A druggable cascade links methionine metabolism to epigenomic reprogramming in squamous cell carcinoma.

Upper aerodigestive squamous cell carcinoma (UASCC) is a common and aggressive malignancy with few effective therapeutic options. Here, we investigate amino acid metabolism in this cancer, surprisingly noting that UASCC exhibits the highest methionine level across all human cancers, driven by its transporter LAT1. We show that LAT1 is also expressed at the highest level in UASCC, transcriptionally activated by UASCC-specific promoter and enhancers, which are directly coregulated by SCC master regulators TP63/KLF5/SREBF1. Unexpectedly, unbiased bioinformatic screen identifies EZH2 as the most significant target downstream of the LAT1-methionine pathway, directly linking methionine metabolism to epigenomic reprogramming. Importantly, this cascade is indispensable for the survival and proliferation of UASCC patient-derived tumor organoids. In addition, LAT1 expression is closely associated with cellular sensitivity to inhibition of the LAT1-methionine-EZH2 axis. Notably, this unique LAT1-methionine-EZH2 cascade can be targeted effectively by either pharmacological approaches or dietary intervention in vivo. In summary, this work maps a unique mechanistic cross talk between epigenomic reprogramming with methionine metabolism, establishes its biological significance in the biology of UASCC, and identifies a unique tumor-specific vulnerability which can be exploited both pharmacologically and dietarily.

"Atomic Topping" of MnOx on Al2O3 to Create Electron-Rich, Aperiodic, Lattice Oxygens that Resemble Noble Metals for Catalytic Oxidation.

Enhancing the catalytic oxidation activity of traditional transition-metal oxides to rival that of noble metals has been a prominent focus in the field of catalysis. However, existing synthesis strategies that focus on controlling the electronic states of metal centers have not yet fully succeeded in achieving this goal. Our current research reveals that manipulating the electronic states of oxygen centers can yield unexpected results. By creating electron-rich, aperiodic lattice oxygens through atomic topping of MnOx, we have produced a catalyst with performance that closely resembles supported Pt. Spherical aberration-corrected transmission electron microscopy and X-ray absorption spectra have confirmed that the atomic topping of the MnOx layer on Al2O3 can form an aperiodic arrangement oxide structure. Near-ambient pressure X-ray photoelectron spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy, reaction kinetics test, and theoretical calculations demonstrated that this structure significantly increases the electron density around the oxygen in MnOx, shifting the activation center for CO adsorption from Mn to O, thereby exhibiting catalytic activity and stability close to that of the precious metal Pt. This study presents a fresh perspective on designing efficient oxide catalysts by targeting electron-rich anionic centers, thereby deepening the understanding of how these centers can be altered to enhance catalytic efficiency in oxidation reactions.

Sodium oligomannate activates the enteroendocrine-vagal afferent pathways in APP/PS1 mice.

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.

Aspirin-Loaded Cross-Linked Lipoic Acid Nanodrug Prevents Postoperative Tumor Recurrence by Residual Cancer Cell Killing and Inflammatory Microenvironment Improvement.

In addition to residual cancer cells, the surgery resection-induced hyperinflammatory microenvironment is a key factor that leads to postsurgical cancer recurrence. Herein, we developed a dual-functional nanodrug Asp@cLANVs for postsurgical recurrence inhibition by loading the classical anti-inflammatory drug aspirin (Asp) into cross-linked lipoic acid nanovesicles (cLANVs). The Asp@cLANVs can not only kill residual cancer cells at the doses comparable to common cytotoxic drugs by synergistic interaction between Asp and cLANVs, but also improve the postsurgical inflammatory microenvironment by their strongly synergistic anti-inflammation activity between Asp and cLANVs. Using mice bearing partially removed NCI-H460 tumors, we found that Asp@cLANVs gave a much lower recurrence rate (33.3%) compared with the first-line cytotoxic drug cisplatin (100%), and no mice died for at least 60 days after Asp@cLANV treatment while no mouse survived beyond day 43 in the cisplatin group. This dual-functional nanodrug constructs the first example that combines residual cancer cell killing and postoperative inflammation microenvironment improvement to suppress postsurgical cancer recurrence.

