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Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin (‘pigment’) stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general. Gallstones are masses in the gallbladder or biliary tract. This Primer by Lammert et al . focuses on the formation of gallstones, summarizes the current principles of treatment of the stones and their potential complications and envisions future approaches for this widespread disease.

The largest surface of the human body exposed to the external environment is the gut. At this level, the intestinal barrier includes luminal microbes, the mucin layer, gastrointestinal motility and secretion, enterocytes, immune cells, gut vascular barrier, and liver barrier. A healthy intestinal barrier is characterized by the selective permeability of nutrients, metabolites, water, and bacterial products, and processes are governed by cellular, neural, immune, and hormonal factors. Disrupted gut permeability (leaky gut syndrome) can represent a predisposing or aggravating condition in obesity and the metabolically associated liver steatosis (nonalcoholic fatty liver disease, NAFLD). In what follows, we describe the morphological-functional features of the intestinal barrier, the role of major modifiers of the intestinal barrier, and discuss the recent evidence pointing to the key role of intestinal permeability in obesity/NAFLD.

A major challenge in tokamak fusion research is first-wall erosion caused by steady heat loads and sudden energy bursts known as edge-localized modes. Divertor detachment reduces steady-state heat flux, while resonant magnetic perturbations can suppress these instabilities. However, integrating the two has been difficult because they require conflicting operating conditions. Here we demonstrate simultaneous achievement of resonant magnetic perturbations mitigated small edge-localized modes and impurity seeded partial divertor detachment in plasmas with an ITER-similar shape on the DIII-D tokamak. Experiments and simulations show that resonant magnetic perturbations facilitate detachment by redistributing particles, lowering the core density and increasing the scrape-off layer density, thereby reducing the amount of injected gas required. Cooling-gas injection eliminates the secondary heat-flux peak created by three-dimensional magnetic lobes, while edge cooling weakens the plasma response to the applied magnetic fields. These advances illustrate a viable pathway for integrating edge stability control with power exhaust in future fusion reactors. Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.

Divertor detachment offers a promising solution to the challenge of plasma-wall interactions for steady-state operation of fusion reactors. Here, we demonstrate the excellent compatibility of actively controlled full divertor detachment with a high-performance ( β N ~ 3, H 98 ~ 1.5) core plasma, using high-β p (poloidal beta, β p  > 2) scenario characterized by a sustained core internal transport barrier (ITB) and a modest edge transport barrier (ETB) in DIII-D tokamak. The high- β p high-confinement scenario facilitates divertor detachment which, in turn, promotes the development of an even stronger ITB at large radius with a weaker ETB. This self-organized synergy between ITB and ETB, leads to a net gain in energy confinement, in contrast to the net confinement loss caused by divertor detachment in standard H-modes. These results show the potential of integrating excellent core plasma performance with an efficient divertor solution, an essential step towards steady-state operation of reactor-grade plasmas. Plasma fusion devices like tokamaks are important for energy generation but there are many challenges for their steady state operation. Here, the authors show that full divertor detachment is compatible with high-confinement high-poloidal-beta core plasmas and this prevents the damage to the divertor target plates and the first wall.

Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.

High-performance and long-pulse operation is a crucial goal of current magnetic fusion research. Here, we demonstrate a high-confinement plasma regime known as an H-mode with a record pulse length of over 30 s in the Experimental Advanced Superconducting Tokamak sustained by lower hybrid wave current drive (LHCD) with advanced lithium wall conditioning. We find that LHCD provides a flexible boundary control for a ubiquitous edge instability in H-mode plasmas known as an edge-localized mode, which leads to a marked reduction in the heat load on the vessel wall compared with standard edge-localized modes. LHCD also induces edge plasma ergodization that broadens the heat deposition footprint. The heat transport caused by this ergodization can be actively controlled by regulating the edge plasma conditions. This potentially offers a new means for heat-flux control, which is a key issue for next-step fusion development. A high-confinement plasma that is potentially useful for controlled fusion has now been sustained for over 30 s. The Experimental Advanced Superconducting Tokamak in Hefei, China, achieved this record pulse length by first confining the plasma using lithium-treated vessel walls, and then maintaining it with a so-called lower hybrid current drive.

Currently, calcite produced in sediments by microbial-induced carbonate precipitation (MICP) is mainly used as a strengthening binder in sand because sands are porous and have good permeability. Conventional wisdom does not consider MICP to be suitable for use in soft clay because of the clay particles’ small size and its minimal porosity. Because of the clay’s high water content and complex chemical composition, very little research has been done and not much is known about the use of MICP in soft clay for strength enhancement. For this paper, soft clay specimens were prepared by mixing a solution containing Sporosarcina pasteurii bacteria, solutions with different concentrations of nutrient salts, and soft clay. Unconfined compressive strength tests were carried out on these specimens after they had cured for 28 days in a moisture-controlled environment. These laboratory tests were used to study the chemical reactions, the clay’s strength, and other influencing factors. The results are as follows: (1) directly mixing a S. pasteurii solution, nutrient salts, and soft clay considerably improves the uniformity of the spatial distribution of the bacteria and the nutrients in the soft clay. Directly mixing these constituents promotes the formation of calcium carbonate and greatly simplifies soft clay sample preparation. (2) It is feasible to use MICP to increase the strength of soft clay. Compared to control specimens cured under the same conditions but without introduced nutrients and bacteria solution, the unconfined compressive strength of MICP-treated specimens can be increased by as much as 2.42 times to an unconfined compressive strength of 43.31 kPa. The water content in MICP-treated specimens was significantly reduced by the MICP reactions and in one case decreased from 40% to 30.73%. (3) The strength enhancement of microbially solidified soft clay is the result of two processes: urea hydration catalyzed by enzymes consumes water in the clay and the bacterially precipitated calcite forms in the sediment’s pores. (4) The micro-organism-produced calcite in the soft clay increases the calcite abundance from 0% to as much as 3.5%. (5) The MICP-treated strength of soft clay varies with the concentration of the nutrients provided. For the experimental conditions used for this paper, the optimum concentration of the CaCl2·2H2O and CH4N2O nutrients is 0.5 mol/L.

Activating transcription factor (ATF)3 is known to have an anti-inflammatory function, yet the role of hepatic ATF3 in lipoprotein metabolism or atherosclerosis remains unknown. Here we show that overexpression of human ATF3 in hepatocytes reduces the development of atherosclerosis in Western-diet-fed Ldlr −/− or Apoe −/− mice, whereas hepatocyte-specific ablation of Atf3 has the opposite effect. We further show that hepatic ATF3 expression is inhibited by hydrocortisone. Mechanistically, hepatocyte ATF3 enhances high-density lipoprotein (HDL) uptake, inhibits intestinal fat and cholesterol absorption and promotes macrophage reverse cholesterol transport by inducing scavenger receptor group B type 1 (SR-BI) and repressing cholesterol 12α-hydroxylase (CYP8B1) in the liver through its interaction with p53 and hepatocyte nuclear factor 4α, respectively. Our data demonstrate that hepatocyte ATF3 is a key regulator of HDL and bile acid metabolism and atherosclerosis. Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism.