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Carbon dioxide electroreduction facilitates the sustainable synthesis of fuels and chemicals 1 . Although Cu enables CO 2 -to-multicarbon product (C 2+ ) conversion, the nature of the active sites under operating conditions remains elusive 2 . Importantly, identifying active sites of high-performance Cu nanocatalysts necessitates nanoscale, time-resolved operando techniques 3 – 5 . Here, we present a comprehensive investigation of the structural dynamics during the life cycle of Cu nanocatalysts. A 7 nm Cu nanoparticle ensemble evolves into metallic Cu nanograins during electrolysis before complete oxidation to single-crystal Cu 2 O nanocubes following post-electrolysis air exposure. Operando analytical and four-dimensional electrochemical liquid-cell scanning transmission electron microscopy shows the presence of metallic Cu nanograins under CO 2 reduction conditions. Correlated high-energy-resolution time-resolved X-ray spectroscopy suggests that metallic Cu, rich in nanograin boundaries, supports undercoordinated active sites for C–C coupling. Quantitative structure–activity correlation shows that a higher fraction of metallic Cu nanograins leads to higher C 2+ selectivity. A 7 nm Cu nanoparticle ensemble, with a unity fraction of active Cu nanograins, exhibits sixfold higher C 2+ selectivity than the 18 nm counterpart with one-third of active Cu nanograins. The correlation of multimodal operando techniques serves as a powerful platform to advance our fundamental understanding of the complex structural evolution of nanocatalysts under electrochemical conditions. By investigation of structural dynamics during the life cycle of Cu nanocatalysts, correlation of multimodal operando techniques was found to serve as a powerful platform to advance understanding of their complex structural evolution.

Coastal areas have been increasingly affected by human activities, marine pollution and climate change are among the most important pressures affecting these environments. Human-induced pressures occur in a cumulative way and generate additive, antagonistic or synergistic effects. Knowledge on synergistic effects is crucial to coastal zone management, since they may imply a change in human uses of these systems, as well as dedicated action plans in order to reduce hazards and environmental risks. In this work, we provide an overview of the available literature on synergistic effects between climate change and chemical pollution, and discuss current knowledge, methodological approaches, and research gaps and needs. Interactions between these two pressures may be climate change dominant (climate change leads to an increase in contaminant exposure or toxicity) or contaminant-dominant (chemical exposure leads to an increase in climate change susceptibility), but the mechanistic drivers of such processes are not well known. Results from a few meta-analyses studies and reviews showed that synergistic interactions tend to be more frequent compared to additive and antagonistic ones. However, most of the studies are individual-based and assess the cumulative effects of a few contaminants individually in laboratory settings together with few climate variables, particularly temperature and pH. Nevertheless, a wide diversity of contaminants have already been individually tested, spanning from metals, persistent organic pollutants and, more recently, emergent pollutants. Population and community based approaches are less frequent but have generated very interesting and more holistic perspectives. Methodological approaches are quite diverse, from laboratory studies to mesocosm and field studies, or based on statistical or modelling tools, each with their own potential and limitations. More holistic comparisons integrating several pressures and their combinations and a multitude of habitats, taxa, life-stages, among others, are needed, as well as insights from meta-analyses and systematic reviews.

Acute lymphoblastic leukemia (ALL) is a significant concern in both pediatric and adult demographics. Despite 156 approved cancer therapies based on small molecules, a mere five apply to all types of leukemia. Unfortunately, adherence to these treatments is low due to adverse side effects. Consequently, there is an urgent need to identify more effective treatment options for ALL. This study presents a potential solution. We have designed over fifty analogs of carbamazepine, utilizing a combination of ligand-based and structure-based drug design methodologies. Among these analogs, we identified the CR80 analog, which demonstrated predicted binding values of -8.66 kcal/mol against beta-tubulin, a favorable LogP, and IC 50 values suitable for in vitro evaluation. The CR80 compound was synthesized with a yield of 50% and subsequently assessed in vitro against the U-937 cell line. It obtained an IC 50 value of 0.8 micromolar to 1 micromolar and a selectivity index of two, thus marking it as a promising candidate for in vivo studies.

Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

Food production is challenged by changes in climate and land use and expanding human population growth. Proper pollination can increase the production and quality of fruit, nut, oil, and fiber crops.We reviewed crop dependence on pollinators and estimated the economic value of pollination per year for each crop in Brazil. We analyzed 141 crops and found that 85 depend on pollinators. Almost one-third of these crops have an essential or great dependence on pollinators. The economic contribution of pollinators totals ∼30% (∼US$12 billion) of the total annual agricultural income of the dependent crops (totalizing almost US$45 billion). However, half of these figures includes soybean crop (US$5.7 billion of pollinators' contribution and US$22 billion of annual income). Soybean was considered as having a modest dependence on pollinators, but this remains controversial because pollinator dependence might vary among different varieties cultivated in Brazil. Moreover, we have no information about pollinator dependence regarding some important crops, showing the urgent need for basic research into reproductive biology and pollination ecology.

