The applications of the most promising Fe-N-C catalysts are prohibited by their limited intrinsic activities. Manipulating the Fe energy level through anchoring electron-withdrawing ligands is found effective in boosting the catalytic performance. However, such regulation remains elusive as the ligands are only uncontrollably introduced oweing to their energetically unstable nature. Herein, we report a rational manipulation strategy for introducing axial bonded O to the Fe sites, attained through hexa-coordinating Fe with oxygen functional groups in the precursor. Moreover, the O modifier is stabilized by forming the Fe-O-Fe bridge bond, with the approximation of two FeN4 sites. The energy level modulation thus created confers the sites with an intrinsic activity that is over 10 times higher than that of the normal FeN4 site. Our finding opens a novel strategy to manage coordination environments at an atomic level for high activity ORR catalysts.Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation due to the progressive nature of T2D, this appears to be suboptimal in Japanese real-world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean HbA1c >9%). Although basal insulin (BI) therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose (PPG) often remains uncontrolled. Basal-bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed-ratio combinations (FRCs) of BI and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown efficacy in reducing both FPG and PPG with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide is currently available in Japan and USA/EU at a ratio of 1 U (unit)0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 11 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D. This article is protected by copyright. All rights reserved.Background/objectives There is an increasing volume of evidence which supports the link between psoriasis and cardiometabolic risk including obesity, metabolic syndrome, diabetes, hyperlipidemia, and myocardial infarction. Although one-third to one-half of psoriasis cases start during childhood, it is unclear whether childhood psoriasis is similarly associated with a cardiometabolic risk profile. Methods Electronic database searches were performed to identify studies comparing the proportion of pediatric psoriasis cases with controls in terms of dichotomous outcomes including the proportion of patients with overweight BMI, obese BMI, metabolic syndrome, diabetes, hypertension, hyperlipidemia, ischemic heart disease, or heart failure; continuous outcomes recorded include BMI, systolic blood pressure, diastolic blood pressure, HDL, LDL, triglycerides, and total cholesterol. Results A statistically significant association was found between pediatric psoriasis and overweight/obesity as well as waistheight ratio >0.5, in addition to metabolic syndrome, diabetes, hyperlipidemia, hypertension, and cardiac ischemia and failure. The association with obesity is dependent on the severity of disease, where moderate-severe psoriasis patients have higher odds of obesity compared to mild psoriasis. Conclusions Our systematic review and pooled meta-analysis demonstrate a significant association between childhood psoriasis and obesity, central adiposity, and other cardiometabolic comorbidities. Clinicians should consider the assessment of comorbidities in children with psoriasis, which may allow for early lifestyle interventions and education.The APETALA2 (AP2) subfamily of transcription factors are key regulators of angiosperm root, shoot, flower and embryo development. The broad diversity of anatomical and morphological structures is potentially associated with the genomic dynamics of the AP2 subfamily. However, a comprehensive phylogenomic analysis of the AP2 subfamily across angiosperms is lacking. We combined phylogenetic and synteny analysis of distinct AP2 subclades in the completed genomes of 107 angiosperm species. We identified major changes in copy number variation and genomic context within subclades across lineages, and discuss how these changes may have contributed to the evolution of lineage-specific traits. Multiple AP2 subclades show highly conserved patterns of copy number and synteny across angiosperms, while others are more dynamic and show distinct lineage-specific patterns. As examples of lineage-specific morphological divergence due to AP2 subclade dynamics, we hypothesize that loss of PLETHORA1/2 in monocots correlates with the absence of taproots, whereas independent lineage-specific changes of PLETHORA4/BABY BOOM and WRINKLED1 genes in Brassicaceae and monocots point towards regulatory divergence of embryogenesis between these lineages. Additionally, copy number expansion of TOE1 and TOE3/AP2 in asterids is implicated with differential regulation of flower development. Moreover, we show that the genomic context of AP2s is in general highly specialized per angiosperm lineage. To our knowledge, this study is the first to shed light on the evolutionary divergence of the AP2 subfamily subclades across major angiosperm lineages and emphasizes the need for lineage-specific characterization of developmental networks to understand trait variability further.Aim A growing number of studies suggest a role of neuroinflammation and oxidative stress in the pathophysiology of psychosis. Sulforaphane (SFN), a natural compound extracted from cruciferous vegetables, has shown anti-inflammatory and anti-oxidative effects which imply a potential effect on decreasing the risk of psychosis. However, there is no study testing the efficacy of SFN for this purpose. It’s necessary to evaluate its efficacy on individuals at clinical high risk (CHR) for psychosis. Methods This is a randomized, double-blind, placebo-controlled, multi-centre trial. LY2874455 cell line A total of 300 CHR subjects will be identified in the course of face-to-face interviews using the Structured Interview for Prodromal Syndromes. All participants will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The study duration includes an intervention for 52 consecutive weeks, and additional 1-year follow-up. Results The primary outcome is 2-year conversion rate of psychosis. Secondary outcomes include 1-year conversion rate of psychosis, the severity and duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and peripheral blood biomarkers of inflammation, oxidative stress and metabolism.