Aptamer-Based Smart Targeting and Spatial Trigger-Response Drug-Delivery Systems for Anticancer Therapy.

In recent years, the field of drug delivery has witnessed remarkable progress, driven by the quest for more effective and precise therapeutic interventions. Among the myriad strategies employed, the integration of aptamers as targeting moieties and stimuli-responsive systems has emerged as a promising avenue, particularly in the context of anticancer therapy. This review explores cutting-edge advancements in targeted drug-delivery systems, focusing on the integration of aptamers and stimuli-responsive platforms for enhanced spatial anticancer therapy. In the aptamer-based drug-delivery systems, we delve into the versatile applications of aptamers, examining their conjugation with gold, silica, and carbon materials. The synergistic interplay between aptamers and these materials is discussed, emphasizing their potential in achieving precise and targeted drug delivery. Additionally, we explore stimuli-responsive drug-delivery systems with an emphasis on spatial anticancer therapy. Tumor microenvironment-responsive nanoparticles are elucidated, and their capacity to exploit the dynamic conditions within cancerous tissues for controlled drug release is detailed. External stimuli-responsive strategies, including ultrasound-mediated, photo-responsive, and magnetic-guided drug-delivery systems, are examined for their role in achieving synergistic anticancer effects. This review integrates diverse approaches in the quest for precision medicine, showcasing the potential of aptamers and stimuli-responsive systems to revolutionize drug-delivery strategies for enhanced anticancer therapy.

Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications.

Tissue engineering is a sophisticated field that involves the integration of various disciplines, such as clinical medicine, material science, and life science, to repair or regenerate damaged tissues and organs. To achieve the successful regeneration of damaged or diseased tissues, it is necessary to fabricate biomimetic scaffolds that provide structural support to the surrounding cells and tissues. Fibrous scaffolds loaded with therapeutic agents have shown considerable potential in tissue engineering. In this comprehensive review, we examine various methods for fabricating bioactive molecule-loaded fibrous scaffolds, including preparation methods for fibrous scaffolds and drug-loading techniques. Additionally, we delved into the recent biomedical applications of these scaffolds, such as tissue regeneration, inhibition of tumor recurrence, and immunomodulation. The aim of this review is to discuss the latest research trends in fibrous scaffold manufacturing methods, materials, drug-loading methods with parameter information, and therapeutic applications with the goal of contributing to the development of new technologies or improvements to existing ones.

Examining the effect of safety climate on accident risk through job stress: a path analysis.

BACKGROUND: Job stress is a probable mediator of the relationship between safety climate and accident occurrence. To demonstrate this, this study investigates the relationship between safety climate, job stress, and accident risk using a large number of surveys. The study will use structural equation modeling (SEM) to analyze the data collected from the surveys to examine the effect of safety climate on accident risk through job stress. METHODS: The study is a cross-sectional study that was conducted on 1,530 male workers of a petrochemical company. The subjects were asked to complete several questionnaires during rest periods, which included demographic information, the Nordic safety climate questionnaire (NOSACQ-50), and the generic job stress questionnaire (GJSQ). Additionally, data on the frequency and intensity of accidents among participants were gathered from the health unit of the company. Path analysis was conducted by structural equation modeling (SEM) in Analysis of Moment Structures (AMOS) software. RESULTS: The results revealed that the latent variable of safety climate with an effect coefficient of - 0.112 did not have a direct effect on accident risk (P = 0.343). However, safety climate with an effect coefficient of - 0.633 had an indirect effect on accident risk through job stress (P < 0.001). The total score of job stress had a significant direct effect (0.649) on accident risk (P < 0.001). Among the dimensions of safety climate, the variables of management's safety priority, commitment, and competence (- 0.108) and workers' safety commitment (- 0.107) had the highest indirect effect coefficients on accident risk. Among the dimensions of job stress, the highest indirect effects belonged to the variables of conflict at work (0.636), physical environment (0.631), and workload and responsibility (0.631), respectively. CONCLUSION: The results of the study revealed that job stress mediates the relationship between safety climate and accident risk. This finding suggests that organizations can potentially decrease accidents in industries by addressing and managing job stress in the workplace.

Design and Prediction of Aptamers Assisted by In Silico Methods.

An aptamer is a single-stranded DNA or RNA that binds to a specific target with high binding affinity. Aptamers are developed through the process of systematic evolution of ligands by exponential enrichment (SELEX), which is repeated to increase the binding power and specificity. However, the SELEX process is time-consuming, and the characterization of aptamer candidates selected through it requires additional effort. Here, we describe in silico methods in order to suggest the most efficient way to develop aptamers and minimize the laborious effort required to screen and optimise aptamers. We investigated several methods for the estimation of aptamer-target molecule binding through conformational structure prediction, molecular docking, and molecular dynamic simulation. In addition, examples of machine learning and deep learning technologies used to predict the binding of targets and ligands in the development of new drugs are introduced. This review will be helpful in the development and application of in silico aptamer screening and characterization.

