The in situ hydrothermal mineralization for a mixture of graphene oxide (GO) and Co-responsive supramolecular hydrogels led to a hybrid graphene aerogel, doped with Co and N elements. The as-prepared aerogels exhibited a competitive half-wave potential (0.840 V, versus RHE) and peak current density (2.35 mA cm−2) to that of Pt/C (0.836 V, 2.23 mA cm−2, respectively). Furthermore, they demonstrated a significantly perfect catalytic efficiency (nearly 100% of 4e− ORR) toward the oxygen reduction reaction (ORR). Insight into the structural details of the hybrid aerogels indicates that the CoOX active sites anchored on the graphene matrix play a central role in the upgrading of the catalytic performance of graphene aerogels.

A surface enhanced Raman scattering (SERS)-based immunosensor based on functional core-shell nanoparticles (Au@1,4-benzenedithiol@Au NPs) was developed for ultra-sensitive and high specific tumor marker detection. The engaged rigid dithiol molecule 1,4-benzenedithiol (1,4-BDT), which was used as a Raman reporter as well as a core-shell gap maker, connected the Au core and shell, facilitated the thickness controls of the shell and the core-shell gap. The thin Au shell in Au@1,4-BDT@Au prevented the dissociation of 1,4-BDT and its nonspecific interactions with co-existing proteins in complicated biological environment, which significantly improve the stability and sensitivity of the probe. To verify the validation of the Au@1,4-BDT@Au SERS immunosensor, a well-known prostate cancer marker, f-PSA antigen, was detected. As expected, the non-specific adsorption of co-existing proteins was significantly reduced, and the detection sensitivity of f-PSA was greatly enhanced with a limit of detection of 2.0 pg/mL. The linear correlation with the logarithm of concentration in wider range from 10 pg/mL to 10 ng/mL was achieved. The analysis of f-PSA-spiked human serum samples revealed that the method had high accuracy. Therefore, the dithiol Raman reporter-encoded Au@Au core-shell structure-based immunosensor is promising for the ultra-sensitive and high specific tumor marker detections.

•Porous gold nanoparticles were facilely and rapidly electro-fabricated.•The material displayed good electric contact and rapid mass transport.•The material displayed high electrocatalytic activity for oxygen reduction.Small-size Au nanoparticles (AuNPs) and nanoporous Au films (npAuFs) are two potential catalysts for electrocatalysis, electrochemical analysis and synthesis. However, the large contact resistance among AuNPs and the poor mass transfer within npAuFs significantly limits their electrocatalysis application. Therefore, how to fabricate available high-active Au catalyst with facile and low-cost method is still a big challenge. In this study, porous gold nanoparticles (pAuNPs) were facilely and rapidly fabricated from gold nanoparticle-loaded electrode through a repeated Au/Hg alloying-dealloying process. In situ electrochemical fabrication ensured good electric contact of pAuNPs on the electrode surface; meanwhile, the pAuNPs were in tenths of nanometer length scales, which ensured rapid mass transport near the liquid/solid interface, facilitating the maximum exploitation of the high binding energy sites within nanoporous structures on electrocatalysis. Testing of the pAuNPs at a proof-of-concept level demonstrated its higher electrocatalytical activity than other two structures towards oxygen reduction in both acidic and alkaline media. The ease of sample preparation in combination with high activity suggested that pAuNPs can potentially cause a wide range of practical applications of Au catalysis.Download high-res image (77KB)Download full-size image

