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Tissue engineered cardiac patches have great potential as a therapeutic treatment for myocardial infarction (MI). However, for successful integration with the native tissue and proper function of the cells comprising the patch, it is crucial for these patches to mimic the ordered structure of the native extracellular matrix and the electroconductivity of the human heart. In this study, a new composite construct that can provide both conductive and topographical cues for human induced pluripotent stem cell derived cardiomyocytes (iCMs) is developed for cardiac tissue engineering applications. The constructs are fabricated by 3D printing conductive titanium carbide (Ti3C2Tx) MXene in pre-designed patterns on polyethylene glycol (PEG) hydrogels, using aerosol jet printing, at a cell-level resolution and then seeded with iCMs and cultured for one week with no signs of cytotoxicity. The results presented in this work illustrate the vital role of 3D-printed Ti3C2Tx MXene on aligning iCMs with a significant increase in MYH7, SERCA2, and TNNT2 expressions, and with an improved synchronous beating as well as conduction velocity. This study demonstrates that 3D printed Ti3C2Tx MXene can potentially be used to create physiologically relevant cardiac patches for the treatment of MI.

The electrocatalytic reduction of nitrogen (N2) to ammonia (NH3) has broad prospects for green and sustainable NH3 production. Due to the electrocatalytic nitrogen reduction reaction (eNRR) performance of transition metal compound may be restricted with low yield rate, we develop transition metal interface engineering to improve the eNRR performance. Although the edge of MoS2 catalyst is active, the MoS2(0 0 1) surface is inert for N2 electroreduction. Through the hydrothermal and electrodeposition methods, Fe(OH)3 as N2 and H+ channels coated on MoS2 nanosheets array (MoS2@Fe(OH)3/CC) is synthesized. Such catalyst exhibits excellent eNRR performance in 0.1 M Na2SO4 with high Faradaic efficiency (2.76%) and NH3 yield rate (4.23 × 10−10 mol s−1 cm−2) at − 0.45 V (vs. RHE). This work may provide a new electrocatalyst synthesis pathway for artificial N2 fixation. Density functional theory calculations show that electrodeposition Fe(OH)3 can accelerate eNRR process rate of MoS2.

Interesting double-channel microfluidic chip integration with a sandwich-type cathodic photo-electrochemical (PEC) biosensor is utilized for ultrasensitive and efficient detection of cardiac troponin I (cTnI) based on a signal amplification strategy. The Pd nanoparticles loading on the I-doped bismuth oxybromide with oxygen vacancies (Pd/I:BiOBr-OVs) as a sensing platform can effectively enhance cathodic photocurrent response by improving the visible light absorption ability with I doping, facilitating the efficiency separation of photogenerated electron-hole pairs with OVs, and increasing the electron-transfer rate with Pd loading, where the photogenerated electron could be captured by dissolved O2 to boost generation of a superoxide anion radical (•O2-). To further enhance the PEC response, a novel superoxide dismutase loaded on gold@polyaniline (SOD-Au@PANI) as a signal amplification label is developed for incubating the detection antibody (dAb). It is particularly noteworthy that SOD can effectively catalyze dismutation of the •O2- to produce H2O2 and O2, and Au@PANI with a good reduction and catalytic property can catalyze the produced H2O2 into H2O and O2. Then, the produced O2 that has been dissolved or adsorbed can capture more photogenerated electrons, resulting in more electron-hole pairs to separate, so as to the cathodic photocurrent signal of this system which can be amplified more significantly. Therefore, a signal amplification cathodic PEC biosensor is prepared for sensitively detecting cTnI, in which a good linearity ranging from 0.1 pg/mL to 100 ng/mL with a low detection limit of 0.042 pg/mL is obtained. Furthermore, the proposed biosensor exhibits excellent sensitivity and high selectivity, which could be extended to detect other disease markers in biological analysis and early disease diagnosis.

The nitrogen reduction reaction (NRR) has become an ideal alternative to the Haber‐Bosch process, as NRR possesses, among others, the advantage of operating under ambient conditions and saving energy consumption. The key to efficient NRR is to find a suitable electrocatalyst, which helps to break the strong N≡N bond and improves the reaction selectivity. Molybdenum disulfide (MoS2) as an emerging layered two‐dimensional material has attracted a mass of attention in various fields. In this minireview, we summarize the optimization strategies of MoS2‐based catalysts which have been developed to improve the weak NRR activity of primitive MoS2. Some theoretical predictions have also been summarized, which can provide direction for optimizing NRR activity of future MoS2‐based materials. Finally, an outlook about the optimization of MoS2‐based catalysts used in electrochemical N2 fixation are given.