Bacterial resistance poses a significant public health challenge, particularly for pathogens prioritized by the World Health Organization, such as carbapenem-resistant Escherichia coli . There has been growing interest in exploring animal toxins as potential alternatives to antibiotics. This study centers on the rational design of an antibiotic peptide based on the sequence 115–129 from Myotoxin II, sourced from the venom of the snake Bothrops asper. We modified the original sequence 20 times using molecular docking and found that peptide sequence 20 (KHWYKHYRH) exhibited the highest affinity energy of − 7.6 kcal/mol for lipopolysaccharide (LPS). The in vitro potency was assessed against E. coli , with an IC 50 of 0.27 mg/mL, while P. aeruginosa (ATCC 27853) showed an IC 50 of 2.93 mg/mL. Conversely, the peptide was ineffective against resistant strains, such as the NDM-1-positive Klebsiella pneumoniae (ATCC BAA-2146) and the ESBL clinical isolate E. coli (CTX-M). Additionally, the safety of peptide 20 was evaluated, revealing that none of the tested concentrations caused hemolytic activity or loss of cellular viability in L929 and Caco-2 cells. This indicates that rational, structure-based design is an effective strategy for developing safe peptides.

Aims/hypothesis Type 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy. Moreover, addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia. Vildagliptin is a dipeptidyl peptidase-IV inhibitor, which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion. This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes. Materials and methods This was a multicentre, 24-week, double-blind, randomised, placebo-controlled, parallel-group study in patients with type 2 diabetes that was inadequately controlled (HbA₁c = 7.5-11%) by insulin. Patients received vildagliptin (n = 144; 50 mg twice daily) or placebo (n = 152) while continuing insulin therapy. Results Baseline HbA₁c averaged 8.4 ± 0.1% in both groups. The adjusted mean change from baseline to endpoint (AMΔ) in HbA₁c was -0.5 ± 0.1% and -0.2 ± 0.1% in patients receiving vildagliptin or placebo, respectively, with a significant between-treatment difference (p = 0.01). In patients aged >=65 years, the AMΔ HbA₁c was -0.7 ± 0.1% in the vildagliptin group vs -0.1 ± 0.1% in the placebo group (p < 0.001). The incidence of adverse events was similar in the vildagliptin (81.3%) and placebo (82.9%) groups. However, hypoglycaemic events were less common (p < 0.001) and less severe (p < 0.05) in patients receiving vildagliptin than in those receiving placebo. Conclusions/interpretation Vildagliptin decreases HbA₁c in patients whose type 2 diabetes is poorly controlled with high doses of insulin. Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia. ClinicalTrials.gov ID no.: NCT 00099931.

An increasing number of studies are showing that Antarctic mega- and macrofauna are highly diverse, however, little is known about meiofaunal biodiversity in sediment communities, which are a vital part of a healthy and functional ecosystem. This is the first study to analyse community DNA (targeting meiofauna) using metabarcoding to investigate biodiversity levels in sediment communities of the Antarctic Peninsula. The results show that almost all of the meiofaunal biodiversity in the benthic habitat has yet to be characterised, levels of biodiversity were higher than expected and similar to temperate regions, albeit with the existence of potentially new and locally adapted species never described before at the molecular level. The Rothera meiofaunal sample sites showed four dominant eukaryotic groups, the nematodes, arthropods, platyhelminthes, and the annelids; some of which could comprise species complexes. Comparisons with deep-sea data from the same region suggest little exchange of Operational Taxonomic Units (OTUs) between depths with the nematodes prevalent at all depths, but sharing the shallow water benthos with the copepods. This study provides a preliminary analysis of benthic Antarctic Peninsula meiofauna using high throughput sequencing which substantiates how little is known on the biodiversity of one of the most diverse, yet underexplored communities of the Antarctic: the benthos.

The COVID-19 pandemic has added an enormous toll to the existing challenge of diabetes care world-wide. A large proportion of patients with COVID-19 requiring hospitalization and/or succumbing to the disease have had diabetes and other chronic conditions as underlying risk factors. In particular, individuals belonging to racial/ethnic minorities in the U.S. and other countries have been significantly and disproportionately impacted. Multiple and complex socioeconomic factors have long played a role in increasing the risk for diabetes and now for COVID-19. Since the pandemic began, the global healthcare community has accumulated invaluable clinical experience on providing diabetes care in the setting of COVID-19. In addition, understanding of the pathophysiological mechanisms that link these two diseases is being developed. The current clinical management of diabetes is a work in progress, requiring a shift in patient-provider interaction beyond the walls of clinics and hospitals: the use of tele-medicine when feasible, innovative patient education programs, strategies to ensure medication and glucose testing availability and affordability, as well as numerous ideas on how to improve meal plans and physical activity. Notably, this worldwide experience offers us the possibility to not only prepare better for future disasters but also transform diabetes care beyond the COVID-19 era. •The COVID-19 pandemic has added an enormous toll to the existing challenge of diabetes care worldwide•Diabetes and other chronic conditions increase the risk of hospitalization and death from COVID-19•Comprehensive management of diabetes and common comorbidities is crucial to reducing morbidity and mortality rates•Individuals from racial or ethnic minorities have been disproportionately impacted by diabetes and COVID-19•Socioeconomic factors should be acknowledged and addressed at multiple levels to reduce diabetes & COVID-19 disease burdens•Lessons learned during this pandemic should influence the future of both disaster-based and routine diabetes care

Abstract Context Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D. Objective To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials. Design Post hoc analysis of data from phase 3 randomized SUSTAIN 1–5 and 7 (pooled), and SUSTAIN 6 trials. Participants 3074 subjects (SUSTAIN 1–5 and 7) and 1648 subjects (SUSTAIN 6). Interventions Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg). Main Outcome Measures Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints. Results HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders. Conclusions In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity.