S-induced Phase Change Forming In2 O3 /In2 S3 Heterostructure for Photoelectrochemical Glucose Sensor.

In the past several decades, Photoelectrochemical (PEC) sensing still remains a great challenge to design highly-efficient semiconductor photocatalysts via a facile method. It is of much importance to design and synthesize various novel nanostructured sensing materials for further improving the response performance. Herein, we present an In2 O3 /In2 S3 heterostructure obtained by combining microwave assisted hydrothermal method with S-induced phase change, whose energy band and electronic structure could be adjusted by changing the S content. Combining theoretical calculation and spectroscopic techniques, the introduction of sulfur was proved to produce multifunctional interfaces, inducing the change of phase, oxygen vacancies and band gap, which accelerates the separation of photoexcited carriers and reduces their recombination, improving the electronic injection efficiency around the interface of In2 O3 /In2 S3 . As anticipated, an enhanced glucose response performance with a photocurrent of 0.6 mA cm-2 , a linear range of 0.1-1 mM and a detection limit as low as 14.5 µM has been achieved based on the In2 O3 /In2 S3 heterostructure, which is significant superior over its pure In2 O3 and S-doped In2 O3 counterparts. This efficient interfacial strategy may open a new route to manipulate the electrical structure, and energy band structure regulation of sensing material to improve the performance of photoelectrodes for PEC.

High-performance Vo-ZnO/ZnS benefiting nanoarchitectonics from the synergism between defect engineering and surface engineering for photoelectrochemical glucose sensors.

In this study, a ZnO/ZnS nanocluster heterojunction photoelectrode rich in surface oxygen defects (Vo-ZnO/ZnS) was prepared by applying a simple in situ anion substitution and nitrogen atmosphere annealing method. The synergism between defect and surface engineering significantly improved the photocatalysts. Given this synergism, Vo-ZnO/ZnS was endowed with a long carrier lifetime, narrow band gap, high carrier density, and high performance toward electron transfer under light conditions. Thus, Vo-ZnO/ZnS had three times the photocurrent density of ZnO under light illumination. To further evaluate its advantages in the field of photoelectric bioassay, Vo-ZnO/ZnS was applied as the photocathode of photoelectric sensor system for glucose detection. Vo-ZnO/ZnS showed excellent performance in glucose detection in various aspects, including a low detection limit, high detection sensitivity, and a wide detection range.

In situ growth of TiO2/Ti3C2 MXene Schottky heterojunction as a highly sensitive photoelectrochemical biosensor for DNA detection.

In this work, a heterojunction composed of a TiO2 nanosheet and layered Ti3C2 was synthesized by directly growing TiO2 in Ti3C2 MXene. Compared with pure TiO2, TiO2/Ti3C2 composites had increased surface area, and a light absorption range that extended from ultraviolet to visible light, which greatly extended the life of photogenerated carriers. A photoelectrochemical biosensor for DNA detection was constructed based on the TiO2/Ti3C2 heterogeneous structure, which was comprehensively studied based on photocurrent responses. In the absence of the target, the CdSe QDs were close to the surface of the electrode, resulting in enhanced sensitization and increased photocurrent. In the presence of the target, the photocurrent decreases due to the formation of rigid double strands with the probe DNA, which caused the CdSe QDs to be far away from the electrode surface. The sensor had stability and sensitivity for DNA detection in the range of 10 nM-10 fM, and the lower detection limit was 6 fM. Its outstanding characteristics also provided ideas for detecting various other target DNA for early diagnosis of various diseases.

Kinetics-accelerated one-step detection of MicroRNA through spatially localized reactions based on DNA tile self-assembly.

The localization of isothermal amplification systems has elicited extensive attention due to the enhanced reaction kinetics when detecting ultra-trace small-molecule nucleic acids. Therefore, the seek for an appropriate localization cargo of spatially confined reactions is urgent. Herein, we have developed a novel approach to localize the catalytic hairpin assembly (CHA) system into the DNA tile self-assembly nanostructure. Thanks to the precise programming and robust probe loading capacity, this strategy achieved a 2.3 × 105-fold higher local reaction concentration than a classical CHA system with enhanced reaction kinetics in theory. From the experimental results, this strategy could reach the reaction plateau faster and get access to a magnified effect of 1.57-6.99 times higher in the linear range of microRNA (miRNA) than the simple CHA system. Meanwhile, this strategy satisfied the demand for the one-step detection of miRNA in cell lysates at room temperature with good sensitivity and specificity. These features indicated its excellent potential for ultra-trace molecule detection in clinical diagnosis and provided new insights into the field of bioassays based on DNA tile self-assembly nanotechnology.