Apoptosis induced by doxorubicin, bortezomib, or paclitaxel, targeting DNA, 26S proteasome, and microtubules respectively, was assessed in two osteosarcoma cells, p53 wild-type U2OS and p53-null MG63 cells. Doxorubicin-induced apoptosis only occurred in U2OS, not in MG63. In contrast, bortezomib and paclitaxel could drive U2OS or MG63 toward apoptosis effectively, suggesting that apoptosis induced by bortezomib or paclitaxel is p53-independent. The expressions of Bcl2 family members such as Bcl2, Bcl-xl, and Puma could be seen in U2OS and MG63 cells with or without doxorubicin, bortezomib, or paclitaxel treatment. In contrast, another member, Bim, only could be observed in U2OS, not in MG63, under the same conditions. Bim knockdown did not affect the doxorubicin-induced apoptosis in U2OS, suggested that a BH3-only protein other than Bim might participate in apoptosis induced by doxorubicin. Using a BH3-mimetic, ABT-263, to inhibit Bcl2 or Bcl-xl produced a limited apoptotic response in U2OS and MG63 cells, suggesting that this BH3-mimetic cannot activate the Bax/Bak pathway efficiently. Significantly, ABT-263 enhanced doxorubicin- and bortezomib-induced apoptosis synergistically in U2OS and MG63 cells. These results implied that the severe cellular stress caused by doxorubicin or bortezomib might be mediated through a dual process to control apoptosis. Respectively, doxorubicin or bortezomib activates a BH3-only protein in one way and corresponding unknown factors in another way to affect mitochondrial outer membrane permeability, resulting in apoptosis. The combination of doxorubicin with ABT-263 could produce synergistic apoptosis in MG63 cells, which lack p53, suggesting that p53 has no role in doxorubicin-induced apoptosis in osteosarcoma. In addition, ABT-263 enhanced paclitaxel to induce moderate levels of apoptosis.

Metal nanoclusters (NCs) possess high light stability and biocompatibility because of their unique quantum size effect, which has gradually become a new type of electrochemiluminescence (ECL) nanomaterial for immunoassays. However, the luminescence efficiency of metal NCs is too low to meet the needs of trace analysis, which limits its application. Herein, Ag NCs served as signal probes and Pd-Cu2O hybrid nanoconcaves served as coreaction promoters, developing a highly efficient peptide-based biosensor for neuron-specific enolase (NSE) detection. Utilizing the reversible cycle of Cu+/Cu2+ and the reduction characteristics of Pd NPs, Pd-Cu2O greatly accelerates the reduction of S2O82-. Meanwhile, Pd-Cu2O has good hydrogen evolution activity, which promotes the generation of oxygen by improving the redox efficiency of the overall reaction, thus increasing the yield of active intermediates (OH•) to promote the reduction of S2O82-. Specially, this is an effective attempt to use the hydrogen evolution reaction (HER) to accelerate the ECL emission of the S2O82- system. In addition, a short peptide ligand (NARKFYKGC, NFC) was developed to implement the targeted immobilization of antibodies, which can specifically bind to the Fc fragment of antibodies, thereby avoiding the occupation of the antigen binding site (Fab fragment). The introduction of NFC not only improves the binding efficiency of antibodies but also protects its bioactivity, thus significantly improving the sensitivity of the biosensor. Based on these strategies, the proposed biosensor provides a new perspective for the applications of metal NCs in ECL systems.

Here, we reported for the first time an iron-catalyzed highly enantioselective hydrogenation of minimally functionalized 1,1-disubstituted alkenes to access chiral alkanes with full conversion and excellent ee. A novel chiral 8-oxazoline iminoquinoline ligand and its iron complex have been designed and synthesized. This protocol is operationally simple by using 1 atm of hydrogen gas and shows good functional group tolerance. A primary mechanism has been proposed by the deuterium-labeling experiments.

Herein, a split-type immunoassay strategy instigated by cation exchange (CE) and changing the capacity of an electron donor in an electrolyte solution is optimized, namely, for differentiating the biological-specific binding assay and photoelectrochemical (PEC) analysis. MoSe2/CdSe, a Z-scheme heterojunction with efficient visible light absorption and a low recombination of carriers, is used as a photoelectrode substrate. Silver ions (Ag+) as the initiator of CE are generated by the acidolysis of evenly loaded silver nanoparticles on mesoporous silica nanospheres (MSNs). The theoretical calculation and experimental results confirm that Ag+ replaces Cd2+ in CdSe and retains the crystal structure of MoSe2. However, this behavior destroys the perfectly matched heterojunction structure and introduces defects, which led to the reduction of the photocurrent response. In addition, ascorbate oxidase in combination with MSNs can be used as a consumptive agent of the electron donor, which further improves the sensitivity and reliability of the sensor. As a proof of principle, neuron-specific enolase was applied to elucidate the potential application of the PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was from 0.0001 to 100 ng/mL with a detection limit of 28 fg/mL (S/N = 3).

Steady and efficient sensitized emission of Eu2+ to Eu3+ can be achieved through a rare mixed-valence Eu-MOF (L4EuIII2EuII). Compared with the sensitization of other substances, the similar ion radius and configuration of the extranuclear electron between Eu2+ and Eu3+ make sensitization easier and more efficient. The sensitization of Eu2+ to Eu3+ is of great assistance for the self-enhanced luminescence of L4EuIII2EuII, the longer luminous time, and the more stable electrochemiluminescence (ECL) signal. Simultaneously, L4EuIII2EuII possesses near-infrared (NIR) fluorescence of around 900 nm and a mighty self-luminous characteristic, which render it useful as a NIR fluorescent probe and as a luminophore to establish a NIR ECL biosensor. This NIR biosensor can greatly reduce the damage to the detected samples and even achieve a nondestructive test and improve the detection sensitivity by virtue of strong susceptibility and environmental suitability of NIR. In addition, the CeO2@Co3O4 triple-shelled microspheres further enhanced the ECL intensity due to two redox pairs of Ce3+/Ce4+ and Co2+/Co3+. The NIR ECL biosensor based on these strategies owns an ultrasensitive detection ability of CYFRA 21-1 with a low limit of detection of 1.70 fg/mL and also provides a novel idea for the construction of a highly effective nondestructive immunodetection biosensor.

