Diversity-oriented synthesis of indole-fused scaffolds and bis(indolyl)methane from tosyl-protected tryptamine.

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

Effects of Thermal Damage on Impact Response Characteristics of High-Energy Propellants.

Thermal damage due to microstructure changes will occur in propellants under thermal stimulation. It can significantly affect the sensitization, combustion, and other properties of the propellant, which, in turn, affects the impact safety of the solid propellant rocket engine. A new component which uniformly heats the sample was designed to conduct the Lagrange test and EFP impact test at different temperatures. The thermal decomposition and damage characteristics of the propellant during the heating process were quantitatively analyzed. Additionally, the effects of ambient temperature on impact initiation and detonation growth of the high-energy propellant were elucidated at a mesoscopic level. The results showed that the porosity of the specimen increased by 0.89% under the thermomechanical mechanism, which was mainly characterized by interfacial de-bonding between the AP and the binder. The increase in thermal damage changed the hot spot reaction rate and significantly affected the growth process of propellant impact initiation. A method was proposed to systematically calibrate the reaction rate model for the propellant at different temperatures. The theoretical model parameters of the high-energy propellant at two typical temperatures were calibrated in this way. The critical shell thicknesses computed using LS-DYNA, which, for 20 and 70 °C, were obtained as 15 and 20 mm, respectively.

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations.

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

Controllable Synthesis of N-Heterocycles via Hydride Transfer Strategy-Enabled Formal [5 + 1] and [5 + 2] Cyclizations.

The Brønsted acid-controlled switchable synthesis of indoline-fused tetrahydroquinolines and indole-fused benzazepines was developed through hydride transfer-enabled formal [5 + 1] and [5 + 2] cyclization reactions from indoles and N-alkyl o-aminobenzoketones. Indoline, furanone, and tetrahydroquinoline hybridized pentacyclic products were unprecedentedly accessed via a cascade condensation/hydride transfer/dearomatization-cyclization/deethylation/nucleophilic addition process. In addition, the undeveloped hydride transfer-involved [5 + 2] cyclizations were also realized for direct construction of indole-fused benzazepines.

Controllable Synthesis of N- and O-Containing Heterocycles via Formal [3 + 2] and [5 + 2] Cyclizations.

The controllable synthesis of spirooxindole-dihydrofurans and spirooxindole-benzazepines was developed through formal [3 + 2] and [5 + 2] cyclization reactions from 2-(2-oxoindolin-3-yl)malononitriles and ortho-aminobenzaldehydes, respectively. A variety of spirooxindole-benzazepines were facilely constructed via a furan ring-open-involved hydride transfer/cyclization process. It is noteworthy that the application of the hydride-transfer-involved [5 + 2] cyclization strategy for construction of spirobenzazepines was unprecedented. In addition, the spiro N- and O-containing heterocycles were highly functionalized by amino, amide, and cyano groups, which were conducive to late-stage functionalization.

Relationship between the postoperative lactate dynamic levels, the acute gastrointestinal injury and the prognosis among patients who undergo surgical treatment for acute type A aortic dissection.

Introduction: This study aimed to determine the relationship between the postoperative lactate dynamic levels, the postoperative acute gastrointestinal injury (AGI), and the prognosis among the patients who underwent surgical treatment for an acute Stanford type-A aortic dissection (aTAAD). Methods: A total of 271 aTAAD patients were recruited and monitored. Of the 271 aTAAD patients, 29.2% developed an AGI and were designated as the AGI group (n = 79); the other patients (n = 192) were designated as the non-AGI group. According to the 2-year follow up, the aTAAD patients were also divided into the alive and death subgroups for further analysis. Results: Binary logistic regression analysis revealed that the postoperative 4-h lactate (P4L) level, time-to-return to the normal blood lactate level (TRNL), postoperative 16-h lactate (P16L) level, and neutrophil granulocyte (NEU) count had a good predictive value for an AGI after aTAAD. The 8-week and 2-year mortality rates were higher in the AGI group than the non-AGI group (P < 0.05). Basic data and clinical characteristics were significantly different between the alive and death groups (P < 0.05). A higher AGI rate and mortality occurred in the P4L level ≥10.15 mmol/L subgroup, TRNL ≥21-h subgroup, P16L level ≥2.95 mmol/L subgroup, NEU count ≥10.9 × 109/L subgroup, PaO2 < 77.7 mmHg subgroup, WBC count ≥9.58 × 109/L subgroup, and the operative time ≥427 min subgroup than the corresponding comparison subgroups (P < 0.05). The postoperative 0-h lactate (P0L) level, TRNL, postoperative 24-h lactate (P24L) level, D-dimer level, fibrinogen degradation products (FDP) level, duration of mechanical ventilation, and length of hospitalization were independent factors influencing the 30-day mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Cox regression multivariate analysis after univariate analysis of all-cause mortality showed the TRNL, postoperative 12-h lactate (P12L) level, P16L level, P24L level, D-dimer level, FDP level, and length of hospitalization were independently associated with the 2-year mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Conclusion: The postoperative lactate changes and TRNL effectively predicted postoperative AGI and the mortality rate in patients with who underwent surgery for an aTAAD. The TRNL and P24L level were independent risk factors for the 30-day and 2-year mortality rates in patients who underwent surgery for an aTAAD.