Inhibition of A1 Astrocytes and Activation of A2 Astrocytes for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious injury to the central nervous system that causes significant physical and psychological trauma to the patient. SCI includes primary spinal cord injuries and secondary spinal cord injuries. The secondary injury refers to the pathological process or reaction after the primary injury. Although SCI has always been thought to be an incurable injury, the human nerve has the ability to repair itself after an injury. However, the reparability is limited because glial scar formation impedes functional recovery. There is a type of astrocyte that can differentiate into two forms of reactive astrocytes known as 'A1' and 'A2' astrocytes. A1 astrocytes release cytotoxic chemicals that cause neurons and oligodendrocytes to die and perform a harmful role. A2 astrocytes can produce neurotrophic factors and act as neuroprotectors. This article discusses ways to block A1 astrocytes while stimulating A2 astrocytes to formulate a new treatment for spinal cord injury.

Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway.

Proteasomes are overexpressed in multiple myeloma (MM) and proteasomal inhibitors (PIs) have been widely used for the treatment of MM. PIs are reported to induce MM cell apoptosis but impair necroptosis. In the present study, we found that PIs MG132 and bortezomib induce MM cell pyroptosis, a novel type of cell death, in a GSDME-dependent manner. Lack of GSDME totally blocks PI-induced pyroptosis. Interestingly, we found that Caspase-3/6/7/9 are all involved in pyroptosis triggered by PIs because the specific inhibitor of each caspase ablates GSDME activation. PIs markedly reduce mitochondrial membrane potential. Moreover, PIs disrupt the interaction of Bcl-2 and BAX, induce cytochrome c release from mitochondria to cytosol and activate GSDME. Furthermore, we found that overexpression of an N-terminal portion of GSDME suffices to release cytochrome c from mitochondria and to activate Caspase-3/9, suggesting N-GSDME might penetrate the mitochondrial membrane. Consistent with Bcl-2 inhibition, BAX can induce MM cell pyroptosis in a GSDME-dependent manner. In accordance with these findings, inhibition of Bcl-2 synergizes with PIs to induce MM cell pyroptosis. Therefore, the present study indicates that PIs trigger MM cell pyroptosis via the mitochondrial BAX/GSDME pathway and provides a rationale for combined treatment of MM with Bcl-2 and proteasome inhibitors to increase therapeutic efficiency via induction of pyroptosis.

Enhancing maize's nitrogen-fixing potential through ZmSBT3, a gene suppressing mucilage secretion.

Maize (Zea mays) requires substantial amounts of nitrogen, posing a challenge for its cultivation. Recent work discovered that some ancient Mexican maize landraces harbored diazotrophic bacteria in mucilage secreted by their aerial roots. To see if this trait is retained in modern maize, we conducted a field study of aerial root mucilage (ARM) in 258 inbred lines. We observed that ARM secretion is common in modern maize, but the amount significantly varies, and only a few lines have retained the nitrogen-fixing traits found in ancient landraces. The mucilage of the high-ARM inbred line HN5-724 had high nitrogen-fixing enzyme activity and abundant diazotrophic bacteria. Our genome-wide association study identified 17 candidate genes associated with ARM across three environments. Knockouts of one candidate gene, the subtilase family gene ZmSBT3, confirmed that it negatively regulates ARM secretion. Notably, the ZmSBT3 knockout lines had increased biomass and total nitrogen accumulation under nitrogen-free culture conditions. High ARM was associated with three ZmSBT3 haplotypes that were gradually lost during maize domestication, being retained in only a few modern inbred lines such as HN5-724. In summary, our results identify ZmSBT3 as a potential tool for enhancing ARM, and thus nitrogen fixation, in maize.

OsClo5 functions as a transcriptional co-repressor by interacting with OsDi19-5 to negatively affect salt stress tolerance in rice seedlings.