•sP1 and sP2 were integrated into one DNA architecture to develop the ISP.•The ISP can eliminate the interface microenvironmental changes for sP1 and sP2.•The cross interference between sP1 and sP2 can be successfully prevented.•The ISP was more reproducible and accurate for the dual-analyte detection.•The simultaneous detection was simply achieved by one-step incubation of targets.For the multi-analyte detection, although the sensitivity has commonly met the practical requirements, the reliability, reproducibility and stability need to be further improved. In this work, two different aptamer probes labeled with redox tags were used as signal probe1 (sP1) and signal probe2 (sP2), which were integrated into one unity DNA architecture to develop the integrated signal probe (ISP). Comparing with the conventional independent signal probes for the simultaneous multi-analyte detection, the proposed ISP was more reproducible and accurate. This can be due to that ISP in one DNA structure can ensure the completely same modification condition and an equal stoichiometric ratio between sP1 and sP2, and furthermore the cross interference between sP1 and sP2 can be successfully prevented by regulating the complementary position of sP1 and sP2. The ISP-based assay system would be a great progress for the dual-analyte detection. Combining with gold nanoparticles (AuNPs) signal amplification, the ISP/AuNPs-based aptasensor for the sensitive dual-analyte detection was explored. Based on DNA structural switching induced by targets binding to aptamer, the simultaneous dual-analyte detection was simply achieved by monitoring the electrochemical responses of methylene blue (MB) and ferrocene (Fc) This proposed detection system possesses such advantages as simplicity in design, easy operation, good reproducibility and accuracy, high sensitivity and selectivity, which indicates the excellent application of this aptasensor in the field of clinical diagnosis or other molecular sensors.

A new strategy to fabricate CoNx single cluster supported nanocarbon catalysts (C/P/2Co600) with enhanced atomic utilization towards the oxygen reduction reaction (ORR) is reported. N-Coordination protection and low-temperature pyrolysis are the two key factors for the formation of CoNx single clusters on nanocarbon supports. Morphological and structural identification confirmed the simultaneous anchoring of homo-dispersed CoNx single clusters and N-doping on the nanocarbon under relatively mild thermal treatment conditions. Expectedly, the obtained single cluster catalyst with a trace amount of metal atoms exhibited excellent ORR performance including a positive half-wave potential (0.846 V), a high mass activity (0.98 A mgCo−1, ampere per milligram of cobalt) and outstanding chemical durability after 8000 potential cycles. We believe that our findings provide a new route for the rational design of low-cost and highly active ORR catalytic materials.

In this work, the dual signal-tagged hairpin structured DNA (dhDNA)-based ratiometric probe was developed by the combination of ferrocene-labeled signal probe (Fc-sP) and methylene blue-modified inner reference probe (MB-rP) in one hairpin-structured DNA. On the basis of this, a high-performance ratiometric electrochemical method was proposed for biomarker detection. In contrast to the conventional ratiometric electrochemical probe, this dhDNA ratiometric probe integrated sP and rP into one structure, which ensured the completely same modification condition and the interdependence of sP and rP on one sensing interface. As a result, the dhDNA ratiometric probe possesses a stronger ability to eliminate the disturbance of environmental change, which was proven by the fact that the changes of the surface roughness and pH value had no significant effects on the reproducibility and stability of the sensor. Moreover, in the proposed strategy, the initial ratio responses of Fc-sP to MB-rP ((IFc-sP/IMB-rP)0) are controllable and can be kept constant at 1:1, which is favorable for the increase in signal-to-noise ratio and sensitivity. When the sequence of Fc-sP is designed as the aptamer of mucin 1 (MUC1), the dhDNA ratiometric sensor with signal amplification of Au nanoparticles becomes feasible for the sensitive detection of MUC1 by one-step incubation procedure. Compared with the conventional ratiometric sensor, the proposed dhDNA sensor has higher reproducibility, accuracy, stability, sensitivity, and simplicity, which are significant for the development of the sensor in various fields for practical applications.

