Intermetallic Compound with CuNi Sites for Enhancing the Selectivity of Electrochemical CO2 Conversion.

Although single-metal-site (SMS) catalysts have long been explored for the electrochemical CO2 reduction reaction (EC-CO2RR), the reactivity and selectivity of SMS catalysts remain rather low due to the competing hydrogen evolution reaction (HER). To improve the selectivity, in this work, a novel intermetallic particle of CuNi is decorated on the N-doped carbon substrate, which was first precisely fabricated by scarifying the bimetal-doped metal-organic framework (MOF). Thanks to the neighboring synergistic functions of Cu and Ni sites, CuNi/NC prominently boosts the electroreduction of CO2, far more than the SMS catalysts of Cu/NC and Ni/NC. Further, CuNi/NC presents superior selectivity toward CO with faradaic efficiency over a wide range of potentials (surpassing 90% at 0.6-1.0 V vs RHE, up to 98% at 0.6 V vs RHE) and excellent durability. The experimental results and theoretical calculations reveal that the Ni species can be highly activated due to the neighboring Cu species, which considerably facilitates the formation of an intermediate of COOH* and consequently enhances the selectivity of the reduction of CO2 to CO. This work paves a general way to precisely fabricate catalysts with multiple metal species and also demonstrates the significant synergetic efficiency between the neighboring sites to improve the catalytic performance.

Endowing Nanoparticles with High Stability on the Hydrogenation Reaction by the Amino Group-Assisted Strategy.

In the field of a heterogeneous industrial catalysis process, the encapsulated structure plays a crucial role in preventing active sites from leaching during the reaction; however, related studies on the strategy to fabricate encapsulated catalysts under control remain rare. Herein, we develop an amino-assisted strategy to construct a highly stable catalyst with core-shell copper nanoparticles (NPs), namely, Cu@NC (NC represents the nitrogen-doped carbon), presenting not only excellent activity but also high durability on the hydrogenation of quinolines even in the large-scale tests, which is very vital in practical application. In contrast, in the absence of the amino group, the Cu NPs were dispersed out of the carbon surface to form Cu/NC, leading to readily lose activity in the recycling tests due to the leaching occurred during the catalytic process. This work offers a promising method to fabricate a stable catalyst to enhance durability in heterogeneous catalysis.

Biomimetic nanomaterial-facilitated oxygen generation strategies for enhancing tumour treatment outcomes.

Hypoxia, as a typical hallmark of the tumour microenvironment (TME), has been verified to exist in most malignancies and greatly hinders the outcome of tumour treatments, including chemotherapy, photodynamic therapy, radiotherapy, and immunotherapy. Various approaches to alleviate tumour hypoxia have been reported. Among them, biomimetic nanomaterial-facilitated tumour oxygenation strategies, based on the engagement of human endogenous proteins, red blood cells, the cell membrane, and catalase, are the most impressive due to their excellent tumour active-targeting ability and superior tumour-selective capability, which, however, have not yet been systematically reviewed. Herein, we are ready to describe the current progress in biomimetic nanomaterial-facilitated tumour oxygenation strategies and corresponding improvements in tumour treatment outputs. In this review, the underlying mechanism behind the superior effect of these biomimetic nanomaterials, compared with other materials, on alleviating the hypoxic TME is highlighted. Additionally, the ongoing problems and potential solutions are also discussed.

Atomically Dispersed Iron Sites on the Hollow Nitrogen-Doped Carbon Framework with a Highly Efficient Performance on Carbon Dioxide Cycloaddition.

The exploration of efficient and low-consumption catalysts for carbon dioxide (CO2) conversion is desirable yet remains a great challenge. Herein, a novel catalyst composed of a hollow nitrogen-doped carbon framework (HNF) enriched with high-loading (9.8 wt %) atomically dispersed iron sites (defined as FeSAs/HNF) has been fabricated by a polymer-assisted strategy. As a result, FeSAs/HNF has an excellent performance on the cycloaddition reactions of CO2 with epoxides (the conversion >96%) under milder conditions because of its ultrahigh loading of atomically dispersed iron sites. This study not only provides an advanced catalyst for driving CO2 cycloaddition but also furnishes a novel perspective on the rational design of superior catalysts with high-loading active sites for diverse heterogeneous catalytic reactions.

