AbstractObjectiveTo assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients’ ...characteristics.DesignIndividual patient level meta-analysis of randomised controlled trials.Data sourcesSearches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data.Eligibility criteriaRandomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation.Main outcome measuresThe primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding.ResultsThe meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen.ConclusionsP2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT.RegistrationPROSPERO CRD42020176853.
Red cabbage (Brassica oleracea L. var. capitata f. rubra DC.) is a fresh edible vegetable consumed globally that contains high levels of antioxidant compounds including anthocyanins. In this study, ...fresh-cut red cabbage was treated with different Ultraviolet-C (UV-C) dosages. Fifteen cyanidin derivatives were observed in UV-C treated fresh-cut red cabbage; four of these were anthocyanins absent in control samples. The optimum dose of UV-C for enhancing total anthocyanin content in fresh-cut red cabbage was 3.0 kJ/m
. Different UV-C irradiation doses resulted in miscellaneous responses for each of the anthocyanin compounds, and these alterations appeared to be dose-dependent. The expression of genes relating to anthocyanin metabolism was altered by UV-C irradiation. For example, genes for biosynthetic enzymes including glycosyltransferase and acyltransferase, as well as R2R3 MYB transcription factors (production of anthocyanin pigment 1 and MYB114), had strongly increased expression following UV-C treatment. These results are in accord with the roles of these gene products in anthocyanin metabolism. This is, to the authors' knowledge, the first report demonstrating that UV-C treatment can increase the antioxidant activity in fresh-cut red cabbage in storage. Moreover, our detailed phytochemical and gene expression analysis establish specific roles for both anthocyanins and metabolism genes in this process.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
It remains unclear whether P2Y12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary ...intervention (PCI).
We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity.
We pooled patient-level data from randomized controlled trials comparing P2Y12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.
Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; Pinteraction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; Pinteraction = 0.920).
P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials; CRD42020176853)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Zeolites, Prussian blue analogues (PBAs), and metal-organic frameworks (MOFs) rely on surface-like internal pore diffusions, which have generically low activation barriers to enable the rapid uptake ...of chemical species. Here we show that Wadsley-Roth oxides (WROs) with pore diameters of 2.5 Å <
d
< 2.8 Å, while excluding molecules, enable very rapid diffusion of Li
+
in single-crystal particles >10 μm size. This supports full charge cycles at high rates of
∼
30C, which would rival the filling up of gasoline vehicles, while reducing the contact and side reactions with the electrolyte and enhancing the cycle life up to 10
000 cycles. Pore diffusion in WRO mixed ionic and electronic conductors (MIECs) differs from that in lithium intercalation compounds in the off-centered Li storage and low-coordination saddle points for migration. The reduced topological constraints per atom and large free volume in the host also lead to abnormally low or even negative thermal expansion and soft phonons, similar to other open frameworks such as zeolites, PBAs, and MOFs. Based on these guidelines, we have synthesized new composition (Nb
9
W
4
Ti
4
O
42.5
) and crystal size-coarsened H-Nb
2
O
5
(>20 μm single crystals) with unprecedented performance.
New physical insights and a robust approach are provided to develop super-MIEC anodes for high-rate batteries, which would bridge two materials families-nanoporous framework materials and conductive oxides.
Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair ...adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR’s metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.
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•IgG accumulates in adipose tissue during aging and is reduced by caloric restriction•IgG activates macrophages to induce adipose tissue fibrosis•Preventing IgG accumulation in aging prolongs healthspan and lifespan•Targeting IgG recycling receptor FcRn rejuvenates metabolic health in aged mice
In this study, Yu et al. demonstrate that IgG accumulates during aging, inducing adipose tissue fibrosis and metabolic dysfunction. Preventing IgG buildup by targeting the recycling receptor FcRn increases lifespan and improves the metabolic health of aged mice.
Abstract
The environment disseminates antimicrobial-resistance genes; however, it remains challenging to distinguish whether human activities exacerbate antimicrobial resistance or what is natural. ...Here, we quantified ~300 resistance-related genes in 200+ Scottish soil samples. Location or land use does not explain gene differences, but nutrient levels reduce gene richness. Elevated levels of metals increased gene richness, and selenium increased transposase levels. Rainfall and persistent organic pollutants also increased transposase relative abundance, possibly promoting conditions conducive to the horizontal transfer of antimicrobial-resistance genes. Selenium and polychlorinated biphenyls were primary factors in gene abundance, while polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and pH influenced gene diversity. Polychlorinated biphenyls are derived from anthropogenic activities, highlighting human activities’ potential impact on gene prevalence. This is the first national-scale, high spatial resolution dataset of antimicrobial-resistance genes in Scottish soils and provides a novel resource on which to build future studies.
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