Principles and Applications of Loop-Mediated Isothermal Amplification to Point-of-Care Tests.

For the identification of nucleic acids, which are important biomarkers of pathogen-mediated diseases and viruses, the gold standard for NA-based diagnostic applications is polymerase chain reaction (PCR). However, the requirements of PCR limit its application as a rapid point-of-care diagnostic technique. To address the challenges associated with regular PCR, many isothermal amplification methods have been developed to accurately detect NAs. Isothermal amplification methods enable NA amplification without changes in temperature with simple devices, as well as faster amplification times compared with regular PCR. Of the isothermal amplifications, loop-mediated isothermal amplification (LAMP) is the most studied because it amplifies NAs rapidly and specifically. This review describes the principles of LAMP, the methods used to monitor the process of LAMP, and examples of biosensors that detect the amplicons of LAMP. In addition, current trends in the application of LAMP to smartphones and self-diagnosis systems for point-of-care tests are also discussed.

Temperature Detectable Surface Coating with Carbon Nanotube/Epoxy Composites.

In the construction and machinery industry, heat is a major factor causing damage and destruction. The safety and efficiency of most machines and structures are greatly affected by temperature, and temperature management and control are essential. In this study, a carbon nanotube (CNT) based temperature sensing coating that can be applied to machines and structures having various structural types was fabricated, and characteristics analysis and temperature sensing performance were evaluated. The surface coating, which detects temperature through resistance change is made of a nanocomposite composed of carbon nanotubes (CNT) and epoxy (EP). We investigated the electrical properties by CNT concentration and temperature sensing performance of CNT/EP coating against static and cyclic temperatures. In addition, the applicability of the CNT/EP coating was investigated through a partially heating and cooling experiment. As a result of the experiment, the CNT/EP coating showed higher electrical conductivity as the CNT concentration increased. In addition, the CNT/EP coating exhibits high sensing performance in the high and sub-zero temperature ranges with a negative temperature coefficient of resistance. Therefore, the proposed CNT/EP coatings are promising for use as multi-functional coating materials for the detection of high and freezing temperatures.

Improved intrusion accident management using haptic signals in roadway work zone.

INTRODUCTION: Roadway work zones are known for hazard vulnerability, with many injuries and fatalities each year, due mostly to intrusions. Despite several available measures to improve safety, existing mechanisms are unreliable for workers to perceive alerts, due to the harsh working environment, with loud noise and limited vision. This research attempts to overcome hazard perception difficulties by introducing a new communication mechanism for intrusion hazard perception. METHOD: The presented communication mechanism is based on past tactile sensing research, and is enhanced by signal profile and message modeling investigations. Experimental field trials were conducted for mechanism evaluation with a goal of improved situational awareness through tactile sensing. RESULTS: The trial results show that users perceive warning messages well, even when their vision and hearing are limited, and that the signalized messages perceived could augment users' understanding of a potential hazard, allowing immediate precautionary actions. Practical Applications: The application of haptic signals in vulnerable work zones has the potential to improve upon limitations in innate sensing (e.g., vision and hearing), thus presenting an opportunity to better protect workers from potential accidents.

Investigation of Tactile Sensory System Configuration for Construction Hazard Perception.

The application of tactile-based wearable devices to assist in navigation for people with low sight/low memory has demonstrated the feasibility of using such devices as a means of communication. Accordingly, a previous study in construction research investigated various parameters of tactile signals to develop a communicable system for potential application in construction hazard communication. However, the nature of construction limits the application of such devices to the body of construction workers, and it is important to understand sensor design parameters for improved communication, which has not been given significant attention yet. Therefore, this study aims to determine key design factors such as the number of motors, spacing between sensors and the layout of a tactile sensory system to be used for communicating construction hazards to workers. For this purpose, this study focused on identifying the number of motors based on extensive literature and the problem of construction safety as to hazard communication, determining the arrangement that allowed for effective delivery and perception of information with minimum effort. The researchers conducted two experimental studies: First, to determine the minimum spacing between vibration motors that allows for the identification of each individual motor with high accuracy; and second, to determine the layout of motors that is suitable for effective communication of multiple types of information. More importantly, the tactile-sensor configuration identified from this study allows the workers to learn the signal patterns easily in order to identify multiple types of information related to hazards. Using such a communication system on construction sites will assist in transmitting hazard-related information to workers, and thus, protect the lives of workers. Such wearable technologies enable the detection of individual-level hazards and prevent worker fatalities and severe injuries.

High-throughput label-free molecular fingerprinting flow cytometry.

