Experimental study on the flow structures and dynamics of turbulent Rayleigh-Bénard convection in an annular cell.

We conduct an experimental study on the flow structures and dynamics of turbulent Rayleigh-Bénard convection in an annular cell with radius ratio η≃0.5 and aspect ratio Γ≃4. The working fluid is water with a Prandtl number of Pr≃5.4, and the Rayleigh number (Ra) ranges from 5.05×10^{7} to 5.05×10^{8}. The multithermal-probe method and the particle image velocimetry technique are employed to measure the temperature profiles and the velocity fields, respectively. Two distinct states with multiroll standing waves are observed, which are the quadrupole state (QS) characterized by a four-roll structure and the sextupole state (SS) by a six-roll structure. The scaling exponents of Reynolds number Re with Ra are different for the two states, which are 0.56 for QS and 0.41 for SS. In addition, the standing waves become unstable upon tilting the cell by 1^{∘} in relation to the horizontal plane, and they evolve into traveling waves. At relatively high Ra, for instance, Ra⩾2.55×10^{8}, it is observed that the traveling wave state SS undergoes a transition to the traveling wave state QS. However, the opposite transition from QS to SS is not observed in our experiments. Our findings provide insights into the flow structures and dynamics in the convection flow with rotation symmetry.

The Pharmacokinetics and Pharmacodynamics of A Novel Recombinant Activated Human Factor VII, GEN-0828, in Hemophilia B Mice.

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED50) of GEN-0828 (10.91 KIU·kg-1) and NovoSeven® (18.91 KIU·kg-1) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg-1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (Cmax) and area under the plasma concentration-time curve (AUClast) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles.

Rare Recurrent EWSR1-PLAGL1 Rearranged Intracranial Tumor With Biphasic Epithelioid Differentiation: One Case Report With Literature Review.

EWSR1-rearranged tumors encompass a rare and heterogeneous group of entities with features of the central nervous system (CNS) mesenchymal and primary glial/neuronal tumors. EWSR1-PLAGL1 gene fusion is a particularly rare form of rearrangement. We presented a recurrent intracranial EWSR1-PLAGL1 rearranged tumor and reviewed the relevant literature. In this case, histopathology and immunohistochemistry (IHC) were evaluated for both the primary and relapsed tumors. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were performed for the relapsed tumor. We compared the morphology, IHC results and molecular features with the previously reported EWSR1-PLAGL1 rearranged CNS tumors. Our case exhibited a unique feature with a variable biphasic pattern of epithelioid differentiation, which differed from the two reported groups. The primary and relapsed tumors both expressed cytokeratin of the focal area with epithelioid differentiation. The recurrent tumor showed an increased proliferation index (average Ki-67 index of 15%) compared with the primary tumor (average Ki-67 index of 5%). NGS showed that TERT promoter mutation was the only molecular change besides EWSR1-PLAGL1 fusion. Our study provides further insight into intracranial tumors with EWSR1-PLAGL1 fusion, representing a distinct CNS tumor with no-reported histological and immunohistochemical features. Future studies, particularly for the biphasic differentiation and the role of TERT promoter mutation were needed to clarify this unusual chromosomal rearrangement in the CNS tumor.

miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer.

PURPOSE: Neoadjuvant chemotherapy (NAC) is widely used to treat breast cancer (BC). The prediction and evaluation of chemotherapy responses remains a significant challenge. METHODS: MicroRNAs (miRNAs) play a crucial role in cancer drug resistance. We used a miRNA microarray and identified that miR-638 is downregulated in chemoresistant cases. However, the exact role of miR-638 and the underlying mechanisms of chemoresistance remain unclear. Using real-time quantitative reverse transcription polymerase chain reaction, we found significant downregulation of miR-638 in chemoresistant patients compared with chemosensitive patients. To explore the function of miR-638, we overexpressed and inhibited miR-638 expression in MDA-MB-231 and MCF-7 cells by transfecting them with miR-638 mimics and miR-638 inhibitor, respectively. Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. A minimal patient-derived xenograft (MiniPDX™) model was established to evaluate the chemosensitivity to different drugs. RESULTS: The results showed that cell proliferation decreased and cell apoptosis increased in cells transfected with the miR-638 mimic, and cell proliferation and apoptosis were reversed with transfection of miR-638 inhibitor compared with the control group. Among patients who received 5-fluorouracil (5-FU), miR-638 expression levels were lower in the chemoresistant group than in the chemosensitive group. The MiniPDX™ model showed that MDA-MB-231 cells overexpressing miR-638 were more susceptible to 5-FU treatment in vivo. CONCLUSION: We provided evidence of acquired resistance to 5-FU caused by miR-638 deficiency. Alterations in miR-638 may be used with 5-FU chemotherapy during NAC for BC.

