymorphs, α- and ß-chitin, showing different mechanical enhancement and molecular interactions due to different inherent configurations in the crystal structure, resulting in solvent and polymer susceptibility. The collagen/α-chitin has two distinctive phases in the composite, but ß-chitin composite has a relatively homogeneous phase. The ß-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that ß-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled crystalline regions, unlike α-chitin.

Investigation of the Phase Transition Mechanism in LiFePO4 Cathode Using In Situ Raman Spectroscopy and 2D Correlation Spectroscopy during Initial Cycle.

The phase transition of the LiFePO4 and FePO4 in Li-ion cell during charging-discharging processes in the first and second cycles is elucidated by Raman spectroscopy in real time. In situ Raman spectroscopy showed the sudden phase transition between LiFePO4 and FePO4. Principal component analysis (PCA) results also indicated that the structural changes and electrochemical performance (charge-discharge curve) are correlated with each other. Phase transition between LiFePO4 and FePO4 principally appeared in the second charging process compared with that in the first charging process. 2D correlation spectra provided the phase transition mechanism of LiFePO4 cathode which occurred during the charging-discharging processes in the first and second cycles. PCA and 2D correlation spectroscopy are very helpful methods to understand in situ Raman spectra for the Li-ion battery.

Controllable Preparation of SERS-Active Ag-FeS Substrates by a Cosputtering Technique.

In this work, we introduced an ordered metal-semiconductor molecular system and studied the resulting surface-enhanced Raman scattering (SERS) effect. Ag-FeS nanocaps with sputtered films of different thicknesses were obtained by changing the sputtering power of FeS while the sputtering power of Ag and the deposition time remained constant. When metallic Ag and the semiconductor FeS are cosputtered, the Ag film separates into Ag islands partially covered by FeS and strong coupling occurs among the Ag islands isolated by FeS, which contributes to the SERS phenomenon. We also investigated the SERS enhancement mechanism by decorating the nanocap arrays produced with different FeS sputtering powers with methylene blue (MB) probe molecules. As the FeS sputtering power increased, the SERS signal first increased and then decreased. The experimental results show that the SERS enhancement can mainly be attributed to the surface plasmon resonance (SPR) of the Ag nanoparticles. The coupling between FeS and Ag and the SPR displacement of Ag vary with different sputtering powers, resulting in changes in the intensity of the SERS spectra. These results demonstrate the high sensitivity of SERS substrates consisting of Ag-FeS nanocap arrays.

Coacervation of Interfacial Adhesive Proteins for Initial Mussel Adhesion to a Wet Surface.

Coacervation of mussel adhesive proteins (MAPs) is proposed as a potential strategy that mussels may use during secretion due to their high concentration density, lack of dispersion into seawater, and low interfacial tension. Particularly, coacervations of interfacial MAPs, foot protein type-3 fast variant (fp-3F) and type-5 (fp-5), are important in the initial mussel adhesion process due to the relationship between the easy secretion/surface wetting properties of the coacervate and primer-like surface adhesive role of interfacial MAPs, which directly contact the marine surface. To the best of the authors' knowledge, this is the first report on coacervate formation of major recombinant interfacial MAPs with high charge densities and the highest 3,4-dihydroxyphenylalanine (Dopa) contents. Specifically, salt-induced coacervation of fp-3F is observed at low pH values corresponding to the acidified environment of the distal depression during mussel secretion. In addition, it shows enthalpy driven upper critical solution temperature behavior, possibly relying on bridging interactions between like-charged cationic fp-3Fs including salt-bridge and cation-π/π-π interactions in the presence of specific counterions, supported by Raman spectroscopy. It is believed that this study has broadened the scope of the understanding of coacervation of MAPs and may provide new insight for responsive biomaterial design.

IL-1ß induces IL-6 production and increases invasiveness and estrogen-independent growth in a TG2-dependent manner in human breast cancer cells.

