Five-Year Outcomes After Endovascular Treatment for Large Vessel Occlusion Stroke.

Background: The long-term outcomes of acute large vessel occlusion (LVO) in anterior circulation treated by endovascular treatment (EVT) remains to be determined. The aim of this study was to assess the 5-year outcomes of patients with LVO who underwent EVT. Methods: This study was an observational, nationwide registry of consecutive patients with acute LVO who received EVT in 28 comprehensive stroke centers in China. The primary outcome was the proportion of favorable outcome [modified Rankin Scale score (mRS) 0-2] at 5 years. Secondary outcomes included proportions of patients with excellent outcome (mRS 0-1), all-cause mortality and risk of stroke recurrence at 5 years. Results: A total of 807 patients were included into the study and had 90-day follow-up data, 657 patients had 5-year follow-up data. At 90 days, 218 patients (27.0%) had an excellent outcome, 349 patients (43.2%) had a favorable functional outcome. 199 patients (24.7%) died. At 5 years, 190 patients (28.9%) had an excellent outcome, 261 patients (39.7%) had a favorable functional outcome, 317 patients (48.2%) died and 129 (28.2%) had stroke recurrence. Because of missing 5-year follow-up data, among available 269 patients who achieved functional independence at 90 days, 208 (77.3%) maintained favorable outcome, 19 (7.1%) had disability (mRS 3-5) and 42 (15.6%) died at 5 years. Furthermore, among available 189 patients with mRS 3-5 at 90 days, 53 (28.0%) patients achieved favorable functional outcome, 60 (31.7%) patients maintained unfavorable functional outcome and 76 (40.2%) patients died within 5 years. Multivariate analyses identified that younger age [odds ratio (OR): 0.96; 95% CI, 0.93-0.99; P = 0.009], lower mRS at 90 days (OR: 0.15; 95% CI, 0.10-0.23; P < 0.001) and absence of stroke recurrence (OR: 0.001; 95% CI, 0.000-0.006; P < 0.001) were significantly associated with favorable outcome at 5 years. Advanced age (OR: 1.06, 95% CI, 1.04-1.08; P < 0.001), higher mRS at 90 days (OR: 0.84; 95% CI, 0.73-0.98; P = 0.021) and atrial fibrillation (OR: 1.63; 95% CI, 1.02-2.60; P = 0.04) were independent factors for stroke recurrence. Conclusion: Our results indicated that the beneficial effect of EVT in patients with acute LVO can be sustained during the course of at least 5 years. Reducing the risk of stroke recurrence by anticoagulation for atrial fibrillation may be a crucial strategy to improve long-term outcome.

Efficient immobilization of catalase on mesoporous MIL-101 (Cr) and its catalytic activity assay.

Enzyme immobilization using metal-organic frameworks (MOFs) as carriers has aroused significant interest owing to the unique pore structure and versatile surface functional groups of MOFs. Catalase (CAT) is an important industrial enzyme that is widely used in the catalytic decomposition of hydrogen peroxide in the fields of food and biological products. In this study, mesoporous MIL-101 (Cr), synthesized through a facile hydrothermal process, was applied for CAT immobilization for the first time. The immobilization capacity of MIL-101 (Cr) for CAT was studied systematically by batch adsorption tests under different adsorption conditions, including the variation of the solution pH, operation temperature, adsorption time, and initial concentration of CAT. Based on these test findings, the optimum adsorption conditions and maximum adsorption capacity were determined. The adsorption kinetics were simulated to further explore the adsorption mechanism, and they suggest that chemical adsorption, rather than physical adsorption, is the main CAT adsorption mechanism. A comparison of Fourier transform infrared (FT-IR) spectra of MIL-101 (Cr) without and with adsorbed CAT reveals the formation of amide bonding between the -NH of CAT and the uncoordinated -CO of MIL-101(Cr). Finally, the stability and activity of the immobilized CAT were assessed, and an improved insensitivity against changes in pH and a prolonged storage time demonstrate the enhanced stability of immobilized CAT by MIL-101 (Cr) carriers. This study demonstrates the application of MOFs as functional supports for the efficient immobilization of versatile enzymes.

