BINDTI: A bi-directional Intention network for drug-target interaction identification based on attention mechanisms.

The identification of drug-target interactions (DTIs) is an essential step in drug discovery. In vitro experimental methods are expensive, laborious, and time-consuming. Deep learning has witnessed promising progress in DTI prediction. However, how to precisely represent drug and protein features is a major challenge for DTI prediction. Here, we developed an end-to-end DTI identification framework called BINDTI based on bi-directional Intention network. First, drug features are encoded with graph convolutional networks based on its 2D molecular graph obtained by its SMILES string. Next, protein features are encoded based on its amino acid sequence through a mixed model called ACmix, which integrates self-attention mechanism and convolution. Third, drug and target features are fused through bi-directional Intention network, which combines Intention and multi-head attention. Finally, unknown drug-target (DT) pairs are classified through multilayer perceptron based on the fused DT features. The results demonstrate that BINDTI greatly outperformed four baseline methods (i.e., CPI-GNN, TransfomerCPI, MolTrans, and IIFDTI) on the BindingDB, BioSNAP, DrugBank, and Human datasets. More importantly, it was more appropriate to predict new DTIs than the four baseline methods on imbalanced datasets. Ablation experimental results elucidated that both bi-directional Intention and ACmix could greatly advance DTI prediction. The fused feature visualization and case studies manifested that the predicted results by BINDTI were basically consistent with the true ones. We anticipate that the proposed BINDTI framework can find new low-cost drug candidates, improve drugs' virtual screening, and further facilitate drug repositioning as well as drug discovery. BINDTI is publicly available at https://github.com/plhhnu/BINDTI.

Repair of Infected Bone Defects with Hydrogel Materials.

Infected bone defects represent a common clinical condition involving bone tissue, often necessitating surgical intervention and antibiotic therapy. However, conventional treatment methods face obstacles such as antibiotic resistance and susceptibility to postoperative infections. Hydrogels show great potential for application in the field of tissue engineering due to their advantageous biocompatibility, unique mechanical properties, exceptional processability, and degradability. Recent interest has surged in employing hydrogels as a novel therapeutic intervention for infected bone repair. This article aims to comprehensively review the existing literature on the anti-microbial and osteogenic approaches utilized by hydrogels in repairing infected bones, encompassing their fabrication techniques, biocompatibility, antimicrobial efficacy, and biological activities. Additionally, the potential opportunities and obstacles in their practical implementation will be explored. Lastly, the limitations presently encountered and the prospective avenues for further investigation in the realm of hydrogel materials for the management of infected bone defects will be deliberated. This review provides a theoretical foundation and advanced design strategies for the application of hydrogel materials in the treatment of infected bone defects.

Preparation of Gold Nanoparticles via Anodic Stripping of Copper Underpotential Deposition in Bulk Gold Electrodeposition for High-Performance Electrochemical Sensing of Bisphenol A.

Bisphenol A is one of the most widely used industrial compounds. Over the years, it has raised severe concern as a potential hazard to the human endocrine system and the environment. Developing robust and easy-to-use sensors for bisphenol A is important in various areas, such as controlling and monitoring water purification and sewage water systems, food safety monitoring, etc. Here, we report an electrochemical method to fabricate a bisphenol A (BPA) sensor based on a modified Au nanoparticles/multiwalled carbon nanotubes composite electrocatalyst electrode (AuCu-UPD/MWCNTs/GCE). Firstly, the Au-Cu alloy was prepared via a convenient and controllable Cu underpotential/bulk Au co-electrodeposition on a multiwalled modified carbon nanotubes glassy carbon electrode (GCE). Then, the AuCu-UPD/MWCNTs/GCE was obtained via the electrochemical anodic stripping of Cu underpotential deposition (UPD). Our novel prepared sensor enables the high-electrocatalytic and high-performance sensing of BPA. Under optimal conditions, the modified electrode showed a two-segment linear response from 0.01 to 1 µM and 1 to 20 µM with a limit of detection (LOD) of 2.43 nM based on differential pulse voltammetry (DPV). Determination of BPA in real water samples using AuCu-UPD/MWCNTs/GCE yielded satisfactory results. The proposed electrochemical sensor is promising for the development of a simple, low-cost water quality monitoring system for the detection of BPA in ambient water samples.

Development of a rapid, sensitive detection method for SARS-CoV-2 and influenza virus based on recombinase polymerase amplification combined with CRISPR-Cas12a assay.

