411 research outputs found
Dissolution of Pre-Existing Platelet Thrombus by Synergistic Administration of Low Concentrations of Bifunctional Antibodies against β3 Integrin
Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC), which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus), APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ∼2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 µM). Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T50%) by APAC (95±6.1 min) or SLK (145±7.1 min) was much longer than that by combined APAC+SLK (65±7.6 min) at the final concentration of 0.025 µM (APAC+SLK vs APAC, p<0.05; APAC+SLK vs SLK, p<0.01). Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo
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Possible Luttinger liquid behavior of edge transport in monolayer transition metal dichalcogenide crystals.
In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics
Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.
We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC
Cytochrome P450-mediated co-metabolism of fluoroquinolones by Haematococcus lacustris for simultaneously promoting astaxanthin and lipid accumulation
Microalgae-based antibiotic removal treatment has attracted attention because of its low carbon and sustainable
advantages. The microalgal co-metabolism system with a suitable carbon source leads to enhanced performance
of pollutant removal. However, currently, limited knowledge is available for the removal of fluoroquinolone
using a microalgae-mediated co-metabolism system. In this study, we first investigated that the biotic processes
by alga Haematococcus lacustris in the co-metabolism system by adding glycerol would be the main contributors
responsible for the removal of 10 mg/L ofloxacin (OFL) with the efficiency of 79.73% and the removal of 10 mg/
L enrofloxacin (ENR) with the efficiency of 54.10%, respectively. Furthermore, we found that pyruvate from
glycerol was converted into substrates and precursors, thereby resulting in the significant accumulations of
microalgal astaxanthin and lipid. The astaxanthin content of H. lacustris was achieved at 4.81% and 4.69%
treated with OFL and ENR in the presence of glycerol, with 16.04% and 14.55% of lipid content, respectively.
The proposed metabolites and pathways were identified to plausibly explain the biodegradation of fluoroquinolone
by H. lacustris. The molecular analyses demonstrated that cytochrome P450 (CYP450) enzymes are
responsible for the biodegradation of fluoroquinolone, and it was further verified that fluoroquinolones might
insert into CYP450 to finally form an efficient and tight binding conformation by molecular dynamic simulation.
These findings provide a microalgae-based route for feasible and sustainable biodegradation of antibiotics using
a co-metabolism strategy comprising glycerol as a carbon source, with the synergistic accumulation of valuable
products.peer-reviewe
Colorimetric Assay for Determination of Lead (II) Based on Its Incorporation into Gold Nanoparticles during Their Synthesis
In this report, we present a new method for visual detection of Pb2+. Gold nanoparticles (Au-NPs) were synthesized in one step at room temperature, using gallic acid (GA) as reducer and stabilizer. Pb2+ is added during the gold nanoparticle formation. Analysis of Pb2+ is conducted by a dual strategy, namely, colorimetry and spectrometry. During Au-NPs synthesis, addition of Pb2+ would lead to formation of Pb-GA complex, which can induce the aggregation of newly-formed small unstable gold nanoclusters. Consequently, colorimetric detection of trace Pb2+ can be realized. As the Pb2+ concentration increases, the color turns from red-wine to purple, and finally blue. This method offers a sensitive linear correlation between the shift of the absorption band (Δλ) and logarithm of Pb2+ concentration ranging from 5.0 × 10−8 to 1.0 × 10−6 M with a linear fit coefficient of 0.998, and a high selectivity for Pb2+ detection with a low detection limit down to 2.5 × 10−8 M
The Mych Gene Is Required for Neural Crest Survival during Zebrafish Development
Background: Amomg Myc family genes, c-Myc is known to have a role in neural crest specification in Xenopus and in craniofacial development in the mouse. There is no information on the function of other Myc genes in neural crest development, or about any developmental role: of zebrafish Myc genes. Principal Findings: We isolated the zebrafish mych (myc homologue) gene. Knockdown of mych leads to sever defects in craniofacial development and in certain other tissues including the eye. These phenotypes appear to be caused by cell death in the neural crest and in the eye field in the anterior brain. Significance: Mych is a novel factor required for neural crest cell survival in zebrafish
DSSylation, a novel protein modification targets proteins induced by oxidative stress, and facilitates their degradation in cells
Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin-proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-013-0018-8) contains supplementary material, which is available to authorized users
Aggregation-Induced Emission (AIE), Life and Health
Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health
The Minimum Variation Timescales of X-ray bursts from SGR J1935+2154
The minimum variation timescale (MVT) of soft gamma-ray repeaters can be an
important probe to estimate the emission region in pulsar-like models, as well
as the Lorentz factor and radius of the possible relativistic jet in gamma-ray
burst (GRB)-like models, thus revealing their progenitors and physical
mechanisms. In this work, we systematically study the MVTs of hundreds of X-ray
bursts (XRBs) from SGR J1935+2154 observed by {\it Insight}-HXMT, GECAM and
Fermi/GBM from July 2014 to Jan 2022 through the Bayesian Block algorithm. We
find that the MVTs peak at 2 ms, corresponding to a light travel time
size of about 600 km, which supports the magnetospheric origin in pulsar-like
models. The shock radius and the Lorentz factor of the jet are also constrained
in GRB-like models. Interestingly, the MVT of the XRB associated with FRB
200428 is 70 ms, which is longer than that of most bursts and implies
its special radiation mechanism. Besides, the median of MVTs is 7 ms, shorter
than the median MVTs of 40 ms and 480 ms for short GRBs or long GRBs,
respectively. However, the MVT is independent of duration, similar to GRBs.
Finally, we investigate the energy dependence of MVT and suggest that there is
a marginal evidence for a power-law relationship like GRBs but the rate of
variation is at least about an order of magnitude smaller. These features may
provide an approach to identify bursts with a magnetar origin.Comment: accepted for publication in ApJ
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