Computational and Experimental Characterization of rDNA and rRNA G-Quadruplexes.

DNA G-quadruplexes in human telomeres and gene promoters are being extensively studied for their role in controlling the growth of cancer cells. G-quadruplexes have been unambiguously shown to exist both in vitro and in vivo, including in the guanine (G)-rich DNA genes encoding pre-ribosomal RNA (pre-rRNA), which is transcribed in the cell's nucleolus. Recent studies strongly suggest that these DNA sequences ("rDNA"), and the transcribed rRNA, are a potential anticancer target through the inhibition of RNA polymerase I (Pol I) in ribosome biogenesis, but the structures of ribosomal G-quadruplexes at atomic resolution are unknown and very little biophysical characterization has been performed on them to date. In the present study, circular dichroism (CD) spectroscopy is used to show that two putative rDNA G-quadruplex sequences, NUC 19P and NUC 23P and their counterpart rRNAs, predominantly adopt parallel topologies, reminiscent of the analogous telomeric quadruplex structures. Based on this information, we modeled parallel topology atomistic structures of the putative ribosomal G-quadruplexes. We then validated and refined the modeled ribosomal G-quadruplex structures using all-atom molecular dynamics (MD) simulations with the CHARMM36 force field in the presence and absence of stabilizing K+. Motivated by preliminary MD simulations of the telomeric parallel G-quadruplex (TEL 24P) in which the K+ ion is expelled, we used updated CHARMM36 force field K+ parameters that were optimized, targeting the data from quantum mechanical calculations and the polarizable Drude model force field. In subsequent MD simulations with optimized CHARMM36 parameters, the K+ ions are predominantly in the G-quadruplex channel and the rDNA G-quadruplexes have more well-defined, predominantly parallel-topology structures as compared to rRNA. In addition, NUC 19P is more structured than NUC 23P, which contains extended loops. Results from this study set the structural foundation for understanding G-quadruplex functions and the design of novel chemotherapeutics against these nucleolar targets and can be readily extended to other DNA and RNA G-quadruplexes.

Stretching single fibrin fibers hampers their lysis.

Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis. Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis. STATEMENT OF SIGNIFICANCE: Fibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has a similar effect on reducing lysis as crosslinking fibers. At the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis.

Wind turbine wake visualization and characteristics analysis by Doppler lidar.

Wind power generation is growing fast as one of the most promising renewable energy sources that can serve as an alternative to fossil fuel-generated electricity. When the wind turbine generator (WTG) extracts power from the wind, the wake evolves and leads to a considerable reduction in the efficiency of the actual power generation. Furthermore, the wake effect can lead to the increase of turbulence induced fatigue loads that reduce the life time of WTGs. In this work, a pulsed coherent Doppler lidar (PCDL) has been developed and deployed to visualize wind turbine wakes and to characterize the geometry and dynamics of wakes. As compared with the commercial off-the-shelf coherent lidars, the PCDL in this work has higher updating rate of 4 Hz and variable physical spatial resolution from 15 to 60 m, which improves its capability to observation the instantaneous turbulent wind field. The wind speed estimation method from the arc scan technique was evaluated in comparison with wind mast measurements. Field experiments were performed to study the turbulent wind field in the vicinity of operating WTGs in the onshore and offshore wind parks from 2013 to 2015. Techniques based on a single and a dual Doppler lidar were employed for elucidating main features of turbine wakes, including wind velocity deficit, wake dimension, velocity profile, 2D wind vector with resolution of 10 m, turbulence dissipation rate and turbulence intensity under different conditions of surface roughness. The paper shows that the PCDL is a practical tool for wind energy research and will provide a significant basis for wind farm site selection, design and optimization.

MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery.

While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes.

