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Human serum is one of the most attractive specimens in biomarker research. However, its overcomplicated properties have hindered the analysis of low-abundance proteins by conventional mass spectrometry techniques. This work proposes an innovative strategy for utilizing nanodiamonds (NDs) in combination with Triton X-114 protein extraction to fractionate the crude serum to six pH-tuned fractions, simplifying the overall proteome and facilitating protein profiling with high efficiency. A total of 663 proteins are identified and evenly distributed among the fractions along with 39 FDA-approved biomarkersâa remarkable increase from the 230 proteins found in unfractionated crude serum. In the low-abundance protein section, 88 proteins with 7 FDA-approved biomarkers are detectedâa marked increase from the 15 proteins (2 biomarkers) observed in the untreated sample. Notably, fractions at pH 11, derived from the aqueous phase of detergent separation, suggest potential applications in rapid and robust serum proteome analysis. Notably, by outlining the excellent properties of NDs for proteomic research, this work suggests a promising extraction protocol utilizing the great compatibility of NDs with streamlined serum proteomics and identifies potential avenues for future developments. Finally, we believe that this work not just improves shotgun proteomics but also opens up studies on the interaction between NDs and the human proteome. Data are available via ProteomeXchange with the identifier PXD029710.
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Nanodiamantes , Proteoma , Humanos , Nanodiamantes/análisis , Octoxinol , Proteoma/análisis , Proteómica/métodos , Extracción en Fase SólidaRESUMEN
Dengue fever is a global mosquito-borne viral infectious disease that has, in recent years, rapidly spread to almost all regions of the world. Lack of vaccination and directed treatment makes detection at the infection's early stages extremely important for disease prevention and clinical care. In this paper, we developed a rapid and highly sensitive dengue detection tool using a novel platform of diagnosis, called spin-enhanced lateral flow immunoassay (SELFIA) with a fluorescent nanodiamond (FND) as a reporter. Taking advantage of the unique magneto-optical properties of negatively charged nitrogen-vacancy centers in the FND, the SELFIA platform utilizes alternating electromagnetic fields to modulate signals from FND's fluorescence to provide sensitive and specific results. With sandwich SELFIA, we could efficiently detect all four dengue non-structural protein (NS1) serotypes (DV1, DV2, DV3, and DV4). The lowest detection concentration of the dengue NS1 antigens varied from 0.1 to 1.3 ng/mL, which is among the lowest limits of detection to date. The FND-based SELFIA technique is up to 500 and 5000 times more sensitive than carbon black and conventional gold nanoparticles, respectively. By using different anti-NS1 antibodies, we could differentiate the NS1 antigen serotypes contained in the tested samples via three simultaneous assays. Proposed SELFIA allows for both qualitative and quantitative differentiation between different NS1 protein serotypes, which will assist in the development of a highly sensitive and specific detection platform for dengue screening that has the potential to detect the disease at its early stages, especially in high-risk and limited-resource areas.
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Virus del Dengue , Dengue , Nanopartículas del Metal , Animales , Humanos , Serogrupo , Oro , Proteínas no Estructurales Virales , Inmunoensayo/métodos , Anticuerpos Antivirales , Dengue/diagnóstico , Sensibilidad y Especificidad , Ensayo de Inmunoadsorción Enzimática/métodosRESUMEN
BACKGROUND: As a result of the COVID-19 global pandemic, many intellectual property (IP) owners have signed on to the "Open COVID Pledge", an agreement that makes corporate and university IP available free of charge for the purpose of facilitating the development of technologies that will end the pandemic and minimize the impact of disease. Joining this pledge is relatively straightforward for already-disclosed IPs. However, few, if any, has considered how to encourage owners of "non-disclosed patent applications" and "trade secrets" to sign on to this meaningful pledge. In other words, so far there is no proposal to extend the Open COVID Pledge for confidential pending patents and trade secrets. METHODS: We propose an innovative and flexible framework to cover both non-disclosed patent applications and trade secrets to mobilize inventors to participate in the Open COVID Pledge. RESULTS: By focusing on immediate publication of the patent-applying technology and extending provisional right to such applications which is subject to the Open Pledge during this pandemic, our recommendations are workable for inventors who would like to pledge their non-disclosed technologies for the detection, prevention and treatment of the COVID-19, in the meantime preserving their IP rights for the post-pledge period. CONCLUSION: This paper offers a way forward to guide pledgers and implementers who are interested in supporting the effort by addressing some of the issues associated with the free sharing of non-disclosed patent applications and trade secrets in the fight against COVID-19.