The Associations of Serum IL-37 With the Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Retrospective Cohort Study.

Background: Recent evidences suggested that IL-37 may participate in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, its exact biological role was unknown. The objective of this study was to determine the associations of serum IL-37 with the severity and prognosis in CAP patients based on a retrospective cohort study. Methods: The whole of 120 healthy subjects and 240 CAP patients were summoned. Peripheral blood was collected and IL-37 was detected using ELISA. Results: Serum IL-37 was obviously decreased in CAP patients on admission. In addition, serum IL-37 was gradually decreased in parallel with CAP severity scores. Correlative analysis revealed that serum IL-37 was negatively associated with CAP severity scores and inflammatory cytokines. Further logistical regression found that reduction of serum IL-37 augmented the severity of CAP patients. Moreover, the follow-up research was performed in CAP patients. Serum lower IL-37 on admission prolonged the hospital stay in CAP patients. Serum IL-37 combination with PSI and CURB-65 had a stronger predictive capacity for death than IL-37 and CAP severity score alone in CAP patients. Conclusion: There are remarkably negative correlations between serum IL-37 with the severity and prognosis in CAP patients. Serum IL-37 on admission prolongs the hospital stay, demonstrating that IL-37 may involve in the process of CAP. Serum IL-37 may be regarded as a biomarker for diagnosis and prognosis for CAP patients.

Light therapy: a new option for neurodegenerative diseases.

ABSTRACT: Given the increasing incidence of neurodegenerative disease (ND), recent research efforts have intensified the search for curative treatments. Despite significant research, however, existing therapeutic options for ND can only slow down the progression of the disease, but not provide a cure. Light therapy (LT) has been used to treat some mental and sleep disorders. This review illustrates recent studies of the use of LT in patients with ND and highlights its potential for clinical applications. The literature was collected from PubMed through June 2020. Selected studies were primarily English articles or articles that could be obtained with English abstracts and Chinese main text. Articles were not limited by type. Additional potential publications were also identified from the bibliographies of identified articles and the authors' reference libraries. The identified literature suggests that LT is a safe and convenient physical method of treatment. It may alleviate sleep disorders, depression, cognitive function, and other clinical symptoms. However, some studies have reported limited or no effects. Therefore, LT represents an attractive therapeutic approach for further investigation in ND. LT is an effective physical form of therapy and a new direction for research into treatments for ND. However, it requires further animal experiments to elucidate mechanisms of action and large, double-blind, randomized, and controlled trials to explore true efficacy in patients with ND.

Statistics of velocity and temperature fluctuations in two-dimensional Rayleigh-Bénard convection.

We investigate fluctuations of the velocity and temperature fields in two-dimensional (2D) Rayleigh-Bénard (RB) convection by means of direct numerical simulations (DNS) over the Rayleigh number range 10^{6}≤Ra≤10^{10} and for a fixed Prandtl number Pr=5.3 and aspect ratio Γ=1. Our results show that there exists a counter-gradient turbulent transport of energy from fluctuations to the mean flow both locally and globally, implying that the Reynolds stress is one of the driving mechanisms of the large-scale circulation in 2D turbulent RB convection besides the buoyancy of thermal plumes. We also find that the viscous boundary layer (BL) thicknesses near the horizontal conducting plates and near the vertical sidewalls, δ_{u} and δ_{v}, are almost the same for a given Ra, and they scale with the Rayleigh and Reynolds numbers as ∼Ra^{-0.26±0.03} and ∼Re^{-0.43±0.04}. Furthermore, the thermal BL thickness δ_{θ} defined based on the root-mean-square (rms) temperature profiles is found to agree with Prandtl-Blasius predictions from the scaling point of view. In addition, the probability density functions of turbulent energy ɛ_{u^{'}} and thermal ɛ_{θ^{'}} dissipation rates, calculated, respectively, within the viscous and thermal BLs, are found to be always non-log-normal and obey approximately a Bramwell-Holdsworth-Pinton distribution first introduced to characterize rare fluctuations in a confined turbulent flow and critical phenomena.

