A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and ...low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.
Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, ...or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.
We show that cold dark matter axions thermalize and form a Bose-Einstein condensate (BEC). We obtain the axion state in a homogeneous and isotropic universe, and derive the equations governing small ...axion perturbations. Because they form a BEC, axions differ from ordinary cold dark matter in the nonlinear regime of structure formation and upon entering the horizon. Axion BEC provides a mechanism for the production of net overall rotation in dark matter halos, and for the alignment of cosmic microwave anisotropy multipoles.
In the field of nanofluidics, it has been an ultimate but seemingly distant goal to controllably fabricate capillaries with dimensions approaching the size of small ions and water molecules. We ...report ion transport through ultimately narrow slits that are fabricated by effectively removing a single atomic plane from a bulk crystal. The atomically flat angstrom-scale slits exhibit little surface charge, allowing elucidation of the role of steric effects. We find that ions with hydrated diameters larger than the slit size can still permeate through, albeit with reduced mobility. The confinement also leads to a notable asymmetry between anions and cations of the same diameter. Our results provide a platform for studying the effects of angstrom-scale confinement, which is important for the development of nanofluidics, molecular separation, and other nanoscale technologies.
The dielectric constant ε of interfacial water has been predicted to be smaller than that of bulk water (ε ≈ 80) because the rotational freedom of water dipoles is expected to decrease near surfaces, ...yet experimental evidence is lacking. We report local capacitance measurements for water confined between two atomically flat walls separated by various distances down to 1 nanometer. Our experiments reveal the presence of an interfacial layer with vanishingly small polarization such that its out-of-plane ε is only ~2. The electrically dead layer is found to be two to three molecules thick. These results provide much-needed feedback for theories describing water-mediated surface interactions and the behavior of interfacial water, and show a way to investigate the dielectric properties of other fluids and solids under extreme confinement.
Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal ...tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.
To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual ...glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options.
Systematic review and network meta-analysis.
Ovid Medline, Embase, and Cochrane Central up to 14 October 2022.
Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach.
The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes).
This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.
PROSPERO CRD42022325948.
There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship.
This study utilized large-scale genome-wide ...association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and OA risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for OA. Comprehensively sensitive analyses were performed to validate the robustness of results and novel multivariable MR analyses were further conducted to ensure the independence of causal association. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. Finally, enrichment analyses were used to investigate the biofunction.
After correction, three microbial taxa were identified to be causally associated with diverse joint OA (PFDR < 0.100), namely Methanobacteriaceae family for knee OA (PFDR = 0.043) and any OA (PFDR = 0.028), Desulfovibrionales order for knee OA (PFDR = 0.045) and Ruminiclostridium5 genus for knee OA (PFDR = 0.063). In addition, we also identified five suggestive microbial taxa that were significant with three different methods under the nominal significance (P < 0.05). Sensitive analysis excluded the influence of heterogeneity and horizontal pleiotropy and multivariable MR analysis ruled out the possibility of horizontal pleiotropy of BMI. GO enrichment analysis illustrates the protective mechanism of the identified taxa against OA.
This study found that several microbial taxa were causally associated with diverse joint OA. The results enhanced our understanding of gut microbiota in the pathology of OA.
Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity ...and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT).
CD1 female mice (5-month old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout.
Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation.
Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.
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