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COVID-19 , COVID-19/prevención & control , Humanos , Propiedad Intelectual , Tecnología , UniversidadesRESUMEN
Researchers expect a high quality of biospecimens/data and value-added services from biobanks. Therefore, the concept of "biobank 3.0" was introduced so that biobanks could better meet the needs of stakeholders and maintain sustainable operations. Theoretically, the Taiwan Biobank (TWB) has already gone through the concepts of biobank 1.0 and 2.0. However, three challenges still need to be addressed before it can be transformed into a new generation of the TWB (namely, the TWB 3.0): (1) the difficulty of integrating other biobanks' resources, (2) the efficiency and effectiveness of the release and use of biospecimens/data, and (3) the development of income and revenue models of sustainability. To address these issues, this paper proposes a framework for the TWB 3.0 transformation based on a dual-pillar approach composed of a "physically" vertical integration driven by the TWB and a "virtually" horizontal network led by the National Health Research Institutes (NHRI) of Taiwan. Using prominent biobanks such as the Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC), the UK Biobank, and the National Institutes of Health (NIH)'s All of Us Research Program as models, the TWB can strengthen its on-going TWB 2.0 operations in regional and/or international collaboration, increase the value of data collected and develop closer relationships with biobank participants and users. To these ends, the authors highlight key issues that include, but are not limited to, the harmonization of relevant ELSI standards for various biobanks' integrations; the value-added services and the efficiency of Big Data Era related research and/or precision medicine development, and financial concerns related to biobank sustainability. This paper concludes by discussing how greater participant engagement and the uptake of Information Technology (IT) and Artificial Intelligence (AI) applications can be used in partnership with vertical and horizontal integration as part of a four-pronged approach to promote biobank sustainability, and facilitate the TWB 3.0 transformation.
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Bancos de Muestras Biológicas , Salud Poblacional , Inteligencia Artificial , Humanos , Investigadores , TaiwánRESUMEN
Fluorescent nanodiamond (FND) has recently played a central role in fueling new discoveries in interdisciplinary fields spanning biology, chemistry, physics, and materials sciences. The nanoparticle is unique in that it contains a high density ensemble of negatively charged nitrogen-vacancy (NV(-)) centers as built-in fluorophores. The center possesses a number of outstanding optical and magnetic properties. First, NV(-) has an absorption maximum at â¼550 nm, and when exposed to green-orange light, it emits bright fluorescence at â¼700 nm with a lifetime of longer than 10 ns. These spectroscopic properties are little affected by surface modification but are distinctly different from those of cell autofluorescence and thus enable background-free imaging of FNDs in tissue sections. Such characteristics together with its excellent biocompatibility render FND ideal for long-term cell tracking applications, particularly in stem cell research. Next, as an artificial atom in the solid state, the NV(-) center is perfectly photostable, without photobleaching and blinking. Therefore, the NV-containing FND is suitable as a contrast agent for super-resolution imaging by stimulated emission depletion (STED). An improvement of the spatial resolution by 20-fold is readily achievable by using a high-power STED laser to deplete the NV(-) fluorescence. Such improvement is crucial in revealing the detailed structures of biological complexes and assemblies, including cellular organelles and subcellular compartments. Further enhancement of the resolution for live cell imaging is possible by manipulating the charge states of the NV centers. As the "brightest" member of the nanocarbon family, FND holds great promise and potential for bioimaging with unprecedented resolution and precision. Lastly, the NV(-) center in diamond is an atom-like quantum system with a total electron spin of 1. The ground states of the spins show a crystal field splitting of 2.87 GHz, separating the ms = 0 and ±1 sublevels. Interestingly, the transitions between the spin sublevels can be optically detected and manipulated by microwave radiation, a technique known as optically detected magnetic resonance (ODMR). In addition, the electron spins have an exceptionally long coherence time, making FND useful for ultrasensitive detection of temperature at the nanoscale. Pump-probe-type nanothermometry with a temporal resolution of better than 10 µs has been achieved with a three-point sampling method. Gold/diamond nanohybrids have also been developed for highly localized hyperthermia applications. This Account provides a summary of the recent advances in FND-enabled technologies with a special focus on long-term cell tracking, super-resolution imaging, and nanoscale temperature sensing. These emerging and multifaceted technologies are in synchronicity with modern imaging modalities.