Purpose: To investigate the protective effect of floroindole against cecal ligation and puncture (CLP)- induced sepsis, as well as the underlying mechanism of action. Methods: Thirty-five 10–week-old male Wistar rats weighing 190 - 210 g (mean: 200.00 ± 10.10 g) were used for this study. The rats were randomly assigned to seven groups of five rats each, viz, normal control group, and six CLP groups. The CLP groups were those subjected to cecal ligation and puncture (CLP). The first 5 CLP groups received 2, 4, 6, 8 or 10 mg/kg floroindole, respectively, 1 h after CLP, via intraperitoneal route (i.p.) while the 6th CLP group served as untreated control. Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) were used for the assessment of the expression levels of tumor necrosis factor-α (TNF- α), interleukn-6 (IL-6), nucleotide-binding oligomerization domain 2 (NOD2) and p-NF-κB p65. Results: Cecal ligation and puncture (CLP) significantly and time-dependently upregulated the expressions of TNF-α, IL-6 and NOD2 in intestinal tissues of rats (p < 0.05). However, treatment with floroindole significantly, and dose-dependently down-regulated CLP-induced expressions of these proteins (p < 0.05). Treatment of rats with floroindole also significantly and dose-dependently inhibited CLP-induced phosphorylation of NF-κB p65 in rat ileum (p < 0.05). Conclusion: The results obtained in this study demonstrate that floroindole confers some degree of protection against CLP-induced sepsis via inhibition of NF-κB p65 phosphorylation.

In this work, we have successfully in-situ synthesized Na+ and Co2+ co-doped Li0.9Na0.1Mn1-xCoxPO4/C nanoparticles on the surface of Li2.7Na0.3PO4 self-sacrificing template by the co-precipitation process combined with the hydrothermal method. The crystal lattice structure, crystal appearance and electrochemical parameters are characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), galvanostatic charge and discharge test, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). SEM analysis indicates that Li0.9Na0.1Mn0.9Co0.1PO4/C composite shows uniform porous structure and nanosized grain particles. The electrochemical measurements show that the double ions co-doping routine plays a vital influence on the rate capability and electrochemical lithium storage property of LiMnPO4 material. The initial discharge specific capacity of Li0.9Na0.1Mn0.9Co0.1PO4/C reaches 164.3 mAh/g (0.05 C) and 148.0 mAh/g (1 C), respectively. The excellent rate capability is attributed to the synergetic doping effect of Na+ and Co2+ on improving the Li-ion diffusion rate and broadening the Li-ion diffusion channels.

Diabetic retinopathy (DR) is a kind of severe retinal neurodegeneration. The advanced glycation end products (AGEs) affect autophagy, and mitochondrial function is involved in DR. Adenosine-activated protein kinase (AMPK) is an important metabolic sensor that can regulate energy homeostasis in cells. However, the effect of AMPK in DR is still not fully understood. In this study, we investigated the effect of AMPK on diabetes-induced photoreceptor cell degeneration. In vivo, a diabetic mouse model was established by streptozotocin (STZ) injection. Haematoxylin-eosin (HE) staining was used to observe retinal morphology and measure the thicknesses of different layers in the retina. Electroretinogram (ERG) was used to evaluate retinal function. In vitro, 661w cells were treated with AGEs with/without an AMPK agonist (metformin) or AMPK inhibitor (compound C). Flow cytometry and CCK-8 assays were used to analyse apoptosis. Mitochondrial membrane potential was analysed by JC-1. Western blotting and qRT-PCR were used to examine the expression of related proteins and genes, respectively. The wave amplitude and the thickness of the outer nuclear layer were decreased in diabetic mice. The expression of rhodopsin and opsin was also decreased in diabetic mice. In vitro, the percentage of apoptotic cells was increased, the expression of the apoptosis-related protein Bax was increased, and Bcl-2 was decreased after AGE treatment in 661w cells. The expression of the autophagy-related protein LC3 was decreased, and p62 was increased. The mitochondrial-related gene expression and membrane potential were decreased, and mitochondrial morphology was abnormal, as observed by TEM. However, AMPK stimulation ameliorated this effect. These results indicate that AMPK stimulation can delay diabetes-induced photoreceptor degeneration by regulating autophagy and mitochondrial function.

An intriguing self-powered cathodic photoelectrochemical (PEC) microfluidic aptasensor with enhanced cathodic photocurrent response is proposed for sensitive detection of prostate-specific antigen (PSA). The self-powered system is constructed by a cadmium sulfide-sensitized zinc oxide nanorod array (CdS/ZnO NA) as a photoanode with an iodide-doped bismuth oxychloride flower-array (I0.2:BiOCI0.8) as a photocathode, which can generate the electrical output under visible light irradiation with no external power supply. In addition, the p-type semiconductor I0.2:BiOCI0.8 with a special internal electric field between the iodide ion layer and the [Bi2O2]2+ layer could increase the cathodic photocurrent response by facilitating the separation of electron/hole pairs under visible light excitation. It is worth noting that dissolved oxygen as an electron acceptor can be reduced by the photogenerated electron to form a superoxide radical (•O2-) in the self-powered cathodic PEC system. The further enhanced cathodic photocurrent response can be achieved by eliminating •O2- that reacts with the luminol anion radical (L•-) to produce chemiluminescence emission, which serves as an inner excitation light source. What is more exciting is that the integration of the photoanode and the photocathode into a microfluidic chip could realize automatic sample injection and detection. On this basis, the proposed aptasensor presents excellent reproducibility and high sensitivity for detecting PSA and exhibits a good linearity range (50 fg·mL-1 to 50 ng·mL-1) with a low detection limit (25.8 fg·mL-1), which opens up a new horizon of potential for sensitively detecting other kinds of disease markers.