Flow cytometry is an indispensable tool in biology for counting and analyzing single cells in large heterogeneous populations. However, it predominantly relies on fluorescent labeling to differentiate cells and, hence, comes with several fundamental drawbacks. Here, we present a high-throughput Raman flow cytometer on a microfluidic chip that chemically probes single live cells in a label-free manner. It is based on a rapid-scan Fourier-transform coherent anti-Stokes Raman scattering spectrometer as an optical interrogator, enabling us to obtain the broadband molecular vibrational spectrum of every single cell in the fingerprint region (400 to 1600 cm-1) with a record-high throughput of ~2000 events/s. As a practical application of the method not feasible with conventional flow cytometry, we demonstrate high-throughput label-free single-cell analysis of the astaxanthin productivity and photosynthetic dynamics of Haematococcus lacustris.

Sensor-Based Safety Performance Assessment of Individual Construction Workers.

Over the last decade, researchers have explored various technologies and methodologies to enhance worker safety at construction sites. The use of advanced sensing technologies mainly has focused on detecting and warning about safety issues by directly relying on the detection capabilities of these technologies. Until now, very little research has explored methods to quantitatively assess individual workers' safety performance. For this, this study uses a tracking system to collect and use individuals' location data in the proposed safety framework. A computational and analytical procedure/model was developed to quantify the safety performance of individual workers beyond detection and warning. The framework defines parameters for zone-based safety risks and establishes a zone-based safety risk model to quantify potential risks to workers. To demonstrate the model of safety analysis, the study conducted field tests at different construction sites, using various interaction scenarios. Probabilistic evaluation showed a slight underestimation and overestimation in certain cases; however, the model represented the overall safety performance of a subject quite well. Test results showed clear evidence of the model's ability to capture safety conditions of workers in pre-identified hazard zones. The developed approach presents a way to provide visualized and quantified information as a form of safety index, which has not been available in the industry. In addition, such an automated method may present a suitable safety monitoring method that can eliminate human deployment that is expensive, error-prone, and time-consuming.

Microfluidic single-particle chemical analyzer with dual-comb coherent Raman spectroscopy.

Label-free particle analysis is a powerful tool in chemical, pharmaceutical, and cosmetic industries as well as in basic sciences, but its throughput is significantly lower than that of fluorescence-based counterparts. Here we present a label-free single-particle analyzer based on broadband dual-comb coherent Raman scattering spectroscopy operating at a spectroscopic scan rate of 10 kHz. As a proof-of-concept demonstration, we perform broadband coherent anti-Stokes Raman scattering measurements of polystyrene microparticles flowing on an acoustofluidic chip at a high throughput of >1000 particles per second. This high-throughput label-free particle analyzer has the potential for high-precision statistical analysis of a large number of microparticles including biological cells.

An Embedded Sensory System for Worker Safety: Prototype Development and Evaluation.

At a construction site, workers mainly rely on two senses, which are sight and sound, in order to perceive their physical surroundings. However, they are often hindered by the nature of most construction sites, which are usually dynamic, loud, and complicated. To overcome these challenges, this research explored a method using an embedded sensory system that might offer construction workers an artificial sensing ability to better perceive their surroundings. This study identified three parameters (i.e., intensity, signal length, and delay between consecutive pulses) needed for tactile-based signals for the construction workers to communicate quickly. We developed a prototype system based on these parameters, conducted experimental studies to quantify and validate the sensitivity of the parameters for quick communication, and analyzed test data to reveal what was added by this method in order to perceive information from the tactile signals. The findings disclosed that the parameters of tactile-based signals and their distinguishable ranges could be perceived in a short amount of time (i.e., a fraction of a second). Further experimentation demonstrated the capability of the identified unit signals combined with a signal mapping technique to effectively deliver simple information to individuals and offer an additional sense of awareness to the surroundings. The findings of this study could serve as a basis for future research in exploring advanced tactile-based messages to overcome challenges in environments for which communication is a struggle.

Acoustofluidic harvesting of microalgae on a single chip.

We present an on-chip acoustofluidic platform for harvesting a target microalgal species from a heterogeneous population of cells and particles based on their size, density, and compressibility in a rapid, non-invasive, energy-efficient, continuously running, and automated manner. For our proof-of-principle demonstration, we use Euglena gracilis as a target species. Specifically, we show the simultaneous separation and enrichment of E. gracilis from a mixed population of E. gracilis in pond water (consisting of other microalgae and various kinds of particles as contaminants) on a single acoustofluidic chip with a recovery ratio of 92.6%, a target separation ratio of 90.1%, a concentration factor of 3.43, an enrichment factor of 12.76, and a cell viability rate of 98.3% at a high volume rate of 500 µl/min. Our results indicate that the on-chip acoustofluidic platform is an effective tool for harvesting target microalgae from mixed populations of microalgae and other contaminants.

Acousto-microfluidics for screening of ssDNA aptamer.