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Nanodiamantes , Temperatura , FluorescenciaRESUMEN
BACKGROUND: Toxocariasis, which is predominantly caused by Toxocara canis (T. canis) infection, is a common zoonotic parasitosis worldwide; however, the status of toxocariasis endemicity in the Republic of the Marshall Islands (RMI) remains unknown. METHODS: A seroepidemiological investigation was conducted among 166 primary school children (PSC) aged 7-12 years from the capital area of the RMI. Western blots based the excretory-secretory antigens of larval T. canis (TcES) was employed, and children were considered seropositive if their serum reacted with TcES when diluted at a titer of 1:64. Information regarding demographic characteristics of and environmental risk factors affecting these children was collected using a structured questionnaire. A logistic regression model was applied to conduct a multivariate analysis. RESULTS: The overall seropositive rate of T. canis infection was 86.75% (144/166). In the univariate analysis, PSC who exhibited a history of feeding dogs at home (OR = 5.52, 95% CI = 1.15-26.61, p = 0.02) and whose parents were employed as nonskilled workers (OR = 2.86, 95% CI = 1.08-7.60, p = 0.03) demonstrated a statistically elevated risk of contracting T. canis infections. Cleaning dog huts with gloves might prevent infection, but yielded nonsignificant effects. The multivariate analysis indicated that parental occupation was the critical risk factor in this study because its effect remained significant after adjusting for other variables; by contrast, the effect of dog feeding became nonsignificant because of other potential confounding factors. No associations were observed among gender, age, consuming raw meat or vegetables, drinking unboiled water, cleaning dog huts with gloves, or touching soil. CONCLUSIONS: This is the first serological investigation of T. canis infection among PSC in the RMI. The high seroprevalence indicates the commonness of T. canis transmission and possible human risk. The fundamental information that the present study provides regarding T. canis epidemiology can facilitate developing strategies for disease prevention and control.
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Toxocara canis/inmunología , Toxocariasis/epidemiología , Animales , Western Blotting , Niño , Técnicas de Cultivo , Perros , Heces/parasitología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Micronesia/epidemiología , Factores de Riesgo , Estudios Seroepidemiológicos , Toxocara canis/aislamiento & purificación , Toxocariasis/inmunologíaRESUMEN
Acebutolol (ACE) is commonly used to treat hypertension and high blood pressure. Large doses of ACE can have adverse effects with potentially life-threatening consequences. It is, therefore, essential to develop a simple, low-cost, reliable, and reproducible device for detecting ACE in biofluids. This study explores the potential of unique two-dimensional nano-flakes, such as tungsten trioxide (WO3). Graphene oxide (GO) typically exhibits lower electrical conductivity than pristine graphene due to the presence of oxygen-containing functional groups that interfere with the π-conjugated structure. Functionalizing GO with tannic acid (TA) can partially reinstate the π-conjugation and limit the amount of oxygen, resulting in enhanced electrical conductivity. Ultrasonic techniques were utilized to create WO3 NFs@TA-rGO, and a range of spectroscopic and microscopic methods were applied to examine the formation of the resulting WO3 NFs@TA-rGO nanocomposites. Under optimal conditions, modified sensors resulted in lower limits of detection (0.0055 µM) and good sensitivity (0.40 µA µM-1 cm-2). They also exhibited a broad linear range spanning from 0.009 to 568.6 µM. Fabricated sensors have significant anti-interference properties with high specificity and excellent storage stability (RSD = 4.3 %), reproducibility (RSD = 3.9 %), and repeatability (RSD = 3.3 %). Ultimately, the sensor's efficacy was confirmed through the successful detection of ACE in biological samples (with recoveries ranging from 99.1 to 99.6 %). Lastly, this study highlights the substantial potential of ACE detection and extends its applications in biomedical diagnostics and pharmaceutical research.
