RNA therapeutics for infectious diseases.

Ribonucleic acids (RNAs), including the messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), play important roles in living organisms and viruses. In recent years, the RNA-based technologies including the RNAs inhibiting other RNA activities, the RNAs targeting proteins, the RNAs reprograming genetic information, and the RNAs encoding therapeutical proteins, are useful methods to apply in prophylactic and therapeutic vaccines. In this review, we summarize and highlight the current application of the RNA therapeutics, especially on mRNA vaccines which have potential for prevention and treatment against human and animal infectious diseases.

Fluorescent Carbon Dot-Supported Imaging-Based Biomedicine: A Comprehensive Review.

Carbon dots (CDs) provide distinctive advantages of strong fluorescence, good photostability, high water solubility, and outstanding biocompatibility, and thus are widely exploited as potential imaging agents for in vitro and in vivo bioimaging. Imaging is absolutely necessary when discovering the structure and function of cells, detecting biomarkers in diagnosis, tracking the progress of ongoing disease, treating various tumors, and monitoring therapeutic efficacy, making it an important approach in modern biomedicine. Numerous investigations of CDs have been intensively studied for utilization in bioimaging-supported medical sciences. However, there is still no article highlighting the potential importance of CD-based bioimaging to support various biomedical applications. Herein, we summarize the development of CDs as fluorescence (FL) nanoprobes with different FL colors for potential bioimaging-based applications in living cells, tissue, and organisms, including the bioimaging of various cell types and targets, bioimaging-supported sensing of metal ions and biomolecules, and FL imaging-guided tumor therapy. Current CD-based microscopic techniques and their advantages are also highlighted. This review discusses the significance of advanced CD-supported imaging-based in vitro and in vivo investigations, suggests the potential of CD-based imaging for biomedicine, and encourages the effective selection and development of superior probes and platforms for further biomedical applications.

Removal of Thiol-SAM on a Gold Surface for Re-Use of an Interdigitated Chain-Shaped Electrode.

The self-assembled monolayer (SAM) is the most common organic assembly utilized for the formation of the monolayers of alkane-thiolates on gold electrode, resulting in a wide range of applications for the modified SAM on gold in various research areas. This study examined the desorption of a SAM that was developed on the gold surface of an interdigitated chain-shaped electrode (the ICE, a unique electrode design, was fabricated by our group) with the goal of determining the most efficient strategy of SAM removal for the ICE to be re-used. A simple and proficient solution-based cleaning procedure was applied for the removal of a SAM on the gold surface of the ICE by using a sodium borohydride solution within short-term treatment, resulting in efficiency for the recovery of the originally electrochemical characteristic of ICE of 90.3%. The re-use of ICE after the removal process was confirmed by the successful re-deposition of a SAM onto the electrode surface, resulting in the high efficiency percentage of 90.1% for the reusability of ICE with the SAM modification. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used as tools to investigate the changes in the electrode interface at each stage of the SAM removal and the electrode recycling. X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy were employed, being powerful spectrum techniques, for the characterization of the bonding structure and chemical state of the bare ICE and the modified ICE at each treatment step. Based on the comprehensive discussion of analytical chemistry from the obtained EIS and CV data in this study, we confirmed and proved the effectiveness of this promising method for the removal of a SAM from the ICE and the re-use of ICE in the field of material deposition, with the aims of saving money, improving experimental handling, and protecting the environment.

Ten-Year Outcome of Topography-Guided Transepithelial Surface Ablation for Refractive Myopia Treatment.