Early Prognosis Effect of Cellular Immune Paralysis on Brain Complications of Extracorporeal Membrane Oxygenation Children with Severe Sepsis.

OBJECTIVE: The aim of the study was to explore the relationship between criticality, brain complications, and immune mechanisms in extracorporeal membrane oxygenation (ECMO) children with pneumonia and severe sepsis. METHODS: Patients with simple pneumonia (group I), ECMO patients with pneumonia and severe sepsis accompanied by brain complications (group II), and those without brain complication (group III) admitted to our pediatric intensive care unit were selected to be investigated. The relationship among the peripheral blood subgroups of immune cells, immune factors, adaptive immune responses, endothelial factors, and criticality and brain complications was then studied. RESULTS: Severe paralysis of normal immunity, excess abnormal immunity, and endothelial injury were consistent with the increase in the absolute value of base excess, lactic acid (Lac) content, and average hospitalization days and brain complications involved in group II (vs. group I). The ratio of CD63+ macrophage and CD63+ neutrophil subpopulation increased (p < 0.05); the expression levels of elastase+ neutrophil denatured subgroup (p < 0.05), the ratio of CCR2highCX3CR1low/CCR2lowCX3CR1high of macrophages and neutrophils (p < 0.0001), high-mobility group box 1 (HMGB1), YTHDF1, interleukin-17 protein and mRNA, and RAGE gene decreased to some extent (p < 0.05); the expression levels of Th1 cells chemokine CXCL9 protein and mRNA and sTIE2 protein increased to some extent (p < 0.05); the adaptive immune response of CD8+ CTL stimulated by lipopolysaccharide (LPS) was slightly enhanced (p < 0.05) in group III(vs. group II), which was consistent with the improvement of criticality, average hospitalization days, and the absence of brain complications in group III (vs. group II). CONCLUSION: ECMO support with brain complication was related to the upregulation of HMGB1 and YTHDF1 protein; the decreased number of CD63+ macrophages and neutrophils; the increased denatured neutrophil subgroup, especially the upregulated ratio of CCR2highCX3CR1low/CCR2lowCX3CR1high of macrophages and neutrophils; the imbalance of Th17/Th1, LPS-specific CD8+ CTL adaptive immune response paralysis; and the reduced endothelial sTIE2 protein expression level which caused clinical deterioration and prolonged average hospitalization days.

Optimizing parenteral nutrition to achieve an adequate weight gain according to the current guidelines in preterm infants with birth weight less than 1500 g: a prospective observational study.

AIM: European Society for Clinical Nutrition and Metabolism released the guidelines on pediatric parenteral nutrition in 2018. We aimed to compare the parenteral nutrition (PN) regimen with the current guidelines, evaluate weight gain and explore the correlation of parenteral macronutrient and energy intakes with weight gain outcome in preterm infants with birth weight less than 1500 g. METHODS: A prospective observational study was conducted. Parenteral macronutrients and energy intakes were described. Weight gain during PN was assessed. Nutritional factors associated with weight gain outcome after PN were identified using a cox proportional hazards model. RESULTS: A total of 163 infants were included in this study, in which 41 were extremely low birth weight (ELBW) infants and 122 were very low birth weight (VLBW) infants. Average glucose, amino acid, lipid, and energy during the first postnatal week were 7.5 g/kg/d, 2.4 g/kg/d, 0.8 g/kg/d, 48 kcal/kg/d. Median maximum glucose, amino acid, lipid, and energy were 11.1 g/kg/d, 3.5 g/kg/d, 3 g/kg/d, 78 kcal/kg/d. Median days to maximum glucose, amino acid, lipid, and energy were 10, 9, 12, 11 days. The proportion of appropriate for gestational age (AGA) infants was 76.9%. The ratio of infants without poor weight gain outcome after PN was 38%. With every 0.1 g/kg/d decrease of maximum amino acid and average lipid during the first postnatal week, the probability of appropriate weight gain outcome decreased by 77.6 and 74.4% respectively. With each additional day to maximum glucose and energy, the probability of appropriate weight gain outcome decreased by 5.6 and 6.1% respectively. CONCLUSIONS: Most preterm infants with birth weight less than 1500 g remain below the latest recommended nutrition goals. The poor weight gain outcome of these infants after PN is related to insufficient parenteral macronutrient and energy intakes. PN strategies should be improved according to the latest evidence-based recommendations.