Respiratory tract infections are associated with the most common diseases transmitted among people and remain a huge threat to global public health. Rapid and sensitive diagnosis of causative agents is critical for timely treatment and disease control. Here, we developed a novel method based on recombinase polymerase amplification (RPA) combined with CRISPR-Cas12a to detect three viral pathogens, including SARS-CoV-2, influenza A, and influenza B, which cause similar symptom complexes of flu cold in the respiratory tract. The detection method can be completed within 1 h, which is faster than other standard detection methods, and the limit of detection is approximately 102 copies/µL. Additionally, this detection system is highly specific and there is no cross-reactivity with other common respiratory tract pathogens. Based on this assay, we further developed a more simplified RPA/CRISPR-Cas12a system combined with lateral flow assay on a manual microfluidic chip, which can simultaneously detect these three viruses. This low-cost detection system is rapid and sensitive, which could be applied in the field and resource-limited areas without bulky and expensive instruments, providing powerful tools for the point-of-care diagnostic.

A Ratiometric Fluorescence Biosensor for Detection of Alkaline Phosphatase Via an Advanced Chemometric Model.

In this paper, a ratiometric fluorescence biosensor was introduced for alkaline phosphatase (ALP) detection based on 2-aminopurine (2-Amp) and thioflavin T (ThT)-G-quadruplex system. We designed a special DNA (5'-AGGGTTAGGGTTAGGGTTAGGGAAA/i2-Amp/AAAA-PO4-3', AP) modified with a phosphate moiety at the 3'-end, G-quadruplex at the 5'-end, and a fluorophore (2-Amp) in the middle. In the absence of ALP, the G-rich AP strand could be prone to fold into G-quadruplex structures in the presence of K+. Then, ThT combined with G-quandruplex, resulting in the enhancement of fluorescence emission peak at 485 nm. However, ALP-mediated hydrolysis of the 3'-phosphoryl end promoted the cleavage of AP by the exonuclease I (Exo I), releasing 2-Amp which displayed a strong fluorescence emission peak at 365 nm. Moreover, the quantitative fluorescence model (QFM) was derived for the analysis of the fluorescence measurements obtained by the proposed ratiometric fluorescent biosensor. With the aid of the advanced model, the proposed ratiometric fluorescent biosensor possessed satisfactory results for the detection of ALP in the human serum samples, with accuracy comparable to that of the reference method-the commercial ALP assay kit. Under the optimized experimental conditions, this method exhibited good selectivity and higher sensitivity, and the detection limit was found to be as low as 0.017 U/L. Therefore, it is reasonable to expect that the method had a great potential to detect ALP quantitatively in clinical diagnosis.

Recent Progress in Single-Nucleotide Polymorphism Biosensors.

Single-nucleotide polymorphisms (SNPs), the most common form of genetic variation in the human genome, are the main cause of individual differences. Furthermore, such attractive genetic markers are emerging as important hallmarks in clinical diagnosis and treatment. A variety of destructive abnormalities, such as malignancy, cardiovascular disease, inherited metabolic disease, and autoimmune disease, are associated with single-nucleotide variants. Therefore, identification of SNPs is necessary for better understanding of the gene function and health of an individual. SNP detection with simple preparation and operational procedures, high affinity and specificity, and cost-effectiveness have been the key challenge for years. Although biosensing methods offer high specificity and sensitivity, as well, they suffer drawbacks, such as complicated designs, complicated optimization procedures, and the use of complicated chemistry designs and expensive reagents, as well as toxic chemical compounds, for signal detection and amplifications. This review aims to provide an overview on improvements for SNP biosensing based on fluorescent and electrochemical methods. Very recently, novel designs in each category have been presented in detail. Furthermore, detection limitations, advantages and disadvantages, and challenges have also been presented for each type.

Highly Stereodivergent Synthesis of Chiral C4-Ester-Quaternary Pyrrolidines: A Strategy for the Total Synthesis of Spirotryprostatin A.

In this work, we disclose two sets of highly diastereo- and enantioselective [3 + 2] cycloadditions of iminoesters with various α-substituted acrylates, especially for sterically hindered and weakly activated α-aryl or alkyl-substituted acrylates and alkenal, alkynal, or unstable aliphatic aldehyde-derived iminoesters, catalyzed by the AgHMDS/DTBM-Segphos or Ag2O/CA-AA-Amidphos catalytic system, achieving the stereodivergent synthesis of chiral C4-ester-quaternary exo- or endo-pyrrolidines with high yields and excellent diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). More importantly, the gram-scale synthetic exo-adduct displays significant applications in the aspect of realizing the total synthesis of the spirotryprostatin A alkaloid via nine steps in a 36% overall yield.