BACKGROUND: To evaluate 10-year long-term refractive visual stability and participants' satisfaction in the refractive treatment of myopic eyes undergoing topography-guided transepithelial surface ablation using a 1KHz excimer laser. PATIENTS AND METHODS: This single-center prospective survey assessed participants' satisfaction 10 years after the treatment using a non-validated questionnaire with regards to visual outcome, dry eye, and visual disturbance symptoms. Pre- and postoperative visual and refractive data were evaluated. RESULTS: Of 106 participants (54% females) with a mean patient age of 36 (± 8.6) years, 166 eyes were included. Mean preoperative spherical equivalent (SE) was - 4.23 (± 2.48) diopters (D). Uncorrected distant visual acuity (UCVA) after 10 years was ≥ 1.0 (Snellen) in 92% of the eyes. Manifest SE was within ± 1.0 D of the desired refraction in 86% of the eyes after 10 years. Mean quality of life (QOL) improvement was high (9.15 out of 10 points). Dry eye symptoms were reported by 35 out of 104 (34%) patients. Visual symptoms like halos or starbursts were reported by 24 out of 101 (24%) and 12 out of 100 (12%) patients, respectively. CONCLUSIONS: Topography-guided transepithelial surface ablation for myopia provided stable long-term results in terms of UCVA and SE. Participant satisfaction was high, with only low rates of dry eye or visual symptoms.

Fluorescent Aptasensor and Colorimetric Aptablot for p-tau231 Detection: Toward Early Diagnosis of Alzheimer's Disease.

The pathology of Alzheimer's disease (AD), the most common cause of dementia, is considered to be mainly driven by two major hallmarks (tau and amyloid beta). It is highly desirable to develop an affordable medicinal diagnostic that can be utilized worldwide for the early diagnosis of AD. Hence, p-tau231 was selected as a specific target, which appears both in AD serum and cerebrospinal fluid, for the development of a sensing platform for the diagnosis of AD. To the best of our knowledge, these are the first aptamer-mediated biosensors that rely on sensitive fluorescent and colorimetric aptasensors for the rapid monitoring of p-tau231. The nitrogen-doped carbon dot-based turn-on fluorescent aptasensor could rapidly analyze p-tau231 down to 3.64 ng/mL within 40 min, and the colorimetric Cu-enhanced-Au aptablot displayed high sensitivity at 4.71 pg/mL through a digital camera, with visibility to the naked eye down to 8 ng/mL p-tau231 within 140 min. Owing to their advantages, which include affordability, rapidity, high sensitivity, and dependence on complicated instruments, these aptamer-based biosensors offer significant potential for the early diagnosis of AD worldwide.

Fluorescent Carbon Dots for Sensitive and Rapid Monitoring of Intracellular Ferrous Ion.

Although iron is an essential constituent for almost all living organisms, iron dyshomeostasis at a cellular level may trigger oxidative stress and neuronal damage. Hence, there are numerous reported carbon dots (CDs) that have been synthesized and applied to determine intracellular iron ions. However, among reported CDs focused to detect Fe3+ ions, only a few CDs have been designed to specifically determine Fe2+ ions over Fe3+ ions for monitoring of intracellular Fe2+ ions. We have developed the nitrogen-doped CDs (NCDs) for fluorescence turn-off detection of Fe2+ at cellular level. The as-synthesized NCDs exhibit a strong blue fluorescence and low cytotoxicity, acting as fluorescence probes to detect Fe2+ as low as 0.702 µM in aqueous solution within 2 min and visualize intracellular Fe2+ in the concentration range from 0 to 500 µM within 20 min. The as-prepared NCDs possess some advantages such as high biocompatibility, strong fluorescence properties, selectivity, and rapidity for intracellular Fe2+ monitoring, making NCDs an excellent nanoprobe for biosensing of intracellular ferrous ions.

Fluorescent Carbon Dots as Prospective Nanoagents for Imaging-assisted Biomedical Applications.

Carbon dots (CDs), an emerging nanoagent providing an alternative to conventional fluorescent agents, are sparking the scientist's interest in biomedical applications owing to their unique advantages, including ease of synthesis, large scale production, low cost, prominent photoluminescence, good photostability, easy functionalization, sufficient biocompatibility, good nanocarrier, and excellent ability to generate reactive oxygen species or heat. Herein, this perspective provides a viewpoint about imaging-assisted biomedical applications using fluorescent CDs regarding in vitro and in vivo bioimaging, imaging-assisted sensing, and imaging-guided therapy. The opinions about their potential and challenges in applicable biomedical applications are discussed to develop, further ameliorated CDs for their intense exploitation in diverse imaging-assisted biomedical applications.