The protective role of YTHDF1-knock down macrophages on the immune paralysis of severe sepsis rats with ECMO.

OBJECTIVE: To examine the role of YTHDF1 knock-down macrophages on the immunity of severe sepsis rats with ECMO. METHODS: 15 SD rats were randomly allocated into 3 groups: mild sepsis (I), severe sepsis with ECMO (II), and YTHDF1 knock-down macrophages treatment groups (III). Blood biochemical indexes, different immune factors and brain changes were detected by RT-PCR, ELISA, ELISPOT and HE staining. Isolated macrophages subtypes and signal proteins were detected by flow cytometry, western blot and m6A RNA methylation test. RESULTS: The levels of HMGB1, RAGE, YTHDF1 and IL-17 in peripheral blood were significantly higher (p < 0.01), while the level of CXCL9 and TNF-α, and LPS-specific CD8+CTL function were significantly decreased in group II compared with group I (p < 0.01). The ratio of CD63+ macrophages (p < 0.05) and CD64+ macrophages (p< 0.05) decreased and the level of elastase (p < 0.01) and CCR2highCX3CR1low/CCR2lowCX3CR1high (p < 0.01) of macrophages increased in group II. The above were consistent with the severity of biochemical indicators, the increasing endothelial injury factor (Ang2/Ang1), lower endothelial protective factor (sTie2), severer brain injury in group II. After YTHDF1 knock-down macrophages treatment, the above indexes' changes were opposite when Group III versus Group II through the down-regulation of m6A RNA methylation of JAK2/STAT3 (p < 0.01) and protein expression of PJAK2/PSTAT3 (p < 0.05) in isolated macrophages. CONCLUSIONS: YTHDF1 knock-down macrophages improved the immune paralysis of macrophages, Th1/Th17 and CTL and reduced the entry of macrophages into the brain to cause endothelial damage of severe sepsis rats with ECMO through the inhibition of HMGB1/RAGE and YTHDF1, m6A RNA methylation of JAK2/STAT3 and PJAK2/PSTAT3 proteins expression in macrophages.

[Protective effect of Shenfu injection on the endothelium of severe sepsis by inhibiting CD11b+ cell paralysis induced by high mobility group protein B1].