Herein, a dual-mode sensing platform using cationic N,N-bis(2-(trimethylammonium iodide)propylene)perylene-3,4,9,10-tetracarboxydiimide (PDA+)-assembled DNA strands as a quencher was suggested for estradiol (E2) detection. The aptamer chain was initially anchored with the Ru(II) novel molecule (Ru complex), which was recombined with carbohydrazide (CON4H6) and tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)ruthenium(II) dichloride [Ru(dcbpy)32+] modified on copper oxide (CuO) nanospheres. Intramolecular electrochemiluminescence (ECL) occurring between CON4H6 and Ru(dcbpy)32+ effectively improved the reaction rate and increased the ECL efficiency. By employing effective van der Waals' force, PDA+ was endowed with an efficient ECL quenching probe on an electrode. The signal on the ECL interface can be converted into quenching because of energy transfer between the intercalator and the emitter. Notably, cationic PDA+ possessing a large planar π-π skeleton improved advantageous activity of redox and DNA aptamer indurative loading capacity and directly generated a well-defined cathodic peak to execute the EC bio-detection. This method not only avoids the difficulty of assembling various signal indicators but also improves the sensitivity greatly using the quenching mechanism. In addition, disparate double-response signals coming from different principles of transduction are in a position to verify each other to improve the accuracy. Hence, examination areas of 0.001-100 nM with E2 for ECL and EC were obtained, supplying a novel sensing strategy with promising ideas and perspectives of detection platform construction.

A novel ratiometric electrochemical (EC) sensing platform was established for sensitive immunoassay of target cytokeratin 19 fragment 21-1 (CYFRA21-1) biomarker by combining competitive immunoreact...

In this study, an environmentally benign electrochemical protocol for intramolecular oxidative amination is developed, which offers an efficient and sustainable route to access diverse fused tricyclic systems of pyrido[1,2-e]purine-2,4-dione derivatives with pharmacological interest, exhibiting broad scope and generality (>50 examples, yields up to 99%). This electrochemical strategy features good functional group tolerance and permits access to compounds that were previously not achievable under thermal conditions. The photoluminescence properties of the representative N9-fused tricyclic xanthines have also been investigated.

As a carbon-free reaction process, the electrocatalytic nitrogen reduction reaction (eNRR) under mild conditions has broad prospects for green and sustainable NH3 production. In this work, bimetallic RhRu nanoalloys (NAs) with cross-linked curly nanosheets were successfully prepared and exhibited exciting results in the eNRR process. Furthermore, the composition effect of RhRu NAs on eNRR activity was studied systematically, and the results showed that Rh0.6Ru0.4 NAs/CP exhibited the highest NH3 yield rate of 57.75 μg h−1 mgcat.−1 and faradaic efficiency of 3.39%. As an eNRR catalyst with great potential, Rh0.6Ru0.4 NAs extend the possibility of alloy-nanomaterials in the eNRR field and further provide an idea for the precise structure of more effective and stable electrocatalysts.

The industrial-scale NH3 production still heavily depends on the Haber–Bosch process, which not only demands high energy consumption but also emits a large amount of CO2. The electrochemical fixation of N2 to NH3 under ambient conditions is regarded as an eco-friendly and sustainable approach, but stable and efficient electrocatalysts are demanded for the N2 reduction reaction under ambient conditions. In this communication, ReS2 nanosheet array on carbon cloth (ReS2/CC) is first utilized in NRR. This ReS2/CC exhibits high catalytic activity and strong long-term electrochemical durability. The Faraday efficiency of ReS2/CC is 0.78% and the NH3 yield of ReS2/CC is 3.61 × 10−10 mol s−1 cm−2 at −0.4 V versus reversible hydrogen electrode in 0.1 M HCl.

Polymer-based hydrogels used in the vitreous cavity could lead to an unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects in the surrounding tissues. To address the concerns, a poly(ethylene glycol)-engineered hydrogel capable of fast in situ gel formation (less than 1 min), with an ultralow swelling ratio and no cytotoxicity in the rabbits' eyes, was constructed as a vitreous substitute. The multi-arm polyethylene glycols (PEGs) modified with functional groups (thiol and maleimide) possess high reaction efficiency in the vitreous cavity and present excellent biomimetic characteristics of the natural vitreous humor in vitro. After injection with a double syringe via a 25-gauge needle in the eyes of rabbits for 6 months, the hydrogel functioned as an artificial vitreous body that could highly promote retinal detachment repair, with excellent biocompatibility and high transparency, and without bio-degradation or ocular complications. Collectively, the fast in situ forming hydrogel could achieve quick and good filling in the vitreous cavity without cytotoxicity, which makes it a promising long-term endotamponade substitute.

