Search

Aims To prospectively examine the association between arthritis and type 2 diabetes (T2D) in the Chinese population and confirm this association through a comprehensive meta-analysis of cohort studies. Meterials and methods Data were from the China Health and Retirement Longitudinal Study which was started in 2011-2013 and followed up in 2013-2014 and 2015-2016. Arthritis was defined as self-reported physician diagnosis at baseline, and incident T2D was determined by self-reported physician diagnosis, fasting blood glucose ≥7.0 mmol/L or glycosylated haemoglobin ≥6.5% during the follow-ups. Cox proportional hazards regression models were used to assess the association between arthritis and risk for T2D. A meta-analysis was conducted to pool our effect estimate and those from other cohort studies using a random-effects model. Results Eleven thousand four hundred and eight participants (47.9% men; mean age: 59.3 years) were included in final analyses. During a 4-year follow-up, 981 participants reported incident T2D. Compared with individuals without arthritis, those with arthritis at baseline had an 18% higher risk for incident T2D (multivariable-adjusted hazard ratio: 1.18; 95% confidence interval: 1.04, 1.34). In the meta-analysis of 13 cohort studies including ours, a total of 2,473,514 participants were included with 121,851 incident diabetes. The pooling HR was 1.32 (95% CI: 1.21, 1.44) for the association between arthritis and diabetes. Conclusion Arthritis was associated with an increased risk of incident diabetes in Chinese adults, and the positive association was confirmed in the meta-analysis of cohort studies. Our work can inform clinical trials to assess the effectiveness of arthritis treatments in reducing risk of diabetes.

The refractive index (RI) of a sample as an endogenous contrast agent plays an important role in transparent live cell imaging. In tomographic phase microscopy (TPM), 3D quantitative RI maps can be reconstructed based on the measured projections of the RI in multiple directions. The resolution of the RI maps not only depends on the numerical aperture of the employed objective lens, but also is determined by the accuracy of the quantitative phase of the sample measured at multiple scanning illumination angles. This paper reports an analogous on-axis interference TPM, where the interference angle between the sample and reference beams is kept constant for projections in multiple directions to improve the accuracy of the phase maps and the resolution of RI tomograms. The system has been validated with both silica beads and red blood cells. Compared with conventional TPM, the proposed system acquires quantitative RI maps with higher resolution (420 nm @λ = 633 nm) and signal-to-noise ratio that can be beneficial for live cell imaging in biomedical applications.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known about whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at the G1 phase, and inducing apoptosis in dose- and time-dependent manners. Verteporfin also inhibited the tumor growth on the PDAC xenograft model. Treatment with verteporfin led to downregulation of cyclinD1 and cyclinE1, modulation of Bcl-2 family proteins and activation of PARP. In addition, verteporfin exhibited an inhibitory effect on angiogenesis and vasculogenic mimicry via suppressing Ang2, MMP2, VE-cadherin, and α-SMA expression in vitro and in vivo. Mechanism studies demonstrated that verteporfin impaired YAP and TEAD interaction to suppress the expression of targeted genes. Our results provide a foundation for repurposing verteporfin as a promising anti-tumor drug in the treatment of pancreatic cancer by targeting the Hippo pathway.

The zonal velocity produced by a Regional Ocean Modeling System (ROMS)-based Pacific Ocean circulation model was validated against in situ measurements along the 137 degrees E longitude. The Pacific model successfully reproduced the position and the shape of the North Equatorial Current (NEC) as well as the latitude of maximum surface velocity in the NEC region (8-17 degrees N). The flow field produced by the Pacific model was then used to conduct numerical Lagrangian experiments, in which passive particles were released along a transect (142.5 degrees E, 12.5-17 degrees N) that traverses the known Japanese eel spawning area, and the effects of NEC strength and bifurcation latitude on the particle advection in the northwest Pacific were studied. Our results suggest that, in the 20-yr period (1993-2012), the variability of the currents alone can cause interannual variability of one order of magnitude in the Kuroshio Entrance (KE), the percentage of particles entering the Kuroshio, the range of which varies from 43% in 1997 to 6% in 2012. The yearly-averaged KE is not sensitive to the NEC bifurcation latitude. Instead, it is controlled by the average zonal velocity of a fixed domain (125-143 degrees E, 13.5-17 degrees N) and related to a recently-developed climate index, the Philippines-Taiwan Oscillation (PTO). During the positive phase of the PTO, the zonal velocity in the domain, hence the yearly-averaged KE, increases, and the opposite is true in the negative phase of the PTO. Considering only the trajectories, diel vertical migrations (DVM) in the top 400 m do not significantly affect Japanese eel larval transport, as incorporating DVM schemes does not increase the KE.

Titanium-based implants possessing adequately low elasticity modulus and custom­designed structures are urgently demanded in recent years for orthopedic applications. Electron beam melting (EBM) provides an opportunity to fabricated porous titanium scaffolds that meet the as-mentioned requirements, and it further allows for improved bone regeneration and increased contact area at implant–tissue interface. As a novel additive manufacturing (AM) technique, EBM could conveniently produce scaffolds with tunable porosity and shapes and complex structures based on the popular “bottom-up” concept. In the present work, EBM-produced Ti6Al4V cylinders designed with either a small pore size (EBMS, 640 μm) or a large one (EBML, 1200 μm) were characterized in respect of microstructure, permeability and specific surface area, and their cytocompatibility and osteogenic ability were evaluated subsequently in vitro. Both samples EBMS and EBML could support the attachment and proliferation of hMSCs with minimal inflammatory cytokines secretion. The EBMS scaffolds were relatively more compatible with hMSCs than the EBML and they better sustained osteogenesis probably for their larger specific surface area.

