Heat-activated growth of metastable and length-defined DNA fibers expands traditional polymer assembly.

Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers - or 'curlamers' - determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

Chemo- and enantioselective intramolecular silver-catalyzed aziridinations of carbamimidates.

Transition metal-catalyzed asymmetric nitrene transfer is a powerful method to generate enantioenriched amines found in natural products and bioactive molecules. A highly chemo- and enantioselective intramolecular silver-catalysed aziridination of 2,2,2-trichloroethoxysulfonyl (Tces)-protected carbamimidates gives [4.1.0]-bicyclic aziridines in good yields and up to 99% ee.

Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs.

Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics.

Responsive Nucleic Acid-Based Organosilica Nanoparticles.

The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol-gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing.

A 10-km CMIP6 downscaled dataset of temperature and precipitation for historical and future Vietnam climate.

High-resolution climate projections are mandatory for many applications and impact assessments in environmental and management studies. In response to the needs in Vietnam, this study constructs a new precipitation and temperature daily dataset for Vietnam, at a high spatial resolution of 0.1° × 0.1°, based on the outputs of 35 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The Bias Correction and Spatial Disaggregation (BCSD) method is adopted to bias-correct monthly GCM simulations using observation data, then subsequently temporally disaggregate them into daily data. The new dataset is called CMIP6-VN, covering the present-time period 1980-2014 and future projections for 2015-2099 from both CMIP6 tier-1 (Shared Socioeconomic Pathways (SSPs) 1-1.26, 2-4.5, 3-7.0, and 5-8.5) and tier-2 (SSPs 1-1.9, 4-3.4, 4-6.0) experiments. Results indicated the good performance of CMIP6-VN for the historical period, suggesting that the dataset could be used for studies on climate change assessment and impacts in Vietnam.

Flap application in reconstructive surgery to manage severe radiation-induced ulcers: a case series.

INTRODUCTION: Radiation-induced ulceration is a late-stage skin reaction after RT for cancer treatment. OBJECTIVE: The present study examined the use of a single-stage reconstructive procedure to manage radiation-related wounds. MATERIALS AND METHODS: Nine patients with radiation-induced chronic ulcer with accompanying severe complications were admitted to the Plastic, Reconstructive, and Regenerative Center of Viet Nam National Burn Hospital between October 2015 and September 2019. The patients ranged in age from 49 to 77 years. Complications included exposed cheekbone (n = 1), exposed trachea (n = 1), exposed carotid artery (n = 2), exposed axillary artery (n = 2), exposed pleura (n = 1), and exposed pericardium (n = 2). Flap type used to achieve defect coverage after debridement was individualized to each patient and included ALT, LD, SCA, and DIEP flaps. Additionally, a high-density polyethylene was used to reconstruct the trachea to recover breathing function in the patient with exposed trachea. RESULTS: Complete survival of all flaps was achieved. Most vital organs (the trachea, axillary artery, and carotid artery) were covered. Hospital length of stay ranged from 15 to 120 days. CONCLUSIONS: The successful management of patients with severe complications suggests that immediate single-stage reconstruction may be a valuable option for managing radiation-induced ulcers.

A Photoresponsive Intramolecular Triplex Motif That Enables Rapid and Reversible Control of Aptamer Binding Activity.

DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we report the design of an intramolecular triplex photoswitch (TPS) design based on single-stranded DNA that undergoes rapid and reversible photoswitching between folded and unfolded states through isomerization of internal azobenzene modifications. After optimizing the performance of our photoswitch design, we used molecular dynamics simulations to reveal how individual azobenzenes contribute to the stabilization or destabilization of the triplex depending on their photoisomerization state. By coupling our TPS to an existing aptamer, we can reversibly modulate its binding affinity with less than 15 s of UV light exposure. We further demonstrate reproducible shifting in affinity over multiple cycles of UV and blue light irradiation without substantial photobleaching.

Controlled synthesis of various Fe2O3 morphologies as energy storage materials.