Electrocatalytic nitrogen reduction reaction (NRR), as a green and sustainable method for ammonia synthesis, has become one of the candidates to substitute industrial Haber-Bosch ammonia synthesis in the near future. In this work, gold nanoparticles (Au NPs) were successfully anchored on bismuth sulfide nanorods (Bi

We present an approach for the elucidation of C=C bond position and cis/trans isomers, which is achieved by the reaction of ambient water radical cations and double bonds, followed by the fragmentation of epoxide radical cations to generate diagnostic ions in tandem mass spectrometry. Hexenol double bond positional isomers and cis/trans isomers which exhibit different properties and biological functions are characterized as a proof of concept. The merits of the approach include the simplicity of experimental setup, rapid derivatization (within seconds), the obviation of organic solvents, as well as easy spectral interpretation.

12-O-tetradecanoylphorbol-13-acetate (TPA), is a major active constituent of the seed oil of Croton tiglium L., has pharmacological activity for the treatment of acute myeloid leukemia patients. Diethyldithiocarbamate (DTC) is a potent inhibitor of NF-κB show activity of anticancer. In this study, we determined the effect of DTC and TPA in combination on HL-60 cells cultured in vitro and in vivo. In this study, we have shown that DTC and TPA synergistically inhibited the growth of HL-60 cells and strongly induced apoptosis in the cells. Mechanistic studies showed that the combined effects of DTC and TPA were associated with a decrease in Bcl-2. The animal experiment showed that the combination of DTC and TPA more potently inhibited the growth of HL-60 tumors than either agent alone. Our results indicate that the administration of TPA and DTC in combination may be an effective strategy for inhibiting the growth of acute myeloid leukemia cells.

This work outlines an electrochemiluminescence (ECL) platform with versatile and high-performance, which using the complex luminescent molecules [Ru(Ⅱ) complex] formed by carbohydrazide (...

An ultrasensitive controlled release system electrochemical aptasensor (CRSEA) has been developed for supersensitive determination of mercury ions (Hg2+), using gold nanoparticle-linked specific single-stranded DNA (Au NPs-ssDNA) as a molecular gate and mesoporous silica nanocontainers (MSNs) as containers. MSNs have a rich porous structure, thus entrapping the toluidine blue (TB) molecules inside. It is worth noting that Hg2+ binds to the ssDNA with multiple thymine (T) and induces the ssDNA to form a hairpin structure, which makes the separation of the Au NPs-ssDNA from the MSNs. Eventually, the stored TB molecules were released from MSNs. The electron transfer signals of TB were detected stably by a differential pulse voltammetry (DPV) detection method, which are correlated with the concentration of Hg2+. Therefore, the wide linear range (10 pM-100 μM) and low limit of detection (2.9 pM) were obtained, and the system also displayed an apparent electrochemical signal response in real sample detection and showed a promising possibility in actual monitoring.

A novel luminol electrochemiluminescence (ECL) sensing platform was developed based on the closed indium tin oxide bipolar electrode (ITO BPE) for detecting the biomarkers of squamous cell carcinomas named cytokeratin 19 fragments (CYFRA 21-1). A strategy of in situ-generated coreactant H2O2 and O2 was proposed to enhance luminol ECL intensity. CaO2, possessing a high capacity of self-supplying H2O2 and O2, was encapsulated by ZIF-67, glucose oxidase, and horseradish peroxidase (GOD/HRP-loaded ZIF-67@CaO2). In the presence of glucose, gluconic acid and H2O2 were generated via the catalytic effect of GOD; then, gluconic acid induced the degradation of ZIF-67, leading to the hydrolysis of the unprotected CaO2 to produce both O2 and H2O2. Therefore, the generated coreactants O2 and H2O2, via the oxidation of glucose and the hydrolysis of CaO2, can effectively enhance the luminol ECL behavior. According to the luminol ECL reaction occurring on the anode surface of the ITO BPE, a sandwich immunosensor was fabricated on the anodic ITO BPE and GOD/HRP-loaded ZIF-67@CaO2 as labels incubated with secondary antibodies. Owing to the cathodic reaction rate influencing the anodic reaction rate, Au nanoparticles were electrodeposited on the cathode surface of the ITO BPE, which not only meliorated oxygen reduction but also further enhanced the ECL intensity of luminol. Under optimal experiments, an ECL immunosensor for detecting CYFRA 21-1 with a wider linear range from 0.0075 to 50 ng mL-1 and a detection limit of 1.89 pg mL-1 (S/N = 3) was obtained.

Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of the a-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression of GRP78, Txnip and TNFα was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation and Txnip expression through the activation of the AMPK pathway.

An intramolecular photoelectrochemical (PEC) system is designed from the novel electron donor YYYHWRGWV (Y3-H) peptide ligand for the first time. The bifunctional nonapeptide cannot only rely on the HWRGWV sequence as a site-oriented immobilizer to recognize the crystallizable fragment (Fc) domains of the antibody but also acts as electron donors for PEC generation via three tyrosine (Y) of the N-terminal. The Bi2WO6/AgInS2 heterojunction with a significant visible-light absorption is utilized as a photoelectric generator, and the motivation is ascribed to a proven proposition, namely, that short-wavelength illuminant radiates proteins, causing a decline in bioactivity of immune protein. An innovative biosensor is fabricated using the above strategies for the detection of CYFRA21-1, a biomarker of squamous cell lung carcinoma. This sort of PEC-based sensing platform shows convincing experimental data and could be an effective candidate for clinical application in the future due to their extremely skillful conception.

