Search

Alkaline anion‐exchange membrane water electrolyzers (AEMWEs) for green hydrogen production have received intensive attention due to their feasibility of using earth‐abundant platinum group metal (PGM)‐free catalysts. Herein, the third metal is incorporated into NiFe‐based catalysts to regulate their electronic structures and morphologies, aiming to achieve sufficient oxygen evolution reaction (OER) activity and performance in AEMWEs. The ternary NiFeM (M: Cu, Co, or Mn) catalysts are featured with multiple layered structures and nanofoam network morphologies, consisting of highly OER‐active amorphous Ni‐rich oxide shells and electrically conductive metallic alloy cores. The physical and electronic perturbations to the NiFe induced by a third element lead to a fine‐tuning of the redox ability of the metal sites at the reaction centers, which breaks the scaling relationship between OH* and O* intermediates at the reaction centers. Thus, the unique structural configuration and electronic regulation simultaneously benefit catalytic activity and performance improvements. These NiFeM nanofoam catalysts demonstrated promising anode performance in actual AEMWEs, comparable to the IrO2 reference, especially at high current densities. Notably, using various electrolytes (e.g., KOH solution or pure water) for AEMWEs exhibited a different performance trend among studied NiFeM catalysts, likely due to dynamic changes of catalysts under various OER environments. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is a severe disease with a complex pathogenesis and is an important factor in the mortality of patients in intensive care units (ICUs). The administration of vitamin C and its combination treatment in sepsis was not supported by the results of multiple randomized controlled clinical trials. However, the efficacy of a higher vitamin C dose in treating patients with sepsis remains unclear. Therefore, the effectiveness of administering a larger dosage of vitamin C to patients with sepsis remains unclear. Methods and Analysis: The Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS) trial is a multicenter, single-blind, randomized, placebo-controlled trial with 234 individuals with sepsis. The following adult patients will be enrolled: those with procalcitonin (PCT) ≥ 2 ng/mL and sepsis 3.0 diagnostic criteria. Patients will be randomly assigned to receive 12 g vitamin C or the same volume of 5% glucose injection intravenously pumped every 12 h for 4 days or up to the moment they are discharged from ICU. The primary outcome will be the mortality within 28 days. Secondary outcomes will mainly include protection and support of organ functions, improvement in inflammatory status, and length of ICU stay. Moreover, adverse events and serious adverse events will be meticulously recorded. Ethics: This study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2020-KY-069-05). The trial results will be published in peer-reviewed journals or at national or international conferences. Trial registration: clinicaltrials.gov, NCT05194189, Registered 3 January 2022, URL: https://www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Atomically thin Pt nanolayers were synthesized on the surface of Mo2TiC2 MXenes and used for the catalytic dehydrogenation of ethane and propane into ethylene and propylene, two important chemicals for the petrochemical industry. As compared with Pt nanoparticles, the atomically thin Pt nanolayer catalyst showed superior coke-resistance (no deactivation for 24 h), high activity (turnover frequencies (TOFs) of 0.4–1.2 s−1), and selectivity (> 95%) toward ethylene and propylene. The unique Pt nanolayer has a similar geometric surface to Pt nanoparticles, enabling the investigations of the electronic effect on the catalytic performance, where the geometric effect is negligible. It is found that the electronic effect plays a critical role in dehydrogenative product selectivity and catalyst stability. The metal–support interaction is found dependent on the substrate and metal components, providing wide opportunities to explore high-performance MXene-supported metallic catalysts. [ABSTRACT FROM AUTHOR]

Heterogeneous catalysts are widely used to promote chemical reactions. Although it is known that chemical reactions usually happen on catalyst surfaces, only specific surface sites have high catalytic activity. Thus, identifying active sites and maximizing their presence lies at the heart of catalysis research1–4, in which the classic model is to categorize active sites in terms of distinct surface motifs, such as terraces and steps1,5–10. However, such a simple categorization often leads to orders of magnitude errors in catalyst activity predictions and qualitative uncertainties of active sites7,8,11,12, thus limiting opportunities for catalyst design. Here, using stepped Pt(111) surfaces and the electrochemical oxygen reduction reaction (ORR) as examples, we demonstrate that the root cause of larger errors and uncertainties is a simplified categorization that overlooks atomic site-specific reactivity driven by surface stress release. Specifically, surface stress release at steps introduces inhomogeneous strain fields, with up to 5.5% compression, leading to distinct electronic structures and reactivity for terrace atoms with identical local coordination, and resulting in atomic site-specific enhancement of ORR activity. For the terrace atoms flanking both sides of the step edge, the enhancement is up to 50 times higher than that of the atoms in the middle of the terrace, which permits control of ORR reactivity by either varying terrace widths or controlling external stress. Thus, the discovery of the above synergy provides a new perspective for both fundamental understanding of catalytically active atomic sites and design principles of heterogeneous catalysts. Stress release at stepped platinum surfaces is shown to influence the strain experienced by atoms near the steps, resulting in effects on the catalytic activity of the whole surface. [ABSTRACT FROM AUTHOR]

Platinum alloys are highly efficient electrocatalysts for the oxygen reduction reaction (ORR) in acidic conditions. However, these alloys are susceptible to metal loss through leaching and degradation, leading to reduced catalyst stability and activity. Recently, it has been shown that doping with oxophilic elements can significantly alleviate these problems, with a prominent example being Mo‐doped Pt alloys. Here, to achieve atomic scale understanding of the exceptional activity and stability of these alloys, we present a detailed density functional theory description of the dopants' structures and impact on electrocatalyst properties. Beginning with the Mo/Pt system, we demonstrate that Mo can be stabilized in the form of low‐dimensional oxyhydroxide moieties on Pt defects. The resulting structures enhance stability and activity via distinct physical processes, with the Mo moieties both directly inhibiting Pt dissolution at defects and indirectly enhancing ORR activity by generation of strain fields on surrounding Pt terraces. We then generalize these analyses to other metal dopant elements, and we demonstrate that similar low‐dimensional oxyhydroxide structures control the electrocatalytic properties through an intricate interplay of the structures' acid stability, intrinsic activity for the ORR, and ability to induce ORR‐promoting strain fields on Pt. [ABSTRACT FROM AUTHOR]

Platinum alloys are highly efficient electrocatalysts for the oxygen reduction reaction (ORR) in acidic conditions. However, these alloys are susceptible to metal loss through leaching and degradation, leading to reduced catalyst stability and activity. Recently, it has been shown that doping with oxophilic elements can significantly alleviate these problems, with a prominent example being Mo‐doped Pt alloys. Here, to achieve atomic scale understanding of the exceptional activity and stability of these alloys, we present a detailed density functional theory description of the dopants' structures and impact on electrocatalyst properties. Beginning with the Mo/Pt system, we demonstrate that Mo can be stabilized in the form of low‐dimensional oxyhydroxide moieties on Pt defects. The resulting structures enhance stability and activity via distinct physical processes, with the Mo moieties both directly inhibiting Pt dissolution at defects and indirectly enhancing ORR activity by generation of strain fields on surrounding Pt terraces. We then generalize these analyses to other metal dopant elements, and we demonstrate that similar low‐dimensional oxyhydroxide structures control the electrocatalytic properties through an intricate interplay of the structures' acid stability, intrinsic activity for the ORR, and ability to induce ORR‐promoting strain fields on Pt. [ABSTRACT FROM AUTHOR]

A growing number of studies have shown that melatonin is a potent agonist of SIRT3 (sirtuin 3) and effectively protects mitochondria, suggesting melatonin as a promising therapeutic drug to treat sepsis-induced acute kidney injury (SAKI). In this study, we first included 48 sepsis patients for cross-sectional analysis and the result revealed that plasma melatonin levels are inversely proportional to the mitochondrial injury of renal tubular epithelial cells and directly proportional to the acute kidney injury recovery in sepsis patients. We further explored the effects of exogenous melatonin on SAKI and its mechanism in animal model of cecal ligation and puncture-treated mice, and cellular model of LPS-challenged HK-2 cells. The results demonstrate that the protective effect of melatonin on the progression of SAKI depends on SIRT3 activation as well as mitophagic flux. Mechanistically, TFAM (transcription factor A, mitochondrial)-K154 site deacetylation via SIRT3 is indispensable for melatonin-enhanced mitophagic flux on SAKI. Together, our study unveils a previously unappreciated mechanism of melatonin as agonists of SIRT3 to hold promise for treatment of patients with SAKI. AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid – Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine. [ABSTRACT FROM AUTHOR]

Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxCly catalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+ and Cl- ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm−2 and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl- prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O* sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl- itself can work as a promoter toward enhancing chlorine evolution in acidic brine. Achieving stable and selective chlorine production is of high interest yet challenging. Here the authors report an amorphous CoOxCly catalyst prepared by in situ electrodeposition in acidic saline electrolyte which shows ~100% chlorine evolution selectivity with low overpotential and high stability over 500 h. [ABSTRACT FROM AUTHOR]

Hydrogen economy, as the most promising alternative energy system, relies on the hydrogen production through sustainable water splitting which in turn relies on the high efficiency electrocatalysts. PtAuCu A1-phase alloy has been predicted to be a promising electrocatalyst for the hydrogen evolution. As such preferred phase of Pt-Au-Cu is not thermodynamically favored, herein, we stabilize PtAuCu alloy by engineering the high-entropy phase in the form of nanowire. Density functional theory (DFT) calculations indicate that, in comparison with the ordered phase and segregated phases with discrete hydrogen binding energy, the high-entropy phase provides a diverse combination of site composition to continuously tune the hydrogen binding energy, and thus generate a series of highly active sites for the hydrogen evolution. Reflecting the theoretical prediction, electrochemical tests show that the A1-phase PtAuCu nanowire significantly outperforms its nanoparticle counterpart with phase segregation, toward the electrocatalysis of hydrogen evolution, offering one of the best hydrogen evolution electrocatalysts. [ABSTRACT FROM AUTHOR]

Dissolution is the primary route of Pt nanoparticle degradation in electrochemical devices, e.g., fuel cells. Investigation of potential-dependent dissolution kinetics of Pt nanoparticles is crucial to optimize the nanoparticle size and operating conditions for better performance. A mean-field kinetic theory under the steady-state approximation, combined with atomistic thermodynamics and Wulff construction, was developed to study the interplay between oxygen chemisorption, electrode potential, and particle size on the dissolution of Pt nanoparticles. We found that although oxygen chemisorption from electrode potential-induced water splitting can stabilize Pt nanoparticles through decreasing the surface energy and increasing the redox potential, the electrode potential plays a more decisive role in facilitating the dissolution of Pt nanoparticles. In comparison with the minor effect of oxygen chemisorption, an increase in the particle size, though reducing the dispersion, has a more significant effect on the suppression of the dissolution. These theoretical understandings on the effects of electrode potential and particle size on the dissolution are crucial for optimizing the nanoparticle size under oxidative operating conditions. [ABSTRACT FROM AUTHOR]

Strategies to generate high-valence metal species capable of oxidizing water often employ composition and coordination tuning of oxide-based catalysts, where strong covalent interactions with metal sites are crucial. However, it remains unexplored whether a relatively weak “non-bonding” interaction between ligands and oxides can mediate the electronic states of metal sites in oxides. Here we present an unusual non-covalent phenanthroline-CoO2 interaction that substantially elevates the population of Co4+ sites for improved water oxidation. We find that phenanthroline only coordinates with Co2+ forming soluble Co(phenanthroline)2(OH)2 complex in alkaline electrolytes, which can be deposited as amorphous CoOxHy film containing non-bonding phenanthroline upon oxidation of Co2+ to Co3+/4+. This in situ deposited catalyst demonstrates a low overpotential of 216 mV at 10 mA cm−2 and sustainable activity over 1600 h with Faradaic efficiency above 97%. Density functional theory calculations reveal that the presence of phenanthroline can stabilize CoO2 through the non-covalent interaction and generate polaron-like electronic states at the Co-Co center.If and how non-bonding ligands mediate the electronic states of metal sites is interesting yet remains to be explored. Here the authors show that a non-covalent phenanthroline can promote the population of Co4+ and induce polaron-like Co sites for improved water oxidation. [ABSTRACT FROM AUTHOR]