A simple paper-based nickel nanocluster-europium mixed ratio fluorescent probe for rapid visual sensing of tetracyclines.

In this work, a ratiometric fluorometric sensor based on nickel nanoclusters (NiNCs)-europium complex (NiNCs-Eu3+) was constructed for the highly selectivity detection of tetracyclines (TCs) in water samples. In the presence of TCs, the blue fluorescence of the sensor NiNCs-Eu3+ was quenched at 430 nm and the characteristic red fluorescence of Eu3+-TCs appeared at 620 nm because of the combined help of inner filter effect (IFE) and antenna effect. Under the optimized conditions (100 mM Eu3+ (100 µL); temperature (25℃); reaction time (10 min), HEPES buffer solution (pH = 7.0)), the sensor offered a wide detection range of tetracycline (TC) and oxytetracycline (OTC) from 0.1 to 50 µM with the detection limit (LOD) of 25 nM and 21 nM, respectively. Moreover, the sensor was able to detect of TC and OTC in tap and lake water with high recovery rate (89.10%-97.60%). In addition, the portable paper-based sensor was constructed using filter paper embedded with NiNCs-Eu3+. The distinct fluorescent color of the paper-based sensor varied from bright blue to red against different concentrations of TC and OTC. These above findings demonstrated the potential for wide application of as-prepared ratio metric fluorescence sensor for visual detection of TCs in water samples.

Recent progress of microfluidic chips in immunoassay.

Microfluidic chip technology is a technology platform that integrates basic operation units such as processing, separation, reaction and detection into microchannel chip to realize low consumption, fast and efficient analysis of samples. It has the characteristics of small volume need of samples and reagents, fast analysis, low cost, automation, portability, high throughout, and good compatibility with other techniques. In this review, the concept, preparation materials and fabrication technology of microfluidic chip are described. The applications of microfluidic chip in immunoassay, including fluorescent, chemiluminescent, surface-enhanced Raman spectroscopy (SERS), and electrochemical immunoassay are reviewed. Look into the future, the development of microfluidic chips lies in point-of-care testing and high throughput equipment, and there are still some challenges in the design and the integration of microfluidic chips, as well as the analysis of actual sample by microfluidic chips.

Single-crystal ordered macroporous metal-organic framework as support for molecularly imprinted polymers and their integration in membrane formant for the specific recognition of zearalenone.

Zearalenone is a fungal contaminant that is widely present in grains. Here, a novel molecularly imprinted membrane based on SOM-ZIF-8 was developed for the rapid and highly selective identification of zearalenone in grain samples. The molecularly imprinted membrane was prepared using polyvinylidene fluoride, cyclododecyl 2,4-dihydroxybenzoate as a template and SOM-ZIF-8 as a carrier. The factors influencing the extraction of zearalenone using this membrane, including the solution pH, extraction time, elution solvent, elution time, and elution volume, were studied in detail. The optimized conditions were 5 mL of sample solution at pH 6, extraction time of 45 min, 4 mL of acetonitrile:methanol = 9:1 as elution solvent, and elution time of 20 min. This method displayed a good linear range of 12-120 ng/g (R2  = 0.998) with the limits of detection and quantification of this method are 1.7 and 5.5 ng/g, respectively. In addition, the membrane was used to selectively identify zearalenone in grain samples with percent recoveries ranging from 87.9 to 101.0% and relative standard deviation of less than 6.6%. Overall, this study presents a simple and effective chromatographic pretreatment method for detecting zearalenone in food samples.

Highly Selectivity Molecularly Imprinted Fluorescence Sensor Based on Carbon Quantum Dots for the Determination of Anthraquinones.

Due to the complexity of traditional Chinese medicines (TCMs), it is very important to develop a method that can recognize anthraquinones, the active ingredients in TCMs, with high selectivity. Here, a molecularly imprinted fluorescence sensor was coated on the surface of carbon quantum dots (CDs). Allobarbital was used as functional monomer for this application using theoretical calculations and was successfully synthesized and characterized. The template molecule chrysophanol was combined with the functional monomer allobarbital using a hydrogen bond array. Then, a series of adsorption experiments were performed to study the specific recognition of anthraquinones by the prepared sensors. The results showed that the prepared sensor had a good linear response to concentrations of chrysophanol in the concentration range 0.5 mg · L-1 to 8.0 mg · L-1, a low detection limit (5.0 µg · L-1), high stability, and a short response time (20 min). Additionally, the obtained fluorescence sensor was successfully applied to selectively recognize anthraquinones in TCMs with recoveries of 90.1% to 101.7%. The prepared sensor displays excellent sensitivity and high selectivity towards anthraquinones, mainly due to the specific hydrogen binding sites for the target molecules. Overall, this fluorescence sensor can selectively recognize anthraquinones in TCMs, and provide a method for quality monitoring and rational utilization of TCMs.

