Tumor-associated macrophages (TAMs) play an essential role in metastasis. However, what enables TAMs to have a superior capacity to establish pre-metastatic microenvironment in distant organs is ...unclear. Here we have begun to uncover the effects of cytochrome P450 (CYP) 4A in TAMs on lung pre-metastatic niche formation and metastasis. CYP4A
TAM infiltration was positively associated with metastasis, pre-metastatic niche formation and poor prognosis in breast cancer patients. The pharmacological inhibition of CYP4A reduced lung pre-metastatic niche formation (evidenced by a decrease in vascular endothelial growth factor receptor 1 positive (VEGFR1
) myeloid cell recruitment and pro-metastatic protein expression) and metastatic burden, accompanied with TAM polarization away from the M2 phenotype in spontaneous metastasis models of 4T1 breast cancer and B16F10 melanoma. Co-implantation of 4T1 cells with CYP4A10
macrophages promoted lung pre-metastatic niche formation and metastasis. Depletion of TAMs disrupted lung pre-metastatic niches and thereby prevented metastasis. Treatment with the CM from CYP4A10
M2 macrophages (M2) increased pre-metastatic niche formation and metastatic burden in the lungs, whereas CYP4A inhibition attenuated these effects. In vitro TAM polarization away from the M2 phenotype induced by CYP4A inhibition decreased VEGFR1
myeloid cell migration and fibronectin expression, accompanied with downregulation of STAT3 signaling. Conversely, overexpression of CYP4A or exogenous addition of 20-hydroxyeicosatetraenoic acid promoted M2 polarization and cytokine production of macrophages and thereby enhanced migration of VEGFR1
myeloid cells, which were reversed by siRNA or pharmacological inhibition of STAT3. Importantly, a combined blocking M2 macrophage-derived factors TGF-β, VEGF and SDF-1 abolished VEGFR1
myeloid cell migration and fibroblast activation induced by CYP4A. In summary, CYP4A in TAMs is crucial for lung pre-metastatic niche formation and metastasis, and may serve as a potential therapeutic target in human cancer.
During chemotherapy for lymphoma, the administration of cytotoxic agents and rituximab often results in hepatitis B reactivation (incidence, 14–72%). This study was designed to compare the efficacy ...of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients. Between January 2007 and February 2009, patients treated in four hospitals in China were screened to identify those most appropriate for analysis. These patients received either entecavir or lamivudine during chemotherapy and for 6 months after completion of chemotherapy. A total of 34 patients received entecavir and 89 patients received lamivudine. Compared with the lamivudine group, the entecavir group had significantly lower rates of hepatitis (5.9 vs 27.0%, P = 0.007), hepatitis B reactivation (0 vs 12.4%, P = 0.024) and disruption of chemotherapy (5.9 vs 20.2%, P = 0.042). All patients with hepatitis B reactivation had B‐cell non‐Hodgkin’s lymphoma (stage III–IV). In lymphoma patients under chemotherapy treatment, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
We present a three-dimensional (3D) extinction map of the southern sky. The map covers the SkyMapper Southern Survey (SMSS) area of ∼14,000 deg2 and has spatial resolutions between 6 9 and 27′. Based ...on the multi-band photometry of SMSS, the Two Micron All Sky Survey, the Wide-Field Infrared Survey Explorer Survey, and the Gaia mission, we have estimated values of the r-band extinction for ∼19 million stars with the spectral energy distribution analysis. Together with the distances calculated from the Gaia data release 2 (DR2) parallaxes, we have constructed a 3D extinction map of the southern sky. By combining our 3D extinction map with those from the literature, we present an all-sky 3D extinction map, and use it to explore the 3D distribution of the Galactic dust grains. We use two different models, one consisting of a single disk and another of two disks, to fit the 3D distribution of the Galactic dust grains. The data is better fitted by a two-disk model, yielding smaller values of the Bayesian Information Criterion. The best-fit model has scale heights of 73 and 225 pc for the "thin" and "thick" dust disks, respectively.
Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from pathogens or endogenous signals. Under various pathological conditions, ...the central nervous system (CNS) mounts a well-organized innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction, TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological control of chronic pain.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
The planetary boundary layer (PBL) governs the vertical transport of mass, momentum, and moisture between the surface and the free atmosphere, and thus the determination of PBL height (BLH) is ...recognized as crucial for air quality, weather, and climate analysis. Although reanalysis products can provide important insight into the global view of BLH in a seamless way, the BLH observed in situ on a global scale remains poorly understood due to the lack of high-resolution (1 or 2 s) radiosonde measurements. The present study attempts to establish a near-global BLH climatology at synoptic times (00:00 and 12:00 UTC) and in the daytime using high-resolution radiosonde measurements over 300 radiosonde sites worldwide for the period 2012 to 2019, which is then compared against the BLHs obtained from four reanalysis datasets, including ERA5, MERRA-2, JRA-55, and NCEP-2. The variations in daytime BLH exhibit large spatial and temporal dependence, and as a result the BLH maxima are generally discerned over the regions such as the western United States and western China, in which the balloon launch times mostly correspond to the afternoon. The diurnal variations in BLH are revealed with a peak at 17:00 local solar time (LST). The most promising reanalysis product is ERA5, which underestimates BLH by around 130 m as compared to radiosondes released during daytime. In addition, MERRA-2 is a well-established product and has an underestimation of around 160 m. JRA-55 and NCEP-2 might produce considerable additional uncertainties, with a much larger underestimation of up to 400 m. The largest bias in the reanalysis data appears over the western United States and western China, and it might be attributed to the maximal BLH in the afternoon when the PBL has risen. Statistical analyses further indicate that the biases of reanalysis BLH products are positively associated with orographic complexity, as well as the occurrence of static instability. To our best knowledge, this study presents the first near-global view of high-resolution radiosonde-derived boundary layer height and provides a quantitative assessment of the four frequently used reanalysis products.
The material class of rare earth nickelates with high Ni3+ oxidation state is generating continued interest due to the occurrence of a metal-insulator transition with charge order and the appearance ...of non-collinear magnetic phases within this insulating regime. The recent theoretical prediction for superconductivity in LaNiO3 thin films has also triggered intensive research efforts. LaNiO3 seems to be the only rare earth nickelate that stays metallic and paramagnetic down to lowest temperatures. So far, centimeter-sized impurity-free single crystal growth has not been reported for the rare earth nickelates material class since elevated oxygen pressures are required for their synthesis. Here, we report on the successful growth of centimeter-sized LaNiO3 single crystals by the floating zone technique at oxygen pressures of up to 150 bar. Our crystals are essentially free from Ni2+ impurities and exhibit metallic properties together with an unexpected but clear antiferromagnetic transition.
Summary
This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn ...and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men.
Introduction
The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach.
Methods
A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived.
Results
The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was −0.16 (95 % CI, −0.19 to −0.14) between total Ocn (tOcn) and FPG and −0.15 (95 % CI, −0.20 to −0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was −0.16 (95 % CI, −0.18 to −0.14) for tOcn and −0.16 (95 % CI, −0.23 to −0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (
r
= −0.18, 95 % CI, −0.21 to −0.14;
r
= −0.09, 95 % CI, −0. 13 to −0.05, respectively;
P
for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men,
r
= −0.19, 95 % CI, −0.24 to −0.14; for women,
r
= −0.09, 95 % CI, −0.22 to 0.04, respectively;
P
for interaction > 0.05). No indication of significant publication bias was found in any method.
Conclusions
This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.
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