Imaging and Downstaging Bladder Cancer with the 177Lu-Labeled Bioorthogonal Nanoprobe.

Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.

The association between serum adipokines levels with senile osteoporosis: a systematic review and meta-analysis.

Objective: The clinical correlation between adipokines levels in the blood and the incidence of senile osteoporosis (SOP) has not been clearly studied. We conducted this meta-analysis to elucidate the relationship between three common adipokines levels (leptin, adiponectin, and chemerin) and the incidence of SOP. Methods: We searched databases such as CNKI, CBM, VIP, Wanfang, PubMed, Web of Science, Embase, and the Cochrane Library to collect articles published since the establishment of the database until July 30, 2022. Results: In total, 11 studies met the selection criteria. Our meta-analysis showed that serum leptin levels were significantly lower (mean difference [MD], -2.53, 95% CI: -3.96 to -1.10, I2 = 96%), chemerin levels were significantly higher (MD, 30.06, 95% CI: 16.71 to 43.40, I2 = 94%), and adiponectin levels were not significantly different (MD, -0.55, 95% CI: -2.26 to 1.17, P = 0.53, I2 = 98%) in SOP patients compared with healthy older individuals with normal bone mineral density (BMD). In addition, correlation analysis showed that leptin levels were positively correlated with lumbar bone mineral density (LBMD) (r = 0.36) and femoral bone mineral density (FBMD) (r = 0.38), chemerin levels were negatively correlated with LBMD (r = -0.55) and FBMD (r = -0.48), and there were significant positive correlations between leptin and adiponectin levels and body mass index (BMI) (r = 0.91 and 0.97). Conclusions: The likelihood of having SOP was higher in older individuals with low levels of leptin and higher levels of chemerin. In addition, BMI was somewhat lower with low levels of leptin and adiponectin. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022356469.

Vision for Ratiometric Nanoprobes: In Vivo Noninvasive Visualization and Readout of Physiological Hallmarks.

Lesion areas are distinguished from normal tissues surrounding them by distinct physiological characteristics. These features serve as biological hallmarks with which targeted biomedical imaging of the lesion sites can be achieved. Although tremendous efforts have been devoted to providing smart imaging probes with the capability of visualizing the physiological hallmarks at the molecular level, the majority of them are merely able to derive anatomical information from the tissues of interest, and thus are not suitable for taking part in in vivo quantification of the biomarkers. Recent advances in chemical construction of advanced ratiometric nanoprobes (RNPs) have enabled a horizon for quantitatively monitoring the biological abnormalities in vivo. In contrast to the conventional probes whose dependency of output on single-signal profiles restricts them from taking part in quantitative practices, RNPs are designed to provide information in two channels, affording a self-calibration opportunity to exclude the analyte-independent factors from the outputs and address the issue. Most of the conventional RNPs have encountered several challenges regarding the reliability and sufficiency of the obtained data for high-performance imaging. In this Review, we have summarized the recent progresses in developing highly advanced RNPs with the capabilities of deriving maximized information from the lesion areas of interest as well as adapting themselves to the complex biological systems in order to minimize microenvironmental-induced falsified signals. To provide a better outlook on the current advanced RNPs, nanoprobes based on optical, photoacoustic, and magnetic resonance imaging modalities for visualizing a wide range of analytes such as pH, reactive species, and different derivations of amino acids have been included. Furthermore, the physicochemical properties of the RNPs, the major constituents of the nanosystems and the analyte recognition mechanisms have been introduced. Moreover, the alterations in the values of the ratiometric signal in response to the analyte of interest as well as the time at which the highest value is achieved, have been included for most of RNPs discussed in this Review. Finally, the challenges as well as future perspectives in the field are discussed.

Reversing Acute Kidney Injury through Coordinated Interplay of Anti-Inflammation and Iron Supplementation.

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD+ ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, herein, an ultrasmall Fe3 O4 nanoparticle is used as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD+ . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe3 O4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD+ precursor into renal cells through nicotinamide riboside kinase 1 on the cell membrane. It is demonstrated that NMN-loaded Fe3 O4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicate that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti-ROS (reactive oxygen species), anti-inflammation, or even iron elimination.

Structural and photoactive properties of self-assembled peptide-based nanostructures and their optical bioapplication in food analysis.

