Cyclic nucleotide in oocyte In vitro maturation in Assisted Reproductive Technology

In vitro maturation (IVM) is a promising assisted reproductive technology (ART) for human infertility treatment. However, when cumulus oocyte complexes (COCs) are removed from their follicular environment when manipulated in vitro, it can lead to a decrease of intra-oocyte cyclic adenosine 3’, 5’-monophosphare (cAMP) causing spontaneous nuclear maturation and an asynchrony with the oocytes’ cytoplasmic maturation, resulting in poor embryo developmental outcomes. Nuclear and cytoplasmic synchrony is important during oocyte maturation within antral follicles.It is maintained partially by the actions of c-type natriuretic peptide (CNP) binding with natriuretic peptide receptor 2 (NPR2), supporting high cAMP levels thus holding the oocyte in meiotic arrest. Addition of CNP to pre-IVM media has the capacity of maintaining cAMP levels and thus improve synchrony. Moreover, in women with advanced maternal age, successful IVM of aging oocytes faces significant challenges due to the morphological and cellular changes.  Inhibiting initiation of nuclear maturation by cAMP modulator, CNP during pre-IVM period and thus improve oocyte developmental competence regardless of oocyte age

Fourth-order compact schemes for solving multidimensional heat problems with Neumann boundary conditions

In this article, two sets of fourth-order compact finite difference schemes are constructed for solving heat-conducting problems of two or three dimensions, respectively. Both problems are with Neumann boundary conditions. These works are extensions of our earlier work (Zhao et al., Fourth order compact schemes of a heat conduction problem with Neumann boundary conditions, Numerical Methods Partial Differential Equations, to appear) for the one-dimensional case. The local one-dimensional method is employed to construct these two sets of schemes, which are proved to be globally solvable, unconditionally stable, and convergent. Numerical examples are also provided. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57369/1/20255_ftp.pd

Development and evaluation of a versatile semi-active suspension system for high-speed railway vehicles

With the increase in speed of high-speed trains, their vibration will become fiercer and fiercer, especially when the lateral resonance of the car body occurs. This paper develops a versatile semi-active suspension system with variable stiffness (VS) magnetorheological elastomer (MRE) isolators and variable damping (VD) magnetorheological (MR) dampers for high-speed trains, aiming to improve ride comfort by avoiding car body resonance and dissipating vibration energy. As the first step, a multifunction VSVD semi-active suspension system for high-speed railway vehicles was designed and prototyped, including four VS-MRE isolators and two VD-MR dampers. After that, a scaled train model, composing of a car body and a secondary lateral suspension system was designed and built to evaluate the performance of the new VSVD suspension system; a control strategy based on short-time Fourier transform (STFT) and sky-hook was proposed to control the new suspension system. Two different excitations, harmonic excitation and random excitation, were applied to evaluate the train\u27s VSVD suspension. As a comparison, four alternative suspension systems, including passive-off suspension, passive-on suspension, pure VS suspension, and pure VD suspension were also evaluated. The evaluation results verified that the VSVD suspension of the train can avoid lateral resonance of car body and dissipate the vibration energy efficiently. The comparison verified that the VSVD suspension system outperforms the passive-off suspension, passive-on suspension, pure VS suspension, and pure VD suspension

Potential Biomarkers for Physical Exercise-Induced Brain Health

Physical exercise has long been recognized as an effective and economic strategy to promote brain health in humans. The cellular and structural changes in the brains of exercised animals, including enhancements of neurogenesis and synaptogenesis, dendritic remodeling, and synaptic plasticity, have been considered as the key biological alterations accounting for exercise-elicited benefits to brain health. However, what transduces body movements into the above-mentioned changes remains largely unknown. Emerging theories indicate that physical activity triggers the release of various factors into the circulation from skeletal muscle (neurotrophins, myokines, and cytokines) and/or adipose tissue (adipokines). In this chapter, we review several of these molecules that are potentially implicated in this process, including neurotrophic factors (BDNF, IGF-1, and VEGF), adipokines (adiponectin and irisin), and myokines/cytokines (IL-15). The relationship, either causal or concomitant, between levels of these molecules (particularly in the blood) and brain function after exercise may help to identify biomarkers that can serve as objective indicators to evaluate exercise therapy on diseased or ageing brain. In addition, unmasking biomarkers may be instrumental in elucidating the mechanisms mediating exercise-induced brain health, thereby contributing to novel drug discovery for treatments to maintain brain health