Background: Amnestic mild cognitive impairment (aMCI) is regarded as a transitional state of Alzheimer's disease, with working memory (WM) impairment. Objective: To investigate the brain activity in aMCI patients during WM tasks with the functional near-infrared spectroscopy (fNIRS) technique, as well as explore the association between brain activity and cognitive function in multiple domains. Methods: This study is a case-control study of 54 aMCI patients and 33 cognitively healthy elderly (NC). All participants underwent neuropsychological assessments. fNIRS was applied to examine the brain activation during the WM task. Multivariable linear regression analysis was applied to evaluate associations between brain activation and cognitive function in multiple domains. Results: Compared to NC subjects, aMCI patients had lower activation in the bilateral prefrontal, parietal, and occipital cortex during the WM task. Additionally, activation in the left prefrontal, bilateral parietal, and occipital cortex during the encoding and maintenance phase was positively associated with memory function. During memory retrieval, higher activity in the left prefrontal, parietal, and occipital cortex were correlated with higher memory scores. Besides, a positive association also formed between attention function and the activation in the left prefrontal, parietal, and occipital cortex during the WM task. Conclusion: These findings demonstrated that reduced activation in the prefrontal, parietal and occipital cortex during WM might reflect the risk of cognitive impairment, especially memory and attention function in aMCI patients. Given the brain activation visualization, fNIRS may be a convenient and alternative tool for screening the risk of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Amnestic mild cognitive impairment (aMCI) is regarded as a transitional state of Alzheimer's disease, with working memory (WM) impairment. Objective: To investigate the brain activity in aMCI patients during WM tasks with the functional near-infrared spectroscopy (fNIRS) technique, as well as explore the association between brain activity and cognitive function in multiple domains. Methods: This study is a case-control study of 54 aMCI patients and 33 cognitively healthy elderly (NC). All participants underwent neuropsychological assessments. fNIRS was applied to examine the brain activation during the WM task. Multivariable linear regression analysis was applied to evaluate associations between brain activation and cognitive function in multiple domains. Results: Compared to NC subjects, aMCI patients had lower activation in the bilateral prefrontal, parietal, and occipital cortex during the WM task. Additionally, activation in the left prefrontal, bilateral parietal, and occipital cortex during the encoding and maintenance phase was positively associated with memory function. During memory retrieval, higher activity in the left prefrontal, parietal, and occipital cortex were correlated with higher memory scores. Besides, a positive association also formed between attention function and the activation in the left prefrontal, parietal, and occipital cortex during the WM task. Conclusion: These findings demonstrated that reduced activation in the prefrontal, parietal and occipital cortex during WM might reflect the risk of cognitive impairment, especially memory and attention function in aMCI patients. Given the brain activation visualization, fNIRS may be a convenient and alternative tool for screening the risk of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background and aims: Esmolol is a common short-acting drug to control ventricular rate. This study aimed to evaluate the association between use of esmolol and mortality in critically ill patients. Methods: This is a retrospective cohort study from MIMIC-IV database containing adult patients with a heart rate of over 100 beats/min during the intensive care unit (ICU) stay. Multivariable Cox proportional hazard models and logistic regression were used to explore the association between esmolol and mortality and adjust confounders. A 1:1 nearest neighbor propensity score matching (PSM) was performed to minimize potential cofounding bias. The comparison for secondary outcomes was performed at different points of time using an independent t-test. Results: A total of 30,332 patients were reviewed and identified as critically ill. There was no significant difference in 28-day mortality between two groups before (HR=0.90, 95% CI =0.73-1.12, p=0.343) and after PSM (HR =0.84, 95% CI=0.65- 1.08, p=0.167). Similar results were shown in 90-day mortality before (HR =0.93, 95% CI =0.75-1.14, p=0.484) and after PSM (HR =0.85, 95% CI =0.67-1.09, p=0.193). However, esmolol treatment was associated with higher requirement of vasopressor use before (HR =2.89, 95% CI =2.18-3.82, p < 0.001) and after PSM (HR =2.66, 95% CI =2.06-3.45, p < 0.001). Esmolol treatment statistically reduced diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (all p < 0.001) and increased fluid balance at 24 hours (p < 0.05) but did not significantly lower SBP (p=0.721). Patients in esmolol group showed no significant difference in lactate levels and daily urine output when compared with those in non-esmolol group when adjusted for confounders (all p > 0.05). Conclusion: Esmolol treatment was associated with reduced heart rate and lowered DBP and MAP, which may increase vasopressor use and fluid balance at the timepoint of 24 hours in critically ill patients during ICU stay. However, after adjusting for confounders, esmolol treatment was not associated with 28-day and 90-day mortality. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a group of systemic disorders threatening human health with complex pathogenesis, among which mitochondrial energy metabolism reprogramming has a critical role. Mitochondria are cell organelles that fuel the energy essential for biochemical reactions and maintain normal physiological functions of the body. Mitochondrial metabolic disorders are extensively involved in the progression of CVD, especially for energy-demanding organs such as the heart. Therefore, elucidating the role of mitochondrial metabolism in the progression of CVD is of great significance to further understand the pathogenesis of CVD and explore preventive and therapeutic methods. In this review, we discuss the major factors of mitochondrial metabolism and their potential roles in the prevention and treatment of CVD. The current application of mitochondria-targeted therapeutic agents in the treatment of CVD and advances in mitochondria-targeted gene therapy technologies are also overviewed. [ABSTRACT FROM AUTHOR]