Two-Photon Fluorescent Nanomaterials and Their Applications in Biomedicine.

In recent years, two-photon excited (TPE) materials have attracted great attentions because of their excellent advantages over conventional one-photon excited (OPE) materials, such as deep tissue penetration, three-dimensional spatial selectivity and low phototoxicity. Also, they have been widely applied in lots of field, such as biosensing, imaging, photo-catalysis, photoelectric conversion, and therapy. In this article, we review recent advances in vibrant topic of two-photon fluorescent nanomaterials, including organic molecules, quantum dots (QDs), carbon dots (CDs) and metal nanoclus-ters (MNCs). The optical properties, synthetic methods and important applications of TPE nanomaterials in biomedical field, such as biosensing, imaging and therapy are introduced. Also, the probable challenges and perspectives in the forthcoming development of two-photon fluorescent nanomaterials are addressed.

Synthesis of a Molecularly Imprinted Polymer on NH2-MIL-101(Cr) for Specific Recognition of Diclofenac Sodium.

A novel molecularly imprinted polymer material based on the metal-organic framework NH2-MIL-101(Cr) (MOF-MIP) was prepared. The synthesized MOF-MIP was characterized by IR, XRD, SEM and N2 absorption. The characterization results displayed that the MOF-MIP which exhibited an octahedral shape had good dispersibility, good thermal stability and a high surface area. Subsequently, the adsorption behavior of MOF-MIP to diclofenac sodium (DS) in aqueous solution was examined. A series of adsorption experiments demonstrated that the MOF-MIP had high transfer mass rates and high sensitivity and selectivity for DS. Then the MOF-MIP was used as the adsorbent of dispersive micro-solid phase extraction (DMSPE) for the detection of DS in urine. Under optimum conditions, the average recovery of DS ranged from 88.3 to 101.6% with RSD of 5.6%. The described method provides a rapid route for determination of DS in human urine.

Applications of Gold Nanoparticles in Non-Optical Biosensors.

Due to their unique properties, such as good biocompatibility, excellent conductivity, effective catalysis, high density, and high surface-to-volume ratio, gold nanoparticles (AuNPs) are widely used in the field of bioassay. Mainly, AuNPs used in optical biosensors have been described in some reviews. In this review, we highlight recent advances in AuNP-based non-optical bioassays, including piezoelectric biosensor, electrochemical biosensor, and inductively coupled plasma mass spectrometry (ICP-MS) bio-detection. Some representative examples are presented to illustrate the effect of AuNPs in non-optical bioassay and the mechanisms of AuNPs in improving detection performances are described. Finally, the review summarizes the future prospects of AuNPs in non-optical biosensors.

A Portable Multi-Channel Turbidity System for Rapid Detection of Pathogens by Loop-Mediated Isothermal Amplification.

This study aimed at developing a portable multi-channel turbidity system (21 cm in length, 15.5 cm in width and 11.5 cm in depth) by real-time loop-mediated isothermal amplification (LAMP) method for rapid detection of pathogens. The developed system herein includes temperature control unit, photoelectric detection unit, turbidity calibration unit, power management unit, human machine unit, communication unit and ARM-based microcontroller. The coefficient of variation for eight channels is less than 0.25% in noise analysis. Legionella bacteria (LEG) and H7 subtype virus (H7) were successively detected by the designed and developed system within 60 minutes. Moreover, its specificity for LEG is satisfactory and its sensitivity for H7 is 10 copies/mL. Besides, this system for point-of-care diagnosis allows a rapid, small size, low cost, and automatic detection with the characteristics of high-efficiency, excellent stability and high uniformity.

Applications of gold nanoparticles in optical biosensors.