Computational and experimental characterizations of silver nanoparticle-apolipoprotein biocorona.

With the advancement of nanotoxicology and nanomedicine, it has been realized that nanoparticles (NPs) interact readily with biomolecular species and other chemical and organic matter to result in biocorona formation. The field of the environmental health and safety of nanotechnology, or NanoEHS, is currently lacking significant molecular-resolution data, and we set out to characterize biocorona formation through electron microscopy imaging and circular dichroism spectroscopy that inspired a novel approach for molecular dynamics (MD) simulations of protein-NP interactions. In our present study, we developed a novel GPU-optimized coarse-grained MD simulation methodology for the study of biocorona formation, a first in the field. Specifically, we performed MD simulations of a spherical, negatively charged citrate-covered silver nanoparticle (AgNP) interacting with 15 apolipoproteins. At low ion concentrations, we observed the formation of an AgNP-apolipoprotein biocorona. Consistent with the circular dichroism (CD) spectra, we observed a decrease in α-helices coupled with an increase in ß-sheets in apolipoprotein upon biocorona formation.

Sequence-dependent base-stacking stabilities guide tRNA folding energy landscapes.

The folding of bacterial tRNAs with disparate sequences has been observed to proceed in distinct folding mechanisms despite their structural similarity. To explore the folding landscapes of tRNA, we performed ion concentration-dependent coarse-grained TIS model MD simulations of several E. coli tRNAs to compare their thermodynamic melting profiles to the classical absorbance spectra of Crothers and co-workers. To independently validate our findings, we also performed atomistic empirical force field MD simulations of tRNAs, and we compared the base-to-base distances from coarse-grained and atomistic MD simulations to empirical base-stacking free energies. We then projected the free energies to the secondary structural elements of tRNA, and we observe distinct, parallel folding mechanisms whose differences can be inferred on the basis of their sequence-dependent base-stacking stabilities. In some cases, a premature, nonproductive folding intermediate corresponding to the Ψ hairpin loop must backtrack to the unfolded state before proceeding to the folded state. This observation suggests a possible explanation for the fast and slow phases observed in tRNA folding kinetics.

Iodine-filter-based high spectral resolution lidar for atmospheric temperature measurements.

This paper presents a method for measuring atmosphere temperature profile using a single iodine filter as frequency discriminator. This high spectral resolution lidar (HSRL) is a system reconfigured with the transmitter of a mobile Doppler wind lidar and with a receiving subsystem redesigned to pass the backscattering optical signal through the iodine cell twice to filter out the aerosol scattering signal and to allow analysis of the molecular scattering spectrum, thus measuring temperatures. We report what are believed to be the first results of vertical temperature profiling from the ground to 16 km altitude by this lidar system (power-aperture product=0.35 Wm(2)). Concurrent observations of an L band radiosonde were carried out on June 14 and August 3, 2008, in good agreement with HSRL temperature profiles.

Status and distribution pattern of black crested gibbon (Nomascus concolor jingdongensis) in Wuliang Mountains, Yunnan, China: implication for conservation.

The western black crested gibbon (Nomascus concolor), or black gibbon, one of the lesser apes (Hylobatidae), is mainly distributed in Yunnan, China. Of the four recognized subspecies, N. c. jingdongensis is endemic to the Wuliang Mountain, central Yunnan, China. Of all the subspecies, this one has the largest population of any black gibbon. However, the data were all based on brief estimates. We carried out an extensive field survey on population and group distribution of the black gibbon in the Wuliang Mountains by use of loud morning songs and interviews with local people. Ninety-eight groups were confirmed and located in the mid-montane range of Wuliang Mountains. More groups are found on the east slope and the southern region than in the west and the north. Gibbons are more disjunctly distributed on the west slope, especially in the northern part. Deforestation in the late 1950s, 1960s and 1970s was the main reason for rapid loss of habitat and population decline. Hunting was another key reason for population decline and, in many cases, the main reason for local extinction.