OBJECTIVE: To investigate the relationship between the biochemical parameters, the pulmonary pathologic injury and the immune mechanism of severe sepsis in infant porcine, and the intervention effect of Shenfu injection. METHODS: Panamanian infant porcine (2-3 months old) were divided into sham operation group (Sham group; intravenous injection of normal saline), lipopolysaccharide (LPS) induced severe sepsis model group (LPS group; intravenous injection of LPS 1 mg/kg, and continuing at 0.5 mg×kg-1×h-1 for 12 hours), and Shenfu injection intervention group (SF group; intravenous injection of Shenfu injection 10 mL/kg at the same time of modeling, twice a day) according to the random number table method, with 5 in each group. Forty-eight hours after the challenge, the changes of C-reactive protein (CRP), procalcitonin (PCT), oxygenation index (PaO2/FiO2), base excess (BE), blood lactate (Lac) and other biochemical indexes were detected with blood sampling; the number of neutrophils [myeloperoxidase positive (MPO+)] and their activated subsets CD11b+CD64+, M1 macrophages (CD80+CD64+), CD4+ and CD8+ T cells were analyzed in peripheral blood by flow cytometry. The levels of plasma cytokines were detected by enzyme linked immunosorbent assay (ELISA). The pathological damage of lung tissue was observed by hematoxylin-eosin (HE) staining. The mRNA expression of lung injury related molecules and their receptors, chemokines, cytokines, vascular endothelial related molecules and tight junction protein were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with Sham group, the levels of CRP, PCT and Lac in LPS group significantly increased, and PaO2/FiO2 and BE significantly decreased. In the peripheral blood, CD80+CD64+ macrophages, CD11b+CD64+ and MPO+ neutrophils, CD4+, CD8+ T cells and tumor necrosis factor-α (TNF-α) significantly decreased, but interleukin-10 (IL-10) and vascular endothelial cell growth factor (VEGF) significantly increased; the mRNA expressions of high mobility group protein B1 (HMGB1), receptor for advanced glycation end products (RAGE), angiopoietin 2/angiopoietin 1 (Ang2/Ang1) significantly increased, Toll like receptor 9 (TLR9), chemokines (CXCL9 and CXCL10), TNF-α, IL-27, Tek tyrosine kinase 2 (TIE2), vascular endothelial cadherin (VE-CAD) and Occludin significantly decreased in lung tissue. HE staining showed inflammatory cell infiltration and exudation in the alveolar cavity, alveoli consolidation, thickening of the alveolar interstitial layer and emphysema. Compared with LPS group, Lac in SF group significantly decreased (mmol/L: 4.2±1.0 vs. 6.3±1.1, P < 0.05), while BE and PaO2/FiO2 significantly increased [BE (mmol/L): -6.4±2.6 vs. -11.6±2.5, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 180±36 vs. 105±35, both P < 0.05]; the percentage of CD80+CD64+ macrophages, CD11b+CD64+ and MPO+ neutrophils significantly increased [CD80+CD64+: (7.13±2.01)% vs. (3.80±0.46)%, CD11b+CD64+: (8.33±2.55)% vs. (2.15±0.47)%, MPO+: (21.22±2.33)% vs. (8.31±0.46)%, all P < 0.05]; the mRNA expressions of HMGB1 and RAGE decreased to some extent [HMGB1 mRNA (2-ΔΔCT): 1.81±0.45 vs. 2.23±0.85, RAGE mRNA (2-ΔΔCT): 6.69±3.48 vs. 11.60±6.91, both P < 0.05], the mRNA expressions of CXCL9 and TIE2 increased to a certain extent [CXCL9 mRNA (2-ΔΔCT): 1.06±0.63 vs. 0.50±0.12, TIE2 mRNA (2-ΔΔCT): 1.42±0.68 vs. 0.27±0.16, both P < 0.05]; the pathological damage of lung tissue were significantly alleviated. CONCLUSIONS: The increased abnormality of BE, Lac, and PaO2/FiO2, the immune exhausting and paralysis may be important factors leading to the fatal lung injury in infant porcine with severe sepsis. The possible mechanism is that the excessive activation of HMGB1 and its receptor RAGE, the suppression of TLR9 and corresponding chemokine and inflammatory factors lead to increased endothelial damage and decreased tight connection, which in turn induces capillary leakage. The intervention of immune disorders by Shenfu injection in the severe pneumonia accompanied by sepsis may be related to elevated M1 macrophages and activated neutrophils in the peripheral blood, inhibition of HMGB1 and its receptor RAGE mRNA expression, and elevated CXCL9 and TIE2 expression.

MiR-424 overexpression protects alveolar epithelial cells from LPS-induced apoptosis and inflammation by targeting FGF2 via the NF-κB pathway.

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung injury disease with high morbidity and mortality. However, the underlying pathogenic mechanism remains unknown. In this study, lipopolysaccharide (LPS)-stimulated alveolar epithelial cells were used to mimic the inflammatory pathogenesis of ARDS in vitro. We here investigated the role of miR-424 in LPS-stimulated alveolar epithelial cells and found it to be substantially downregulated. Overexpression of miR-424 inhibited apoptosis and inflammation in LPS-stimulated alveolar epithelial cells, and the miR-424 inhibitor exhibited the opposite effect. A bioinformatic analysis revealed a potential binding site of miR-424 in the 3'-UTR of fibroblast growth factor 2 (FGF2). A luciferase reporter assay suggested that miR-424 targeted FGF2 in alveolar epithelial cells. The level of FGF2 protein was inhibited by miR-424 mimic, whereas was significantly upregulated after miR-424 suppression in LPS-stimulated alveolar epithelial cells. MiR-424 also exhibited the protective role in LPS-induced apoptosis and inflammation by directly targeting FGF2 via the NF-κB pathway. In conclusion, our results demonstrate that miR-424 had a protective role in LPS-induced apoptosis and inflammation of alveolar epithelial cells by targeting FGF2 via regulating NF-κB pathway. This might contribute novel evidence to help identify a therapeutic target for treating ARDS.