A facile strategy was developed to fabricate structure controllable microcrystals of ferrocene-based metal–organic (Fc-Ala-BCB) materials through evaporation-induced self-assembly. Two distinctive microcrystals, microrods and microtubes had been achieved by tuning the solvents during the self-assemblies. X-ray diffraction analysis was conducted on single crystals to investigate the packing mode of Fc-Ala-BCB molecules, which indicated the two crystals with the hexagonal system. Inheriting the aromaticity and chirality of ferrocenyl and l-Ala, this organic molecule self-assembled into a single-helix structure through intermolecule hydrogen bonds and π–π stacking. Theoretical analysis and stimulated computations were carried out to compare the surface energies of certain planes. Among those microcrystals, the microrods exhibited a higher chemical activity in catalyzing the decomposition of H2O2, due to the high-density atomic steps and kinks on the high energy surfaces. However, the hollow hexagonal tubes displayed appropriate catalytic activity and novel maneuverability toward catalyzing H2O2. The O2 bubbles accumulated at the inner walls of the microtube were periodically released as individual bubbles, suggesting their potential application as a new kind of microengine (e.g., the microrotor).

•The interaction of amyloid β peptide (Aβ) and dopamine (DA) was explored.•Tyrosine was the strong binding site, serine-asparagine-lysing was the weak one.•DA can inhibit Aβ aggregation and enhance OH generation.•DA/Cu2 +/Aβ mixture had high cell toxicity, indicating the DA-induced neuron damage.With the capability to inhibit the formation of amyloid β peptides (Aβ) fibril, dopamine (DA) and other catechol derivatives have been considered for the potential treatment of Alzheimer's disease (AD). Such treatment, however, remains debatable because of the diverse functions of Aβ and DA in AD pathology. Moreover, the complicated oxidation accompanying DA has caused the majority of the previous research to focus on the binding of DA oxides onto Aβ. The molecular mechanism by which Aβ interacts with the reduction state of DA, which is correlative with the brain function, should be urgently explored. By controlling rigorous anaerobic experimental conditions, this work investigated the molecular mechanism of the Aβ/DA interaction, and two binding sites were revealed. For the binding of DA, Tyrosine (Tyr10) was identified as the strong binding site, and serine-asparagine-lysing (SNK(26–28)) segment was the weak binding segment. Furthermore, the Thioflavin T (THT) fluorescence confirmed DA's positive function of inhibiting Aβ aggregation through its weakly binding with SNK(26–28) segment. Meanwhile, 7-OHCCA fluorescence exhibited DA's negative function of enhancing OH generation through inhibiting the Aβ/Cu2 + coordination. The viability tests of the neuroblastoma SH-SY5Y cells displayed that the coexistence of DA, Cu2 +, and Aβ induced lower cell viability than free Cu2 +, indicating the significant negative effect of excessive DA on AD progression. This research revealed the potential DA-induced damage in AD brain, which is significant for understanding the function of DA in AD neuropathology and for designing a DA-related therapeutic strategy for AD.For the interaction of amyloid β peptide (Aβ) and dopamine, tyrosin was the strong binding site and serine-asparagine-lysing(26–28) was the weak binding segment. Dopamine can affect Aβ-related neurotoxicity through three pathways.

The interaction of amyloid β-peptide (Aβ) with Cu2+ is crucial to the development of neurotoxicity in Alzheimer’s disease (AD). Many recent studies show a variation on the dissociation constant of Aβ–Cu2+ under different solvent conditions. Among various buffers, the Tris(hydroxymethyl)aminomethane (Tris) buffer is the most reliable chelator of Cu2+. However, as a typical nucleophilic reagent capable of binding peptides, the behavior of Tris should be more complicated. In this work, the effect of Tris on the interaction of Aβ with Cu2+ was investigated. Under acidic conditions, Tris–Aβ–Cu2+ ternary complex was identified by electrospray ionization mass spectrometry and transmission electron microscopy. The results of surface plasmon resonance reveal that the formation of the ternary complex increases the dissociation constant by almost 1 order of magnitude. Consequently, the assessment of toxicity indicates that the generation of · OH induced by the Aβ–Cu2+ complex was enhanced in the presence of Tris. The work reveals the significant side effect of Tris on the interaction of Aβ with Cu2+, which will greatly improve the quantitative investigation on Aβ–Cu2+ interaction and be helpful for the in-depth understanding of the roles of Aβ and Cu2+ in AD neuropathology.