Engineering exposed vertical nano-TiO2 (001) facets/BiOI nanosheet heterojunction film for constructing a satisfactory PEC glucose oxidase biosensor.

In the field of photoelectrochemical (PEC) enzyme biosensors, constructing efficient photoelectrodes, in which the recombination of photogenerated carriers is an important factor affecting the performance, is of great significance. Herein, to enhance the separation efficiency of photogenerated carriers, titanium dioxide (TiO2) nanosheet (NS)/bismuth oxyiodide (BiOI) NS/glucose oxidase (GOx) composites were prepared via hydrothermal and solvothermal methods. Single-crystal anatase TiO2 NSs with a high percentage of (001) facets lead to better photocarrier separation due to heterojunctions between facets. After coupling with BiOI NSs, the photoelectrochemical performance of the electrode was greatly improved. The photogenerated electrons from TiO2 and BiOI gathered at TiO2 (101) and were exported through the fluorine-doped tin oxide (FTO) substrate to generate electrical signals. Photogenerated holes were transferred to TiO2 (001) and BiOI to participate in the enzymatic reaction, showing the outstanding separation of electrons and holes. The prepared TiO2 NS/BiOI NS/GOx glucose biosensor achieved satisfactory results, with sensitivity of 14.25 µA mM-1 cm-2, a linear measurement range of 0-1 mM, and a limit of detection (3S/N) of 0.01 mM in phosphate buffered saline (PBS) at a pH of 7.4. The mechanism for the efficient separation of photogenerated carriers based on the facet heterojunctions introduced in this paper also provides new insights into other optoelectronic biosensors.

Identification of Key Prognostic Genes of Triple Negative Breast Cancer by LASSO-Based Machine Learning and Bioinformatics Analysis.

Improved insight into the molecular mechanisms of triple negative breast cancer (TNBC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify key genes which may affect the prognosis of TNBC patients by bioinformatic analysis. In our study, the RNA sequencing (RNA-seq) expression data of 116 breast cancer lacking ER, PR, and HER2 expression and 113 normal tissues were downloaded from The Cancer Genome Atlas (TCGA). We screened out 147 differentially co-expressed genes in TNBC compared to non-cancerous tissue samples by using weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were constructed, revealing that 147 genes were mainly enriched in nuclear division, chromosomal region, ATPase activity, and cell cycle signaling. After using Cytoscape software for protein-protein interaction (PPI) network analysis and LASSO feature selection, a total of fifteen key genes were identified. Among them, BUB1 and CENPF were significantly correlated with the overall survival rate (OS) difference of TNBC patients (p value < 0.05). In addition, BUB1, CCNA2, and PACC1 showed significant poor disease-free survival (DFS) in TNBC patients (p value < 0.05), and may serve as candidate biomarkers in TNBC diagnosis. Thus, our results collectively suggest that BUB1, CCNA2, and PACC1 genes could play important roles in the progression of TNBC and provide attractive therapeutic targets.

Cross-Platform in-silico Analyses Exploring Tumor Immune Microenvironment with Prognostic Value in Triple-Negative Breast Cancer.