Background/Aim: Pancreatic adenocarcinoma is a highly malignant tumor. Synergistic combinations of anticancer agents for the effective treatment of pancreatic cancer patients are urgently needed. Here, we investigated the combined effect of celecoxib (CEL) and salirasib (SAL) on pancreatic cancer cells. Methods: Cell viability and apoptosis were measured by the trypan blue assay, three-dimensional cultures, propidium iodide staining, and caspase-3 assay. NF-κB activation and the protein levels of Akt, pAkt, and Bcl-2 were determined by the luciferase reporter assay and western blot. Results: Co-treatment with CEL and SAL had stronger effects on decreasing cell viability and inducing apoptosis in Panc-1 cells as compared with each agent individually. This combination strongly inhibited NF-κB activity and reduced pAkt and Bcl-2 levels in Panc-1 cells. Conclusion: SAL in combination with CEL may represent a new approach for effective inhibition of pancreatic cancer.

2-(N-tert-butoxycarbonylamino) pyridine and 2-(N-tert-butoxycarbonylamino)-3-methylpyridine were synthesized in a one-step method using either 2-aminopyridine or 2-amino-3-methyphyridine with tert-butylcarbonyl anhydride as the starting materials. The products were characterized by single-crystal X-ray diffraction, 1H NMR, 13C NMR, and HRMS. The biological activity of the two compounds against five fungi was determined. 2-(N-tert-butoxycarbonylamino) pyridine has more than 50% inhibitory activity against Pyricularia oryzae, Colletotrichum gloeosporioides, and Alternaria alternate. In addition, the inhibitory activity of 2-(N-tert-butoxycarbonylamino)-3-methylpyridine against Alternaria alternate reached 67.69%. Two 2-BOC aminopyridine derivatives were synthesized and structurally characterized by 1H NMR, 13C NMR, HRMS analysis and X-ray crystal diffraction. The inhibitory activity both compounds was studied.

This study proposes a competitive photoelectrochemical (PEC) immunosensor for detecting diethylstilbestrol (DES). The PEC sensing platform uses a zinc and molybdenum codoped BiVO4 nanoarray ((Zn,Mo):BiVO4) as the photoactive matrix and manganese hexacyanoferrate hydrate loading silicon dioxide layer composite nanocubes (MHCF@SiO2 NCs) as the signal quencher. The (Zn,Mo):BiVO4 nanoarray demonstrated brilliant PEC behavior, by virtue of the local electric field formed by the codoped Zn and Mo. This doping accelerated the electron transfer and improved the photoelectric conversion efficiency in BiVO4 nanoarray under visible light. Furthermore, the nanoarray structure with its large surface area provided abundant binding sites for the immune response. As the MHCF@SiO2 NCs-anti-DES competitively bonded with either free DES or bovine serum albumin conjugated DES (BSA-DES), hydrogen peroxide (H2O2) as electron donor was competitively consumed and meanwhile steric resistance blocked electrons transfer. For the above reasons, the photocurrent signal was reduced. Thus, the standard sample free DES was accurately detected, and the fabricated PEC immunosensor displayed an outstanding photocurrent response from 0.1 pg/mL to 50 ng/mL with a detection limit of 0.05 pg/mL. Simultaneously, the acceptable stability, selectivity, and reproducibility of the designed dual-competitive sensing platform suggest its applicability to small molecule detection.

In this work, a triple-amplified biosensor with a bioactivity-maintained peculiarity was constructed for quantitative procalcitonin (PCT) detection. As everyone knows, a strong electrochemiluminescence (ECL) signal is the premise to ensure high sensitivity for trace target detection. Hence, a valid tactic was developed to achieve signal amplification of luminophor by using Co2+-based metal-organic frameworks (ZIF-67) and silver-cysteine (AgCys). The ZIF-67 particles, which have more atomically dispersed Co2+, could play the role of a co-reaction accelerator to catalyze S2O82- to generate abundant Co3+ and sulfate radical anions (SO4•-). Afterward, a mass of Co3+ was reduced to more hydroxyl radicals (OH•) by H2O, thus ulteriorly reducing S2O82- to generate more SO4•-. Remarkably, S2O82- was reduced to SO4•- continuously with the recycling of Co2+ and Co3+, which realized an effective signal amplification. Meanwhile, the AgCys complex with superior catalysis and biocompatibility was prepared to further improve the ECL signal and maintain the bioactivity of the biomolecule. Furthermore, HWRGWVC, a heptapeptide that was used for combining the Fc fragments of an antibody by Au-S bonding to achieve the fixed point fixation, could not only maintain bioactivity of an antibody but also improved its incubation efficiency, thus further enhancing biosensor sensitivity. Under optimum conditions, the proposed biosensor realized highly sensitive assay for PCT with a wide dynamic range from 10 fg/mL to 100 ng/mL and a detection limit as low as 3.67 fg/mL. With superior stability, selectivity, and repeatability, the prepared biosensor revealed immense potential application of ultrasensitive assay for PCT in human serum.

