Activity

  • Mcguire Hein posted an update 5 days, 3 hours ago

    Encapsulation technologies are imperative for the safe delivery of live bacteria into the gut where they regulate bodily functions and human health. In this study, we develop alginate-based nanofibers that could potentially serve as a biocompatible, edible probiotic delivery system. By systematically exploring the ratio of three components, the biopolymer alginate (SA), the carrier polymer poly(ethylene oxide) (PEO), and the FDA approved surfactant polysorbate 80 (PS80), the surface tension and conductivity of the precursor solutions were optimized to electrospin bead-free fibers with an average diameter of 167 ± 23 nm. Next, the optimized precursor solution (2.8/1.2/3 wt% of SA/PEO/PS80) was loaded with Escherichia coli (E. coli, 108 CFU mL-1), which served as our model bacterium. We determined that the bacteria in the precursor solution remained viable after passing through a typical electric field (∼1 kV cm-1) employed during electrospinning. This is because the microbes are pulled into a sink-like flow, which encapsulates them into the polymer nanofibers. Upon electrospinning the E. coli-loaded solutions, beads that were much smaller than the size of an E. coli were initially observed. To compensate for the addition of bacteria, the SA/PEO/PS80 weight ratio was reoptimized to be 2.5/1.5/3. Smooth fibers with bulges around the live microbes were formed, as confirmed using fluorescence and scanning electron microscopy. By dissolving and plating the nanofibers, we found that 2.74 × 105 CFU g-1 of live E. coli cells were contained within the alginate-based fibers. This work demonstrates the use of electrospinning to encapsulate live bacteria in alginate-based nanofibers for the potential delivery of probiotics to the gut.Amphiphilic phospholipid-iodinated polymer conjugates were designed and synthesized as new macromolecular probes for a highly radiopaque and biocompatible imaging technology. selleck chemical Bioconjugation of PEG 2000-phospholipids and iodinated polyesters by click chemistry created amphiphilic moieties with hydrophobic polyesters and hydrophilic PEG units, which allowed their self-assemblies into vesicles or spiked vesicles. More importantly, the conjugates exhibited high radiopacity and biocompatibility in in vitro X-ray and cell viability measurements. This new type of bioimaging contrast agent with a Mn value of 11 289 g mol-1 was found to have a significant X-ray signal at 3.13 mg mL-1 of iodine equivalent than baseline and no cytotoxicity after 48 hours incubation of with HEK and 3T3 cells at 20 μM (20 picomoles) concentration of conjugates per well. The potential of adopting the described macromolecular probes for bioimaging was demonstrated, which could further promote the development of a field-friendly and highly sensitive bioimaging contrast agent for point-of-care diagnostic applications.The flexibility and stiffness of small DNA molecules play a fundamental role ranging from several biophysical processes to nano-technological applications. Here, we estimate the mechanical properties of short double-stranded DNA (dsDNA) with lengths ranging from 12 base-pairs (bp) to 56 bp, paranemic crossover (PX) DNA and hexagonal DNA nanotubes (DNTs) using two widely used coarse-grained models – Martini and oxDNA. To calculate the persistence length (Lp) and the stretch modulus (γ) of the dsDNA, we incorporate the worm-like chain and elastic rod model, while for the DNTs, we implement our previously developed theoretical framework. We compare and contrast all of the results with previously reported all-atom molecular dynamics (MD) simulations and experimental results. The mechanical properties of dsDNA (Lp ∼ 50 nm, γ ∼ 800-1500 pN), PX DNA (γ ∼ 1600-2000 pN) and DNTs (Lp ∼ 1-10 μm, γ ∼ 6000-8000 pN) estimated using the Martini soft elastic network and oxDNA are in very good agreement with the all-atom MD and experimental values, while the stiff elastic network Martini reproduces values of Lp and γ which are an order of magnitude higher. The high flexibility of small dsDNA is also depicted in our calculations. However, Martini models proved inadequate to capture the salt concentration effects on the mechanical properties with increasing salt molarity. oxDNA captures the salt concentration effect on the small dsDNA mechanics. But it is found to be ineffective for reproducing the salt-dependent mechanical properties of DNTs. Also, unlike Martini, the time evolved PX DNA and DNT structures from the oxDNA models are comparable to the all-atom MD simulated structures. Our findings provide a route to study the mechanical properties of DNA and DNA based nanostructures with increased time and length scales and has a remarkable implication in the context of DNA nanotechnology.Residual microtumours after surgical resection leading to tumour relapse is one of the major challenges for cancer therapy. Herein, we developed a nano-hybrid oligopeptide hydrogel for topical delivery of a chemotherapeutic drug, docetaxel (DTX), to inhibit the post-surgical tumour recurrence. This nano-hybrid hydrogel (DTX-CTs/Gel) was prepared by encapsulating DTX in cell-penetrating peptide-modified transfersomes followed by embedment in an oligopeptide hydrogel. The obtained DTX-CTs/Gel showed paintable and injectable properties, and could support prolonged retention at the administrated sites after topical administration. DTX-CTs released from the hydrogel presented high skin and tumour penetration capabilities, and increased the accumulation of DTX in the cancer cells leading to enhanced cell death. We showed that the topical delivery of DTX using DTX-CTs/Gel efficiently slowed down the tumour relapse in post-surgical mouse melanoma and breast tumour models.

    The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the U.S. initially, but the temporal trends during the year-long pandemic remain unknown.

    We examined the temporal association between the county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the U.S. in the year starting in March 2020.

    Counties (n=3091) with ≥ 50 COVID-19 cases by March 6

    , 2021 were included in the study. Associations between SVI (and its subcomponents) and county level racial composition with the incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, comorbidities using the average Hierarchical Condition Category (HCC) score, and environmental factors including average fine particulate matter (PM

    ), temperature and precipitation.