Air pollution from vehicle emissions is a major problem in developing countries. Consequently, the use of iron-based rechargeable batteries, which is an effective method of reducing air pollution, have been extensively studied for electric vehicles. The structures and morphologies of iron particles significantly affect the cycle performance of iron-based rechargeable batteries. The synthesis parameters for these iron materials also remarkably influence their structures, shapes, sizes, and electrochemical properties. In this study, we fabricated α-Fe2O3 materials with various shapes and sizes via a facile hydrothermal route and investigated the effects of raw materials on their structures, morphologies, and properties. The structural characteristics of the synthesized iron oxides were studied via X-ray diffraction using scanning electron microscopy. Results indicate that changing the concentration of raw materials modified the structure and morphology of the synthesized α-Fe2O3 particles, that is, the desired shape and size of α-Fe2O3 can be controlled. The effects of the structure and morphology of α-Fe2O3 particles on their electrochemical characteristics were investigated. The results show that the morphology and shape of the iron oxide particles remarkably affected the redox reaction rate and discharge capacity of the Fe2O3/C composite electrodes. Among the synthesized α-Fe2O3 materials, the cubic-shaped α-Fe2O3 exhibited the highest discharge capacity. This material is a potential candidate for application in iron-based aqueous batteries. Our results may facilitate not only the controlled synthesis of α-Fe2O3 nanoparticles for potential technical applications but also the production of electrode materials with high capacity and good cycle performance for iron-based rechargeable batteries.

Hydrothermal Synthesis of α-Fe2O3 as Anode for Fe/Air Battery.

The size, shape and structure of iron particles in iron electrode influence the electrochemical properties of Fe/air cells. In order to improve the electrochemical performance of Fe/air cells, an attempt has been made successfully to synthesize iron oxide particles with different surface morphologies and have been used as negative electrodes. Fe2O3 nanoparticles were synthesized by hydrothermal method, in which their different morphologies viz., hollow spheres, tubes and plates have been controlled by the concentration of precursors. All the results showed better cycleability, good discharge capacity of synthesized Fe2O3 exhibited improved performance compared to commercial Fe2O3. Among the synthesized Fe2O3, hollow sphere provided the highest discharge capacity.

Prolonged neuromuscular block after rocuronium administration in laparoscopic pyloromyotomy patients: A retrospective bayesian regression analysis.

BACKGROUND: Infants undergoing pyloromyotomy are at a high risk of aspiration, making rapid sequence induction the preferred method of induction. Since succinylcholine use in infants can be associated with complications, rocuronium is frequently substituted despite its prolonged duration of action. AIMS: To examine the likelihood of non-reversibility to neostigmine at the end of surgery in laparoscopic pyloromyotomies and its correlation to both rocuronium dose and out of operating room time. METHODS: Patients who underwent laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis, received rocuronium, and were reversed with neostigmine were included. Bayesian multivariable logistic regression was utilized to determine the probability of non-reversibility, and Bayesian multivariable median regression was performed to ascertain the correlation between out of operating room time and non-reversibility. RESULTS: 306 patients were analyzed with a median surgical duration of 19 min (interquartile range 16 to 23). 74% received succinylcholine for intubation followed by rocuronium, and the remaining received rocuronium alone. The median rocuronium dose was 0.41 mg/kg (interquartile range 0.27 - 0.56 mg/kg). Prolonged block occurred in 68 (22.2%) patients. There was a non-trivial probability of prolonged block with low rocuronium doses, and each 0.1 mg/kg increase in total rocuronium dose was associated with an odds ratio of 1.36 (95% credible interval: 1.17-1.58) of neostigmine non-reversibility at the end of surgery. Non-reversibility was correlated with a substantial increase in median out of operating room time (13.4 min, 95% credible interval: 5.5-20.8 min), which was compounded by high rocuronium dosing (2.2 min increase per 0.1 mg/kg for doses greater than 0.5 mg/kg, 95% credible interval: 0.7-3.6 min). CONCLUSION: Prolonged blockade can occur from rocuronium administration in infants undergoing pyloromyotomy even at low doses. Therefore, consideration of appropriate rocuronium dosing or the use of sugammadex should be considered.

Asymmetric patterning drives the folding of a tripodal DNA nanotweezer.