Risk factors of hemorrhagic transformation in acute ischaemic stroke : A systematic review and meta-analysis

Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)]. Methods: Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. Results: A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT. Conclusion: Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927

Electrospun Polyaniline Fibers as Highly Sensitive Room Temperature Chemiresistive Sensors for Ammonia and Nitrogen Dioxide Gases

Electrospun polyaniline (PAni) fibers doped with different levels of (+)-camphor-10-sulfonic acid (HCSA) are fabricated and evaluated as chemiresistive gas sensors. The experimental results, based on both sensitivity and response time, show that doped PAni fibers are excellent ammonia sensors and that undoped PAni fibers are excellent nitrogen dioxide sensors. The fibers exhibit changes in measured resistances up to 60-fold for ammonia sensing, and more than five orders of magnitude for nitrogen dioxide sensing, with characteristic response times on the order of one minute in both cases. A time-dependent reaction-diffusion model is used to extract physical parameters from fitting experimental sensor data. The model is then used to illustrate the selection of optimal material design parameters for gas sensing by nanofibers.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract ARO W911NF-07-D-0004

Myocardial Injury, Obesity, and the Obesity Paradox

To examine whether pre-heart failure (HF) myocardial injury explains the differential mortality after HF across weight categories

The impact of multiple single day blood pressure readings on cardiovascular risk estimation: The Atherosclerosis Risk in Communities study

To determine the magnitude of change in estimated cardiovascular disease risk when multiple same day blood pressure measurements are used in estimating coronary heart disease (CHD), heart failure (HF) and stroke risks

Antileukemic Activity of Nuclear Export Inhibitors that Spare Normal Hematopoietic Cells

Drugs that target the chief mediator of nuclear export, chromosome region maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic effects. Here, we report the structural analysis and antileukemic activity of a new generation of small-molecule inhibitors of CRM1. Designated selective inhibitors of nuclear export (SINE), these compounds were developed using molecular modeling to screen a small virtual library of compounds against the nuclear export signal (NES) groove of CRM1. The 2.2-Å crystal structure of the CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class of inhibitors, shows that the drug occupies part of the groove in CRM1 that is usually occupied by the NES, but penetrates much deeper into the groove and blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human acute myeloid leukemia (AML) cell lines representing different molecular subtypes of the disease. When administered orally to immunodeficient mice engrafted with human AML cells, KPT-251 had potent antileukemic activity with negligible toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent a novel class of drugs that warrant further testing in AML patients

Midlife Determinants of Healthy Cardiovascular aging: the atherosclerosis Risk in Communities (Aric) Study

BACKGROUND AND AIMS: Risk factor cutoffs are derived from associations with clinical cardiovascular disease (CVD), but how these risk factors associate with preserved cardiovascular health into old age is not well studied. We investigated midlife determinants of healthy versus nonhealthy cardiovascular aging in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: ARIC participants were categorized by cardiovascular status in older age (mean age 75.8 ± 5.3 years, range 66-90): healthy, subclinical disease (assessed by biomarkers and left ventricular function), clinical CVD (coronary heart disease, stroke, or heart failure), or prior death. We examined associations of midlife (mean age 52.1 ± 5.1 years) systolic and diastolic blood pressure (SBP, DBP), low-density lipoprotein cholesterol (LDL-C), triglycerides, hemoglobin A1c (HbA1c), and body mass index (BMI) with cardiovascular status in older age using multinomial logistic regression analyses. RESULTS: Compared with healthy status, odds for subclinical disease (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.09-1.55) and clinical CVD (OR 1.87, 95% CI 1.53-2.29) at older age increased starting with midlife SBP 120-129 mmHg, whereas odds for death increased starting with SBP 110-119 mmHg (OR 1.29, 95% CI 1.10-1.52); findings were similar for DBP. Odds for subclinical disease increased for HbA1c ≥ 6.5% and BMI starting at 30-/m CONCLUSIONS: More-stringent levels of modifiable risk factors in midlife beyond current clinical practice and guidelines were associated with preserved cardiovascular health in older age