Heat stroke (HS) is a severe condition characterized by increased morbidity and high mortality. Acute liver injury (ALI) is a well-documented complication of HS. The tumor suppressor p53 plays an important role in regulation of mitochondrial integrity and mitophagy in several forms of ALI. However, the role of p53-regulated mitophagy in HS-ALI remains unclear. In our study, we discovered the dynamic changes of mitophagy in hepatocytes and demonstrated the protective effects of mitophagy activation on HS-ALI. Pretreatment with 3-MA or Mdivi-1 significantly exacerbated ALI by inhibiting mitophagy in HS-ALI mice. Consistent with the animal HS-ALI model results, silencing Parkin aggravated mitochondrial damage and apoptosis by inhibiting mitophagy in HS-treated normal human liver cell line (LO2 cells). Moreover, we described an increase in the translocation of p53 from the nucleus to the cytoplasm, and cytosolic p53 binds to Parkin in LO2 cells following HS. p53 overexpression using a specific adenovirus or Tenovin-6 exacerbated HS-ALI through Parkin-dependent mitophagy both in vivo and in vitro , whereas inhibition of p53 using siRNA or PFT-α effectively reversed this process. Our results demonstrate that cytosolic p53 binds to Parkin and inhibits mitophagy by preventing Parkin's translocation from the cytosol to the mitochondria, which decreases mitophagy activation and leads to hepatocyte apoptosis in HS-ALI. Overall, pharmacologic induction of mitophagy by inhibiting p53 may be a promising therapeutic approach for HS-ALI treatment. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent studies have shown that autophagy upregulation can attenuate sepsis-induced acute kidney injury (SAKI). The tumor suppressor p53 has emerged as an autophagy regulator in various forms of acute kidney injury (AKI). Our previous studies showed that p53 acetylation exacerbated hemorrhagic shock-induced AKI and lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. However, the role of p53-regulated autophagy in SAKI has not been examined and requires clarification. In this study, we observed the dynamic changes of autophagy in renal tubular epithelial cells (RTECs) and verified the protective effects of autophagy activation on SAKI. We also examined the changes in the protein expression, intracellular distribution (nuclear and cytoplasmic), and acetylation/deacetylation levels of p53 during SAKI following cecal ligation and puncture (CLP) or LPS treatment in mice and in a LPS-challenged human RTEC cell line (HK-2 cells). After sepsis stimulation, the autophagy levels of RTECs increased temporarily, followed by a sharp decrease. Autophagy inhibition was accompanied by an increased renal tubular injury score. By contrast, autophagy agonists could reduce renal tubular damage following sepsis. Surprisingly, the expression of p53 protein in both the renal cortex and HK-2 cells did not significantly change following sepsis stimulation. However, the translocation of p53 from the nucleus to the cytoplasm increased, and the acetylation of p53 was enhanced. In the mechanistic study, we found that the induction of p53 deacetylation, due to either the resveratrol/quercetin -induced activation of the deacetylase Sirtuin 1 (Sirt1) or the mutation of the acetylated lysine site in p53, promoted RTEC autophagy and alleviated SAKI. In addition, we found that acetylated p53 was easier to bind with Beclin1 and accelerated its ubiquitination-mediated degradation. Our study underscores the importance of deacetylated p53-mediated RTEC autophagy in future SAKI treatments. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) are among the most active and studied catalysts for the oxygen evolution reaction (OER) in alkaline electrolytes. However, previous studies have generally either focused on a small number of LDHs, applied synthetic routes with limited structural control, or used non‐intrinsic activity metrics, thus hampering the construction of consistent structure–activity‐relations. Herein, by employing new individually developed synthesis strategies with atomic structural control, we obtained a broad series of crystalline α‐MA(II)MB(III) LDH and β‐MA(OH)2 electrocatalysts (MA=Ni, Co, and MB=Co, Fe, Mn). We further derived their intrinsic activity through electrochemical active surface area normalization, yielding the trend NiFe LDH > CoFe LDH > Fe‐free Co‐containing catalysts > Fe‐Co‐free Ni‐based catalysts. Our theoretical reactivity analysis revealed that these intrinsic activity trends originate from the dual‐metal‐site nature of the reaction centers, which lead to composition‐dependent synergies and diverse scaling relationships that may be used to design catalysts with improved performance. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) are among the most active and studied catalysts for the oxygen evolution reaction (OER) in alkaline electrolytes. However, previous studies have generally either focused on a small number of LDHs, applied synthetic routes with limited structural control, or used non‐intrinsic activity metrics, thus hampering the construction of consistent structure–activity‐relations. Herein, by employing new individually developed synthesis strategies with atomic structural control, we obtained a broad series of crystalline α‐MA(II)MB(III) LDH and β‐MA(OH)2 electrocatalysts (MA=Ni, Co, and MB=Co, Fe, Mn). We further derived their intrinsic activity through electrochemical active surface area normalization, yielding the trend NiFe LDH > CoFe LDH > Fe‐free Co‐containing catalysts > Fe‐Co‐free Ni‐based catalysts. Our theoretical reactivity analysis revealed that these intrinsic activity trends originate from the dual‐metal‐site nature of the reaction centers, which lead to composition‐dependent synergies and diverse scaling relationships that may be used to design catalysts with improved performance. [ABSTRACT FROM AUTHOR]

Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1–7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-intestine injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction. [ABSTRACT FROM AUTHOR]

Background: Fluid therapy is a cornerstone in the treatment of sepsis. Recently, the guidelines have recommended the combined administration that using crystalloids plus albumin for septic patients, but the optimal timing for albumin combined is still unclear. The objective of this study was to investigate the association of timing of albumin combined with 28-day mortality in patients with sepsis. Methods: We involved septic patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and these patients were categorized into crystalloids group (crystalloids alone) and early combination group (crystalloids combined albumin at 0–24 h). The primary outcome was 28-day mortality. We used propensity score matching (PSM) to adjust confounding and restricted mean survival time (RMST) analysis was conducted to quantify the beneficial effect on survival due to the combination group. Results: We categorized 6597 and 920 patients in the "crystalloids alone" and "early combination", respectively. After PSM, compared to the crystalloids group, the combination group was associated with the increased survival among 28-day (increased survival: 3.39 days, 95% CI 2.53–4.25; P < 0.001) after ICU admission. Patients who received albumin combination at the first 24-h was associated with prolonged LOS in ICU (10.72 days vs. 8.24 days; P < 0.001) but lower risk of 28-day mortality (12.5% vs 16.4%, P = 0.003) than those received crystalloids alone. Conclusion: In septic patients, receiving albumin combined within the first 24-h after crystalloids administration was associated with an increment of survival in 28 days. [ABSTRACT FROM AUTHOR]

Strain and support effects play a crucial role in heterogeneous catalysis, which has been intensively studied over metal-based catalysts. In contrast, there is little discussion about the two effects in oxide systems. In this work, using an ultrathin ZnO film as an example, we investigate strain and support effects on the structure and surface reactivity of oxide catalysts through density functional theory calculations. Our results suggest that tensile strain increases the surface reactivity of ZnO films as indicated by enhanced CO and NH3 adsorptions and compressive strain renders an early phase transition from an inert graphene-like phase to a more reactive wurtzite-like phase. The support (Au, Pt, and Ru) can promote the phase transition and surface reactivity concurrently, which exhibits a larger effect on the reactivity than the strain. The support effect can be ascribed to the increasing rumple and polarization of ZnO films through the strong ZnO–substrate interaction, which enhances the surface reactivity. The insight helps us to develop advanced oxide-based catalysts through the strain and/or substrate engineering. [ABSTRACT FROM AUTHOR]

