A percutaneous ventricular assist device (pVAD) is an effective method to treat heart failure, but its complications, mainly hemolysis and thrombus formation, cannot be ignored. Accurate evaluation ...of hemolysis and thrombus formation in pVAD is essential to guide the development of pVAD and reduce the incidence of complications.
This study optimized the numerical model to predict hemolysis and thrombus formation in pVAD. The hemolysis model is based on the power law function, and the multi-component thrombus prediction model is improved by introducing the von Willebrand factor.
The error between the numerical simulation and the hydraulic performance experiment is within 5%. The numerical results of hemolysis are in good agreement with those of in vitro experiments. Meanwhile, the thrombus location predicted by the numerical model is the same as that found in the in vivo experiment.
The numerical model suggested in this study may therefore accurately assess the possible hemolytic and thrombotic dangers in pVAD, making it an effective tool to support the development of pVAD.
Matrices of low rank can be uniquely determined from fewer linear measurements, or entries, than the total number of entries in the matrix. Moreover, there is a growing literature of computationally ...efficient algorithms which can recover a low rank matrix from such limited information; this process is typically referred to as matrix completion. We introduce a particularly simple yet highly efficient alternating projection algorithm which uses an adaptive stepsize calculated to be exact for a restricted subspace. This method is proven to have near-optimal order recovery guarantees from dense measurement masks and is observed to have average case performance superior in some respects to other matrix completion algorithms for both dense measurement masks and entry measurements. In particular, this proposed algorithm is able to recover matrices from extremely close to the minimum number of measurements necessary. PUBLICATION ABSTRACT
Drp1 is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including ...interaction with mitochondrial receptors such as Mff, MiD49, MiD51, and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is associated with ER in mammalian cells and is distinct from mitochondrial or peroxisomal Drp1 populations. Subpopulations of Mff and Fis1, which are tail-anchored proteins, also localize to ER. Drp1 oligomers assemble on ER, from which they can transfer to mitochondria. Suppression of Mff or inhibition of actin polymerization through the formin INF2 significantly reduces all Drp1 oligomer populations (mitochondrial, peroxisomal, and ER bound) and mitochondrial division, whereas Mff targeting to ER has a stimulatory effect on division. Our results suggest that ER can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division.
The data association problem of multi-object tracking (MOT) aims to assign IDentity (ID) labels to detections and infer a complete trajectory for each target. Most existing methods assume that each ...detection corresponds to a unique target and thus cannot handle situations when multiple targets occur in a single detection due to detection failure in crowded scenes. To relax this strong assumption for practical applications, we formulate the MOT as a Maximizing An Identity-Quantity Posterior (MAIQP) problem on the basis of associating each detection with an identity and a quantity characteristic and then provide solutions to tackle two key problems arising. Firstly, a local target quantification module is introduced to count the number of targets within one detection. Secondly, we propose an identity-quantity harmony mechanism to reconcile the two characteristics. On this basis, we develop a novel Identity-Quantity HArmonic Tracking (IQHAT) framework that allows assigning multiple ID labels to detections containing several targets. Through extensive experimental evaluations on five benchmark datasets, we demonstrate the superiority of the proposed method.
While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is ...recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a different model, progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Drp1 oligomers also translocate directionally along mitochondria. Ionomycin, a calcium ionophore, causes rapid mitochondrial accumulation of actin filaments followed by Drp1 accumulation at the fission site, and increases fission rate. Inhibiting actin polymerization, myosin IIA, or the formin INF2 reduces both un-stimulated and ionomycin-induced Drp1 accumulation and mitochondrial fission. Actin filaments bind purified Drp1 and increase GTPase activity in a manner that is synergistic with the mitochondrial protein Mff, suggesting a role for direct Drp1/actin interaction. We propose that Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites.
Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting ...hematoma growth in patients with intracerebral hemorrhage.
Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth.
A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of back hole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model.
The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage.
Dry powder inhalers (DPIs) can be used with a wide range of drugs such as small molecules and biologics and offer several advantages for inhaled therapy. Early DPI products were intended to treat ...asthma and lung chronic inflammatory disease by administering low-dose, high-potency drugs blended with lactose carrier particles. The use of lactose blends is still the most common approach to aid powder flowability and dose metering in DPI products. However, this conventional approach may not meet the high demand for formulation physical stability, aerosolisation performance, and bioavailability. To overcome these issues, innovative techniques coupled with modification of the traditional methods have been explored to engineer particles for enhanced drug delivery. Different particle engineering techniques have been utilised depending on the types of the active pharmaceutical ingredient (e.g., small molecules, peptides, proteins, cells) and the inhaled dose. This review discusses the challenges of formulating DPI formulations of low-dose and high-dose small molecule drugs, and biologics, followed by recent and emerging particle engineering strategies utilised in developing the right inhalable powder formulations for enhanced drug delivery.
G-quadruplex (G4) structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and serve as important drug targets. The genome-wide detection ...of G4s in living cells is important for exploring the functional role of G4s but has not yet been achieved due to the lack of a suitable G4 probe. Here we report an artificial 6.7 kDa G4 probe (G4P) protein that binds G4s with high affinity and specificity. We used it to capture G4s in living human, mouse, and chicken cells with the ChIP-Seq technique, yielding genome-wide landscape as well as details on the positions, frequencies, and sequence identities of G4 formation in these cells. Our results indicate that transcription is accompanied by a robust formation of G4s in genes. In human cells, we detected up to >123 000 G4P peaks, of which >1/3 had a fold increase of ≥5 and were present in >60% promoters and ∼70% genes. Being much smaller than a scFv antibody (27 kDa) or even a nanobody (12-15 kDa), we expect that the G4P may find diverse applications in biology, medicine, and molecular devices as a G4 affinity agent.
The design of multicomponent materials has captured considerable attention due to its extraordinary ability to tailor functional properties. However, how a single element affects the behavior of the ...overall material has yet to be explored in depth. In this study, the heteroepitaxy of high entropy (Fe, Co, Ni, Cr, Mn)3O4 films with varying strain states are investigated in magnetic performance. It is discovered that the high entropy oxide thin film with compressive strain exhibits an effect of crystalline magnetic anisotropy. Diverse analyses provide a detailed understanding of high entropy magnetic oxide systems, including X‐ray diffraction, reciprocal space mapping, macroscopic magnetic characterization, X‐ray absorption spectroscopy (XAS), etc. Notably, the element‐specific XAS technique proves effective in uncovering the origin of the crystalline magnetic anisotropy. Due to the substrate‐induced epitaxial strain, the eg orbitals of Mn3+ form different energy levels, leading to different preferred electron occupancy. The exploration of magnetic properties in epitaxial high entropy oxide film is then raveled. By navigating the complexities introduced by the random atom distribution and intricate magnetic interactions, this study pioneers novel methodologies for probing the core physics of high entropy oxides.
In a strain‐driven local environment, the magnetic properties of high entropy oxide (Fe, Co, Ni, Cr, Mn)3O4 induced by individual elements are discovered. By utilizing atomic‐spatial‐resolution scanning transmission electron microscopy and element‐specific X‐ray absorption techniques, a thorough understanding of the high entropy oxide can be achieved, establishing a novel methodology for investigating the magnetic origin of high entropy oxides.
Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth ...and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells
and their dissemination at distal organs
. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and β-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors. SIGNIFICANCE: These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4869/F1.large.jpg.
PDF