Introduction: Only a proportion of triple-negative breast cancer (TNBC) is immunotherapy-responsive. We hypothesized that the tumor microenvironment (TME) influences the outcomes of TNBC and investigated the relevant signaling pathways. Materials and Methods: Immune score (IS) and stromal score (SS) were calculated using the ESTIMATE and correlated with the overall survival (OS) in TNBC. RNA-seq data from 115 TNBC samples and 112 normal adjacent tissues were retrieved. Validations in the methylation levels in 10 TNBC and five non-TNBC cell lines were obtained. Cox model overall survival (OS) validated the derived transcription factor (TF) genes in cBioPortal breast cancer patients. Results: SS-low predicts a higher OS compared with SS-high patients (P = 0.0081 IS-high/SS-low patients had better OS (P = 0.045) than IS-low/SS-high patients. More macrophages were polarized to the M2 state in patients with IS-low/SS-high patients (P < 0.001). Moreover, CIBERSORTx showed more CD8+ cytotoxic T-cells in IS-high/SS-low patients (p = 0.0286) and more resting NK cells in the IS-low/SS-high TME (P = 0.0108). KEGG pathway analysis revealed that overexpressed genes were enriched in the IL-17 and cytokine-cytokine receptor interaction pathways. The lncRNA DRAIC, a tumor suppressor, was consistently deactivated in the 10 TNBC cell lines. On the cBioPortal platform, we validated that 13% of ER-negative, HER2-unamplified BC harbored IL17RA deep deletion and 25% harbored TRAF3IP2 amplification. On cBioPortal datasets, the nine altered TF genes derived from the X2K analysis showed significantly worse relapse-free survival in 2377 patients and OS in 4819 invasive BC patients than in the unaltered cohort. Conclusion: Of note, the results of this integrated in silico study can only be generalized to approximately 17% of patients with TNBC, in which infiltrating stromal cells and immune cells play a determinant prognostic role.

Construction of eight mixed-valence pentanuclear CuI4CuII clusters using ligands with inhomogeneous electron density distribution: synthesis, characterization and photothermal properties.

To enhance light absorption in the visible region for the utilization of sunlight, eight mixed-valence polynuclear CuI/CuII clusters have been synthesized for evaluating their photothermal conversion performance. They are fabricated considering the ligand's electron density distribution inhomogeneity using 1,2,3-triazole (3N) or tetrazole (4N) and different mono-phosphine ligands. We report here the synthesis, crystal structure, characterization, optical properties, and photothermal conversion performance of these clusters. X-ray crystal structures reveal that those pentanuclear clusters are neutral clusters with octahedrally-coordinated copper(II) ion being surrounded by four tetrahedrally coordinated copper(I) ions. Interestingly, with the introduction of the mixed-valence centers, these compounds show additional light absorption centers in 350-600 nm via the IVCT transition mechanism, compared with our previously reported Cu(II) compounds. These clusters show excellent photothermal conversion performance, with an average equilibrium temperature (∼60 °C) and a temperature increment (∼40 °C), which are also superior to Cu(II) complexes (the average equilibrium temperature ∼55 °C). This work proves that it is possible to design and prepare new polynuclear mixed-valence CuI/CuII clusters for achieving high-performance photothermal conversion materials.

Photoelectrochemical Enzyme Biosensor Based on TiO2 Nanorod/TiO2 Quantum Dot/Polydopamine/Glucose Oxidase Composites with Strong Visible-Light Response.

Although photoelectrochemical (PEC) enzyme biosensors based on visible-light detection would have a high practical value, their development has been limited by the weak visible-light response of available photoactive substrates. Here, to enhance the visible-light response of a photoelectric substrate, a TiO2 nanorods (NRs)/TiO2 quantum dots (QDs)/polydopamine (PDA)/glucose oxidase nanocomposite was prepared via hydrothermal synthesis, followed by photopolymerization. TiO2 QDs with strong light absorption and excellent photocatalytic activity were introduced between the TiO2 NRs and the PDA. An efficient electron transport interface that formed as a result of the combination of the TiO2 NRs, TiO2 QDs, and the PDA could not only transfer electrons quickly and orderly, but also substantially improve the response of the TiO2 NRs under visible light. Through a series glucose detection, a sensor based on the nanocomposite was found to exhibit superior sensing performance under visible light with a sensitivity of 4.63 µA mM-1 cm-2, a linear response over the concentration 0.1-4 mM, and a detection limit of 8.16 µM. This work proposes a biosensor that can detect under visible light, thereby expanding the application range of PEC enzyme biosensors.

Gold and Platinum Nanoparticle-Functionalized TiO2 Nanotubes for Photoelectrochemical Glucose Sensing.