•An electrochemical impedimetric aptasensor for detection of tumor markers was built.•MUC1 was quantitatively detected by electrochemical impedance analysis (EIS).•Gold nanoparticles are used as the signal enhancer.•The detection sensitivity for MUC1 was greatly improved.•This work provides a general model for the detection of other tumor markers.A simple and sensitive electrochemical impedimetric aptasensor based on gold nanoparticles (AuNPs) signal amplification was developed for the ultrasensitive detection of tumor markers (mucin 1 protein, MUC1 as a model). The designed cDNA, which is partly complementary with the aptamer of MUC1 was immobilized on the gold electrode. The detection of MUC1 could be carried out by virtue of switching structures of aptamers from DNA/DNA duplex to DNA/target complex. The change of the interfacial feature of the electrode was characterized by electrochemical impedance analysis (EIS) with the redox probe [Fe(CN)6]3−/4−. The quantitative detection of MUC1 protein was obtained from the changes of electron-transfer resistance (ΔRet). Moreover, as the signal enhancer, the aptamer-modified AuNPs (Apt@AuNPs) conjugates was introduced on the electrode by the hybridization of cDNA with aptamer. As expected, the detection sensitivity for MUC1 was greatly improved, which may be due to the specific binding of MUC1 onto the surface of the Apt@AuNPs modified electrode. This proposed simple aptasensor has a low detection limit of 0.1 nM, and also exhibits several advantages of high sensitivity and good selectivity. This present work may provide a general model for the detection of tumor marker based on impedimetric aptasensor.

Lead is a toxic heavy metal whose detoxification in organisms is mainly carried out by its coordination with some metalloproteins such as metallothioneins (MTs). Two Pb–MT complexes, named as Pb7–MT2(I) and Pb7–MT2(II), form under neutral and weakly acidic conditions, respectively. However, the structures of the two complexes, which are crucial for a better understanding of the detoxification mechanism of Pb–MTs, have not been clearly elucidated. In this Work, coordination of Pb2+ with rabbit liver apo–MT2, as well as with the two individual domains (apo−αMT2 and apo−βMT2) at different pH, were studied by combined spectroscopic (UV–visible, circular dichroism, and NMR) and computational methods. The results showed that in Pb7–MT2(I) the Pb2+ coordination is in the trigonal pyramidal Pb–S3 mode, whereas the Pb7–MT2(II) complex contains mixed trigonal pyramidal Pb–S3, distorted trigonal pyramidal Pb–S2O1, and distorted quadrilateral pyramidal Pb–S3O1 modes. The O-donor ligand in Pb7–MT2(II) was identified as the carboxyl groups of the aspartic acid residues at positions 2 and 56. Our studies also revealed that Pb7–MT2(II) has a greater acid tolerance and coordination stability than Pb7–MT2(I), thereby retaining the Pb2+ coordination at acidic pH. The higher flexibility of Pb7–MT2(II) renders it more accessible to lysosomal proteolysis than Pb7–MT2(I). Similar spectral features were observed in the coordination of Pb2+ by human apo-MT2, suggesting a commonality among mammalian MT2s in the Pb2+ coordination chemistry.

•The asynchronous competitive inhibition immunoassay for f-PSA was developed.•The detection sensitivity of f-PSA was greatly enhanced.•A simple method for eliminating the non-specific adsorption was explored.•The f/t-PSA ratios in serum samples of patients were obtained.•The ratio distributions between BPH and PCa show significant difference.Free/total prostate antigen (f/t-PSA) ratio in serum as a promising parameter has been used to improve the differentiation of benign and malignant prostate disease. In order to obtain the accurate and reliable f/t-PSA ratio, the simultaneous detection of f-PSA and t-PSA with high sensitivity and specificity is required. In this work, the dual-channel surface plasmon resonance (SPR) has been employed to meet the requirement. In one channel, t-PSA was directly measured with a linear range from 1.0 to 20.0 ng/mL. In another channel, due to the low concentration of f-PSA in serum, the asynchronous competitive inhibition immunoassay with f-PSA@Au nanoparticles (AuNPs) was developed. As expected, the detection sensitivity of f-PSA was greatly enhanced, and a linear correlation with wider linear range from 0.010 to 0.40 ng/mL was also achieved. On the other hand, a simple method was explored for significantly reducing the non-specific adsorption of co-existing proteins. On basis of this, the f/t-PSA ratios in serum samples from prostate cancer (PCa) or benign prostatic hyperplasia (BPH) patients were measured. And it was found that there was significant difference between the distributions of f/t-PSA ratio in BPH patients (16.44±1.77%) and those in PCa patients (24.53±4.97%). This present work provides an effective method for distinguishing PCa from BPH, which lays a potential foundation for the early diagnosis of PCa.