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Biopolymer-derived polyelectrolyte complexes (PECs) are a class of materials that have emerged as promising candidates for developing advanced electrochemical sensors due to their tunable properties, biocompatibility, cost-effective production, and high surface area. PECs are formed by combining positively and negatively charged polymers, resulting in a network with intriguing properties that can be tailored for specific sensing applications. The resultant PECs-based nanocomposites were used to modify the glassy carbon electrode (GCE) to detect the sulfamethazine (SFZ) antibiotic drug. In addition, electrochemical studies using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV) are used to evaluate the SFZ detection ability. Similarly, various microscopic and spectroscopic studies investigated the nano composite's structural features and morphological behavior. The κ-CGN/P(Am-co-DMDAAc)-GO modified GCE demonstrated excellent detection ability of SFZ with the nano molar range and without interference with similar structural components. Furthermore, the newly fabricated electrode κ-CGN/P(Am-co-DMDAAc)-GO was derived from naturally available materials, water-soluble, low cost, biocompatible, exhibits good conductivity, and excellent catalytic properties. Finally, κ-CGN/P(Am-co-DMDAAc)-GO- modified GCE has versatile, practical applications for detecting SFZ in real-time samples and determining the efficacy of an antibacterial activity.
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Técnicas Electroquímicas , Sulfametazina , Polielectrolitos , Carragenina , Técnicas Electroquímicas/métodos , Antibacterianos/farmacología , Carbono/químicaRESUMEN
Cancer has become a primary global health concern, which has prompted increased attention towards targeted therapeutic approaches like photothermal therapy (PTT). The unique optical and magnetic properties of nanodiamonds (NDs) have made them versatile nanomaterials with promising applications in biomedicine. This comprehensive review focuses on the potential of NDs as a multifaceted platform for anticancer therapy, mainly focusing on their dual functionality in PTT and temperature sensing. The review highlighted NDs' ability to enhance PTT through hybridization or modification, underscoring their adaptability in delivering small molecule reagents effectively. Furthermore, NDs, particularly fluorescent nanodiamonds (FNDs) with negatively charged nitrogen-vacancy centers, enable precise temperature monitoring, enhancing PTT efficacy in anticancer treatment. Integrating FNDs into PTT holds promise for advancing therapeutic efficacy by providing valuable insights into localized temperature variations and cell death mechanisms. This review highlights new insights into cancer treatment strategies, showcasing the potential of NDs to revolutionize targeted therapeutics and improve patient outcomes.
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Nanodiamantes , Neoplasias , Terapia Fototérmica , Nanodiamantes/química , Nanodiamantes/uso terapéutico , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Temperatura , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.
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Reduced graphene oxide (rGO) has been used in copper (II) oxide (CuO)-based photocatalysts as an additive material. An application of this CuO-based photocatalyst is in the CO2 reduction process. The preparation of rGO by a Zn-modified Hummers' method has resulted in a high quality of rGO in terms of excellent crystallinity and morphology. However, implementing Zn-modified rGO in CuO-based photocatalysts for the CO2 reduction process has yet to be studied. Therefore, this study explores the potential of combining Zn-modified rGO with CuO photocatalysts and performing these rGO/CuO composite photocatalysts to convert CO2 into valuable chemical products. The rGO was synthesized by using a Zn-modified Hummers' method and covalently grafted with CuO by amine functionalization with three different compositions (1:10, 1:20, and 1:30) of rGO/CuO photocatalyst. XRD, FTIR, and SEM were used to investigate the crystallinity, chemical bonds, and morphology of the prepared rGO and rGO/CuO composites. The performance of rGO/CuO photocatalysts for the CO2 reduction process was quantitively measured by GC-MS. We found that the rGO showed successful reduction using a Zn reducing agent. The rGO sheet could be grafted with CuO particles and resulted in a good morphology of rGO/CuO, as shown from the XRD, FTIR, and SEM results. The rGO/CuO material showed photocatalytic performance due to the advantages of synergistic components and resulted in methanol, ethanolamine, and aldehyde as fuel with amounts of 37.12, 8730, and 17.1 mmol/g catalyst, respectively. Meanwhile, adding CO2 flow time increases the resulting quantity of the product. In conclusion, the rGO/CuO composite could have potential for large-scale CO2 conversion and storage applications.