The significance of the molecular chirality of drugs has been widely recognized due to the thalidomide tragedy. Most of the new drugs reaching the market today are single enantiomers, rather than racemic mixtures. However, many optically pure drugs, including thalidomide, undergo enantiomerization in vivo, thus negating the single enantiomers' benefits or inducing unexpected effects. A detailed atomic level understanding of chiral conversion, which is still largely lacking, is thus critical for drug development. Herein, we use first-principle density function theory (DFT) to explore the mechanism of enantiomerization of thalidomide. We have identified the two most plausible interconversion pathways for isolated thalidomide: 1) proton transfer from the chiral carbon center to an adjacent carbonyl oxygen atom, followed by isomerization and rotation of the glutarimide ring (before the proton hops back to the chiral carbon atom); and 2) a pathway that is the same as "1", but with the isomerization of the glutarimide ring occurring ahead of the initial proton transfer reaction. There are two remarkable energy barriers, 73.29 and 23.59 kcal mol(-1), corresponding to the proton transfer and the rotation of the glutarimide ring, respectively. Furthermore, we found that water effectively catalyzes the interconversion by facilitating the proton transfer with the highest energy barrier falling to approximately 30 kcal mol(-1), which, to our knowledge, is the first time that this important role of water in chiral conversion has been demonstrated. Finally, we show that the hydroxide ion can further lower the enantiomerization energy barrier to approximately 24 kcal mol(-1) by facilitating proton abstraction, which agrees well with recent experimental data under basic conditions. Our current findings highlight the importance of water and hydroxide ions in the enantiomerization of thalidomide and also provide new insights into the mechanism of enantiomerization at an atomic level.

The widespread application of nanomaterials has spurred an interest in the study of interactions between nanoparticles and proteins due to the biosafety concerns of these nanomaterials. In this review, a summary is presented of some of the recent studies on this important subject, especially on the interactions of proteins with carbon nanotubes (CNTs) and metallofullerenols. Two potential molecular mechanisms have been proposed for CNTs' inhibition of protein functions. The driving forces of CNTs' adsorption onto proteins are found to be mainly hydrophobic interactions and the so-called π-π stacking between CNTs' carbon rings and proteins' aromatic residues. However, there is also recent evidence showing that endohedral metallofullerenol Gd@C82 (OH)22 can be used to inhibit tumor growth, thus acting as a potential nanomedicine. These recent findings have provided a better understanding of nanotoxicity at the molecular level and also suggested therapeutic potential by using nanoparticles' cytotoxicity against cancer cells.

Molecular dynamic simulations of the chiral transition of a difluorobenzo[c]phenanthrene molecule (C(18)H(12)F(2), D molecule) in single-walled boron-nitride nanotubes (SWBNNTs) revealed remarkable effects of the nanoscale confinement. The critical temperature, above which the chiral transition occurs, increases considerably with the nanotube diameter, and the chiral transition frequency decreases almost exponentially with respect to the reciprocal of temperature. The chiral transitions correlate closely with the orientational transformations of the D molecule. Furthermore, the interaction energy barriers between the D molecule and the nanotube for different orientational states can characterize the chiral transition. This implies that the temperature threshold of a chiral transition can be controlled by a suitable nanotube. These findings provide new insights to the effect of nanoscale confinement on molecular chirality.

The precision of acoustic logs directly affects the quality of oil and gas formation evaluation, the oil and gas reserve computation and the synthetic seismic records. The characteristics of the responses of a logging system with two transmitter and two receiver at a borehole collapse interval were first simulated by numerical method. It has been found that when the length of hole collapse interval is equal to a specific value, the difference between the recorded values and the true values reaches maximum, while the hole collapse interval is longer or shorter than this value, the differences become smaller, proportionally to the deviation from the value. If the borehole diameter is equal to or large than the critical diameter, mud wave will first arrive to receiver through the hole collapse interval. In a bed with a constant slowness, the critical diameter reaches maximum when the length of borehole collapse interval is equal to the specific value. The critical diameter becomes smaller for any other lengths of the borehole collapse intervals. A chart for determining the critical diameter is developed to identify the borehole conditions of the mud wave being the first arrival in the received signals.

Members belonging to the siderophilin family are iron-binding and iron-transporting proteins, which includes transferrin and lactoferrin. They have only been found in animals previously. If siderophilin could be found in and isolated from a plant, its production and subsequent extensive application could be increased. The present study is the first to report the discovery of a homolog of siderophilin in a plant. In order to purify antifreeze proteins from Ammopiptanthus mongolicus (Maxim.) Cheng f., the authors processed the proteins from the leaves using techniques such as column chromatography using DEAE-Cellu-lose-52, gel filtration via Sephacryl S-100 HR medium, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectroscopy was performed on the three proteins purified and the sequence of one of the proteins (containing 32 amino acids) was found to have 97% homology with the corresponding part of one type of human lactoferrin. Moreover, one of the two peptides belongs to an iron-binding domain. So, it is possible that siderophilin also exists in plants and plays a role as an antibacterial and antifungal, among other actions. (Managing editor: Wei WANG)