Developing stable photoelectrochemistry (PEC) glucose biosensors with high sensitivity and a low detection limit is highly desirable in the biosensor field. Herein, a highly sensitive and stable enzymatic glucose PEC biosensor is rationally designed and fabricated using a TiO2NTs/Au/Pt/GOx electrode. First, we prepared one-dimensional TiO2 nanotube arrays which could realize the orthogonalization of the light-incident direction and the carrier diffusion direction via anodization. Subsequently, we used the method of photoassisted deposition for anchoring Pt nanoparticles on TiO2NTs after electrodepositing Au nanoparticles. Among them, Au nanoparticles promote light absorption via the surface plasmon resonance effect and the separation of photogenerated carriers through forming a Schottky junction. Moreover, the Pt nanoparticles on the electrode surface can react with hydrogen peroxide (H2O2) generated from glucose (Glu) oxidation by glucose oxidase (GOx), accelerating the electron-transfer process during glucose oxidation and greatly improving the sensitivity of the glucose biosensor. As a result, TiO2NTs/Au/Pt/GOx exhibited excellent PEC performance, achieving a high sensitivity of 81.93 µA mM-1 cm-2 and a low detection limit (1.39 µM), far exceeding the performance of TiO2NTs/M/GOx (M = Au, Pt). Therefore, the introduction of Pt nanoparticles as active substances to promote enzymatic reactions is important for designing high-performance enzyme biosensors.

LASSO and Bioinformatics Analysis in the Identification of Key Genes for Prognostic Genes of Gynecologic Cancer.

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium-calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.

Highly Accurate and Fast Electrochemical Detection of Scrub Typhus DNA via a Nanoflower NiFe-Based Biosensor.

Owing to the lack of specific diagnostic methods, Scrub typhus can sometimes be difficult to diagnose in the Asia-Pacific region. Therefore, an efficient and rapid detection method urgently needs to be developed. Based on competitive single-stranded DNA over modified glassy carbon electrode (GCE), an electrochemical biosensor was established to detect the disease. The nano-flower NiFe layered double hydroxide (NiFe-LDH) modified GCE has a large specific surface area, which supported a large amount of gold nanoparticles, so that a wide linear detection range from 25 fM to 0.5 µM was obtained. The beacon DNA (B-DNA) with the same sequence as the Scrub typhus DNA (T-DNA), but labeled with methylene blue, was used to construct a competitive relationship. When T-DNA and B-DNA were present on the sensor simultaneously, they would hybridize with probe DNA in a strong competition, and the corresponding electrochemical response signal would be generated via testing. It contributed to reducing tedious experimental procedures and excessive response time, and achieved fast electrochemical detection of DNA. The strategy provides a worthy avenue and possesses promising applications in disease diagnosis.

Donor-Acceptor Compensated ZnO Semiconductor for Photoelectrochemical Biosensors.

Hindering the recombination of a photogenerated carrier is a crucial method to enhance the photoelectrochemical performance of ZnO due to its high exciton binding energy. Herein, the intramolecular donor-acceptor compensated semiconductor ZnO (I-D/A ZnO), introducing C dopants and oxygen vacancies, was prepared with the assistance of ascorbic acid (AA). According to the DFT calculations, the asymmetry DOS could lead to the longer carrier lifetime and the smaller electron transfer resistance. Then, the photoelectrochemical biosensor toward glucose was regarded as a model to discuss the application of ZnO in biosensors. As a result, the biosensor based on I-D/A ZnO showed good performance with high sensitivity, low limit of detection, and fine anti-interference, meaning that I-D/A ZnO is a promising semiconductor for photoelectrochemical biosensors.

Enhancing the performance of photoelectrochemical glucose sensor via the electron cloud bridge of Au in SrTiO3/PDA electrodes.

Developing photoelectrochemical biosensors via efficient photogenerated-charge separation remains a challenging task in biomolecular detection. In this study, we utilised a simple approach for constructing an efficient photoactive organic-inorganic heterojunction interface composed of SrTiO3 with high photocatalytic activity and polydopamine (PDA) with high biocompatibility and electrical conductivity. Gold nanoparticles with dense electron cloud properties were introduced as a bridge between SrTiO3 and PDA (SrTiO3/Au/PDA). The Au bridge allowed the PDA to uniformly and tightly attach on the surface of SrTiO3 electrodes and also provided a separate transmission channel for electrons from PDA to SrTiO3. The rapidly transmitted electrons were captured by a signal-acquisition system, thereby improving the photocurrent signal output. The 3D hollowed out SrTiO3/Au/PDA biosensor manufactured herein was used for glucose detection. The biosensor achieved ultrahigh sensitivities reaching 23.7 µA mM-1 cm-2, an extended linear range (1-20 mM), and a low detection limit (0.012 mM). The excellent results of glucose analysis in serum samples further confirmed the feasibility of the biosensor in clinical applications. In summary, the proposed strategy allowed for the use of an electronic cloud bridge in the construction of glucose biosensors with satisfactory performances, which is promising for the future fabrication of high-performance biosensors.