Ultrasensitive capacitance sensor to detect amyloid-beta 1-40 in human serum using supramolecular recognition of ß-CD/RGO/ITO micro-disk electrode.

In this paper, we developed a new ultrasensitive capacitance sensor for detection of amyloid beta 1-40 (aß40) protein (one of Alzheimer's disease core biomarkers) in human serum based on the high supramolecular recognition of the ß-cyclodextrin/reduced graphene oxide (ß-CD/RGO) nanohybrid toward the anti-aß40 antibody molecule. The sensor was established by immobilizing specific anti-aß40 antibody onto the ß-CD/RGO nanohybrid functionalized on indium tin oxide micro-disk electrode (anti-aß40/ß-CD/RGO/ITO). Detection of aß40 in the human serum (HS) using the sensor anti-aß40/ß-CD/RGO/ITO is carried out by capacitance measurement without a redox probe to prevent protein denaturation, serving as a convenient strategy for point-of-care diagnosis. In comparison with other studies, the sensor shows a very low limit of detection of 0.69 fg mL-1 in HS, demonstrating its ability for the ultrasensitive detection of aß40. Using this sensor, the dissociation constant KD of the binding interaction between anti-aß40 and aß40 in HS is found to be 2.9 × 10-7 nM, indicating the high binding affinity of antibody-antigen and the suitability of the anti-aß40/ß-CD/RGO/ITO sensor for aß40 protein detection. The good selectivity of the anti-aß40/ß-CD/RGO/ITO sensor in the presence of differential analytes was also performed in this paper.

A Multi-Chamber Paper-Based Platform for the Detection of Amyloid ß Oligomers 42 via Copper-Enhanced Gold Immunoblotting.

The early diagnosis of Alzheimer's disease (AD) remains a challenge for medical scientists worldwide, leading to a number of research efforts that focus on biosensor development for AD biomarkers. However, the application of these complicated biosensors is limited in medical diagnosis, due to the difficulties in robust sensing platform development, high costs, and the necessity for technical professionals. We successfully developed a robust straightforward manufacturing process for the fabrication of multi-chamber paper devices using the wax printing method and exploited it to detect amyloid beta 42 oligomers (AßO42, a significant biomarker of AD) using copper-enhanced gold nanoprobe colorimetric immunoblotting. Small hydrophilic reaction chambers could concentrate the target sample to the desired size to improve the sensing performance. The copper-enhanced gold nanoprobe immunoblot using the designed multi-chamber platform exhibited a highly sensitive performance with a limit of detection of 320 pg/mL by the naked eye and 23.7 pg/mL by a smartphone camera. This process from sensing manufacture to sensing conduction is simple to perform whenever medical technicians require time- and cost-savings, without complicated instruments or the need for technical professionals, making it feasible to serve as a diagnostic tool worldwide for the early monitoring of AD and scalable devices for the sensing application of various biomarkers in clinical settings.

Clinical Utility of Biosensing Platforms for Confirmation of SARS-CoV-2 Infection.

Despite collaborative efforts from all countries, coronavirus disease 2019 (COVID-19) pandemic has been continuing to spread globally, forcing the world into social distancing period, making a special challenge for public healthcare system. Before vaccine widely available, the best approach to manage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to achieve highest diagnostic accuracy by improving biosensor efficacy. For SARS-CoV-2 diagnostics, intensive attempts have been made by many scientists to ameliorate the drawback of current biosensors of SARS-CoV-2 in clinical diagnosis to offer benefits related to platform proposal, systematic analytical methods, system combination, and miniaturization. This review assesses ongoing research efforts aimed at developing integrated diagnostic tools to detect RNA viruses and their biomarkers for clinical diagnostics of SARS-CoV-2 infection and further highlights promising technology for SARS-CoV-2 specific diagnosis. The comparisons of SARS-CoV-2 biomarkers as well as their applicable biosensors in the field of clinical diagnosis were summarized to give scientists an advantage to develop superior diagnostic platforms. Furthermore, this review describes the prospects for this rapidly growing field of diagnostic research, raising further interest in analytical technology and strategic plan for future pandemics.