Caleosins constitute a small protein family with one calcium-binding EF-hand motif. They are involved in the regulation of development and response to abiotic stress in plants. Nevertheless, how they impact salt stress tolerance in rice is largely unknown. Thereby, biochemical and molecular genetic experiments were carried out, and the results revealed that OsClo5 was able to bind calcium and phospholipids in vitro and localized in the nucleus and endoplasmic reticulum in rice protoplasts. At the germination and early seedlings stages, overexpression transgenic lines and T-DNA mutant lines exhibited reduced and increased tolerance to salt stress, respectively, compared with the wild-type. Yeast two-hybrid, bimolecular fluorescence complementation and in vitro pull-down assays demonstrated that the EF-hand motif of OsClo5 was essential for the interactions with itself and OsDi19-5. Yeast one-hybrid, electrophoretic migration shift and dual-luciferase reporter assays identified OsDi19-5 as a transcriptional repressor via the TACART cis-element in the promoters of two salt stress-related target genes, OsUSP and OsMST. In addition, OsClo5 enhanced the inhibitory effect of OsDi19-5 in the tobacco transient system, which was confirmed by qRT-PCR analysis in rice seedlings under salt stress. The collective results deepen the understanding of the molecular mechanism underlying the roles of caleosin in the salt stress response. These findings will also inform efforts to improve salt tolerance of rice.

Linoleic Acid-Glucosamine Hybrid for Endogenous Iron-Activated Ferroptosis Therapy in High-Grade Serous Ovarian Cancer.

As the most common subtype in ovarian malignancies, high-grade serous ovarian cancer (HGSOC) made less therapeutic progress in past decades due to the lack of effective drug-able targets. Herein, an effective linoleic acid (LA) and glucosamine (GlcN) hybrid (LA-GlcN) was synthesized for the treatment of HGSOC. The GlcN was introduced to recognize the glucose transporter 1 (GLUT 1) overexpressed in tumor cells to enhance the uptake of LA-GlcN, and the unsaturated LA was employed to trigger ferroptosis by iron-dependent lipid peroxidation. Since the iron content of HGSOC was ∼5 and 2 times, respectively, higher than that of the normal ovarian cells and low-grade serous ovarian cancer cells, these excess irons make them a good target to enhance the ferroptosis of LA-GlcN. The in vitro study demonstrated that LA-GlcN could selectively kill HGSOC cells without affecting normal cells; the in vivo study revealed that LA-GlcN at the dose of 50 mg kg-1 achieved a comparable tumor inhibition as doxorubicin hydrochloride (4 mg kg-1) while the overall survival of mice was extended largely due to the low toxicity, and when the dose was increased to 100 mg kg-1, the therapeutic outcomes could be improved further. This dietary hybrid which targets the excess endogenous iron to activate ferroptosis represents a promising drug for HGSOC treatment.

CAQK modification enhances the targeted accumulation of metformin-loaded nanoparticles in rats with spinal cord injury.

Spinal cord injury (SCI) often causes neuronal membrane rupture and immediate death of neurons, followed by complicated secondary injuries. Treatment of SCI still remains a major challenge in clinical practice; thus, a great advance is urgently needed in this field. Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI. In this study, we established a zein-based MET-loaded nanodrug system (CAQK-MET-NPs) for the targeted drug delivery for SCI. The results showed that MET could be effectively encapsulated into zein to obtain the zein-based spherical nanoparticles. Pharmacokinetic analysis indicated that CAQK-MET-NPs exhibited sustained-release and long-term therapeutic effects. The fluorescence imaging and tissue distribution experiments showed that CAQK-MET-NPs could efficiently accumulate at the lesion site of SCI rats. In conclusion, CAQK-MET-NPs may be a promising nanodrug for the treatment of SCI.

The CaM1-associated CCaMK-MKK1/6 cascade positively affects lateral root growth via auxin signaling under salt stress in rice.

Ca2+/calmodulin (CaM)-dependent protein kinases (CCaMKs) and mitogen-activated protein kinase kinases (MAPKKs) are two types of kinases that regulate salt stress response in plants. It remains unclear, however, how they cooperatively affect lateral root growth under salt stress. Here, two conserved phosphorylation sites (S102 and T118) of OsCaM1 were identified, and found to affect the ability to bind to Ca2+in vitro and the kinase activity of OsCCaMK in vivo. OsCCaMK specifically interacted with OsMKK1/6 in a Ca2+/CaM-dependent manner. In vitro kinase and in vivo dual-luciferase assays revealed that OsCCaMK phosphorylated OsMKK6 while OsMKK1 phosphorylated OsCCaMK. Overexpression and antisense-RNA repression expression of OsCaM1-1, and CRISPR/Cas9-mediated gene editing mutations of OsMKK1, OsMKK6, and OsMKK1/6 proved that OsCaM1-1, OsMKK1, and OsMKK6 enhanced the auxin content in roots and lateral root growth under salt stress. Consistently, OsCaM1-1, OsMKK1, and OsMKK6 regulated the transcript levels of the genes of this cascade, and salt stress-related and lateral root growth-related auxin signaling under salt stress in rice roots. These findings demonstrate that the OsCaM1-associated OsCCaMK-OsMKK1/6 cascade plays a critical role in recruiting auxin signaling in rice roots. These results also provide new insight into the regulatory mechanism of the CaM-mediated phosphorylation relay cascade to auxin signaling in lateral root growth under salt stress in plants.

Dipyridyl-Decorated Nitronyl Nitroxide-DyIII Single-Molecule Magnet with a Record Energy Barrier of 146 K.

A nitronyl nitroxide biradical with a capping N-donor group was discovered to improve single-molecule-magnet behavior of the Dy-biradical cluster, generating a magnetic reversal barrier of 146 K. As far as we know, the effective energy barrier of the Dy compound is largest in the nitronyl nitroxide 4f system by far.

An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases.

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

Analysis of soluble components in coals and interpretations for the complex mass spectra.

RATIONALE: The deduction of useful information from the mass spectra of a complex mixture like coals remains difficult, which limits the clean and efficient utilization of coals. It is necessary to explore the data interpretation methods for mass spectra and visualize the analytical data of coals for industrial utilization such as feedstock selection. METHODS: Coal sample and methanol were mixed and heated to 310 °C and kept at that temperature for 2 h. The solvent was under supercritical state at 310 °C and the solubility for the solid mixture increased. Soluble products from thermal dissolution of two Chinese coals were analyzed by high-performance liquid chromatography/atmospheric pressure chemical ionization orbitrap mass spectrometry. RESULTS: The iso-abundance plot for molecules in coals was upgraded to display the distributions of isomers which are indicated as concentric circles or triangles with the same carbon number and value of double-bond equivalent. The concentration ratio was introduced from economics to describe the content inequality of organic species within the same class of coal molecules. CONCLUSIONS: Interpretation methods for mass spectra visualize and simplify the understanding of complex components in coals for industrial utilization. Coals with a high concentration ratio for a specific class should take priority as a feedstock for chemicals and receive more attention. Copyright © 2016 John Wiley & Sons, Ltd.

RNA-Sequence Analysis Reveals Differentially Expressed Genes (DEGs) in Patients Exhibiting Different Risks of Tumor Metastasis.

BACKGROUND Breast cancer is one of the most common malignancies in women. In a previous study, we found that for two patients who had a high risk of lymphatic metastasis, lymphatic metastasis did not occur; whereas, for two patients who had a low risk of lymphatic metastasis, lymphatic metastasis did occur. MATERIAL AND METHODS We analyzed the differential gene expressions of these four patients by RNA-sequence. The data (HRNM_T versus HRNM_N, LRYM_T versus LRYM_N, and HRNM_T versus LRYM_T) was then processed using differentially expressed genes (DEGs) analysis, functional analysis for DEGs, and PPI network construct. RESULTS For HRNM_T versus HRNM_N, there were 224 DEGs. There were 504 DEGs for LRYM_T versus LRYM_N, and 88 DEGs for LRYM_T versus LRYM_N. For HRNM_T versus HRNM_N, DEGs were up-regulated mainly in the cell cycle, the IL-17 signaling pathway, and the progesterone-mediated oocyte maturation; DEGs were down-regulated mainly in the IL-17 signaling pathway. For LRYM_T versus LRYM_N, DEGs were up-regulated mainly in protein digestion and absorption, and cytokine-cytokine receptor interaction; DEGs were down-regulated mainly in ECM-receptor interaction. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in the PPAR signaling pathway; DEGs were downregulated mainly in the adipocytokine signaling pathway. The DEGs were screened to construct PPI networks. CONCLUSIONS The GO and KEGG functional enrichments of HRNM_T versus HRNM_N, and LRYM_T versus LRYM_N were consistent with earlier studies. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in PPAR signaling; DEGs were down-regulated mainly in the adipocytokine pathway.