DNA tweezers have emerged as powerful devices for a wide range of biochemical and sensing applications; however, most DNA tweezers consist of single units activated by DNA recognition, limiting their range of motion and ability to respond to complex stimuli. Herein, we present an extended, tripodal DNA nanotweezer with a small molecule junction. Simultaneous, asymmetric elongation of our molecular core is achieved using polymerase chain reaction (PCR) to produce length- and sequence-specific DNA arms with repeating DNA regions. When rigidified, our DNA tweezer can be addressed with streptavidin-binding ligands. Full control over the number, separation, and location of these ligands enables site-specific streptavidin recognition; all three arms of the DNA nanotweezer wrap around multiple streptavidin units simultaneously. Our approach combines the simplicity of DNA tile arrays with the size regime normally provided by DNA origami, offering an integrated platform for the use of branched DNA scaffolds as structural building blocks, protein sensors, and dynamic, stimuli-responsive materials.

Intraoperative dextrose rate during exploratory laparotomies in neonates and the incidence of postoperative hyperglycemia: A retrospective observational study.

INTRODUCTION: Compared with the older pediatric population, neonates have greater perioperative morbidity and mortality. Difficulty with glucose regulation may be a contributing modifiable risk factor during perioperative anesthetic management. To mitigate the risk of hyperglycemia in neonates, some providers empirically halve the preoperative rate of dextrose-containing infusions during surgery. AIM: To assess the association between halving the preoperative maintenance dextrose rate and postoperative euglycemia in neonatal intensive care unit patients undergoing exploratory laparotomies. METHODS: Neonatal intensive care unit patients who underwent exploratory laparotomy under general anesthesia from 1/1/2014 to 11/21/2019 were included in this analysis. Hyperglycemia and hypoglycemia were defined as >150 mg/dL and <46 mg/dL. A calculated dextrose ratio was utilized to categorize patients into full and half intraoperative dextrose rate cohorts. Univariate analyses were performed with Fisher's exact test, the Wilcoxon rank sum test, or Spearman's correlation. Multivariable analyses with regression models were conducted after graphical evaluation of a predetermined set of independent variables. RESULTS: 107 patients were included in the full dextrose rate cohort and 96 patients in the half dextrose rate cohort with postoperative hyperglycemia occurring in 47 and 28 patients, respectively. On univariate analysis, halving the preoperative dextrose rate was associated with decreased postoperative hyperglycemia (odds ratio: 0.53; 95% CI: 0.28-0.98, P = 0.041). This association continued in the regression model (adjusted odds ratio: 0.49; 95% CI: 0.25-0.80, P = 0.008) after controlling for preoperative dextrose rate, preoperative serum glucose, preoperative pH, surgical duration, postmenstrual age at surgery, and the presence of necrotizing enterocolitis. Only one patient was hypoglycemic postoperatively, and they were in the full dextrose cohort. CONCLUSION: Halving of preoperative dextrose rates intraoperatively during exploratory laparotomy in neonatal intensive care unit patients was associated with a decreased risk of postoperative hyperglycemia without substantially increasing the occurrence of postoperative hypoglycemia. The practice of halving preoperative dextrose rates may be an effective empirical approach for intraoperative glucose management in the high-risk neonatal population when blood glucose monitoring is challenging.

High Incidence of Burst Suppression during Propofol Sedation for Outpatient Colonoscopy: Lessons Learned from Neuromonitoring.

BACKGROUND: Although anesthesia providers may plan for moderate sedation, the depth of sedation is rarely quantified. Using processed electroencephalography (EEG) to assess the depth of sedation, this study investigates the incidence of general anesthesia with variable burst suppression in patients receiving propofol for outpatient colonoscopy. The lessons learned from neuromonitoring can then be used to guide institutional best sedation practice. METHODS: This was a prospective observational study of 119 outpatients undergoing colonoscopy at Thomas Jefferson University Hospital (TJUH). Propofol was administered by CRNAs under anesthesiologists' supervision. The Patient State Index (PSi™) generated by the Masimo SedLine® Brain Root Function monitor (Masimo Corp., Irvine, CA) was used to assess the depth of sedation. PSi data correlating to general anesthesia with variable burst suppression were confirmed by neuroelectrophysiologists' interpretation of unprocessed EEG. RESULTS: PSi values of <50 consistent with general anesthesia were attained in 118/119 (99.1%) patients. Of these patients, 33 (27.7%) attained PSi values <25 consistent with variable burst suppression. The 118 patients that reached PSi <50 spent a significantly greater percentage (53.1% vs. 42%) of their case at PSi levels <50 compared to PSi levels >50 (p=0.001). Mean total propofol dose was significantly correlated to patient PSi during periods of PSi <25 (R=0.406, p=0.021). CONCLUSION: Although providers planned for moderate to deep sedation, processed EEG showed patients were under general anesthesia, often with burst suppression. Anesthesiologists and endoscopists may utilize processed EEG to recognize their institutional practice patterns of procedural sedation with propofol and improve upon it.