Natural products have shown potential to be combined with current cancer therapies to improve patient outcomes. Nobiletin (NBT) is a citrus polymethoxyflavone and has been shown to exert an anticancer effect in various cancer cells. We investigated the effects and mechanisms of NBT in combination with bicalutamide (BCT), a commonly used anti-androgen drug in prostate cancer therapy, on prostate cancer cells. Our results demonstrate that the combined treatment with NBT and BCT produces an enhanced inhibitory effect on the growth of prostate cancer cells compared to either compound alone. The synergistic action of NBT and BCT was confirmed using isobologram analysis. Moreover, this study has shown that NBT and BCT synergistically inhibited colony formation and migration as well as induced apoptosis. Mechanistic studies demonstrate that NBT and BCT combination reduced key cellular signaling regulators including: p-Erk/Erk, p-STAT3/STAT3 and NF-κB. Overall, these results suggest that NBT combination with BCT may be an effective treatment for prostate cancer.

A new strategy for the highly sensitive electrochemiluminescence (ECL) detection of insulin was developed based on curcumin-conjugated Au nanoparticles wrapped in zeolitic Zn2+-imidazolate cross-linked framework nanoparticles (Au-Cur/ZIF-8) quenching the ECL of CdS-decorated TiO2 nanobelts (CdS@TiO2). Curcumin-conjugated Au nanoparticles were embedded in ZIF-8 through epitaxial growth or nucleus coalescence. Herein, dual coreactants H2O2 and K2S2O8 were employed to enhance the ECL emission of CdS@TiO2, and the enhancing mechanism may be due to the electrogenerated hydroxyl radical (OH˙) strengthening the amount of sulfate radical anion (SO4˙-), which was the main species of generating ECL signals. In order to sensitively detect insulin, Au-Cur/ZIF-8 labels were used to anchor secondary antibodies via amidation reaction and inhibit the ECL intensity of CdS@TiO2. Moreover, the possible mechanism of quenching between Au-Cur/ZIF-8 and CdS@TiO2 was ascribed to the poor conductivity of ZIF-8, the consumption of OH˙ and the ECL resonance energy transfer between CdS@TiO2 and Au-Cur. Under optimal conditions, a sandwich immunosensor was prepared to determine insulin with a good linear range from 0.3 pg mL-1 to 20 ng mL-1 and a low detection limit of 0.09 pg mL-1 (S/N = 3).

Herein, a series of new 8-OIQ cobalt complexes were synthesized and used for cobalt-catalyzed chemo- and enantioselective 1,4-hydroboration of enones with HBpin to access chiral β,β-disubstituted ketones with good to excellent chemo- and enantioselectivties. This protocol is operationally simple and shows a broad substrate scope.

This study proposed a novel and high-efficiency strategy, i.e., freezing followed by low-temperature thermal treatment, to significantly promote short-chain fatty acids (SCFAs) production from waste activated sludge compared to traditional freezing/thawing treatment. The maximal production of SCFAs was 212 mg COD/g VSS with a shortened retention time of five days, and the potentially recovered carbon source, including SCFAs, soluble polysaccharides and proteins, reached 321 mg COD/g VSS, increased by 92.1 and 28.3% compared to sole freezing and thermal treatment. Both the solubilization and hydrolysis steps of WAS were accelerated, and the acid-producing microorganisms, such as Macellibacteroides, Romboutsia and Paraclostridium, were greatly enriched, with a total abundance of 13.9%, which was only 0.54% in control. Interestingly, the methane production was inhibited at a shortened retention time, resulting in SCFAs accumulation, whereas it was increased by 32.0% at a longer sludge retention time, providing a potential solution for energy recovery from WAS.

Zinc(II) tetraphenylporphyrin (ZnTPP) has very broad application prospects in the fields of supramolecular chemistry, solar cells and nanomaterials. In this paper, by using scanning tunneling microscopy (STM), we systematically investigated the ZnTPP molecule and its four derivatives formed by thermal annealing were characterized unambiguously by bond-resolved STM (BR-STM). The electronic properties of the ZnTPP molecule and its four cyclodehydrogenation products were investigated by scanning tunneling spectroscopy (STS) combined with DFT calculations. The spatial distribution of molecular frontier orbitals of four products was obtained by dI/dV mappings. This work gives rise to a full-scale investigation of ZnTPP on Au(111), which will be potentially useful in nanodevices and optoelectronics.

A photoelectrochemical (PEC) biosensor capable of detecting cytokeratin 19 fragment 21-1 (CYFRA21-1) was optimized by taking advantage of the powerful conjugate repeats of horseradish peroxidase and tyramine (HRP-tyramine)–triggered enzymatic biocatalytic precipitation (BCP) on high-performance BiVO4/Ag3VO4/SnS2 photoelectrodes. Compared with the ubiquitous BCP strategy, we identified a design supporting conjugate repeats generated by HRP and tyramine–triggered immeasurable insoluble precipitates in the presence of hydrogen peroxide and 4-chloro-1-phenol (4-CN), and the steric hindrance improved sensitivity. Moreover, by virtue of BiVO4, Ag3VO4, SnS2 excellent level matching structure and chemical stability, a heterojunction (BiVO4/Ag3VO4/SnS2) with high light absorption efficiency has been successfully prepared. The novel heterostructure system of BiVO4/Ag3VO4/SnS2 with high detection current and low background signal exhibited high-performance PEC determination. Generally, the hitherto untapped biosensor resource realized the sensitive detection of CYFRA21-1 with a wide linear range from 50 fg/mL to 200 ng/mL, and a detection limit of 15 fg/mL, which illustrated the potential for biotechnological applications.