A near-isogenic line (NIL) DC90 which was generated by introgressing a wild rice (Oryza rufipogon Griff.) locus CTS-12 into the 9311(Oryza sativa L. ssp. indica) background confers chilling tolerance phenotype. Here, our pilot trials showed that chilling tolerance was positively correlated with abscisic acid (ABA) biosynthesis. To understand how CTS-12 mediated the ABA-dependent multi-levels of regulation, the integration of transcriptomic and metabolomic profiling using the two-way orthogonal projections to latent structures (O2PLS) and discriminant analysis (OPLS-DA) modeling was performed to investigate the mechanisms underlying chilling tolerance. Our results revealed that metabolic shifts, including the activation of stachyose biosynthesis, amino acid metabolism pathways, phenylpropanoid/flavonoid biosynthesis, ABA biosynthesis, and perturbation of glycolysis, occurred under chilling treatment; in the recovery period, glutamate-related pathways, β-alanine biosynthesis and degradation, and serotonin biosynthesis pathways were differentiated between 9311 and DC90. Particularly, the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs), including galactinol, β-alanine, glutamate, naringenin, serotonin, ABA, and LOC_Os03g44380 (9- cis -epoxycarotenoid dioxygenase 3, OsNCED3), might be involved in the chilling tolerance variation of 9311 and DC90. CRISPR/Cas9-edited OsNCED3 resulted in chilling sensitive of japonica rice ZH11, demonstrating the involvement of ABA pathway in chilling stress response. In addition, chilling tolerance of rice was associated with the balance of water uptake and loss that was modulated by stomatal movement under chilling stress. Therefore, we speculated that the CTS-12 -mediated ABA signaling pathway leads to transcriptional regulation of chilling-responsive genes and, in turn, triggers metabolic shifts to coordinately regulate the stomatal movement of guard cells. The results of this study improve our understanding of the multilevel regulation of wild rice in response to chilling stress. [ABSTRACT FROM AUTHOR]

NiFe and CoFe (MFe) layered double hydroxides (LDHs) are among the most active electrocatalysts for the alkaline oxygen evolution reaction (OER). Herein, we combine electrochemical measurements, operando X-ray scattering and absorption spectroscopy, and density functional theory (DFT) calculations to elucidate the catalytically active phase, reaction center and the OER mechanism. We provide the first direct atomic-scale evidence that, under applied anodic potentials, MFe LDHs oxidize from as-prepared α-phases to activated γ-phases. The OER-active γ-phases are characterized by about 8% contraction of the lattice spacing and switching of the intercalated ions. DFT calculations reveal that the OER proceeds via a Mars van Krevelen mechanism. The flexible electronic structure of the surface Fe sites, and their synergy with nearest-neighbor M sites through formation of O-bridged Fe-M reaction centers, stabilize OER intermediates that are unfavorable on pure M-M centers and single Fe sites, fundamentally accounting for the high catalytic activity of MFe LDHs. NiFe and CoFe layered double hydroxides are among the most active electrocatalysts for the alkaline oxygen evolution reaction. Here, by combining operando experiments and rigorous DFT calculations, the authors unravel their active phase, the reaction center and the catalytic mechanism. [ABSTRACT FROM AUTHOR]

It remains unclear whether melatonin and its analogues prevent postoperative delirium (POD). Therefore, we conducted a systematic review and meta‐analysis to evaluate the effect of melatonin and its analogues on POD prevention. PubMed, Cochrane Library, Web of Science, Embase and CINAHL databases were searched. Primary outcome was the incidence of POD. Six randomized controlled trials, 2 cohort studies and 1 case‐control study were included in this meta‐analysis. Results showed that melatonin and its analogue ramelteon decreased the incidence of POD in the entire adult surgical population (odds ratio [OR] = 0.45, 95% confidence interval [CI] 0.24‐0.84, P =.01). When administered at a higher dose (5 mg), melatonin was effective in reducing the POD incidence (OR = 0.32, 95% CI 0.20‐0.52, P <.00001). Melatonin administered less than 5 elimination half‐lives before the surgery significantly reduced the POD incidence (OR = 0.31, 95% CI 0.19‐0.49, P <.00001). Current literature supports the effectiveness of melatonin and its analogue ramelteon in POD prevention. However, the present study was limited by the significant heterogeneity of the included studies. More studies are needed to ascertain the preventive effect of melatonin and its analogues on the incidence of delirium after cardiac and noncardiac surgeries. [ABSTRACT FROM AUTHOR]