Sequential ultrasonic extraction of a Chinese coal and characterization of nitrogen-containing compounds in the extracts using high-performance liquid chromatography with mass spectrometry.

Dongming lignite was sequentially extracted with petroleum ether, carbon disulfide, methanol, acetone, and isometric carbon disulfide/acetone mixed solvent at room temperature to afford extracts 1-5, respectively. High-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry was used to separate and characterize heteroatomic species in the extracts at molecular level. Molecular mass of compounds in the extracts is mainly distributed from 300 to 800 u, and the relative abundance of compounds with molecular mass over 800 u in the carbon disulfide extract is 135 times of that in the petroleum ether extract. The acetone extract has the highest relative abundance for organonitrogen compounds. Double bond equivalence numbers of detected species indicate that most of the organonitrogen compounds contain N-heterocyclic aromatic rings, including pyridine, quinoline and pyrrole. Some organonitrogen isomers in Dongming lignite were separated and identified by high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry, and the corresponding structural information was proposed.

Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection.

Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-γ autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-γ autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 × 10(-6); Pc = 3.08 × 10(-5) and odds ratio 7.16; 95% confidence interval, 3.02-17.05; P = 1 × 10(-7); Pc = 1.4 × 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.

Benzimidazole derivatives: selective fluorescent chemosensors for the picogram detection of picric acid.

1,3,5-Tri(1H-benzo[d]imidazol-2-yl)benzene derivatives, as a new kind of fluorescent chemosensor for the detection of nitroaromatic explosives, are designed and synthesized by simple N-hydrocarbylation. Among 16 obtained compounds, compound 4g has the best capability for detection of picric acid (PA), having good selectivity and high sensitivity. The detection of PA with 4g solution-coated paper strips at the picogram level is developed. A simple, portable, and low-cost method is provided for detecting PA in solution and contact mode.

Design, synthesis, and characterization of 1,3,5-tri(1H-benzo[d]imidazol-2-yl)benzene-based fluorescent supramolecular columnar liquid crystals with a broad mesomorphic range.

A new kind of supramolecular columnar liquid crystal T-A with a broad mesomorphic range (up to 164.9 °C), good thermal stability, and strong fluorescence is designed and formed by the H-bonding between 1,3,5-tri(1H-benzo[d]imidazol-2-yl)benzene (T) and serial gallic acid derivatives (A). Two components are easily available because of simple routes, common reactions, high yields, commercial starting materials, and inexpensive catalysts. The introduction of the 1,2,3-triazole structure into component A makes the textures different and is slightly disadvantageous for the T-A complexes.

An amplified electrochemical aptasensor for thrombin detection based on pseudobienzymic Fe3O4-Au nanocomposites and electroactive hemin/G-quadruplex as signal enhancers.

A sensitive and selective electrochemical aptasensor for thrombin detection was constructed based on hemin/G-quadruplex as the signal label and Fe3O4-Au nanocomposites with glucose oxidase (GOx-) and peroxide-mimicking enzyme activity as the signal enhancers. Due to their large surface area and good biocompatibility, Fe3O4-Au nanocomposites were employed to immobilize electroactive hemin/G-quadruplex, which was formed by the conjugation between a single-stranded guanine-rich nucleic acid and hemin. Based on the GOx-mimicking enzyme activity, Au nanoparticles on the surface of the Fe3O4-Au nanocomposites effectively catalyzed the oxidization of glucose in the presence of dissolved O2, accompanied by the production of H2O2. Both the Fe3O4 cores of Fe3O4-Au nanocomposites and hemin/G-quadruplex with H2O2-mimicking enzyme activity could catalyze the reduction of the generated H2O2, which promoted the electron transfer of hemin and amplified the electrochemical signal. The proposed electrochemical aptasensor had a wide dynamic linear range of 0.1 pM to 20 nM with a lower detection limit of 0.013 pM, which provided a promising method for a sensitive assay for the detection of proteins in electrochemical aptasensors.