BACKGROUND: Food processing plays an important role in the modern industry because food quality and security directly affect human health, life safety, and social and economic development. Accurate, efficient, and sensitive detection technology is the basis for ensuring food quality and security. Optosensor-based technology with the advantage of fast and visual real-time detection can be used to detect pesticides, metal ions, antibiotics, and nutrients in food. As excellent optical centres, self-assembled peptide-based nanostructures possess attractive advantages, such as simple preparation methods, controllable morphology, tunable functionality, and inherent biocompatibility. AIM OF REVIEW: Self-assembled peptide nanostructures with good fabrication yield, stability, dispersity in a complex sample matrix, biocompatibility, and environmental friendliness are ideal development goals in the future. Owing to its flexible and unique optical properties, some short peptide self-assemblies can possibly be used to achieve the purpose of rapid and sensitive detection of composition in food, agriculture, and the environment, expanding the understanding and application of peptide-based optics in analytical chemistry. KEY SCIENTIFIC CONCEPT OF REVIEW: The self-assembly process of peptides is driven by noncovalent interactions, including hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, which are the key factors for obtaining stable self-assembled peptide nanostructures with peptides serving as assembly units. Controllable morphology of self-assembled peptide nanostructures can be achieved through adjustment in the type, concentration, and pH of organic solvents and peptides. The highly ordered nanostructures formed by the self-assembly of peptides have been proven to be novel biological structures and can be used for the construction of optosensing platforms in biological or other systems. Optosensing platforms make use of signal changes, including optical signals and electrical signals caused by specific reactions between analytes and active substances, to determine the content or concentration of an analyte.

Thyrotoxicosis after a massive levothyroxine ingestion: A case report.

BACKGROUND: The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited, and most cases reported have involved pediatric clinical studies. CASE SUMMARY: A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine (10 mg). The patient transiently lost consciousness and developed atrial fibrillation during hospitalization. We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine, propranolol to control heart rate, hydrocortisone to correct severe thyrotoxicosis, and hemoperfusion to increase levothyroxine clearance. The patient recovered and was discharged. CONCLUSION: For patients with thyrotoxicosis after taking excess levothyroxine, it is critical to monitor vital signs and initiate effective treatment.

Identification of core genes associated with type 2 diabetes mellitus and gastric cancer by bioinformatics analysis.

Background: Gastric cancer (GC) is the most common type of malignant neoplasm of the digestive system. Diabetes mellitus (DM) or hyperglycemia may increase the incidence or mortality of GC. We aimed to investigate the possible genetic relationship between GC, DM, and type 2 diabetes mellitus (T2DM), and to identify core genes that are associated with T2DM and GC. Methods: The GeneCards database was used to screen DM-, T2DM-, and GC-related genes, and a protein-protein interaction (PPI) network of the genes/proteins associated with overlapping genes between DM, T2DM, and GC was constructed. Molecular Complex Detection (MCODE) was used to identify the significant module. CytoHubba (U.S. National Institute of General Medical Sciences) was utilized to detect hub genes in the PPI. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) resources were used to analyze selected module genes, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment of PPI networks. The Kaplan-Meier plotter database, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and western blot were used to identify the prognostic value of hub genes and their expression in GC and normal tissue. Results: One thousand one hundred and fifty-two DM-related genes, 466 GC-related genes, and 531 T2DM-related genes were obtained. Subsequently, 401 genes/proteins associated with 59 overlapping genes were screened. Two significant modules, which had higher scores, and 10 hub genes were chosen. Finally, caspase 3 (CASP3), and tumor protein P53 (TP53) were identified as core genes. Conclusions: We identified two genes that may play key roles in T2DM and GC: CASP3, TP53. Our study will contribute to further understanding the possible mechanism of diabetes progression to GC and provide useful information to identify new biomarkers for GC, and provided theoretical basis for the prevention of the occurrence and development of GC.

Healing Diabetic Ulcers with MoO3-X Nanodots Possessing Intrinsic ROS-Scavenging and Bacteria-Killing Capacities.

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.

Rational Constructed Ultra-Small Iron Oxide Nanoprobes Manifesting High Performance for T1-Weighted Magnetic Resonance Imaging of Glioblastoma.

Precise diagnosis and monitoring of cancer depend on the development of advanced technologies for in vivo imaging. Owing to the merits of outstanding spatial resolution and excellent soft-tissue contrast, the application of magnetic resonance imaging (MRI) in biomedicine is of great importance. Herein, Angiopep-2 (ANG), which can simultaneously help to cross the blood-brain barrier and target the glioblastoma cells, was rationally combined with the 3.3 nm-sized ultra-small iron oxide (Fe3O4) to construct high-performance MRI nanoprobes (Fe3O4-ANG NPs) for glioblastoma diagnosis. The in vitro experiments show that the resultant Fe3O4-ANG NPs not only exhibit favorable relaxation properties and colloidal stability, but also have low toxicity and high specificity to glioblastoma cells, which provide critical prerequisites for the in vivo tumor imaging. Furthermore, in vivo imaging results show that the Fe3O4-ANG NPs exhibit good targeting ability toward subcutaneous and orthotopic glioblastoma model, manifesting an obvious contrast enhancement effect on the T1-weighted MR image, which demonstrates promising potential in clinical application.

Uncovering the Metabolic Origin of Aspartate for Tumor Growth Using an Integrated Molecular Deactivator.