A novel electrochemical biosensor for ultrasensitive Hg2+ detection via a triple signal amplification strategy.

We developed a novel electrochemical biosensor for ultrasensitive Hg2+ detection via a triple signal amplification strategy of a DNA dual cycle, organic-inorganic hybrid nanoflowers (Cu3(PO4)2 HNFs) and gold nanoparticle (AuNP) probe. The DNA dual cycle was triggered by exonuclease III (Exo III) in the presence of Hg2+, and Cu3(PO4)2 HNFs were synthesized as an AuNP probe carrier. The electrochemical biosensor displayed high stability, high sensitivity and excellent specificity, which was improved by up to seven orders of magnitude compared to the World Health Organization (WHO) allowed Hg2+ levels in drinking water. This signal amplification strategy could be easily modified and extended to detect other hazardous heavy metals and nucleic acids.

Glucose photoelectrochemical enzyme sensor based on competitive reaction of ascorbic acid.

A new method based on the competitive reaction of ascorbic acid (AA) was used to improving the performance of photoelectrochemical glucose enzyme sensor. In this method, amplifying the photoelectric signal of H2O2 by the competitive reaction of AA is the key step. The detection can be well operated at 0 V under optimal AA concentration of 10 mM. In the method, AA was regarded as not only the electron donor to capture the hole in the conduction band of ZnO, but also the remover of H2O2 produced by the oxidation of glucose. Both these factors led to the formation of a pair of competitive reactions that enhanced the response towards glucose detection. Compared to the detection without AA, the stability of the response current, detection ranges of 1-19 mM, detection limit of 80 µM and sensitivity of 2.88 µA mM-1·cm-2 were optimized prominently.

Enhanced photoelectrochemical biosensing performance for Au nanoparticle-polyaniline-TiO2 heterojunction composites.

A new photoelectrochemical (PEC) sensing platform comprising TiO2 nanotube arrays (TiONTAs), polyaniline (PANI), and gold nanoparticles (AuNPs) was successfully fabricated. After loading the enzyme, this Au-PANI-TiONTA electrode showed excellent response to glucose at a linear range of 2-36 mM with a 0.02 mM detection limit. Good PEC performance was obtained due to the following advantages of the material: high visible-light harvesting ability for excellent light trapping capacity of PANI and AuNPs, good separation of the photo-induced charges related to the specific Au-PANI-TiONTA heterostructure, efficient electrode surface reaction kinetics derived from the large specific surface area of TiONTAs and improved electrode catalytic activity. This work proposed a new and general PEC enzymatic format and can be extended to prepare different PEC biosensors for biomolecules such as DNA, proteins and substrates of oxidases.

Simultaneous Electrochemical Detection of Nitrite and Hydrogen Peroxide Based on 3D Au-rGO/FTO Obtained Through a One-Step Synthesis.

In this paper, Au and reduced graphene oxide (rGO) were successively deposited on fluorine-doped SnO2 transparent conductive glass (FTO, 1 × 2 cm) via a facile and one-step electrodeposition method to form a clean interface and construct a three-dimensional network structure for the simultaneous detection of nitrite and hydrogen peroxide (H2O2). For nitrite detection, 3D Au-rGO/FTO displayed a sensitivity of 419 µA mM-1 cm-2 and a linear range from 0.0299 to 5.74 mM, while for the detection of H2O2, the sensitivity was 236 µA mM-1 cm-2 and a range from 0.179 to 10.5 mM. The combined results from scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, X-ray diffraction measurements (XRD) and electrochemical tests demonstrated that the properties of 3D Au-rGO/FTO were attributabled to the conductive network consisting of rGO and the good dispersion of Au nanoparticles (AuNPs) which can provide better electrochemical properties than other metal compounds, such as a larger electroactive surface area, more active sites, and a bigger catalytic rate constant.