Advanced Signal-Amplification Strategies for Paper-Based Analytical Devices: A Comprehensive Review.

Paper-based analytical devices (PADs) have emerged as a promising approach to point-of-care (POC) detection applications in biomedical and clinical diagnosis owing to their advantages, including cost-effectiveness, ease of use, and rapid responses as well as for being equipment-free, disposable, and user-friendly. However, the overall sensitivity of PADs still remains weak, posing a challenge for biosensing scientists exploiting them in clinical applications. This review comprehensively summarizes the current applicable potential of PADs, focusing on total signal-amplification strategies that have been applied widely in PADs involving colorimetry, luminescence, surface-enhanced Raman scattering, photoacoustic, photothermal, and photoelectrochemical methods as well as nucleic acid-mediated PAD modifications. The advances in signal-amplification strategies in terms of signal-enhancing principles, sensitivity, and time reactions are discussed in detail to provide an overview of these approaches to using PADs in biosensing applications. Furthermore, a comparison of these methods summarizes the potential for scientists to develop superior PADs. This review serves as a useful inside look at the current progress and prospective directions in using PADs for clinical diagnostics and provides a better source of reference for further investigations, as well as innovations, in the POC diagnostics field.

Trending Technology of Glucose Monitoring during COVID-19 Pandemic: Challenges in Personalized Healthcare.

The COVID-19 pandemic has continued to spread rapidly, and patients with diabetes are at risk of experiencing rapid progression and poor prognosis for appropriate treatment. Continuous glucose monitoring (CGM), which includes accurately tracking fluctuations in glucose levels without raising the risk of coronavirus exposure, becomes an important strategy for the self-management of diabetes during this pandemic, efficiently contributing to the diabetes care and the fight against COVID-19. Despite being less accurate than direct blood glucose monitoring, wearable noninvasive systems can encourage patient adherence by guaranteeing reliable results through high correlation between blood glucose levels and glucose concentrations in various other biofluids. This review highlights the trending technologies of glucose sensors during the ongoing COVID-19 pandemic (2019-2020) that have been developed to make a significant contribution to effective management of diabetes and prevention of coronavirus spread, from off-body systems to wearable on-body CGM devices, including nanostructure and sensor performance in various biofluids. The advantages and disadvantages of various human biofluids for use in glucose sensors are also discussed. Furthermore, the challenges faced by wearable CGM sensors with respect to personalized healthcare during and after the pandemic are deliberated to emphasize the potential future directions of CGM devices for diabetes management.

Graphene Integrated Hydrogels Based Biomaterials in Photothermal Biomedicine.

Recently, photothermal therapy (PTT) has emerged as one of the most promising biomedical strategies for different areas in the biomedical field owing to its superior advantages, such as being noninvasive, target-specific and having fewer side effects. Graphene-based hydrogels (GGels), which have excellent mechanical and optical properties, high light-to-heat conversion efficiency and good biocompatibility, have been intensively exploited as potential photothermal conversion materials. This comprehensive review summarizes the current development of graphene-integrated hydrogel composites and their application in photothermal biomedicine. The latest advances in the synthesis strategies, unique properties and potential applications of photothermal-responsive GGel nanocomposites in biomedical fields are introduced in detail. This review aims to provide a better understanding of the current progress in GGel material fabrication, photothermal properties and potential PTT-based biomedical applications, thereby aiding in more research efforts to facilitate the further advancement of photothermal biomedicine.

