Summary
A hallmark of obesity is chronic low‐grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors ...influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low‐grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C‐reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low‐grade inflammation such as hsCRP and interleukin (IL)‐6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low‐grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.
The South Pole Telescope (SPT) has systematically identified 81 high-redshift, strongly gravitationally lensed, dusty star-forming galaxies (DSFGs) in a 2500 square degree cosmological ...millimeter-wave survey. We present the final spectroscopic redshift survey of this flux-limited (S870 m > 25 mJy) sample, initially selected at 1.4 mm. The redshift survey was conducted with the Atacama Large Millimeter/submillimeter Array across the 3 mm spectral window, targeting carbon monoxide line emission. By combining these measurements with ancillary data, the SPT sample is now spectroscopically complete, with redshifts spanning 1.9 < z < 6.9 and a median of . We present the millimeter through far-infrared photometry and spectral energy density fits for all sources, along with their inferred intrinsic properties. Comparing the properties of the SPT sources to the unlensed DSFG population, we demonstrate that the SPT-selected DSFGs represent the most extreme infrared-luminous galaxies, even after accounting for strong gravitational lensing. The SPT sources have a median star formation rate of and a median dust mass of . However, the inferred gas depletion timescales of the SPT sources are comparable to those of unlensed DSFGs, once redshift is taken into account. This SPT sample contains roughly half of the known spectroscopically confirmed DSFGs at z > 5, making this the largest sample of high-redshift DSFGs to date, and enabling the "high-redshift tail" of extremely luminous DSFGs to be measured. Though galaxy formation models struggle to account for the SPT redshift distribution, the larger sample statistics from this complete and well-defined survey will help inform future theoretical efforts.
Abstract
We present analysis of a new pulsating helium-atmosphere (DB) white dwarf, EPIC 228782059, discovered from 55.1 days of K2 photometry. The long-duration, high-quality light curves reveal 11 ...independent dipole and quadruple modes, from which we derive a rotational period of 34.1 ± 0.4 hr for the star. An optimal model is obtained from a series of grids constructed using the White Dwarf Evolution Code, which returns
M
*
= 0.685 ± 0.003
M
⊙
,
T
eff
= 21,910 ± 23 K, and
log
g
=
8.14
±
0.01
dex. These values are comparable to those derived from spectroscopy by Koester & Kepler (20,860 ± 160 K, and 7.94 ± 0.03 dex). If these values are confirmed or better constrained by other independent works, it would make EPIC 228782059 one of the coolest pulsating DB white dwarf stars known, and would be helpful for testing different physical treatments of convection, and to further investigate the theoretical instability strip of DB white dwarf stars.
The gut microbiome is associated with diverse diseases
, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, ...exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.
Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative ...determination method is not accurate enough.
We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis.
The DLRN showed good discrimination of the number of LNM on all cohorts overall C-indexes (95% confidence interval): 0.821 (0.785–0.858) in the primary cohort, 0.797 (0.771–0.823) in the external validation cohorts, and 0.822 (0.756–0.887) in the international validation cohort. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271).
A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.
•Evaluation of the lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC).•Deep leaning radiomic nomogram (DLRN) based on CT images can preoperatively determine the number of LNM in LAGC.•DLRN is significantly superior to the routinely used clinical N stages, tumor size, and clinical model.•DLRN is significantly associated with the overall survival of LAGC.
Kruppel-like factor 4 (KLF4) is highly expressed in more than 70% of breast cancers and functions as an oncogene. However, an exact mechanism by which KLF4 enhances tumorigenesis of breast cancer ...remains unknown. In this study, we show that KLF4 was highly expressed in cancer stem cell (CSC)-enriched populations in mouse primary mammary tumor and breast cancer cell lines. Knockdown of KLF4 in breast cancer cells (MCF-7 and MDA-MB-231) decreased the proportion of stem/progenitor cells as demonstrated by expression of stem cell surface markers such as aldehyde dehydrogenase 1, side population and by in vitro mammosphere assay. Consistently KLF4 overexpression led to an increase of the cancer stem cell population. KLF4 knockdown also suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. Furthermore, knockdown of KLF4 reduced colony formation in vitro and inhibited tumorigenesis in immunocompromised non-obese diabetic/severe combined immunodeficiency mice, supporting an oncogenic role for KLF4 in breast cancer development. Further mechanistic studies revealed that the Notch signaling pathway was required for KLF4-mediated cell migration and invasion, but not for CSC maintenance. Taken together, our study provides evidence that KLF4 has a potent oncogenic role in mammary tumorigenesis likely by maintaining stem cell-like features and by promoting cell migration and invasion. Thus, targeting KLF4 may provide an effective therapeutic approach to suppress tumorigenicity in breast cancer.
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