Epigenetic and microRNA regulation during osteoarthritis development

Osteoarthritis (OA) is a common degenerative joint disease, the pathological mechanism of which is currently unknown. Genetic alteration is one of the key contributing factors for OA pathology. Recent evidence suggests that epigenetic and microRNA regulation of critical genes may contribute to OA development. In this article, we review the epigenetic and microRNA regulations of genes related to OA development. Potential therapeutic strategies may be developed on the basis of novel findings

Technical note: Intercomparison of three AATSR Level 2 (L2) AOD products over China

One of four main focus areas of the PEEX initiative is to establish and sustain long-term, continuous, and comprehensive ground-based, airborne, and seaborne observation infrastructure together with satellite data. The Advanced Along-Track Scanning Radiometer (AATSR) aboard ENVISAT is used to observe the Earth in dual view. The AATSR data can be used to retrieve aerosol optical depth (AOD) over both land and ocean, which is an important parameter in the characterization of aerosol properties. In recent years, aerosol retrieval algorithms have been developed both over land and ocean, taking advantage of the features of dual view, which can help eliminate the contribution of Earth's surface to top-of-atmosphere (TOA) reflectance. The Aerosol_cci project, as a part of the Climate Change Initiative (CCI), provides users with three AOD retrieval algorithms for AATSR data, including the Swansea algorithm (SU), the ATSR-2ATSR dual-view aerosol retrieval algorithm (ADV), and the Oxford-RAL Retrieval of Aerosol and Cloud algorithm (ORAC). The validation team of the Aerosol-CCI project has validated AOD (both Level 2 and Level 3 products) and AE (Ångström Exponent) (Level 2 product only) against the AERONET data in a round-robin evaluation using the validation tool of the AeroCOM (Aerosol Comparison between Observations and Models) project. For the purpose of evaluating different performances of these three algorithms in calculating AODs over mainland China, we introduce ground-based data from CARSNET (China Aerosol Remote Sensing Network), which was designed for aerosol observations in China. Because China is vast in territory and has great differences in terms of land surfaces, the combination of the AERONET and CARSNET data can validate the L2 AOD products more comprehensively. The validation results show different performances of these products in 2007, 2008, and 2010. The SU algorithm performs very well over sites with different surface conditions in mainland China from March to October, but it slightly underestimates AOD over barren or sparsely vegetated surfaces in western China, with mean bias error (MBE) ranging from 0.05 to 0.10. The ADV product has the same precision with a low root mean square error (RMSE) smaller than 0.2 over most sites and the same error distribution as the SU product. The main limits of the ADV algorithm are underestimation and applicability; underestimation is particularly obvious over the sites of Datong, Lanzhou, and Urumchi, where the dominant land cover is grassland, with an MBE larger than 0.2, and the main aerosol sources are coal combustion and dust. The ORAC algorithm has the ability to retrieve AOD at different ranges, including high AOD (larger than 1.0); however, the stability deceases significantly with increasing AOD, especially when AOD > 1.0. In addition, the ORAC product is consistent with the CARSNET product in winter (December, January, and February), whereas other validation results lack matches during winter

Probing Primordial Gravitational Waves: Ali CMB Polarization Telescope

In this paper, we will give a general introduction to the project of Ali CMB Polarization Telescope (AliCPT), which is a Sino-US joint project led by the Institute of High Energy Physics (IHEP) and has involved many different institutes in China. It is the first ground-based Cosmic Microwave Background (CMB) polarization experiment in China and an integral part of China's Gravitational Waves Program. The main scientific goal of AliCPT project is to probe the primordial gravitational waves (PGWs) originated from the very early Universe. The AliCPT project includes two stages. The first stage referred to as AliCPT-1, is to build a telescope in the Ali region of Tibet with an altitude of 5,250 meters. Once completed, it will be the worldwide highest ground-based CMB observatory and open a new window for probing PGWs in northern hemisphere. AliCPT-1 telescope is designed to have about 7,000 TES detectors at 90GHz and 150GHz. The second stage is to have a more sensitive telescope (AliCPT-2) with the number of detectors more than 20,000. Our simulations show that AliCPT will improve the current constraint on the tensor-to-scalar ratio $r$ by one order of magnitude with 3 years' observation. Besides the PGWs, the AliCPT will also enable a precise measurement on the CMB rotation angle and provide a precise test on the CPT symmetry. We show 3 years' observation will improve the current limit by two order of magnitude.Comment: 11 pages, 7 figures, 2 table