A copper-based metal-organic framework (JUC-1000) has emerged as a promising electrochemiluminescence (ECL) emitter in the domains of bioanalysis and immunoassay. Herein, a highly efficient signal "on-off" peptide-based biosensor was constructed for trypsin (TPN) assay. JUC-1000 synthesized using an organic ligand of H4BDPO was functionalized as the ECL emitter, whose cathodic ECL behavior in aqueous media was first investigated using potassium persulfate (K2S2O8) as the coreactant. To further amplify the ECL signal, highly catalytic Ag@CeO2 nanoparticles were fabricated as both a substrate and an coreaction accelerator, which can efficiently catalyze the reduction of S2O82- to generate more sulfate anion radicals (SO4•-) for ECL enhancement, thereby generating strong and stable ECL signals in a "signal on" state. The functionalized JUC-1000 emitter was connected to the Ag@CeO2 sensing layer though a heptapeptide (HWRGWVC, HGC), and TPN as the target can specifically cleave the carboxyl side of arginine residues in HGC, leading to the release of emitters in a "signal off" state. Based on the efficient signal-switching, the biosensor exhibited linear ECL responses to the added TPN concentration, realizing sensitive detection of TPN in 10 fg/mL to 100 ng/mL with a limit of detection of 3.46 fg/mL. This work proposed an attractive orientation for the fundamental research of applying transition metal-organic frameworks as ECL emitters in bioanalysis and immunoassay.

The levels of acetone and other ketones in exhaled human breath can be associated with various metabolic conditions, e.g. ketosis, lung cancer, dietary fat loss and diabetes. In this study, ketones in breath samples were charged through the reaction with water radical cations to form [M + H2O]˙+ ions, which were detected by mass spectrometry. Our experimental data indicate that under the optimized experimental conditions, the limit of detection for acetone using our approach is 0.14 ng L−1 (∼0.06 ppb). The linear dynamic range of detection spans four orders of magnitude. The developed approach was applied to real-time semi-quantitative analysis of acetone in the exhaled breath of human volunteers, revealing significantly higher levels of acetone in the breath of smokers compared to non-smokers. The developed approach features the obviation of sample collection, easy operation, high speed of analysis (10 s per run), high sensitivity, and spectral interpretation, which indicates the potential of ambient corona discharge ionization mass spectrometry as a selective, sensitive and noninvasive technique for the determination of exhaled ketones in clinical diagnosis including lung cancer, diabetes, etc.

This research put forward a novel split-type electrochemical (EC) immunosensor which integrated the controlled-release strategy with EC detection for application in the field of biosensing. Concretely, ascorbic acid (AA) was packaged in a cadmium sulfide (CdS)-capped spherical mesoporous bioactive glass (SBG) nanocarrier (SBGCdS) on account of encapsulation technology. To reduce the complexity of the bioanalysis, the detection antibody-labeled SBGCdS-AA bioconjugate was applied in a 96-well microplate for the immunoreaction process, which is independent of the EC determination procedure. Thus, the immune interference and steric hindrance caused by the accumulation of nanomaterials on the electrode could be minimized. Subsequently, AA was released efficiently via the destruction effect of dithiothreitol on the disulfide bond. In addition, for the as-prepared FcAI/l-Cys/gold nanoparticles (GNPs)/porous BiVO4 (p-BVO)/ITO EC sensing platform in the detection solution, the synergetic catalysis of Fc and GNPs/p-BVO toward the oxidation of the released AA could be realized, which triggered AA-mediated significant signal magnification throughout this study. In particular, p-BVO with an ordered nanoarray structure could accelerate the electron transfer to assist in sensitivity improvement of this system. This novel biosensor was capable of assaying the neuron-specific enolase (NSE) biomarker sensitively, from which a linear range of 0.001-100 ng/mL was derived along with a low detection limit of 1.08 pg/mL. An innovative way could be paved in the bioanalysis of NSE and other biomarkers.

In many cases of in-situ or point-of-care testing (POCT), the single pursuit of good detection performance cannot meet the testing requirements, and thus no-wash testing has become one of the most effective methods to develop sustainable biosensing assay, providing more convenient operation procedures and shorting the detection time. Herein, a disposable POC biosensing assay was prepared based on the RGB color detector software on the smartphone and the peroxide-like activity of gold nanoparticles (Au NPs) for aflatoxin B1 (AFB1) sensitive detection. Using syringe filters for a simple physical separation procedure can easily realize washing free detection, which is superior to most biosensing assays with cumbersome detection procedures. The syringe filters with 200 nm pore diameter could only pass through small Au NPs (30 nm) while the large-sized SiO2 nanoparticles (300 nm) was blocked on the membrane. In this work, Au NPs utilized their inherent peroxidase-like activity to catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2 to ox-TMB under acidic conditions, which results in blue color in aqueous solution. The color change due to different antigen concentrations was quantitatively determined by measuring the color intensity with a smartphone and the RGB color detector. By measuring the color intensity, it was known that the linear concentration range of the biosensing assay was 100 fg mL−1 to 50 ng mL−1, and the detection limit of AFB1 was 33 fg mL−1 (S/N = 3). Additionally, the designed biosensing assay exhibited excellent selectivity, storage stability and reproducibility. More importantly, the innovation of detecting and analyzing technology is the outstanding advantage of the biosensing assay, providing a more flexible and convenient strategy for some other small molecule analysis.