Sulfur-containing marine natural products as leads for drug discovery and development.

Among the large series of marine natural products (MNPs), sulfur-containing MNPs have emerged as potential therapeutic agents for the treatment of a range of diseases. Herein, we reviewed 95 new sulfur-containing MNPs isolated during the period between 2021 and March 2023. In addition, we discuss that the widely used strategies and the emerging technologies including natural product-based antibody drug conjugates (ADCs), small-molecule-based proteolysis targeting chimeras (PROTACs), nanotechnology-based drug carriers, artificial intelligence (AI)-driven drug discovery have been used for improving the efficiency and success rate of NP-based drug development. We also provide perspectives regarding the challenges and opportunities in sulfur-containing MNPs based drug discovery and development and future research directions.

SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice.

Secreted frizzled related protein 4 (SFRP4), a member of the SFRPs family, contributes to a significant function in metabolic and cardiovascular diseases. However, there is not enough evidence to prove the antiatherosclerosis effect of SFRP4 in ApoE knock-out (KO) mice. ApoE KO mice were fed a western diet and injected adenovirus (Ad)-SFRP4 through the tail vein for 12 weeks. Contrasted with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing SFRP4 was reduced significantly. Plasma high-density lipoprotein cholesterol was elevated in the Ad-SFRP4 group. RNA sequence analysis indicated that there were 96 differentially expressed genes enriched in 10 signaling pathways in the mRNA profile of aortic atherosclerosis lesions. The analysis data also revealed the expression of a number of genes linked to metabolism, organism system, and human disease. In summary, our data demonstrates that SFRP4 could play an important role in improving atherosclerotic plaque formation in the aorta.

The Preoperative Uric Acid-to-Albumin Ratio as a New Indicator to Predict Long-Term Prognosis After Surgery for Patients with Acute Type A Aortic Dissection.

BACKGROUND: The long-term prognosis of patients with acute type A aortic dissection (AAD) is poor, despite emergency surgical treatment. Therefore, it is imperative to evaluate patient risk factors to improve the prognosis. The aim of this study was to analyze the ability of the uric acid-to-albumin ratio (UAR) to predict the long-term mortality of patients with type A AAD after surgery. METHODS AND RESULTS: A total of 289 patients with type A AAD who had received surgical treatment was enrolled in this study. Peripheral blood samples were collected before anesthesia induction. All patients were divided into the UAR < 9.875 group and the UAR ≥ 9.875 group, and mortality significantly differed between the two groups. The patients were further divided into survival and non-survival groups, according to whether death occurred after the procedure based on a one-year follow up. Factors, including age, hypertension, albumin, UAR, and D-dimer, differed significantly between the survival and non-survival groups. The independent risk factors for long-term death in patients with type A AAD were analyzed by univariable and multivariable COX regression analyses, and the predictive value of these indices for postoperative mortality was assessed based on the receiver operating characteristic (ROC) curves. Preoperative UAR (HR 1.904, 95% CI, 1.097 to 3.305; P < 0.05), D-dimer (HR, 1.991,95% CI, 1.116 to 3.554; P < 0.05 ), and age (HR 2.216, 95% CI, 1.287 to 3.815; P < 0.05) were identified as independent risk factors for one-year mortality in patients with Type A AAD. The area under the ROC curve (AUC) of UAR was 0.618 [95% (0.544, 0.693)], and the sensitivity and specificity were 69.6% and 51.8%, respectively (P = 0.003). The AUC for albumin was 0.349 [95% (0.274, 0.425)], and the sensitivity and specificity were 26.1% and 51.8%, respectively (P = 0.000), The AUC for uric acid was 0.544 [95% (0.470, 0.619)], and the sensitivity and specificity were 78.3% and 34.5%, respectively (P = 0.265). The AUC for UAR + age + D-dimer was 0.751 [95% (0.681, 0.821)], and the sensitivity and specificity were 76.8% and 68.2%, respectively. CONCLUSIONS: UAR in patients with type A AAD may be used as a new independent risk factor for long-term mortality. Its predictive value is superior to that of albumin or uric acid alone. The combination of UAR, age, and D-dimer provide good prognostic value.