BACKGROUND: We previously reported that IL-6 and transglutaminase 2 (TG2) were expressed in more aggressive basal-like breast cancer cells, and TG2 and IL-6 expression gave these cells stem-cell-like phenotypes, increased invasive ability, and increased metastatic potential. In the present study, the underlying mechanism by which IL-6 production is induced in luminal-type breast cancer cells was evaluated, and TG2 overexpression, IL-1ß stimulation, and IL-6 expression were found to give cancerous cells a hormone-independent phenotype. METHODS: Luminal-type breast cancer cells (MCF7 cells) were stably transfected with TG2. To evaluate the requirement for IL-6 neogenesis, MCF7 cells were stimulated with various cytokines. To evaluate tumorigenesis, cancer cells were grown in a three-dimensional culture system and grafted into the mammary fat pads of NOD/scid/IL-2Rγ(-/-) mice. RESULTS: IL-1ß induced IL-6 production in TG2-expressing MCF7 cells through an NF-kB-, PI3K-, and JNK-dependent mechanism. IL-1ß increased stem-cell-like phenotypes, invasiveness, survival in a three-dimensional culture model, and estrogen-independent tumor growth of TG2-expressing MCF7 cells, which was attenuated by either anti-IL-6 or anti-IL-1ß antibody treatment. CONCLUSION: Within the inflammatory tumor microenvironment, IL-1ß increases luminal-type breast cancer cell aggressiveness by stimulating IL-6 production through a TG2-dependent mechanism.

The mechanism of an enzymatic reaction-induced SERS transformation for the study of enzyme-molecule interfacial interactions.

We report the observation of a novel effect in which the vibrational frequencies and spectral intensity of enzyme (E)-conjugated surface-enhanced Raman scattering (SERS)-active reporter molecules (4-mercaptobenzoic acid (4-MBA)) shift and change regularly as a function of the concentration of the substrate molecule (S). We attribute the frequency shifts and intensity changes in the E-reporter complex to the binding of S to the active site of E, which affects the electronic structure, polarizability and electron density of the molecule. Our observations demonstrate the creation of an E-conjugated SERS-active reporter complex as a SERS-active nano-mechanical sensor for bio-detection. Specifically, we used glucose oxidase (GOx), which was capable of achieving detection sensitivity comparable to that of a conventional sandwich enzymatic reaction. Furthermore, 2D correlation SERS spectroscopy was performed to better investigate the glucose-responsive mechanism, and the results of these experiments support our proposed conclusion. These findings pave a new pathway for utilizing the specific response to glucose via the SERS method, which can achieve a detection limit of 10-6 mol L-1 for glucose and cover a much wider concentration range, including the blood glucose concentrations in healthy (3-8 mmol L-1) and diabetic (9-40 mmol L-1) individuals, than the current chromogenic assays.

Understanding the structural differences between spherical and rod-shaped human insulin nanoparticles produced by supercritical fluids precipitation.

In this study, the thermal denaturation mechanism and secondary structures of two types of human insulin nanoparticles produced by a process of solution-enhanced dispersion by supercritical fluids using dimethyl sulfoxide (DMSO) and ethanol (EtOH) solutions of insulin are investigated using spectroscopic approaches and molecular dynamics calculations. First, the temperature-dependent IR spectra of spherical and rod-shaped insulin nanoparticles prepared from DMSO and EtOH solution, respectively, are analyzed using principal component analysis (PCA) and 2D correlation spectroscopy to obtain a deeper understanding of the molecular structures and thermal behavior of the two insulin particle shapes. All-atom molecular dynamics (AAMD) calculations are performed to investigate the influence of the solvent molecules on the production of the insulin nanoparticles and to elucidate the geometric differences between the two types of nanoparticles. The results of the PCA, the 2D correlation spectroscopic analysis, and the AAMD calculations clearly reveal that the thermal denaturation mechanisms and the degrees of hydrogen bonding in the spherical and rod-shaped insulin nanoparticles are different. The polarity of the solvent might not alter the structure or function of the insulin produced, but the solvent polarity does influence the synthesis of different shapes of insulin nanoparticles.

Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.

BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.

Novel Developments and Progress in Two-Dimensional Correlation Spectroscopy (2D-COS).

This first of the two-part series of the comprehensive survey review on the progress of the two-dimensional correlation spectroscopy (2D-COS) field during the period 2021-2022, covers books, reviews, tutorials, novel concepts and theories, and patent applications that appeared in the last two years, as well as some inappropriate use or citations of 2D-COS. The overall trend clearly shows that 2D-COS is continually growing and evolving with notable new developments. The technique is well recognized as a powerful analytical tool that provides deep insights into systems in many science fields.

Diverse Applications of Two-Dimensional Correlation Spectroscopy (2D-COS).

This second of the two-part series of a comprehensive survey review provides the diverse applications of two-dimensional correlation spectroscopy (2D-COS) covering different probes, perturbations, and systems in the last two years. Infrared spectroscopy has maintained its top popularity in 2D-COS over the past two years. Fluorescence spectroscopy is the second most frequently used analytical method, which has been heavily applied to the analysis of heavy metal binding, environmental, and solution systems. Various other analytical methods including laser-induced breakdown spectroscopy, dynamic mechanical analysis, differential scanning calorimetry, capillary electrophoresis, seismologic, and so on, have also been reported. In the last two years, concentration, composition, and pH are the main effects of perturbation used in the 2D-COS fields, as well as temperature. Environmental science is especially heavily studied using 2D-COS. This comprehensive survey review shows that 2D-COS undergoes continuous evolution and growth, marked by novel developments and successful applications across diverse scientific fields.

Physiological and metabolic analyses reveal the proline-mediated flowering delay mechanism in Prunus persica.

Peaches are susceptible to various environmental stresses. Particularly in late spring, freezing temperatures can damage peaches and consequently, affect their productivity. Therefore, flowering delay is a prominent strategy for avoiding spring frost damage. Our previous study confirmed that treatment with 5% sodium alginate and 100 mM CaCl2 (5AG) to avoid frost damage during the blooming stage delays flowering. To reveal the flowering delay mechanism of peaches, this study systematically analyzed the modification of amino acid profiles in control and 5AG-treated peach plants at different day intervals. Our findings indicate that arginine (Arg), glutamate (Glu), and proline (Pro) levels differed between the control and 5AG-treated peach shoots throughout the phenological development of flower buds. Furthermore, two amino acids (Arg and Glu) are involved in the Pro pathway. Thus, using a computational metabolomics method, Pro biosynthesis and its characteristics, gene ontology, gene synteny, cis-regulatory elements, and gene organizations were examined to decipher the involvement of Pro metabolism in peach flowering delay. In addition, qRT-PCR analysis revealed the transcriptional regulation of Pro-related and flowering-responsive genes and their role in flowering delay. Overall, this pilot study provides new insights into the role of Pro in the flowering delay mechanisms in Prunus persica through 5AG treatment.

Effect of a Ag-rGO structure on the SERS activity of PEDOT:PSS films.

π-Conjugated organic semiconductors with tunable electronic structures are new prospective active substrate materials for surface-enhanced Raman scattering (SERS). However, observing higher SERS activity when using organic semiconductors as substrates could be difficult because there is no plasmonic effect of hot electrons. Here, we designed a Ag-reduced graphene oxide (rGO) structure, introduced it into a poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) solution, and spin-coated the solution to obtain a Ag-rGO/PEDOT:PSS (ARPP) film. Our analyses demonstrate that the introduction of this Ag-rGO structure can not only enhance the electromagnetic field effect based on plasmon resonance but also improve the interaction between the target molecule and the substrate in the ARPP film. This innovative approach not only improves the SERS activity of π-conjugated organic polymers but also provides novel ideas for the preparation of other organic semiconductor-based SERS substrates.