Currently gold nanoparticles are widely used in optical bioassays because of their characteristics, such as good biocompatibility, excellent optical performance, special catalytic activity and the convenience of controlled fabrication. This review describes the application development of gold nanoparticles in various optical biosensors, including colorimetry, scanometry, dry-reagent strip, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), chemiluminescence and fluorescent biosensors. Firstly, we present the underlying principles that contribute to the enhanced detection capability of gold nanoparticles, taking advantage of their unique characteristics in these bioassay methods. We then demonstrate selected examples to illustrate the development of each method, focusing on the performance improvement of the biosensor, such as sensitivity, selectivity and so on. Finally, we conclude and discuss the future prospects of using gold nanoparticles in biosensors.

Development of flowing automatic quartz crystal microbalance system for DNA detection.

A novel flowing automatic QCM (Quartz Crystal Microbalance) system for DNA detection was fabricated in this paper. The system included a multi-channel flowing system, a flow cell and a constant temperature controlling system, which integrated multi-functions such as flowing detection, temperature controlling and automatic analysis. Moreover, this system was utilized for DNA immobilization and hybridization detection. The results showed that the system is of good stability and validity.

Magnetic/polymer/nanogold complex using as a novel enzyme support.

A novel enzyme support based on magnetic/polymer/nanogold complex was prepared in this study. At first, carboxymethyl chitosan (CMC) were connected onto the surface of Fe3O4 nanoparticles, and then gold nanoparticles were in situ synthesized and bound to CMC chains, resulting in Fe3O4/CMC/nanogold complex. The complex was determined by UV-vis spectroscopy, transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). Horseradish peroxidase (HRP) was immobilized on the Fe3O4/CMC/nanogold complex. Compared with free HRP, the immobilized HRP exhibits higher catalytic activity and better storage stability. This Fe3O4/CMC/nanogold complex can serve as an excellent support for enzymes.

[Magnetic/luminescent quantum dots bifunctional nanoparticles labeling of rat bone mesenchymal stem cells].

OBJECTIVE: To evaluate the dual-labeling efficiency of magnetic and luminescent quantum dots bifunctional nanoparticles to rat bone mesenchymal stem cells (BMSC). METHODS: Rat BMSC were isolated, purified, and expanded. Magnetic/luminescent bifunctional nanoparticles (Fe(3)O(4)@CdTe@SiO(2)), were prepared by using silicon dioxide (SiO(2)) to encapsulate simultaneously Fe(3)O(4) and CdTe quantum dots. BMSC were incubated with the Fe(3)O(4)@CdTe@SiO(2) nanoparticles which iron concentration was 25 microg/ml. Fluorescence microscope was used to detect the fluorescence of the intracellular nanoparticles. The dual-labeled BMSC with various concentration underwent ex vivo MR imaging with T(1)WI, T(2)WI and T(2)(*)WI sequences. To show the intracellular iron of labeled cells, prussian blue stain was performed. Spectrophotometer was used to detect the iron concentration in the cells. RESULTS: Intracellular red fluorescence of Fe(3)O(4)@CdTe@SiO(2) can be observed via fluorescent microscopy. Rat BMSC could be effectively dual-labeled with approximately 90% efficiency. The MR images with T(2)WI and T(2)(*)WI sequences, especially with T(2)(*)WI sequence, showed that the signals of the dual-labeled BMSC were lower than those of the unlabeled cells. Cellular total iron is 14.05 + or - 4.15 pg per cell. Iron containing intracytoplasmic vesicles could be observed with Prussian blue staining. CONCLUSION: Rat BMSC can be dual-labeled successfully with Fe(3)O(4)@CdTe@SiO(2) magnetic/luminescent bifunctional nanoparticles successfully, and might serve as a tool for magnetic resonance imaging and in vivo optical imaging.

Amplification of fluorescence detection of DNA based on magnetic separation.

A novel nanoparticles-based fluorescence detection method has been developed by taking advantage of magnetic separation and amplified fluorescence detection. This DNA sensor relies on a "sandwich" hybridization strategy, in which the DNA targets are first hybridized to captured oligonucleotide probes immobilized on magnetic nanoparticles, and then hybridized with thiol-modified oligonucleotide probes immobilized on gold nanoparticles. Subsequently, the amplified DNA signals are detected in the form of bio-bar-code DNA using a chip-based fluorescence detection method. The result showed that the detection limit of target DNA probes is 1 pM. Complementary and mismatched sequences were clearly distinguished, and the ratio of the background-subtracted fluorescence values for complementary and single-base mismatched oligonucleotide was 2.12:1. This new system can be applied to both DNA detection and immunoassay, and has broad potential applications in disease diagnosis and immunoassay.