Analogues of natural products yaequinolones as potential inflammatory inhibitors: Design, synthesis and biological evaluation.

Inflammation is connected with a variety of diseases and there is still a need to develop more effective and safer anti-inflammatory drugs. Herein, we synthesized, resolved, and characterized eight enantiopure isomers of yaequinolone J1 (1), yaequinolone J2 (2), 4'-desmethoxyyaequinolone J1 (3), and 4'-desmethoxyyaequinolone J2 (4). The key synthetic steps were extended and 34 racemic analogues modified at the 4-aryl, the N-position, and the pyran ring were designed and synthesized. All the synthesized compounds were evaluated for their anti-inflammatory activities in RAW 264.7 cells of which 13 compounds showed significant inhibition of nitric oxide (NO) production at a concentration of 0.1 µM, which was more potent than that of indomethacin. Furthermore, compounds (-)-3, (-)-4, 5h, and 6g reduced the production of IL-6 in LPS-stimulated RAW 264.7 cells at a concentration of 50 nM. A preliminary SAR indicated that 3'-Br (5h), 4'-NO2 (6g) on 4-phenyl and 3-bromobenzyl (7f) on the N-position were the most effective substituents. This is the first report of the anti-inflammatory yaequinolone alkaloids and the present study provided evidence for exploiting this series of highly efficacious derivatives for new anti-inflammatory agents.

[Corrigendum] Thymoquinone inhibits epithelial­mesenchymal transition in prostate cancer cells by negatively regulating the TGF­ß/Smad2/3 signaling pathway.

After the publication of the article, an interested reader drew to the authors' attention that the Du145 'Control' migration panel in Fig. 2C appeared to overlap with the Du145 'Control' invasion panel in Fig. 5A; furthermore, two of the Du145 panels in Fig. 5A also appeared to overlap. The authors have consulted their original data, and realize that these figures were inadvertently assembled incorrectly. The corrected versions of Figs. 2 and 5, incorporating the correct data for the Du145 'Control' panel in Fig. 2C, and the TQ­/TGF­ß OE­ invasion and migration panels, and the TQ+/TGF­ß OE+ migration panel, in Fig. 5A, are shown on the next page. These further corrections do not grossly affect the results or the conclusions reported in this work. The authors all agree to this Corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to correct the errors that were made during the assembly of these figures. Lastly, the authors apologize to the readership for any inconvenience these errors may have caused. [Oncology Reports 38: 3592­3598, 2017; DOI: 10.3892/or.2017.6012].

Clinical characteristics and risk factors of in-hospital gastrointestinal bleeding in patients with acute myocardial infarction.

Background: Gastrointestinal bleeding (GIB) is one of the most serious complications of acute myocardial infarction (AMI) and is correlated with poor outcomes. Objective: To evaluate the prevalence, risk factors and in-hospital mortality of GIB in patients with AMI. Methods: This observational case-control study retrospectively enrolled consecutive patients with AMI from the Department of Cardiovascular Medicine and Cardiovascular Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020. GIB after AMI was identified by International Classification of Diseases (ICD) codes from inpatient medical settings and validated by medical record review. AMI patients without GIB were accordingly classified as the control group. Propensity score matching (PSM) was used to match with the GIB group and the control group. All anonymized clinical data were provided by the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University. Results: A total of 5,868 AMI patients were enrolled, 0.87% (51/5,868) of whom developed GIB after AMI. On the univariate analysis, history of diabetes, chronic kidney disease, Killip IV, a lower hemoglobin concentration, a higher serum level of creatinine, blood urea nitrogen and D-dimer were closely associated with the risk of GIB (P < 0.05). On the multivariable analysis, a lower hemoglobin concentration (OR: 0.93, 95% CI: 0.89-0.96, P < 0.001) was independently associated with the risk of GIB. Patients with GIB had a much higher in-hospital mortality rate than those without GIB (14.3 vs. 2.1%, P = 0.047). In-hospital mortality among patients with GIB after AMI appeared to be associated with a decreased hemoglobin concentration (OR: 0.93, 95% CI: 0.86-0.99, P = 0.045) and Killip IV (OR: 51.59, 95% CI: 2.65-1,005.30, P = 0.009). Conclusion: The history of diabetes, poor renal function and heart failure were associated with the high risk of GIB in patients experiencing AMI. The in-hospital mortality in patients with AMI complicating GIB was higher than that in patients without GIB and was associated with a decreased hemoglobin concentration and high Killip classification.

