Abstract
Aims
Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed ...randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion.
Methods and results
Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites.
Conclusion
Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.
The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development and tissue homeostasis. Notably, comprehensive genetic studies in Drosophila and mice in the past ...decades have demonstrated the crucial role of Wnt signaling in intestinal stem cell maintenance by regulating proliferation, differentiation, and cell-fate decisions. Wnt signaling has also been implicated in a variety of cancers and other diseases. Loss of the Wnt pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of human colorectal cancers (CRC). Recent advances in high-throughput sequencing further reveal many novel recurrent Wnt pathway mutations in addition to the well-characterized APC and β-catenin mutations in CRC. Despite attractive strategies to develop drugs for Wnt signaling, major hurdles in therapeutic intervention of the pathway persist. Here we discuss the Wnt-activating mechanisms in CRC and review the current advances and challenges in drug discovery.
This investigation identifies a plant growth-promoting rhizobacteria which can improve the heat tolerance of spinach (
Spinacia oleracea
L.)
. Bacillus licheniformis
strain (named
B. licheniformis
...BE-L60) was isolated from the heat-stressed spinach rhizosphere soil.It secretesindole-3-acetic acid, dissolve phosphorus, and produces amylases and proteases. Compared toun-inocculated spinach seedlings, those inoculated with BE-L60 had higher contents of soluble protein, proline, and sugar and enhanced the functions of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. The results indicated that BE-L60 maintained the osmoprotectant levels to improve ion homeostasis and activates the antioxidant defense system. It was also identified via transcriptome analysis that heat stress could be alleviatedthe expression of heat shock protein genes. Overall, BE-L60 enhanced spinach seedlings’ heat tolerance by modulating plants’ physiological and biochemical processes.
Approach and avoidance represent two fundamental behavioral traits that develop early in life. Previous studies have examined the neural correlates of approach and avoidance traits in adults and ...adolescents. Here, using the data set of the Adolescent Brain Cognition Development project, we investigated the structural cerebral bases of behavioral activation system (BAS) and behavioral inhibition system (BIS) in children. We employed voxel-based morphometry to examine how gray matter volumes (GMV) related specifically to BAS and BIS traits in 11,542 children (5491 girls, age 9–10 years) with 648 and 2697 identified as monozygotic twins (MZ) and dizygotic twins/siblings (DZ), respectively. After accounting for the BIS score, higher BAS scores (residuals) were positively correlated with the GMV of the ventral striatum (VS), and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability (h2) of 0.8463. Higher BAS scores were negatively correlated with the GMV of bilateral visual, lateral orbitofrontal, temporal, and inferior frontal cortex, as well as the precuneus. Higher BIS (after accounting for BAS) scores were negatively correlated with the GMVs of the ventral caudate and bilateral putamen/pallidum, hypothalamus, and right anterior insula, and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability of 0.8848. A cluster in the VS showed positive and negative correlation with the BAS and BIS scores, respectively. These findings suggest shared and distinct cerebral volumetric bases of the BAS and BIS traits in children. Whereas both traits have a strong genetic basis, the BAS relative to BIS appears to be more amenable to environmental influences. These findings add to the literature of developmental neuroscience and may help identify genetic risk factors of externalizing and internalizing psychopathology.
•We use VBM to study the volumetric correlates of the BAS and BIS in children.•The VS GMV shows positive and negative correlation each with the BAS and BIS.•Girls and boys do not show distinct regional GMV in association with BAS or BIS.•The volumetric correlates of BAS and BIS are highly heritable.•The BAS relative to BIS appears to be more amenable to environmental influences.
This article reports for the first time:•The nano/microstructural evolution of a 5M KOH-activated slag cement aged 18y.•The Mg/Al ratio of Mg-Al LDH in cement can be determined accurately by powder ...XRD.•The a parameter of Mg-Al LDH phases = 2 × d110 = 3.133–0.278x; Mg/Al = (1–x)/x.
The main hydration products were C-A-S-H(I), present in both inner (Ip) and outer product (Op), and a Mg-Al layered double hydroxide (LDH), present only in the Ip. The composition of C-A-S-H(I) was the same in Op and Ip. Reduced scatter in the data with age suggests a tendency towards compositional homogeneity. The mean length of the aluminosilicate anions in the C-A-S-H(I) increased with age. The layer spacings of the C-A-S-H(I) and Mg-Al LDH had not changed significantly with age. The Mg/Al ratio of the LDH was about 2.6 and had not changed between 1 and 18 years.
Summary
Background
The seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered to be associated with favourable clinical outcomes.
Aims
This ...meta‐analysis was performed to establish the proportion of HBsAg loss rates among CHB patients who received combination treatment based on pegylated interferon (PegIFN). Four combination strategies have been studied with the aim of improving HBsAg loss: “de novo,” “NA‐experienced,” “switch‐to” and “add‐on.” This meta‐analysis was performed to determine which, if any, of these combination strategies was more effective.