TripleSurv: Triplet Time-adaptive Coordinate Loss for Survival Analysis

A core challenge in survival analysis is to model the distribution of censored time-to-event data, where the event of interest may be a death, failure, or occurrence of a specific event. Previous studies have showed that ranking and maximum likelihood estimation (MLE)loss functions are widely-used for survival analysis. However, ranking loss only focus on the ranking of survival time and does not consider potential effect of samples for exact survival time values. Furthermore, the MLE is unbounded and easily subject to outliers (e.g., censored data), which may cause poor performance of modeling. To handle the complexities of learning process and exploit valuable survival time values, we propose a time-adaptive coordinate loss function, TripleSurv, to achieve adaptive adjustments by introducing the differences in the survival time between sample pairs into the ranking, which can encourage the model to quantitatively rank relative risk of pairs, ultimately enhancing the accuracy of predictions. Most importantly, the TripleSurv is proficient in quantifying the relative risk between samples by ranking ordering of pairs, and consider the time interval as a trade-off to calibrate the robustness of model over sample distribution. Our TripleSurv is evaluated on three real-world survival datasets and a public synthetic dataset. The results show that our method outperforms the state-of-the-art methods and exhibits good model performance and robustness on modeling various sophisticated data distributions with different censor rates. Our code will be available upon acceptance.Comment: 9 pages,6 figure

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Polarization-sensitive optical projection tomography for muscle fiber imaging

Optical projection tomography (OPT) is a tool used for three-dimensional imaging of millimeter-scale biological samples, with the advantage of exhibiting isotropic resolution typically in the micron range. OPT can be divided into two types: transmission OPT (tOPT) and emission OPT (eOPT). Compared with eOPT, tOPT discriminates different tissues based on their absorption coefficient, either intrinsic or after specific staining. However, it fails to distinguish muscle fibers whose absorption coefficients are similar to surrounding tissues. To circumvent this problem, in this article we demonstrate a polarization sensitive OPT system which improves the detection and 3D imaging of muscle fibers by using polarized light. We also developed image acquisition and processing protocols that, together with the system, enable the clear visualization of muscles. Experimental results show that the muscle fibers of diaphragm and stomach, difficult to be distinguished in regular tOPT, were clearly displayed in our system, proving its potential use. Moreover, polarization sensitive OPT was fused with tOPT to investigate the stomach tissue comprehensively. Future applications of polarization sensitive OPT could be imaging other fiberlike structures such as myocardium or other tissues presenting high optical anisotropy.This work is supported by the National Basic Research Program of China (973 Program) under Grant 2011CB707700, the National Natural Science Foundation of China under Grant No. 81227901, 61231004, 81501616, 81301346, 81527805 the Chinese Academy of Sciences Fellowship for Young Foreign Scientists under Grant No. 2010Y2GA03, 2013Y1GA0004, the Chinese Academy of Sciences Visiting Professorship for Senior International Scientists under Grant No. 2012T1G0036, 2013T1G0013, the Instrument Developing Project of the Chinese Academy of Sciences under Grant No. YZ201502, YZ201457 and the Strategic Priority Research Program (B) of Chinese Academy of Sciences (XDB02060010). A. Arranz acknowledges support from the Marie Curie Intra-European Fellowship program IEF-2010-275137. J.R. acknowledges support from EC FP7 IMI project PREDICT-TB, the EC FP7 CIG grant HIGH-THROUGHPUT TOMO, and the Spanish MINECO project grant FIS2013-41802-R MESO-IMAGING

N,N′-Bis(2-methoxy­phen­yl)biphenyl-2,2′-dicarboxamide

In the title compound, C28H24N2O4, the dihedral angle between the two rings of the biphenyl unit is 75.34 (9)°. The outer aromatic rings form dihedral angles of 66.96 (1) and 85.69 (8)° with the rings to which they are attached . The mol­ecular structure is stabilized by intra­molecular C—H⋯O and N—H⋯O hydrogen bonds. In the crystal structure, inter­molecular N—H⋯O inter­actions are observed

