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Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti‐inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS‐treated Raw264.7 cells to test the anti‐inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS‐treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO‐1 pathway and suppressing NF‐κB signalling. An ACLT‐induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress. [ABSTRACT FROM AUTHOR]

Age‐related variations in many regions and/or networks of the human brain have been uncovered using resting‐state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large‐scale cross‐sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency‐specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age‐related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro‐vascular coupling and physiological noises. Together, these results provide the first evidence for age‐related effects on global brain activity and its topographic‐dynamic representation in terms of spatiotemporal dedifferentiation. [ABSTRACT FROM AUTHOR]

Threat generalisation is an adaptive process that is essential for individual survival. In contrast, over‐generalisation is a pathological process that underlies the development of anxiety disorders. Intolerance of uncertainty (IU) is an individual characteristic known to influence threat generalisation by altering the responses to threat in uncertain situations. However, how it affects contextual threat generalisation remains unclear. Here, we used a novel paradigm to investigate whether contextual threat generalisation varied between individuals depending on their IU level (high or low) and the predictability of a situation (predictable or unpredictable). We analysed shock expectancy in 82 participants (age: 18–27 years) during threat acquisition and generalisation. Results showed that compared with the low IU group, the high IU group exhibited increased contextual threat generalisation to threat‐related cues in unpredictable situation. These findings suggest that IU could be a marker for anxiety disorder susceptibility, as well as a target for anxiety treatment. [ABSTRACT FROM AUTHOR]

Negative attentional bias is a basic character of depression. The attentional bias modification training (ABMT), being a highly promising and easy‐to‐use depression intervention technique, has attracted much attention to alleviate depressive symptoms in recent years. However, the effectiveness of ABMT programs was mixed across studies, since it remained unclear the underlying mechanisms of ABMT on alleviating depressive symptoms. We systematically analyzed the main ABMT paradigms to clarify possible mechanisms of effective training and reasons of ineffective training. Valid ABMT programs might alleviate depressive symptoms through regulating self‐related rumination or two subcomponents of attentional bias: facilitated attention and impaired attentional disengagement. The reasons for the invalidity of ABMT mainly included the suboptimal design of training procedures, mixed effects of participants' personal characteristics, and the unclear relationship between attentional bias and depression. The ABMT is promising for alleviating depressive symptoms, but training procedures are required to be improved to obtain stable training effects. [ABSTRACT FROM AUTHOR]

Lanthanide‐doped up‐conversion (UC) materials with color tunable property show promising application in many fields, such as biological imaging, optical multiplexing, and information security. Although great efforts have been devoted to regulate UC emission color via modifying chemical composition, crystal structure, or external stimuli condition, it is remain a daunting challenge to develop a general strategy that probably suitable for various lanthanide‐doped nano‐systems. Herein, we verify the cross‐relaxation possibility between sensitizer Yb3+ and activator Er3+ as well as Er3+‐ Er3+ pairs can be well modified by engineering the crystal lattice distortion of matrix, leading to the evident UC emission color variations. Specifically, with incorporating Al3+ or Ca2+ ions into the Yb/Er co‐doped BaF2 nanocrystals (NCs) contained glass ceramics (GCs), the contraction of the crystal lattice lead to the change of UC emission color from green to red. On the contrary, the high laser excitation power results in the lattice expansion of the Al3+‐doped BaF2:Yb/Er GCs at different Yb3+ concentration as well as Al3+ doped CaF2 GCs, which leads to the greatly increased green‐to‐red ratio. These multi‐color UC GCs show potential application in anti‐counterfeiting filed. Our results open up a general avenue for the control of UC emission color via engineering crystal lattice distortion. [ABSTRACT FROM AUTHOR]

Objectives: The decidua is a tissue that contacts both maternal and foetal components and is pivotal to labour onset due to its location. Due to the heterogeneity of decidual tissue, it is challenging to study its role in the peripartum period. Herein, we analysed the transcriptomes of peripartum decidua at single‐cell resolution. Materials and methods: Single‐cell RNA sequencing was performed for 29 231 decidual cells before and after delivery to characterize the transcriptomes. Results: Eight major cell types (including endothelial cells, fibroblasts) and subtypes of decidual stromal cells, extravillous trophoblasts and T cells were identified and found to have various functions. Compared with before delivery, the activation of decidual stromal cell, extravillous trophoblast and T‐cell subtypes to different degrees was observed after delivery. Furthermore, the activation involved multiple functions, such as cell proliferation, and several pathways, such as the activator protein 1 pathway. The results of pseudotemporal ordering showed differentiation of decidual stromal cell and extravillous trophoblast subtypes, suggesting inhomogeneity of these subgroups in decidualization (decidual stromal cell) and invasion (extravillous trophoblast). Conclusions: The peripartum decidual tissue is heterogeneous. This study revealed changes in the decidua and its components at single‐cell resolution; these findings provide a new perspective for the study of peripartum decidua. [ABSTRACT FROM AUTHOR]

Tb3+‐doped germanate glass ceramics containing CaF2 nanocrystals were prepared by melt quenching method with subsequent heat treatment. Their microstructures were investigated by XRD and TEM techniques. Their optical properties were studied by the transmittance, the photoluminescence, and the X‐ray excited luminescence (XEL). The luminescence intensity in the glass ceramics under 377 nm light and X‐ray excitations is significantly enhanced. The maximum integrated XEL intensity of the glass ceramics is about 50% of that of the commercial Bi4Ge3O12 (BGO) scintillating crystal. The results indicate that Tb3+‐doped germanate glass ceramic could be a promising scintillating material used in X‐ray detection for slow event. [ABSTRACT FROM AUTHOR]

Anastrozole is currently used as first‐line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formulation. The aim of the current study was to evaluate the bioequivalence between the test and reference formulations of anastrozole in a single‐dose, 2‐period, 2‐sequence crossover study with a 14‐day washout interval. A total of 20 healthy male Chinese volunteers were enrolled and completed the study, after oral administration of a single dose of 1.0‐mg test and reference formulations of anastrozole. The blood samples were collected at different times and were determined by a fully validated high‐pressure liquid chromatography–tandem mass spectrometry method. The evaluated pharmacokinetic parameters, including Cmax, AUC0–t, and AUC0–∞, were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of anastrozole of the test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax, AUC0−t, and AUC0−∞ were within the bioequivalence acceptance range of 80%–125%. The results obtained from these healthy Chinese subjects in this study suggest that the test formulation of anastrozole 1.0‐mg tablet is bioequivalent to the reference formulation (Arimidex 1.0‐mg tablet). [ABSTRACT FROM AUTHOR]

A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to determine clonidine in human plasma was developed and fully validated. Sample preparation was involved an one-step extraction with diethyl ether. Donepezil was employed as the internal standard (IS). Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3μm) with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v) at a flow rate of 200 μL/min. The peaks were detected by mass spectrometry using the electrospray ion source in selected reaction monitoring mode. The extraction recovery was 72.53-85.25%. The method was found to be linear in a concentration range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL. The within- and between-batch precisions at three concentrations were 4.33-16.47 and 7.24-17.24% with accuracies of −2.47-10.91 and 1.86-10.19%, respectively. This validated method was successfully used for a bioequivalence study of two clonidine transdermal patches on healthy volunteers. The results suggested that the test formulation of clonidine patch met the regulatory criterion for bioequivalence to the reference formulation, but a larger sample size should be needed for the estimation of bioequivalence. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]