It is reported herein that by exploiting the commonly shared bicyclic decahydroquinoline motif, a gold‐catalyzed enamide–alkyne cycloisomerization reaction is developed to access tricyclic cores in a ...simple way. These tricyclic cores further serve as an advanced platform for the divergent enantioselective collective total syntheses of five Lycopodium alkaloids, belonging to three different structural types, in a concise and protecting‐group‐free fashion. The key transformations in the second phase include: 1) a transannular reductive Heck cyclization for installation of the azepane ring in fawcettidine, fawcettimine, and lycoposerramine Q; 2) a domino Mukaiyama hydration/Grob fragmentation process for construction of the ten‐membered lactam system in phlegmariurine B; 3) a Fukuyama one‐pot protocol for the construction of the 2‐pyridone motif in lycoposerramine R. The newly developed strategy is expected to pave the way for the synthesis of other structurally related Lycopodium alkaloids.
The collective total syntheses of five Lycopodium alkaloids were accomplished in an enantioselective and protecting‐group‐free manner. The syntheses included a gold‐catalyzed enamide–alkyne cycloisomerization and the establishment of skeletal diversification approaches at different reactive sites of the tricyclic skeleton to achieve divergent total syntheses of Lycopodium alkaloids.
Abstract
Background
High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our ...multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections.
Methods
The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression.
Results
The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of
Klebsiella pneumoniae
. The mean duration of PMB therapy was 11 days (range 7–38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 10
9
/l vs 9.28 × 10
9
/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%).
Conclusions
Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.
•The adsorption capacity of Ce3+ and La3+ was 234 mg/g and 203 mg/g at pH = 6 under C0 = 400 mg/L.•HKUST-1 exhibited an excellent rare earth ions selectivity of 87% among all kinds of metal ions.•The ...adsorption process followed the Freundlich isotherm model and the pseudo-second-order equation.•The adsorption mechanism can be explained by ion exchange and the covalent bonding between HKUST-1 and metal ions.
Recovery of rare earth ions from wastewater holds an important strategy for the use of the precious resources. In this study, we found that a metal-organic framework (MOF), HKUST-1, exhibited a high affinity and selectivity towards adsorptive recovery of rare earth ions (Ce3+ and La3+) in aqueous solutions. The adsorbent showed a remarkable adsorption capacity of 234 mg/g and 203 mg/g for Ce3+ and La3+ at pH = 6, respectively. More importantly, its adsorption selectivity of the rare earth ions was about 87% against other metal ions. The adsorption isotherm, kinetics, and mechanism in the process were also investigated. The adsorption process can be better fit by the Freundlich model in isotherm and the pseudo-second-order model in kinetics. A plausible mechanism for the adsorption of metal ions on the HKUST-1 was proposed by considering ion exchange and the covalent bonding between the adsorbent and metal ions. The selectivity can be attributed to the different bonding abilities to metal ions.
Display omitted
Two−dimensional (2D) supports confined single−atom catalysts (2D SACs) with unique geometric and electronic structures have been attractive candidates in different catalytic applications, such as ...energy conversion and storage, value−added chemical synthesis and environmental remediation. However, their environmental applications lack of a comprehensive summary and in−depth discussion. In this review, recent progresses in synthesis routes and advanced characterization techniques for 2D SACs are introduced, and a comprehensive discussion on their applications in environmental remediation is presented. Generally, 2D SACs can be effective in catalytic elimination of aqueous and gaseous pollutants via radical or non−radical routes and transformation of toxic pollutants into less poisonous species or highly value−added products, opening a new horizon for the contaminant treatment. In addition, in−depth reaction mechanisms and potential pathways are systematically discussed, and the relationship between the structure−performance is highlighted. Finally, several critical challenges within this field are presented, and possible directions for further explorations of 2D SACs in environmental remediation are suggested. Although the research of 2D SACs in the environmental application is still in its infancy, this review will provide a timely summary on the emerging field, and would stimulate tremendous interest for designing more attractive 2D SACs and promoting their wide applications.
Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.
We conducted a ...clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.
From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial.
Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.
ChiCTR.org.cn, ChiCTR1800019173.
The sluggish kinetics of Fe(Ⅱ) recovery in Fenton/Fenton-like reactions significantly limits the oxidation efficiency. In this study, we for the first time use boron carbide (BC) as a green and ...stable promotor to enhance the reaction of Fe(Ⅲ)/H2O2 for degradation of diverse organic pollutants. Electron paramagnetic resonance analysis and chemical quenching/capturing experiments demonstrate that hydroxyl radicals (•OH) are the primary reactive species in the BC/Fe(Ⅲ)/H2O2 system. In situ electrochemical analysis indicates that BC remarkably boosts the Fe(Ⅲ)/Fe(Ⅱ) redox cycles, where the adsorbed Fe(Ⅲ) cations were transformed to more active Fe(Ⅲ) species with a higher oxidative potential to react with H2O2 to produce Fe(Ⅱ). Thus, the recovery of Fe(Ⅱ) from Fe(Ⅲ) is facilitated over BC surface, which enhances •OH generation via Fenton reactions. Moreover, BC exhibits outstanding reusability and stability in successive cycles and avoids the secondary pollution caused by conventional organic and metalliferous promotors. Therefore, metal-free BC boosting Fe(Ⅲ)/H2O2 oxidation of organics provides a green and advanced strategy for water decontamination.