C1QL1/CTRP14 Is Largely Dispensable for Atherosclerosis Formation in Apolipoprotein-E-Deficient Mice.

The purpose of this study was to investigate the influence of C1QL1 on atherosclerosis as well as the transcriptomic alteration of the aorta. While complement C1ql-like 1 (C1QL1) is one of the C1q/tumor-necrosis-factor-related protein (CTRP) family members, also known as CTRP14, and is synthesized and secreted mainly by the brain and adipose tissues, the functional properties of the C1QL1/CTRP14 protein outside the brain and adipocytes remain, however, unknown. In this regard, apolipoprotein E (ApoE) knockout (KO) mice were fed a Western diet and injected with adenovirus (Ad) green fluorescent protein or Ad-C1QL1 through the tail vein for 12 weeks. In contrast with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing C1QL1 showed no significant difference, and the RNA sequence revealed that there were only 111 differentially expressed genes (DEGs) enriched in 26 signaling pathways of the mRNA profile in the aortic atherosclerosis lesions. This analysis also revealed the expression of several genes related to metabolism, organismal system, and human diseases such as type II diabetes, which are not associated with the formation of atherosclerosis in the aorta. These findings illustrate that C1QL1 is largely dispensable for atherosclerosis formation in ApoE-deficient mice and does not improve atherosclerotic plaque formation in the aorta.

Clinical Efficacy of Catheter Ablation in the Treatment of Vasovagal Syncope.

Catheter ablation of ganglionated plexi (GPs) performed as cardioneuroablation in the left atrium (LA) has been reported previously as a treatment for vasovagal syncope (VVS). However, the efficacy and safety of catheter ablation in the treatment of VVS remains unclear. The objective of this study is to explore the efficacy and safety of catheter ablation in the treatment of VVS and to compare the different ganglion-mapping methods for prognostic effects. A total of 108 patients with refractory VVS who underwent catheter ablation were retrospectively enrolled. Patients preferred to use high-frequency stimulation (HFS) (n = 66), and anatomic landmark (n = 42) targeting is used when HFS failed to induce a positive reaction. The efficacy of the treatment is evaluated by comparing the location and probability of the intraoperative vagal reflex, the remission rate of postoperative syncope symptoms, and the rate of negative head-up tilt (HUT) results. Adverse events are analyzed, and safety is evaluated. After follow-up for 8 (5, 15) months, both HFS mapping and anatomical ablation can effectively improve the syncope symptoms in VVS patients, and 83.7% of patients no longer experienced syncope (<0.001). Both approaches to catheter ablation in the treatment of VVS effectively inhibit the recurrence of VVS; they are safe and effective. Therefore, catheter ablation can be used as a treatment option for patients with symptomatic VVS.

Atrial Cardiomyopathy Predicts Worse Outcome in Patients With Lung Cancer.

Background: Reports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited. Objectives: This study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants. Methods: Newly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi'an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM. Results: A total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042-2.283, p = 0.030). Conclusion: Coexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

Acute Myocardial Infarction and Concomitant Acute Intracranial Hemorrhage: Clinical Characteristics and Outcomes.

This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI and acute ICH admitted to our institution were included retrospectively. The patient demographics, clinical characteristics, neuroimaging and treatment approaches were analyzed, and the outcomes of interest included disability as defined by the modified Rankin Scale (mRS) score and all-cause mortality within 1 year of follow-up. Of a total of 4972 patients with AMI, 8 patients (0.2%) with concomitant acute ICH were recruited for the study, including ST-segment elevation myocardial infarction (STEMI, 5 cases) and non-STEMI (3 cases). New-onset acute ICH in 4 of the 5 patients (80%) occurred within 24 hours after the AMI event, and all these patients had a sudden decrease in the level of consciousness, with an average decrease of 4.6 on the Glasgow Coma Scale. All 5 out of 8 patients had irregular shapes and uncommon sites of hematoma presentation documented on CT scans. Unfortunately, 2 patients died from a progression of ICH within 1 week, and 2 of the 6 survivors had poor functional outcomes (mRS ≥3) at the 1-year follow-up. Concomitant acute ICH and AMI are rare complications displaying unique iconography. Acute ICH caused serious prejudice in AMI with higher mortality and poor functional outcomes, and cardiac catheterization without the administration of antithrombotic or antiplatelet agents was feasible for patients who had unstable hemodynamics or STEMI.

