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Nanotheranostics, which combines optical multiplexed disease detection with therapeutic monitoring in a single modality, has the potential to propel the field of nanomedicine toward genuine personalized medicine. Currently employed mainstream modalities using gold nanoparticles (AuNPs) in diagnosis and treatment are limited by a lack of specificity and potential issues associated with systemic toxicity. Light-mediated nanotheranostics offers a relatively non-invasive alternative for cancer diagnosis and treatment by using AuNPs of specific shapes and sizes that absorb near infrared (NIR) light, inducing plasmon resonance for enhanced tumor detection and generating localized heat for tumor ablation. Over the last decade, significant progress has been made in the field of nanotheranostics, however the main biological and translational barriers to nanotheranostics leading to a new paradigm in anti-cancer nanomedicine stem from the molecular complexities of cancer and an incomplete mechanistic understanding of utilization of Au-NPs in living systems. This work provides a comprehensive overview on the biological, physical and translational barriers facing the development of nanotheranostics. It will also summarise the recent advances in engineering specific AuNPs, their unique characteristics and, importantly, tunability to achieve the desired optical/photothermal properties.Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP-2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP-2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP-2 pathway-associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP-2 removal, suggesting that they act as a "molecular memory unit." Thus, synergistic stimulation with BMP-2 and mechanical cues drives osteogenic differentiation in a programmable fashion.
West Nile virus (WNV) emerged from Central Africa in the 1990s and is now endemic throughout much of the world. Twenty years after its introduction in the USA, it is becoming apparent that neurological impairments can persist for years following infection. Here, we review the epidemiological data in support of such long-term deficits and discuss possible mechanisms that drive these persistent manifestations.
Focusing on the recently discovered antimicrobial roles of amyloid and alpha-synuclein, we connect WNV late pathology to overlapping features encountered in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. We also summarize new research on microglial activation and engulfment of neural synapses seen in recovered WNV as well as in neurodegenerative diseases, and discuss how loss of integrity of the blood-brain barrier (BBB) may exacerbate this process.
Neuroinvasive viral infections such as WNV may be linked epidemiologically and mechanistically to neurodegeneration. This may open doors to therapeutic options for hitherto untreatable infectious sequelae; additionally, it may also shed light on the possible infectious etiologies of age-progressive neurodegenerative dementias.
Neuroinvasive viral infections such as WNV may be linked epidemiologically and mechanistically to neurodegeneration. This may open doors to therapeutic options for hitherto untreatable infectious sequelae; additionally, it may also shed light on the possible infectious etiologies of age-progressive neurodegenerative dementias.Surface-enhanced Raman scattering (SERS) sensing in microfluidic devices, namely optofluidic-SERS, suffers an intrinsic trade-off between mass transport and hot spot density, both of which are required for ultra-sensitive detection. To overcome this compromise, photonic crystal-enhanced plasmonic mesocapsules are synthesized, utilizing diatom biosilica decorated with in-situ growth silver nanoparticles (Ag NPs). In our optofluidic-SERS testing, 100× higher enhancement factors and greater than 1,000× better detection limit were achieved compared with traditional colloidal Ag NPs, the improvement of which is attributed to unique properties of the mesocapsules. First, the porous diatom biosilica frustules serve as carrier capsules for high density Ag NPs that form high density plasmonic hot-spots. Second, the submicron-pores embedded in the frustule walls not only create a large surface-to-volume ratio allowing for effective analyte capture, but also enhance the local optical field through the photonic crystal effect. Last, the mesocapsules provide effective mixing with analytes as they are flowing inside the microfluidic channel. The reported mesocapsules achieved single molecule detection of Rhodamine 6G in microfluidic devices and were further utilized to detect 1 nM of benzene and chlorobenzene compounds in tap water with near real-time response, which successfully overcomes the constraint of traditional optofluidic sensing.Graphitic multi-walled carbon nanotubes (MWCNTs) can function as high-performance cathode materials for rechargeable Al-ion batteries with well-defined discharging plateaus and reasonable charge/discharge C-rates. Tasocitinib However, the main intercalation/deintercalation or adsorption/desorption path of AlCl4- anions into or onto G-MWCNTs has not been elucidated. Herein, we used battery cells comprised of G-MWCNTs with different aspect ratios, Al metal, and AlCl3/1-ethyl-3-methylimidazolium chloride ionic liquid as the cathode, anode, and electrolyte, respectively. The electrochemical performance of the Al||G-MWCNT cell increased as the aspect ratio of the G-MWCNT cathode increased (i. e., longer and thinner). The degree of defects of the G-MWCNTs was similar (0.15-0.22); hence, the results confirm that the main and alternate paths for the AlCl4- intercalation/de-intercalation or adsorption/desorption into/from or onto/from the G-MWCNT are the basal and edge planes, respectively. The step-like structures of defects on the basal plane provide the main reaction site for AlCl4- anions.
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