Association between Nine Types of TCM Constitution and Five Chronic Diseases: A Correspondence Analysis Based on a Sample of 2,660 Participants

Objective. The purpose of this study was to explore the association of nine types of Traditional Chinese Medicine (TCM) constitution with the five chronic diseases: hypertension, hyperlipidemia, diabetes mellitus, heart disease, and obesity. Methods. Chi-squared test was performed to investigate the distribution characteristics of TCM constitutions in the participants with the five chronic diseases in questionnaire. Correspondence analysis was used to explore the correlation between them. Results. A total of 2,660 participants (1,400 males; 1,260 females) were included in this study. The mean age was 52.54 ± 13.92. Of them, 600 were of gentleness type accounting for 22.56%. Proportions of gentleness type in the chronic diseases (16.00%~23.70%) were less than that in general population (32.14%). The gentleness type and yin-deficiency type were significantly correlated with hypertension and diabetes mellitus, qi-deficiency type was correlated with heart disease, phlegm-dampness type was associated with obesity, and dampness-heat type was correlated with hyperlipidemia. Conclusions. The correlations between TCM constitution types and the five chronic diseases were different. This may have a significant implication for TCM practice, and even the people with gentleness type should not be ignored in health management

Direct ink writing of bioactive PCL/laponite bone Implants:Engineering the interplay of design, process, structure, and function

Direct ink writing (DIW) is a room-temperature extrusion-based 3D printing technique that enables the fabrication of dense, customizable implants from viscous inks with precise spatial control. In this study, we present an engineering design framework for DIW-printed PCL/Laponite composites by tuning ink formulations and printing orientations to systematically investigate and control the complex interplay between shape fidelity, mechanical performance, and cellular response. Our findings show that printing at 0° orientation enhances filament-aligned surface topographies, which guide osteoblast attachment and significantly promote cell proliferation and mineralization. In contrast to previous studies using fused deposition modeling (FDM), we observe that printing at 90° orientation (perpendicular to the tensile load direction) results in higher mechanical performance due to improved filament bonding. Increasing Laponite loading (up to 30 ​%) improves shape retention by increasing ink viscosity, raises Young's modulus by up to 110 ​%, and enhances surface bioactivity by introducing hydrophilic and bioactive cues. This study provides a tunable strategy for engineering bioactive and surface-active implants for the clinical need for non-load-bearing orthopaedic applications where structural integrity, surface-mediated osteointegration, and customized geometry are clinically essential.</p

Synergistic anti-atherosclerotic effect of Yerba Maté (Illex Paraguariensis) polyphenols and Lox-1 silencing in foam cell model

Purpose: To elucidate the anti-atherosclerotic effect of Yerba Mate polyphenols (MP) as well as the anti-atherosclerotic effect of a combination of MP and silencing of lectin-like oxidized low-density lipoprotein receptor-1 interference group (LOX)-1.Methods: The anti-atherosclerotic effects of control group (CG), simvastatin group (SG), MP group (MP), LOX-1 interference group (LOX) and MP + LOX-1 interference group (MP-LOX) were determined using Oil Red O staining, enzyme-linked immunosorbent assay (ELISA) and Western blot assay.Results: The levels of foam cells, intracellular lipids, viz, total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1); LOX-1, inflammation (TNF-alpha, IL-6 and pNF-κB/NF-κB); adhesion molecular status (ICAM-1 and VCAM-1), and monocyte chemotactic protein-1 in SG and in MP, LOX and MP-LOX groups were significantly decreased, when compared with CG (p &lt; 0.01). The levels of these parameters were much lower in MPLOX group than in SG (p &lt; 0.01). However, they were synergistically reduced in MP-LOX group, relative to MP group or LOX group (p &lt; 0.01). Combination of LOX-1 gene silencing with MP produced synergistic anti-atherosclerotic effect which was reflected in decreases in foam cell formation, intracellular lipids, inflammatory status, adhesion molecular status, and MCP-1-mediated migration and infiltration of macrophages in foam cells.Conclusion: The synergistic anti-atherosclerotic effects of MP and LOX-1 gene silencing may be potential tools for development of anti-atherosclerotic agents