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Epidemiological control and public health monitoring during the outbreaks of infectious viral diseases rely on the ability to detect viral pathogens. Here we demonstrate a rapid, sensitive, and selective nanotechnology-enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection based on the surface-enhanced Raman scattering (SERS) responses from the plasma-engineered, variant-specific antibody-functionalized silver microplasma-engineered nanoassemblies (AgMEN) interacting with the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. The three-dimensional (3D) porous AgMEN with plasmonic-active nanostructures provide a high sensitivity to virus detection via the remarkable SERS signal collection. Moreover, the variant-specific antibody-functionalization on the SERS-active AgMEN enabled the high selectivity of the SARS-CoV-2 S variants, including wild-type, Alpha, Delta, and Omicron, under the simulated human saliva conditions. The exceptional ultrahigh sensitivity of our SERS biosensor was demonstrated via SARS-CoV-2 S and N proteins at the detection limit of 1 fg mL-1 and 0.1 pg mL-1, respectively. Our work demonstrates a versatile SERS-based detection platform can be applied for the ultrasensitive detection of virus variants, infectious diseases, and cancer biomarkers.
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COVID-19 , Nanoestructuras , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Espectrometría Raman/métodos , Glicoproteína de la Espiga del Coronavirus , Límite de Detección , Nanoestructuras/químicaRESUMEN
Alzheimer's disease (AD) is a pathological disorder defined by the symptoms of memory loss and deterioration of cognitive abilities over time. Although the etiology is complex, it is mainly associated with the accumulation of toxic amyloid-ß peptide (Aß) aggregates and tau protein-induced neurofibrillary tangles (NFTs). Even now, creating non-invasive, sensitive, specific, and cost-effective diagnostic methods for AD remains challenging. Over the past few decades, polymers, and nanomaterials (e.g., nanodiamonds, nanogold, quantum dots) have become attractive and practical tools in nanomedicine for diagnosis and treatment. This review focuses on current developments in sensing methods such as enzyme-linked immunosorbent assay (ELISA) and surface-enhanced Raman scattering (SERS) to boost the sensitivity in detecting related biomarkers for AD. In addition, optical analysis platforms such as ELISA and SERS have found increasing popularity among researchers due to their excellent sensitivity and specificity, which may go as low as the femtomolar range. While ELISA offers easy technological usage and high throughput, SERS has the advantages of improved mobility, simple electrical equipment integration, and lower cost. Both portable optical sensing techniques are highly superior in terms of sensitivity, specificity, human application, and practicality, enabling the early identification of AD biomarkers.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Proteínas tau , Péptidos beta-Amiloides , Ensayo de Inmunoadsorción Enzimática , Neuroimagen , BiomarcadoresRESUMEN
The ability to precisely monitor the intracellular temperature directly contributes to the essential understanding of biological metabolism, intracellular signaling, thermogenesis, and respiration. The intracellular heat generation and its measurement can also assist in the prediction of the pathogenesis of chronic diseases. However, intracellular thermometry without altering the biochemical reactions and cellular membrane damage is challenging, requiring appropriately biocompatible, nontoxic, and efficient biosensors. Bright, photostable, and functionalized fluorescent nanodiamonds (FNDs) have emerged as excellent probes for intracellular thermometry and magnetometry with the spatial resolution on a nanometer scale. The temperature and magnetic field-dependent luminescence of naturally occurring defects in diamonds are key to high-sensitivity biosensing applications. Alterations in the surface chemistry of FNDs and conjugation with polymer, metallic, and magnetic nanoparticles have opened vast possibilities for drug delivery, diagnosis, nanomedicine, and magnetic hyperthermia. This study covers some recently reported research focusing on intracellular thermometry, magnetic sensing, and emerging applications of artificial intelligence (AI) in biomedical imaging. We extend the application of FNDs as biosensors toward disease diagnosis by using intracellular, stationary, and time-dependent information. Furthermore, the potential of machine learning (ML) and AI algorithms for developing biosensors can revolutionize any future outbreak.
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Técnicas Biosensibles , Nanodiamantes , Termometría , Inteligencia Artificial , Polímeros , Luminiscencia , Termometría/métodos , Técnicas Biosensibles/métodosRESUMEN
"Precision medicine" has revolutionized how we respond to diseases by using an individual's genomic data and lifestyle and environment-related information to create an effective personalized treatment. However, issues surrounding regulations, medical insurance payments and the use of patients' medical data, have delayed the development of precision medicine and made it difficult to achieve "true" personalization. We therefore recommend that precision medicine be transformed into precision health: a novel and generalized platform of tools and methods that could prevent, manage, and treat disease at a population level. "Precision health," one of six core strategic industries highlighted in Taiwan's vision for 2030, uses various physiological data, genomic data, and external factors, to develop unique "preventative" solutions or therapeutic strategies. For Taiwan to implement precision health, it has to address three challenges: (1) the high-cost issue of precision health; (2) the harmonization issues surrounding integration and transmission of specimen and data; (3) the legal issue of combining information and communications technology (ICT) with Artificial Intelligence (AI) for medical use. In this paper, we propose an innovative framework with six recommendations for facilitating the development of precision health in Taiwan, including a novel model of precise telemedicine with AI-aided technology. We then describe how these tools can be proactively applied in early response to the COVID-19 crisis. We believe that precision health represents an important shift to more proactive and preventive healthcare that enables people to lead healthier lives.
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Smart nanoexosomes are nanosized structures enclosed in lipid bilayers that are structurally similar to the viruses released by a variety of cells, including the cells lining the respiratory system. Of particular importance, the interaction between smart nanoexosomes and viruses can be used to develop antiviral drugs and vaccines. It is possible that nanoexosomes will be utilized and antibodies will be acquired more successfully for the transmission of an immune response if reconvalescent plasma (CP) is used instead of reconvalescent plasma exosomes (CPExo) in this concept. Convalescent plasma contains billions of smart nanoexosomes capable of transporting a variety of molecules, including proteins, lipids, RNA and DNA among other viral infections. Smart nanoexosomes are released from virus-infected cells and play an important role in mediating communication between infected and uninfected cells. Infections use the formation, production and release of smart nanoexosomes to enhance the infection, transmission and intercellular diffusion of viruses. Cell-free smart nanoexosomes produced by mesenchymal stem cells (MSCs) could also be used as cell-free therapies in certain cases. Smart nanoexosomes produced by mesenchymal stem cells can also promote mitochondrial function and heal lung injury. They can reduce cytokine storms and restore the suppression of host antiviral defenses weakened by viral infections. This study examines the benefits of smart nanoexosomes and their roles in viral transmission, infection, treatment, drug delivery and clinical applications. We also explore some potential future applications for smart nanoexosomes in the treatment of viral infections.
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The development of reliable and robust diagnostic tests is one of the most efficient methods to limit the spread of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, most laboratory diagnostics for COVID-19, such as enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR), are expensive, time-consuming, and require highly trained professional operators. On the other hand, the lateral flow immunoassay (LFIA) is a simpler, cheaper device that can be operated by unskilled personnel easily. Unfortunately, the current technique has some limitations, mainly inaccuracy in detection. This review article aims to highlight recent advances in novel lateral flow technologies for detecting SARS-CoV-2 as well as innovative approaches to achieve highly sensitive and specific point-of-care testing. Lastly, we discuss future perspectives on how smartphones and Artificial Intelligence (AI) can be integrated to revolutionize disease detection as well as disease control and surveillance.
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Prueba de COVID-19/instrumentación , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Inteligencia Artificial , COVID-19/inmunología , Prueba de COVID-19/economía , Humanos , Inmunoensayo , Pruebas en el Punto de Atención , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Sensibilidad y Especificidad , Teléfono InteligenteRESUMEN
Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40-70 nm (ND40) and ~100-250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.
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Immunoassays based on sandwich immuno-complexes of capture and detection antibodies simultaneously binding to the target analytes have been powerful technologies in molecular analyses. Recent developments in single molecule detection technologies enable the detection limit of the sandwich immunoassays approaching femtomolar (10-15 M), driving the needs of developing sensitive and specific antibodies for ever-increasingly broad applications in detecting and quantifying biomarkers. The key components underlying the sandwich immunoassays are antibody-based affinity reagents, for which the conventional sources are mono- or poly-clonal antibodies from immunized animals. The downsides of the animal-based antibodies as affinity reagents arise from the requirement of months of development timespan and limited choices of antibody candidates due to immunodominance of humoral immune responses in animals. Hence, developing animal antibodies capable of distinguishing highly related antigens could be challenging. To overcome the limitation imposed by the animal immune systems, we developed an in vitro methodology based on phage-displayed synthetic antibody libraries for diverse antibodies as affinity reagents against closely related influenza virus nucleoprotein (NP) subtypes, aiming to differentiating avian influenza virus (H5N1) from seasonal influenza viruses (H1N1 and H3N2), for which the NPs are closely related by 90-94% in terms of pairwise amino acid sequence identity. We applied the methodology to attain, within four weeks, a panel of IgGs with distinguishable specificities against a group of representative NPs with pairwise amino acid sequence identities up to more than 90%, and the antibodies derived from the antibody libraries without further affinity refinement had comparable affinity of mouse antibodies to the NPs with the detection limit less than 1 nM of viral NP from lysed virus with sandwich ELISA. The panel of IgGs were capable of rapidly distinguishing infections due to virulent avian influenza virus from infections of seasonal flu, in responding to a probable emergency scenario where avian influenza virus would be transmissible among humans overlapping with the seasonal influenza infections. The results indicate that the in vitro antibody development methodology enables developing diagnostic antibodies that would not otherwise be available from animal-based antibody technologies.
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Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Biblioteca de Péptidos , Proteínas del Núcleo Viral/inmunología , Animales , Perros , Ensayo de Inmunoadsorción Enzimática , Humanos , Gripe Humana/diagnóstico , Gripe Humana/inmunología , Células de Riñón Canino Madin Darby , RatonesRESUMEN
BACKGROUND: In this article, incidental findings (IF) refer to unforeseen findings made possible through biobanking research and advances in medical diagnostic technologies that raise issues regarding the obligation and/or responsibility of biobank-users and biobanks to return clinically significant information to participants. The World Medical Association (WMA) Declaration of Taipei (2016) highlights the possibility of encountering IF and requires that research on biospecimens address biobank feedback policies in their informed consent process, leaving open the possibility that the policy may be "no return". As clinicians and researchers begin to use these "resources", the possibility of finding clinically significant IF is becoming a reality. DISCUSSION: In line with the WMA's Declaration of Taipei, a pragmatic approach is needed to deal with the issue of returning IF in biobank governance. Indeed, the impacts and concerns associated with the return of IF differ across different stakeholder groups and jurisdictions. Therefore, the framework governing IF return needs to be custom-built, taking into account the nature of each research project and the unique features of biobanks. To this end, in addition to facilitating biobank transparency, establishing an endurable and horizontal connection among biobanks and clinical institutions under a public health system will improve efficiency and effectiveness. Hence, subject to contemporary Taiwanese ethical and/or legal regulations, this article argues for the establishment of an updated framework for imaging-related and genetic-related IF return within the Taiwan Biobank (TWB), mainly based on a limited obligation to disclose life-threatening information revealed by imaging, but not genetic, information. SUMMARY: After discussing some of the ethical, legal and social issues encountered by the TWB and accounting for the experiences of other international biobanks, we propose a systematic framework for returning IF, mainly on a "limited obligation" basis, which offers better and more comprehensive protection for biobank-participants' rights and health.