This investigation was performed to verify whether lncRNA CRNDE sponging miR-181a-5p was involved with sepsis-relevant inflammatory dysfunctions. Aggregately 136 sepsis patients and 151 healthy people were recruited, and their fasting peripheral blood was gathered to detect expressions of CRNDE and miR-181a-5p. In addition, THP-1 cells were transfected with si-CRNDE, miR-181a-5p mimic, pcDNA3.1-TLR4 and si-TLR4, and then sepsis-specific inflammatory cytokines within the cells were quantified. The sponging relationships between CRNDE and miR-181a-5p, as well as between miR-181a-5p and TLR4, were ascertained by means of luciferase reporter gene assay. The experimental results revealed that over-expressed CRNDE and under-expressed miR-181a-5p were associated with shortened lifespan of sepsis patients. Mechanically, si-CRNDE-1 and miR-181a-5p mimic were able to reverse the promoting effects of LPS on production of NF-kB, TNF-α, IL-1β and IL-6 by THP-1 cells. Moreover, the expressional change of miR-181a-5p in THP-1 cells was in part owing to its being sponged by CRNDE. Lastly, TLR4, subjected to targeted modification of miR-181a-5p, was capable of disturbing the contribution of CRNDE and miR-181a-5p to THP-1 cells' release of NF-kB, TNF-α, IL-1β and IL-6. Collectively, the CRNDE/miR-181a-5p/TLR4 axis seemed to have potential in modifying sepsis-related inflammatory pathogenesis, which offered a direction for sepsis diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: This study is to explore the effect of SIRT1 deacetylating inactivation on organ-derived high mobility group box 1 (HMGB1) during the development of severe hemorrhagic shock (HS). Methods: Hemorrhagic shock model was reproduced in rats by blood shedding and mimicked in HK-2 cells by hypoxia-reoxygenation (H/R) treatment. The level and acetylation of HMGB1 and the expression and activity of SIRT1 were detected in tissue, serum and cultured cells and supernatant. The deacetylated sites of HMGB1 was determined by Co-IP. Results: Serum HMGB1 in HS rats was increased but were reduced in multiple organs, especially in kidney tissue, with enhanced HMGB1 acetylation, and reduced deacetylase SIRT1 activity in isolated RTECs. HMGB1 in suspension of H/R-treated HK-2 cells was increased, accompanying with enhanced HMGB1 acetylation, and nuclear-plasma translocation. SIRT1 down-regulated by siRNA aggravated acetylation of HMGB1 and nucleus-to-cytoplasm translocation and resulted in increased HMGB1 in cultured HK-2 suspension. Immunoprecipitation data suggested that SIRT1-indcuced deacetylated sites of HMGB1 were K90 and K177 following H/R. SIRT1 overexpression inhibited the acetylation of HMGB1 and reduced the content of extracellular HMGB1 in H/R-treated HK-2 cells. Inhibiting mutation of SIRT1 restored the acetylation of HMGB1 and HMGB1 content in extracellular suspension. In HS rat model, the neutralization of HMGB1 with antibody could reduce serum HMGB1 and pro-inflammatory cytokine contents, but had no effect on SIRT1 protein expression and activity. Polydatin (PD), a potential SIRT1 agonist, up-regulated SIRT1 activity and inhibited nucleus-to-cytoplasm translocation of HMGB1 in RTECs. Moreover, PD also attenuated RTEC apoptosis, protected renal function, and prolonged survival in HS rats. These beneficial effect of PD is largely blocked by specific inhibition of SIRT1 with Ex527. Conclusion: The acetylation of HMGB1 in K99 and K177 is enhanced during HS due to the downregulation of SIRT1. The nucleus-to-cytoplasm translocation and the release of acetylated HMGB1 from RTECs of kidney might exacerbate the pro-inflammatory effects of HMGB1 during the development of HS. [ABSTRACT FROM AUTHOR]

As a nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylase, SIRT3 is highly expressed in tissues with high metabolic turnover and mitochondrial content. It has been demonstrated that SIRT3 plays a critical role in maintaining normal mitochondrial biological function through reversible protein lysine deacetylation. SIRT3 has a variety of substrates that are involved in mitochondrial biological processes such as energy metabolism, reactive oxygen species production and clearance, electron transport chain flux, mitochondrial membrane potential maintenance, and mitochondrial dynamics. In the suppression of SIRT3, functional deficiencies of mitochondria contribute to the development of various cardiovascular disorders. Activation of SIRT3 may represent a promising therapeutic strategy for the improvement of mitochondrial function and the treatment of relevant cardiovascular disorders. In the current review, we discuss the emerging roles of SIRT3 in mitochondrial derangements and subsequent cardiovascular malfunctions, including cardiac hypertrophy and heart failure, ischemia-reperfusion injury, and endothelial dysfunction in hypertension and atherosclerosis. [ABSTRACT FROM AUTHOR]