Intracellular DNA sensing pathway of cGAS-cGAMP is decreased in human newborns and young children.

Newborns are highly susceptible to DNA virus infections, which may result from the characteristics of neonatal innate immune systems. Here we analyzed for the first time the development of innate immune sensing and signaling of intracellular DNA virus infection in human newborns and young children. Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex virus type 1 (HSV-1) or interferon-α (IFNα) stimulation. Furthermore, production of the second messenger cGAMP and activation of the transcriptional factor IRF3 was severely decreased in neonatal cord blood mononuclear cells (CBMCs) or PBMCs compared with adults. In contrast, the downstream signaling STING-TBK1-IRF3 appeared to be functional in neonatal PBMCs, as demonstrated by the fact that IRF3 phosphorylation and IFNß production in these cells could be activated by cGAMP. Intriguingly, decreased expression of cGAS in neonatal cells can be rescued by DNA demethylation, with concomitant enhancement in IFNß induction by HSV-1. Thus, cGAS restoration or STING stimulation by small molecules during infancy might improve the age-dependent susceptibility to DNA virus infection.

Local dissipation scales in two-dimensional Rayleigh-Taylor turbulence.

We examine the distribution of the local dissipation scale η, Q(η), and its temporal evolution in two-dimensional (2D) Rayleigh-Taylor (RT) turbulence using direct numerical simulations at small Atwood number and unit Prandtl number. Within the self-similarity regime of the mixing zone evolution, distributions of η at small scales are found to be insensitive to the large-scale anisotropy of the system and independent of position and of the temporal evolution of the mixing zone. Our results further reveal that the present measured Q(η) agrees with those previously observed in homogeneous isotropic turbulence and in turbulent pipe flows, at least for the smallest scales around the classical Kolmogorov dissipation scale. However, the RT case seems to show a different trend from the other two cases for large scales, which may attributed to the absence of the inertial-range intermittency for the velocity field in 2D RT turbulence.

Single-trial analysis of cortical oscillatory activities during voluntary movements using empirical mode decomposition (EMD)-based spatiotemporal approach.

This study presents a method based on empirical mode decomposition (EMD) and a spatial template-based matching approach to extract sensorimotor oscillatory activities from multi-channel magnetoencephalographic (MEG) measurements during right index finger lifting. The longitudinal gradiometer of the sensor unit which presents most prominent SEF was selected on which each single-trial recording was decomposed into a set of intrinsic mode functions (IMFs). The correlation between each IMF of the selected channel and raw data on other channels were created and represented as a spatial map. The sensorimotor-related IMFs with corresponding correlational spatial map exhibiting large values on primary sensorimotor area (SMI) were selected via spatial-template matching process. Trial-specific alpha and beta bands were determined in sensorimotor-related oscillatory activities using a two-spectrum comparison between the spectra obtained from baseline period (-4 to -3 s) and movement-onset period (-0.5 to 0.5 s). Sensorimotor-related oscillatory activities were filtered within the trial-specific frequency bands to resolve task-related oscillatory activities. Results demonstrated that the optimal phase and amplitude information were preserved not only for alpha suppression (event-related desynchronization) and beta rebound (event-related synchronization) but also for profound analysis of subtle dynamics across trials. The retention of high SNR in the extracted oscillatory activities allow various methods of source estimation that can be applied to study the intricate brain dynamics of motor control mechanisms. The present study enables the possibility of investigating cortical pathophysiology of movement disorder on a trial-by-trial basis which also permits an effective alternative for participants or patients who can not endure lengthy procedures or are incapable of sustaining long experiments.