Nanomaterial-based Optical and Electrochemical Biosensors for Amyloid beta and Tau: Potential for early diagnosis of Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD), a heterogeneous pathological process representing the most common causes of dementia worldwide, has required early and accurate diagnostic tools. Neuropathological hallmarks of AD involve the aberrant accumulation of Amyloid beta (Aß) into Amyloid plaques and hyperphosphorylated Tau into neurofibrillary tangles, occurring long before the onset of brain dysfunction.Areas covered:Considering the significance of Aß and Tau in AD pathogenesis, these proteins have been adopted as core biomarkers of AD, and their quantification has provided precise diagnostic information to develop next-generation AD therapeutic approaches. However, conventional diagnostic methods may not suffice to achieve clinical criteria that are acceptable for proper diagnosis and treatment. The advantages of nanomaterial-based biosensors including facile miniaturization, mass fabrication, ultra-sensitivity, make them useful to be promising tools to measure Aß and Tau simultaneously for accurate validation of low-abundance yet potentially informative biomarkers of AD.. EXPERT OPINION: The study has identified the potential application of advanced biosensors as standardized clinical diagnostic tools for AD, evolving the way for new and efficient AD control with minimum economic and social burden. After clinical trial, nanobiosensors for measuring Aß and Tau simultaneously possess innovative diagnosis of AD to provide significant contributions to primary Alzheimer's care intervention.

Nanobiosensors for Non-Amyloidbeta-Tau Biomarkers as Advanced Reporters of Alzheimer's Disease.

Emerging nanomaterials providing benefits in sensitivity, specificity and cost-effectiveness are being widely investigated for biosensors in the application of Alzheimer's disease (AD) diagnosis. Core biomarkers amyloid-beta (Aß) and Tau have been considered as key neuropathological hallmarks of AD. However, they did not sufficiently reflect clinical severity and therapeutic response, proving the difficulty of the Aß- and Tau-targeting therapies in clinical trials. In recent years, there has still been a shortage of sensors for non-Aß-Tau pathophysiological biomarkers that serve as advanced reporters for the early diagnosis of AD, predict AD progression, and monitor the treatment response. Nanomaterial-based sensors measuring multiple non-Aß-Tau biomarkers could improve the capacity of AD progression characterization and supervised treatment, facilitating the comprehensive management of AD. This is the first review to principally represent current nanobiosensors for non-Aß-Tau biomarker and that strategically deliberates future perspectives on the merit of non-Aß-Tau biomarkers, in combination with Aß and Tau, for the accurate diagnosis and prognosis of AD.

Fabrication of a paper strip for facile and rapid detection of bovine viral diarrhea virus via signal enhancement by copper polyhedral nanoshells.

The detection of bovine viral diarrhea virus (BVDV), which is a pathogen inducing fatal gastrointestinal disease in cattle, is becoming a momentous issue in the livestock farm. In that, BVDV is related to inapparent infection and various diseases with high transmissibility; it has also led to considerable economic losses. In this study, a simple dot-blotting method was devised to construct a rapid screening system for BVDV. Based on the BVDV-specific bioreceptors, it was anchored on the gold nanoparticles (AuNPs) to generate the seeding sites for signaling; then the signals were amplified by adopting the overgrowth of copper nano-polyhedral shells on AuNPs. The developed detection system shows a low detection limit of 4.4 copies per mL, and even this could be distinguished with naked eyes. These results indicate that the designed nanobiosensor possesses not only high sensitivity and selectivity but also potential usage on a point-of-care testing platform for BVDV.

One-pot synthesis of carbon dots with intrinsic folic acid for synergistic imaging-guided photothermal therapy of prostate cancer cells.

Photothermal therapy (PTT) is performed using near-infrared-responsive agents, which is proven to be an effective therapeutic strategy against cancer with several advantages including minimal invasion, high effectiveness, and easy implementation. Herein, we report a facile and novel one-pot synthetic approach for the fabrication of polydopamine-folate carbon dots (PFCDs) as theranostic nanocarriers for the image-guided PTT targeting of prostate cancer (PCa) cells that express a prostate-specific membrane antigen (PSMA) (folate hydrolase 1). The as-fabricated PFCDs exhibited several advantages such as easy preparation, high biocompatibility, low toxicity, good water-solubility, and excellent photothermal effect with robust blue fluorescence emission. The PSMA-directed imaging of PCa using PFCDs showed remarkable fluorescence enhancement in LNCap cells as compared to the case of other cells that did not express PSMA. PFCDs exhibited a photothermal effect in the PCa cells when irradiated with an 808 nm laser, which possibly resulted in the complete elimination of the tumor. Thus, these features make PFCDs a promising candidate for PTT. Moreover, PFCD-based PTT provides an effective biomedical platform for cancer therapy.