•EC-SPR was equipped with a home-compiled calculation software.•The Hg–Au alloying process was investigated using the instrument.•The real-time composition and deposition depth profile was achieved.•The profile facilitates the effective fabrication of well-controlled alloy nanofilms.Electrodeposition is one of the most conventional techniques for fabricating alloyed nanofilms. However, given the lack of in situ and real-time techniques in determining the composition and deposition depth of the alloyed nanofilms, effective optimization of alloying effects is difficult, which limits the application of electrodeposition. In the current study, electrochemical (EC) surface plasmon resonance (SPR) was equipped with home-compiled calculation software to achieve the real-time composition and deposition depth profile of the surface-alloyed nanofilms. The results obtained from the Hg–Au alloy proved that EC-SPR is capable of presenting a real-time profile of the alloying process. The in situ and real-time determination will facilitate the effective fabrication of well-controlled alloyed nanofilms and improve the application of the EC method.

Interactions of amyloid-β peptide (Aβ) with Cu2 + are known to be pH-dependent and believed to play a crucial role in the neurotoxicity of Alzheimer's disease (AD). Some research has revealed that injured brains with lowered pH have higher risks of developing AD. However, reported experiments were performed under neutral or mildly acidic conditions, and no reports about the affinity of Aβ−Cu2 + below pH 6.0. In this study, surface plasmon resonance (SPR) sensor with immobilized Aβ was used to investigate the formation of Aβ−Cu2 + complexes under acidic pH conditions. Dissociation constants were calculated and shown to be pH-dependent, ranging from 3.5 × 10− 8 M to 8.7 × 10− 3 M in the pH range from 7.0 to 4.0. The physiological significance of Kd was preliminarily investigated by monitoring the generation of OH in aerobic solutions containing Aβ−Cu2 + and Cu2 +. The results imply that acidic conditions could aggravate the oxidative stress in the presence of Cu2 +, and the weak affinities of Aβ−Cu2 + under mildly acidic pH of 5.0–6.0 could further enhance the oxidative damage. However, the oxidative stress effect of Aβ is negligible due to the suppressed formation of Aβ−Cu2 + below pH 5.0. This work is useful for the in-depth understanding of the role of Aβ−Cu2 + in AD neuropathology.Acidic conditions could aggravate the oxidative stress in the presence of Cu2 +, and the weak affinities of Aβ−Cu2 + at mildly acidic pH of 5.0–6.0 could further enhance the oxidative damage.Highlights► Kinetics of Cu2 + binding to Aβ was investigated at acidic conditions. ► Dissociation constants range from 3.5 × 10− 8 M to 8.7 × 10− 3 M at pH 7.0 to 4.0. ► Acidic conditions could aggravate the oxidative stress in the presence of Cu2 +. ► The weak affinities of Aβ−Cu2 + at pH 5.0 to 6.0 could further enhance the oxidative damage.