Vitamin D deficiency and clinical outcomes related to septic shock in children with critical illness: a systematic review.

PURPOSE: Low vitamin D blood levels are related to many clinical outcomes in children with critically illness. However, the relationship of it and septic shock has not been systematically analyzed. The objective of this review was to evaluate the effect of vitamin D on septic shock and predict if vitamin D administration can improve prognosis of it. MATERIALS AND METHODS: Online databases were searched up to June 1st, 2017 for studies on the relation of vitamin D deficiency (VDD) and clinical outcomes on septic shock in children with critical illness. The primary end point was the effect of VDD on occurrence of septic shock. The secondary endpoints were the association of VDD and clinical outcomes related to septic shock. We summarized the strength of association between VDD and each factor on septic shock. Individual factors were defined as strong, moderate, weak, or inconclusive according to the numbers of the article supporting the relation between them. RESULTS: Eight studies published between 2012 and 2017, for a total of 1367 patients, were included in the final analysis. We extracted eight patient-level factors and among them one showed strong association of VDD and septic shock. Four factors demonstrated moderate or weak strength of evidence for it: nonresolution of shock, catecholamine refractory shock, fluid boluses, vasopressor use. But evidence for the association between VDD and severity of illness, stay of pediatric intensive care unit (PICU), are weak. Most of the articles showed no significant association between VDD and mortality. CONCLUSIONS: Among critically ill children, VDD might be associated with the occurrence and resolution of septic shock. A larger multicenter trial could conclusively confirm these findings. Further research is also needed to identify vitamin D administration for better outcomes in pediatric patients.

MicroRNA-34a promotes iNOS secretion from pulmonary macrophages in septic suckling rats through activating STAT3 pathway.

Pediatric sepsis is frequently a fatal condition and a major cause of death globally. The mortality rate of sepsis remains high despite that the advanced therapeutic methods have been carried out. Our research aims to investigate the potentials of miR-34a in the treatment of pediatric sepsis. Results indicated that miR-34a was up-regulated in Lipopolysaccharide (LPS)-induced pulmonary macrophages and U937 cell lines. In addition, miR-34a silence reduced the production of iNOS through inactivating STAT3 pathway in U937 cell lines and cecal ligation and puncture (CLP)-induced lung tissues. Besides, high expression of iNOS and STAT3 in cells transfected with miR-34a mimic further validated it. Furthermore, in vivo experiment demonstrated that miR-34a silence protected CLP-induced suckling rats from lung injury. All in all, our study demonstrated that miR-34a promoted iNOS secretion from pulmonary macrophages in LPS-induced sepsis suckling rats through activating STAT3 pathway. These results provided a possibility to convert miR-34a into clinical application.

Efficacy of probiotic therapy in full-term infants with critical illness.

BACKGROUND: Probiotics are microbial supplements that have shown efficacy in a wide range of applications. To assess the safety and effects of enteral probiotics in critically ill neonates. METHODS: A double-blind, randomized controlled trial was conducted in 100 full-term infants with critical illness according to scores of neonatal acute physiology. Fifty neonatal intensive care patients were randomly assigned to receive probiotics three times daily after birth for 8 days, and fifty patients were not given probiotics, but who received a placebo. The incidence of sepsis, multiple organ dysfunction syndrome (MODS), nosocomial pneumonia, and necrotizing enterocolitis were recorded. The prognosis of probiotic treatment was determined based on the rate of recovery and hospital days. Serum IgA, IgG, and IgM concentrations were measured on days 4 and 8. RESULTS: Infants in the probiotics group showed a significantly reduced rate of nosocomial pneumonia (18% versus 36%) and multiple organ dysfunction syndrome (6% versus 16%) compared with the placebo group (p<0.05). Significant results were demonstrated in favour of the probiotics for days of hospital stay (13 ± 3.5 d versus 15.8 ± 5.3 d) (p<0.05). However, there were no significant differences in the occurrence of sepsis, necrotizing enterocolitis, and recovery rate. Patients given probiotics had significantly greater levels of IgA than those in the placebo group (p<0.05). No serious adverse effects in the study population were noted. CONCLUSIONS: Supplements of probiotics to critically ill neonates could enhance immune activity, decrease occurrence of nosocomial pneumonia and MODS, and reduce days in hospital.