C1q/Tumor Necrosis Factor-Related Protein 9: Basics and Therapeutic Potentials.

C1q/tumor necrosis factor-related protein 9 (CTRP9) is a newly discovered adipokine that is the closest paralog of adiponectin. Proteolytic cleavage of CTRP9 leads to the release of the globular domain (gCTRP9), which serves as the major circulating subtype. After binding with adiponectin receptor 1 (AdipoR1) and N-cadherin, CTRP9 activates various signaling pathways to regulate glucose and lipid metabolism, vasodilation and cell differentiation. Throughout human development and adult life, CTRP9 controls many biological phenomena. simultaneously, abnormal gene or protein expression of CTRP9 is accompanied by a wide range of human pathological phenomena. In this review, we briefly introduce CTRP9 and its associated signaling pathways and physiological functions, which may be helpful in the understanding of the occurrence of diseases. Moreover, we summarize the broader research prospects of CTRP9 and advances in therapeutic intervention. In recent years, CTRP9 has attracted extensive attention due to its role in the pathogenesis of various diseases, providing further avenues for its exploitation as a potential biomarker or therapeutic target.

Discovery, total syntheses and potent anti-inflammatory activity of pyrrolinone-fused benzoazepine alkaloids Asperazepanones A and B from Aspergillus candidus.

Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (-)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, and ECD calculations. Furthermore, total syntheses of (±)-1 and (±)-2 have been achieved starting from the commercially L-aspartic acid diethyl ester hydrochloride and monoethyl malonate in 7 and 8 steps, respectively. The key step in the syntheses was an intramolecular Friedel-Crafts reaction to build the unique tricyclic skeleton. Interestingly, (+)-2 not only showed obviously inhibitory activity against NO production, but also inhibited potent LPS-induced expression of TNF-α and IL-6 at the concentration of 0.1 µM. It thus represents a potentially promising lead for anti-inflammatory drug discovery.

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones.

The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner-Wadsworth-Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction. Moreover, two sets of stereoisomers of aniduquinolone A with substantially overlapping NMR data were synthesized completely and assigned unambiguously by comprehensive analysis of both their spectroscopic and X-ray diffraction data. Unexpectedly, aflaquinolones A, C, and D that feature different 2,4-dimethyl cyclohexanone moieties were transformed successfully from (+)-aniduquinolone A by treating with TFA. The methodology delineated herein can be applied broadly to the synthesis of natural alkaloids containing the core structure of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one.

Comparison of Clinical Outcomes of Different Connection Modes of Extracorporeal Membrane Oxygenation Combine with Continuous Renal Replacement Therapy.

OBJECTIVE: To evaluate the effect of different connection modes of ECMO and CRRT on patients with acute kidney injury (AKI). METHODS: Twenty-one patients received ECMO with AKI. These patients were admitted to our center from December 2018 to February 2021, selected, and treated with both ECMO and CRRT. They were divided into A connection mode (pre-membrane-pre-pump connection) and B connection mode (post-membrane-post-pump connection). We compared clinical indicators and outcomes between two connection modes. RESULTS: There were eight cases (38.91%) in A connection mode and 13 cases (61.09%) in B connection mode, with median durations of ECMO assistance of 5 days and 7 days, respectively. Median flow rates of ECMO of 3.0 L/min and 2.5 L/min, respectively; CRRT flow rates of 200 mL/min and 180 mL/min, respectively. CRRT filter lifetime was over 48h in both connection modes. Except for NT-pro BNP, no significant differences in clinical indicators were observed between the two groups before or after the treatment (P > .05). CONCLUSION: Both connection modes could achieve the therapeutic purpose and need no higher level of anticoagulation for patients simultaneously treated with ECMO and CRRT. Two modes had no impact on treatment effect and clinical indicators in patients. It had no effect on length of ICU stay and prognostic.