Understanding the structure of mammal Bi-containing metallothionein-2 (Bi-MT2) is of great physiological significance due to the importance of Bi-MT2 in alleviating adverse effect of anti-cancer drugs. A unique feature of rabbit liver Bi-MT2 is the metal–oxygen bond (BiO), which is absent in well-characterized Zn-MT2 and Cd-MT2. However, the ligand contributing to the BiO bonding in Bi-MT2 remains unidentified. In this study, the coordination of Bi3+ to rabbit liver metal-free metallothionein was investigated using both experimental and theoretical methods. UV–visible and circular dichroism spectra indicate that Bi-MT2 has a different secondary structure from those of Zn-MT2 and Cd-MT2. Three possible Bi3+ coordination structures in Bi7-MT2 and relative binding free energies were calculated using the density functional theory. Absorption spectra corresponding to these coordination structures were evaluated by time-dependent density functional theory. Our computation results are consistent with the UV–vis spectroscopic data and strongly suggest that the carboxyl group in the aspartic acid residues contributes to the BiO bond formation.UV–visible and circular dichroism spectra of Bi3+ binding to metal-free metallothionein, combined with DFT computation results, strongly suggest that the carboxyl group in the aspartic acid residues contributes to the BiO bond formation Bi7-MT.Highlights► The spectral characterizations of Bi3+ binding to thionein are described. ► A new Bi3+ coordination mode in Bi7-MT is proposed. ► The oxygen donating to Bi3+ is found to derive from a carboxyl group of aspartate.

The bismuth-, antimony- and arsenic-containing complexes are known as antibacterial and antitumor drugs in the field of clinical medicine. It is of great physiological significance to understand the structures of these complexes with thiolate ligands. But the optimal theoretical calculation method for these metal thiolate complexes is not certain. In this work, the molecular structures, vibrational spectra and absorption spectra of metal thiolate complexes M(SC6H5)3 (M = Bi, Sb or As) have been calculated with density functional (mPW1PW, B3LYP, TPSSh and OLYP). The theoretical results were compared to the available experimental data. It is demonstrated that mPW1PW functional is superior to other functionals (B3LYP, TPSSh and OLYP) in predicting molecular structures and vibrational spectra of Sb-thiolate and As-thiolate complexes. For Bi-thiolates complex, the hybrid density functional B3LYP gives better performance than other methods. The theoretical absorption spectrum of Bi(SC6H5)3 from B3LYP functional is similar to the available experimental data, which confirms the rationality of theoretical calculation method. Furthermore, the theoretical method was successfully used to predict the formation process of the Bi–O bond in Bi7-metallothionein, an important product in vivo on effectively reducing side effect of metal-containing drugs. The confirmed calculation method for each complex will be helpful for our further understanding on the complexation structure of the Bi-, Sb- and As-containing complexes with thiolate ligands.Graphical abstractIt is of great physiological significance to understand the structure of bismuth-, antimony- and arsenic-containing complexes with thiolate ligands, because they are involved in the antibacterial and antitumor. The optimal calculation method for the structures has been confirmed by compared the calculation results with experimental data. The confirmed optimal method will be helpful for our further understanding on the complexation structure of the metal complexes with thiolate ligand.Highlights► Three metal thiolate complexes have been calculated with four density functional methods. ► mPW1PW is superior to other four theoretical methods for Sb-thiolate and As-thiolate complexes. ► B3LYP gives better performance than other four methods for Bi-thiolate complex. ► B3LYP was used to predict the formation process of Bi–O bond in Bi7-metallothionein.

The in situ hydrothermal mineralization for a mixture of graphene oxide (GO) and Co-responsive supramolecular hydrogels led to a hybrid graphene aerogel, doped with Co and N elements. The as-prepared aerogels exhibited a competitive half-wave potential (0.840 V, versus RHE) and peak current density (2.35 mA cm−2) to that of Pt/C (0.836 V, 2.23 mA cm−2, respectively). Furthermore, they demonstrated a significantly perfect catalytic efficiency (nearly 100% of 4e− ORR) toward the oxygen reduction reaction (ORR). Insight into the structural details of the hybrid aerogels indicates that the CoOX active sites anchored on the graphene matrix play a central role in the upgrading of the catalytic performance of graphene aerogels.