Reprogrammed glucose metabolism is vital for cancer cells, but aspartate, an intermediate metabolic product, is the limiting factor for cancer cell proliferation. However, due to the complexity of metabolic pathways, it remains unclear whether glucose is the primary source of endogenous aspartate. Here, we report the design of an innovative molecular deactivator, based on a multifunctional upconversion nanoprobe, to explore the link between glucose and aspartate. This molecular deactivator mainly works in the acidic, hypoxic tumor microenvironment and deactivates multiple types of glucose transporters on cancer cell membranes upon illumination at 980 nm. Cancer cell proliferation in vivo is strongly inhibited by blocking glucose transporters. Our experimental data confirm that the cellular synthesis of aspartate for tumor growth is glucose-dependent. This work also demonstrates the untapped potential of molecularly engineered upconversion nanoprobes for discovering hidden metabolic pathways and improving therapeutic efficacy of conventional antitumor drugs.

Unravelling calcium-alleviated aluminium toxicity in Arabidopsis thaliana: Insights into regulatory mechanisms using proteomics.

Aluminium (Al) toxicity is a major limiting factor for plant productivity in acidic soils. Calcium (Ca) is an essential element and participates in various physiological responses to environmental stress. Here, the aim of this work was to study the role of exogenous Ca in alleviating Al toxicity in Arabidopsis thaliana. For that we used the methods of physiology and proteomics. Results showed that Ca alleviated Al-induced growth inhibition and decreased Al accumulation. Proteomic analyses showed that 75 differentially expressed protein spots, including those related to organic acid metabolism, cell wall components, cellular transport, signal transduction and antioxidant activity, transcription and protein metabolism were identified during the response of Arabidopsis to Ca alleviated Al toxicity. Ca regulated tricarboxylic acid (TCA) cycle-related protein abundances and affected organic acid concentrations and related enzyme activities under Al stress. Vacuolar and mitochondrion adenosine triphosphate (ATP) synthase, and cell wall component-related proteins played important roles in Ca-alleviated Al toxicity. Ethylene-insensitive 3 (EIN3) participated in Ca-alleviated Al toxicity. Glutathione S-transferase (GST6) and glutathione S-transferase tau 19 (ATGSTU19) were associated with antioxidant activities induced by Ca under Al stress. Our results may contribute to an understanding of the functional mechanism by which Ca alleviates Al stress in plants. SIGNIFICANT: Our results elucidated how Ca alleviate the effects of Al toxicity on the inhibition of plant growth and Al accumulation in plants using the proteomics and physiological methods, which may contribute to a better understanding of the molecular mechanism of Ca alleviation Al stress in plants.

Effects of Vaspin on Insulin Resistance in Rats and Underlying Mechanisms.

Insulin resistance (IR) is the main pathogenesis of metabolic syndrome and a shared pathophysiological change in conditions such as diabetes mellitus, adiposity, hypertension, and atherosclerosis. Visceral adipose tissue-derived serpin (Vaspin) is a newly discovered adipocytokine with insulin-sensitizing and anti-inflammatory effects. To examine if vaspin can improve insulin resistance in rats fed a high-fat diet via the insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B/glucose transport (IRS/PI3K/Akt/Glut) and inhibitory κB alpha/nuclear factor-kappa B (IκBα/NF-κB) signalling pathways, thirty male Sprague-Dawley (SD) rats were randomly divided into three groups: the normal control group (NC group, n = 10), high-fat diet group (HFD group, n = 10) and vaspin intervention group (HFD + vaspin group, n = 10). Results showed that intervention with vaspin significantly decreased fasting blood glucose (FBG) and fasting insulin (FINS) concentrations in HFD - fed rats without significantly affecting body weight or triglyceride (TG) or total cholesterol (TC) levels. The areas under the intraperitoneal glucose tolerance test (IPGTT) and the insulin tolerance test (ITT) curves were significantly decreased in HFD + vaspin group compared with the HFD group, and the glucose infusion rate (GIR) showed the same trends. Western blot, real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining showed that vaspin could improve insulin resistance in liver, skeletal muscle and adipose tissue by activating the IRS/PI3K/Akt/Glut signalling pathway and inhibiting the IκBα/NF-κB signalling pathway.

Effects of vaspin on pancreatic ß cell secretion via PI3K/Akt and NF-κB signaling pathways.

Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a recently discovered adipokine that has been implicated in diabetes mellitus and other metabolic disorders. However, the effects of vaspin on pancreatic ß cell function and related mechanisms are not fully understood. Thus, the present study was performed to investigate the effects of vaspin on pancreatic ß cell function and the potential underlying mechanisms. Both in vitro (rat insulinoma cells, INS-1) and in vivo (high fat diet fed rats) experiments were conducted. The results showed that vaspin significantly increased INS-1 cell secretory function. Potential mechanisms were explored using inhibitors, western blot and real-time PCR techniques. We found that vaspin increased the levels of IRS-2 mRNA and IRS-2 total protein, while decreased the serine phosphorylation level of IRS-2 protein. Moreover, vaspin increased the Akt phosphorylation protein level which was reversed by PI3K inhibitor ly294002. In addition, vaspin increased the phosphorylation levels of mTOR and p70S6K, which was inhibited by rapamycin. Meanwhile, we found that the NF-κB mRNA and protein levels were reduced after vaspin treatment, similar to the effect of NF-κB inhibitor TPCK. Furthermore, vaspin increased the glucose stimulated insulin secretion (GSIS) level, lowered blood glucose level and improved the glucose tolerance and insulin sensitivity of high fat diet fed rats. Hyperglycemic clamp test manifested that vaspin improved islet ß cell function. Together, these findings provide a new understanding of the function of vaspin on pancreatic ß cell and suggest that it may serve as a potential agent for the prevention and treatment of type 2 diabetes.

Combining Protein and miRNA Quantification for Bladder Cancer Analysis.

We combine the telomerase extension reaction and microRNA (miRNA)-induced rolling circle amplification, followed by graphene oxide (GO) and nicking enzyme-assisted signal amplification as a method to analyze telomerase and miRNA-21 in urine samples with the following merits. First, it is a binary assay and can simultaneously output double signals that correspond to the quantities of telomerase and miRNA, respectively. Second, telomerase activity is enhanced by using a DNA molecular beacon probe to inhibit the formation of G-quadruplex. Third, background noise is decreased significantly via introduction of GO. Fourth, performance tests on about 258 urine samples demonstrate that this binary assay can distinguish between urine from bladder cancer patients, those with cystitis, and normal individuals. Finally, this strategy also shows great potential in distinguishing between muscle-invasive bladder cancers and non-muscle-invasive bladder cancers. The proposed strategy will greatly contribute to clinical decision-making and individualized treatments.

Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic ß cells.

Pancreatic ß cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic ß cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic ß cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic ß cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic ß cells.

Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release.

Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.

The development of nanostructure assisted isothermal amplification in biosensors.

Developing simple and inexpensive methods to ultrasensitively detect biomarkers is important for medical diagnosis, food analysis and environmental security. In recent years, isothermal amplifications with sensitivity, high speed, specificity, accuracy, and automation have been designed based on interdisciplinary approaches among chemistry, biology, and materials science. In this article, we summarize the advances in nanostructure assisted isothermal amplification in the past two decades for the detection of commercial biomarkers, or biomarkers extracted from cultured cells or patient samples. This article has been divided into three parts according to the ratio of target-to-signal probe in the detection strategy, namely, the N : N amplification ratio, the 1 : N amplification ratio, and the 1 : N(2) amplification ratio.

Quencher group induced high specificity detection of telomerase in clear and bloody urines by AIEgens.

Telomerase is a widely used tumor biomarker for early cancer diagnosis. On the basis of the combined use of aggregation-induced emission (AIE) fluorogens and quencher, a quencher group induced high specificity strategy for detection of telomerase activity from cell extracts and cancer patients' urine specimens was creatively developed. In the absence of telomerase, fluorescence background is extremely low due to the short distance between quencher and AIE dye. In the addition of telomerase, fluorescence enhances significantly. The telomerase activity in the E-J, MCF-7, and HeLa extracts equivalent to 5-10 000 cells can be detected by this method in ∼1 h. Furthermore, the distinguishing of telomerase extracted from 38 cancer and 15 normal urine specimens confirms the reliability and practicality of this protocol. In contrast to our previous results (Anal. Chem. 2015, 87, 6822-6827), these advanced experiments obtain more remarkable specificity.

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays.

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.

Regulation of DNA self-assembly and DNA hybridization by chiral molecules with corresponding biosensor applications.

Chirality is one of the fundamental biochemical properties in a living system, and a lot of biological and physiological processes are greatly influenced by the chirality of molecules. Inspired by this phenomenon, we study the covalent assembly of DNA on chiral molecule modified surfaces and further discuss the hybridization of DNA on chiral surfaces with nucleic acids. Take methylene blue (MB) modified DNA as a model molecule, we show that the peak current of the L-NIBC (NIBC, N-isobutyryl-L(D)-cysteine) modified gold surface (L-surface) is larger than the D-surface because of a stronger interaction between short-chain DNA and the L-surface; however, the D-surface has a higher hybridization efficiency than the L-surface. Moreover, we apply this result to actual application by choosing an electrochemical DNA (E-DNA) sensor as a potential platform. Furthermore, we further amplify the difference of hybridization efficiency using the supersandwich assay. More importantly, our findings are successfully employed to program the sensitivity and limit of detection.