Metal-free boron carbide exhibits superior capability to intensify the Fe(Ⅲ)/H2O2 oxidation for degrading a wide array of aqueous pollutants. The redox potential of Fe(Ⅲ) is improved upon the adsorption onto the surface of boron carbide as FeOH2+, which further accelerates Fe(Ⅱ) generation by H2O2 reduction and subsequent •OH production. Display omitted
Heteroatom-doping of carbocatalysts has been a powerful strategy to remarkably enhance the catalytic performance. Herein, the underlying nature of N promotional effects on peroxymonosulfate (PMS) ...activation for phenol removal is understood by combining kinetics analysis with multiple techniques. A strategy using mixed acid oxidation of carbon nanotube (CNT) followed by NH3 treatment is employed to yield a series of catalysts with different N-doping contents but similar fraction of sp2-hybridized carbon and defective degree, endowing with a chance to discriminate the dominant N-containing active sites. The multi-sites kinetics analysis suggests the graphitic N-containing sites as the dominant active sites. The mechanism of the surface-bound reactive species is also discriminated as the dominant reaction mechanism. The insights reported here could provide the methodology to fundamentally understand the heteroatom-doping effects of carbocatalysis.
Display omitted
Given the high mortality associated with sepsis, there is an urgent need for a full understanding of sepsis pathophysiology and finding new therapeutic regimens. Adipose-derived mesenchymal stem ...cells (ADMSCs) has been proven to have anti-inflammatory effects and could be used to treat cecal ligation and puncture (CLP) induced lung and liver injury in septic rat models. In this study, we used metabolomics to investigate small molecule metabolites between CLP and ADMSCs treatment groups. Sixty SD rats were randomly assigned to the sham operation group (SC group), the CLP group, and the CLP+ADMSCs group (CLP-ADMSCs group). We used liquid mass spectrometry-chromatography to detect metabolic changes in plasma and lung tissues. Compared with the SC group, the metabolic profile of plasma and lung tissues changed significantly 24 h after CLP. Moreover, 22 and 11 main differential metabolites involved in amino acid and glycerophospholipid metabolism were found in plasma and lung tissues, respectively. After the rats were injected with ADMSCs, these differential metabolites were reverse-regulated both in plasma and lung tissues. Besides, ADMSCs improved the survival rate and down-regulated the concentration of TNF-α and IL-6 at 24 h after CLP. The correlational analysis between plasma of IL-6/TNF-α and metabolites suggested that acetylcholine, spermine, phenylalanine, threonine of plasma and phosphatidylcholine (36:4) of lung tissues were significantly associated with IL-6/TNF-α in CLP and CLP-ADMSCs groups. ADMSCs might reverse abnormal metabolic pathways by reducing anti-inflammatory factors in sepsis-induced ALI. Our findings may provide novel metabolic mechanism of ADMSCs therapy for sepsis.
The purpose of this study was to explore prognostic factors of bloodstream infections (BSIs), a common severe infection and a major cause of mortality worldwide, so as to construct a prognosis model ...of patients with BSI.
Clinical and biochemical test data were obtained retrospectively from the medical records of 562 patients with BSI who had been treated at a single center; the end point was 60 days of all-cause death. The chi-square test was used to compare the mortality of patients grouped by the types of antibiotic treatment. The logistic regression analysis was adopted to identify prognostic factors; the Kaplan-Meier survival curve and log-rank test were conducted to compare the survival rate of patients with different prognostic factors; the receiver operating characteristic (ROC) curve was used to estimate the predictive value of different prognostic factors.
Of the 562 patients, 455 survived (80.96%), and 107 died (19.04%). The mortality rate of patients treated with a combination of antibiotics (25.40%) was higher than that treated with a single antibiotic (15.82%). Univariate analysis identified 19 prognostic factors for patients with BSI, including gender, age, diabetes, malignant tumor (non-blood system), total hospitalization time, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, total bilirubin, direct bilirubin, creatinine, ratio of granulocytes, fibrinogen, D-dimer, platelet, C-reactive protein, shock, and respiratory failure (
< 0.05). Multivariate analysis indicated that albumin (odds ratio OR = 0.94, 95% confidence interval CI: 0.89-0.99), fibrinogen (OR = 0.61, 95%CI: 0.46-0.82), shock (OR = 16.61, 95%CI: 7.00-39.41), and respiratory failure (OR = 47.53, 95%CI: 19.93-133.64) were independent factors. The combination of four indicators demonstrated a favorable predictive value for the 60-day outcome of patients with BSI, with an area under the ROC of 0.96 (95%CI: 0.94-0.99), sensitivity of 90.65%, specificity of 94.95%, and accuracy of 94.13%.
Shock, respiratory failure, albumin, and fibrinogen are potential independent prognostic factors for 60-day mortality.
The intensive human activities in chemical industry and environmental purification urge the development of advanced protocols for green production and waste management. ...
PDF