We demonstrate a new screening method for obtaining a prostate-specific antigen (PSA) binding aptamer based on an acoustofluidic separation (acoustophoreis) technique. Since acoustophoresis provides simultaneous washing and separation in a continuous flow mode, we efficiently obtained a PSA binding aptamer that shows high affinity without any additional washing step, which is necessary in other screening methods. In addition, next-generation sequencing (NGS) was applied to accelerate the identification of the screened ssDNA pool, improving the selecting process of the aptamer candidate based on the frequency ranking of the sequences. After the 8(th) round of the acoustophoretic systematic evolution of ligands by exponential enrichment (SELEX) and following sequence analysis with NGS, 7 PSA binding ssDNA aptamer-candidates were obtained and characterized with surface plasmon resonance (SPR) for affinity and specificity. As a result of the new SELEX method with PSA as the model target protein, the best PSA binding aptamer showed specific binding to PSA with a dissociation constant (Kd) of 0.7 nM.

Aptamer/ISET-MS: a new affinity-based MALDI technique for improved detection of biomarkers.

With the rapid progress in the development of new clinical biomarkers there is an unmet need of fast and sensitive multiplex analysis methods for disease specific protein monitoring. Immunoaffinity extraction integrated with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis offers a route to rapid and sensitive protein analysis and potentially multiplex biomarker analysis. In this study, the previously reported integrated selective enrichment target (ISET)-MALDI-MS analysis was implemented with ssDNA aptamer functionalized microbeads to address the specific capturing of thrombin in complex samples. The main objective for using an aptamer as the capturing ligand was to avoid the inherently high background components, which are produced during the digestion step following the target extraction when antibodies are used. By applying a thrombin specific aptamer linked to ISET-MALDI-MS detection, a proof of concept of antibody fragment background reduction in the ISET-MALDI-MS readout is presented. Detection sensitivity was significantly increased compared to the corresponding system based on antibody-specific binding as the aptamer ligand does not induce any interfering background residues from the antibodies. The limit of detection for thrombin was 10 fmol in buffer using the aptamer/ISET-MALDI-MS configuration as confirmed by MS/MS fragmentation. The aptamer/ISET-MALDI-MS platform also displayed a limit of detection of 10 fmol for thrombin in five different human serum samples (1/10 diluted), demonstrating the applicability of the aptamer/ISET-MALDI-MS analysis in clinical samples.

An ultra-sensitive detection of a whole virus using dual aptamers developed by immobilization-free screening.

In this study, we successfully developed a ssDNA aptamer pairs by using an advanced immobilization-free SELEX method with affinity-based selection and counter-screening process at every round. By implementing this method, two different aptamers specifically binding to bovine viral diarrhea virus type 1(BVDV type 1) with high affinity were successfully screened. This aptamer pair was applied to ultrasensitive detection platform for BVDV type 1 in a sandwich manner. The ultrasensitive detection of BVDV type 1 using one of aptamers conjugated with gold nanoparticles was obtained in aptamer-aptamer sandwich type sensing format, with the limit of detection of 800 copies/ml, which is comparable to a real-time PCR method.

Rapid and sensitive detection of Nampt (PBEF/visfatin) in human serum using an ssDNA aptamer-based capacitive biosensor.

A single-stranded DNA (ssDNA) aptamer was successfully developed to specifically bind to nicotinamide phosphoribosyl transferase (Nampt) through systematic evolution of ligands by exponential enrichment (SELEX) and successfully implemented in a gold-interdigitated (GID) capacitor-based biosensor. Surface plasmon resonance (SPR) analysis of the aptamer revealed high specificity and affinity (K(d)=72.52 nM). Changes in surface capacitance/charge distribution or dielectric properties in the response of the GID capacitor surface covalently coupled to the aptamers in response to changes in applied AC frequency were measured as a sensing signal based on a specific interaction between the aptamers and Nampt. The limit of detection for Nampt was 1 ng/ml with a dynamic serum detection range of up to 50 ng/ml; this range includes the clinical requirement for both normal Nampt level, which is 15.8 ng/ml, and Nampt level in type 2 diabetes mellitus (T2DM) patients, which is 31.9 ng/ml. Additionally, the binding kinetics of aptamer-Nampt interactions on the capacitor surface showed that strong binding occurred with increasing frequency (range, 700 MHz-1 GHz) and that the dissociation constant of the aptamer under the applied frequency was improved 120-240 times (K(d)=0.3-0.6 nM) independent on frequency. This assay system is an alternative approach for clinical detection of Nampt with improved specificity and affinity.

Immobilization-free screening of aptamers assisted by graphene oxide.

Graphene oxide (GO) has the ability to separate free short ssDNA in heterogeneous solution. This feature is applied as a label free platform for screening of aptamers that bind to their target with high affinity and specificity. Herein, we report an aptamer selection strategy for Nampt protein based on GO.