A facile hydrothermal synthesis of highly luminescent NaYF4:Yb3+/Er3+ upconversion nanoparticles and their biomonitoring capability.

Using a facile hydrothermal procedure, hydrophilic NaYF4: Yb3+/Er3+ nanoparticles (NPs) have been prepared as lanthanide-doped upconversion (UC) materials exhibiting different morphologies, crystal phases and luminescence intensity. The upconversion nanoparticles (UCNP) were characterized by means of electron microscopy and spectroscopy, X-ray diffraction (XRD) and photoluminescence analysis. The molar concentration of reactants and volumes of NaF affect the shapes and uniformity of the synthesized NPs. These parameters also have influence on crystal phase and luminescence intensity of the NPs. Adjusting hydrothermal reaction time and dopant concentration also enable the synthesis of NPs with strong UC luminescence. The as-prepared UCNP showed cellular nontoxicity to HeLa cells, and thus they are capable as promising agents for biological imaging.

Tuning of carbon dots emission color for sensing of Fe3+ ion and bioimaging applications.

Herein, we report a facile one-step synthetic strategy for fabrication of three (blue, green and yellow) fluorescent color carbon dots (CDs) from tomato (Solanum lycopersicum). The as-synthesized CDs showed emission peaks at 450, 520 and 560 nm for blue, green and yellow color CDs when excited at 370, 420 and 460 nm, respectively. Using tomato as a carbon source, the fabricated three fluorescent color CDs showed good water dispersity and high quantum yield. The analytical performances of three fluorescent color CDs are evaluated by detecting Fe3+ ion in biofluids and iron tablets. Upon the addition of Fe3+ ion under optimal conditions, the fluorescence intensity of three fluorescent color CDs was quenched linearly over the range of 0.1 to 2.0 µM. This method opens a new analytical strategy to quantify Fe3+ ion in iron tablets and biofluids with high sensitivity. Further, the uptake of three fluorescent color CDs into HeLa cells was confirmed by confocal laser scanning microscopy. Intracellular experiments demonstrated that the three fluorescent color CDs were effectively internalized the cells and show excellent biocompatibility and low toxicity, suggesting that the CDs can be used as good candidates for biomedical applications.

Synthesis of fluorescent silicon quantum dots for ultra-rapid and selective sensing of Cr(VI) ion and biomonitoring of cancer cells.

A facile one-step synthetic approach was developed for fabrication of fluorescent silicon quantum dots (Si QDs) and used as a probe for fluorescence detection of hexavalent chromium (Cr (VI)) in environmental water samples. The as-prepared Si QDs exhibit a strong fluorescence emission peak at 520 nm with a quantum yield of 14.2%. The fluorescent Si QDs were rapidly produced by using ascorbic acid as a reductant at 55 °C. The emission peak of Si QDs at 420 nm was effectively quenched upon the addition of Cr(VI). The Si QDs acted as the best fluorescent probe for the detection of Cr(VI) at PBS pH 7.4. The developed probe possessed a good linear correlation (R2 = 0.992) between Cr(VI) concentration (1.25-40 µM) and the (F0-F)/F0 values with a detection limit of 0.65 µM. Furthermore, the Si QDs served as a bio-probe for fluorescence imaging of A549 lung cancer cells and cell viability results confirmed the good biocompatible nature of Si QDs. The as-fabricated Si QDs show several advantages such as rapidity, selectivity and biocompatibility for sensing of Cr(VI) and imaging of A549 cells, which opens a facile analytical platform for environmental and bioimaging applications.