Methods
Medline, Web of Science and Embase databases were searched from inception to December 2017. The proportion of patients who achieved HBsAg loss after combination therapy was pooled using a random‐effects model.
Results
Twenty‐four studies fulfilled the meta‐analysis criteria. The overall pooled proportion suggested that the rate of HBsAg loss could be increased to 9% (95% CI: 7%‐12%) based on the combination treatment in CHB patients. Compared with “de novo” strategy (8%, 95% CI: 6%‐10%), the “nucleos(t)ide analogues‐experienced” (11%, 95% CI: 8%‐15%) was found to be more likely (P = 0.036) to achieve a response. Compared with the “add‐on” strategy (8%, 95% CI: 5%‐13%), the “switch‐to” (14%, 95% CI: 9%‐20%) was found to be more likely (P = 0.012) to achieve HBsAg loss.
Conclusion
The “nucleos(t)ide analogues‐experienced” strategy was more effective than the “De novo” strategy in achieving HBsAg loss for CHB patients. Combination treatment using regimens based on Peg‐IFN may be useful to help nucleos(t)ide analogues‐treated patients, who have experienced at least 48 weeks of nucleot(s)ide analogue, achieve HBsAg seroclearance.
Linked ContentThis article is linked to Nhu and Pockros paper. To view this article visit https://doi.org/10.1111/apt.14683.
Refugees demonstrate high rates of post-traumatic stress disorder (PTSD) and other psychological disorders. The recent increase in forcible displacement internationally necessitates the understanding ...of factors associated with refugee mental health. While pre-migration trauma is recognized as a key predictor of mental health outcomes in refugees and asylum seekers, research has increasingly focused on the psychological effects of post-migration stressors in the settlement environment. This article reviews the research evidence linking post-migration factors and mental health outcomes in refugees and asylum seekers. Findings indicate that socioeconomic, social, and interpersonal factors, as well as factors relating to the asylum process and immigration policy affect the psychological functioning of refugees. Limitations of the existing literature and future directions for research are discussed, along with implications for treatment and policy.
Z3CN20-09M steels of primary circuit piping in Daya Bay Nuclear Power Plant were studied on the microstructure evolution and fracture behaviors after thermal aging at 400°C for up to 20,000h. The ...impact toughness of aged materials decreases a lot with aging time, and the impact fracture features change from ductile dimples into brittle cleavages in ferrite and tearing in austenite. Nano-indentation tests indicate that hardness in ferrite continuously increases with aging time. After long-term aging, ferrite decomposes into coherent Cr-rich and Fe-rich domains, and extensive G-phases precipitate homogeneously in ferrite, but no precipitate in austenite. Spinodal decomposition in ferrite leads to the thermal aging embrittlement in CASS. G-phase, with the Fm-3m space group and the lattice parameter of 1.14nm, adopts a cube-on-cube orientation relationship with the ferrite matrix.
Dissatisfactory load transfer has been a critical issue in carbon nanotube (CNT)- and graphene-reinforced metal matrix composites (MMCs) mainly because of the intrinsically unpleasant carbon-metal ...interfaces. Here we show by introducing in-situ Al2O3 nanoparticles at aluminum (Al)-CNTs interface, the load transfer efficiency can be noticeably enhanced in powder metallurgy CNTs/Al composites. From in-situ tensile tests, the nanoparticle-modified Al-CNTs interfaces result in CNT fracture, a sign of high load transfer efficiency; while clean interfaces without nanoparticles lead to CNT pulling-out. The nanoparticle-induced enhancement of interface strength can be explained by the increased sliding resistance of CNTs in MMCs at the wake of cracks under tensile loading. Our study provides a new strategy for designing strong carbon-metal interfaces to fabricate high-performance nanocarbon-reinforced MMCs.
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•A type of strong Al-CNT interface was studied by TEM and in-situ tensile tests.•Clean Al-CNT interfaces led to CNT pulling-out.•Al-CNT interfaces with in-situ alumina nanoparticles resulted in CNT fracture.•Alumina nanoparticles increased interfacial strength without damaging CNT structure.
The synchronization behaviors of coupled oscillators under time-varying couplings are of both theoretical and practical significance. While recent studies show that synchronization is suppressed by ...time-varying coupling in general, the underlying mechanism is still not very clear. Here, by the kernel of sinusoidal coupling function, we revisit the effects of periodic coupling on the synchronization of networked phase oscillators. It is found that the suppressed synchronization by periodic coupling is attributed to the formation of synchronization clusters in the transition from desynchronization to global synchronization. The clusters are different in size and frequency but are all locked to the frequency of the periodic coupling. We demonstrate this phenomenon numerically in different network models and conduct a theoretical analysis on the numerical results based on the method of dimension reduction. The findings extend our knowledge on the dynamical responses of a complex network to external drivings, and shed lights on the mechanism of suppressed synchronization in periodically coupled oscillators.
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