Amplified Self-Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA-Minimal Architectures.

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker-recognition properties and as stimuli, notably in amplified small-molecule release by nucleic-acid-templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA-templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.

Fast and accurate compensation of signal offset for T2 mapping.

OBJECTIVE: T2 maps are more vendor independent than other MRI protocols. Multi-echo spin-echo signal decays to a non-zero offset due to imperfect refocusing pulses and Rician noise, causing T2 overestimation by the vendor's 2-parameter algorithm. The accuracy of the T2 estimate is improved, if the non-zero offset is estimated as a third parameter. Three-parameter Levenberg-Marquardt (LM) T2 estimation takes several minutes to calculate, and it is sensitive to initial values. We aimed for a 3-parameter fitting algorithm that was comparably accurate, yet substantially faster. METHODS: Our approach gains speed by converting the 3-parameter minimisation problem into an empirically unimodal univariate problem, which is quickly minimised using the golden section line search (GS). RESULTS: To enable comparison, we propose a novel noise-masking algorithm. For clinical data, the agreement between the GS and the LM fit is excellent, yet the GS algorithm is two orders of magnitude faster. For synthetic data, the accuracy of the GS algorithm is on par with that of the LM fit, and the GS algorithm is significantly faster. The GS algorithm requires no parametrisation or initialisation by the user. DISCUSSION: The new GS T2 mapping algorithm offers a fast and much more accurate off-the-shelf replacement for the inaccurate 2-parameter fit in the vendor's software.

"Printing" DNA Strand Patterns on Small Molecules with Control of Valency, Directionality, and Sequence.

The incorporation of synthetic molecules as corner units in DNA structures has been of interest over the last two decades. In this work, we present a facile method for generating branched small molecule-DNA hybrids with controllable valency, different sequences, and directionalities (5'-3') using a "printing" process from a simple 3-way junction structure. We also show that the DNA-imprinted small molecule can be extended asymmetrically using polymerase chain reaction (PCR) and can be replicated chemically. This strategy provides opportunities to achieve new structural motifs in DNA nanotechnology and introduce new functionalities to DNA nanostructures.

DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns.

As colloidal self-assembly increasingly approaches the complexity of natural systems, an ongoing challenge is to generate non-centrosymmetric structures. For example, patchy, Janus or living crystallization particles have significantly advanced the area of polymer assembly. It has remained difficult, however, to devise polymer particles that associate in a directional manner, with controlled valency and recognition motifs. Here, we present a method to transfer DNA patterns from a DNA cage to a polymeric nanoparticle encapsulated inside the cage in three dimensions. The resulting DNA-imprinted particles (DIPs), which are 'moulded' on the inside of the DNA cage, consist of a monodisperse crosslinked polymer core with a predetermined pattern of different DNA strands covalently 'printed' on their exterior, and further assemble with programmability and directionality. The number, orientation and sequence of DNA strands grafted onto the polymeric core can be controlled during the process, and the strands are addressable independently of each other.

DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for Guest Encapsulation and Cellular Delivery.

Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid-like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single-molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye-mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer-coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.

DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules.

We report a micelle-templated method to enhance the reactivity of DNA with highly hydrophobic molecules. Lipids, chromophores and polymers can be conjugated to DNA in high yield and under mild conditions. This method expands the range of DNA-templated reactions for DNA-encoded libraries, oligonucleotide and drug delivery, nanopore mimetics and DNA nanotechnology.

Correction: Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown.

Correction for 'Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown' by Johans J. Fakhoury, et al., Nanoscale, 2015, 7, 20625-20634.