Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/ß-catenin cascade.

BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.

Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma.

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.

Clinical outcome and prognostic factors of patients with non-traumatic angiography-negative subarachnoid hemorrhage.

Purpose: The cause of spontaneous subarachnoid hemorrhage (SAH) is unknown in 10% of cases. The aim of this study was to demonstrate the characteristics of patients with angiography-negative subarachnoid hemorrhage (anSAH) and to analyze factors influencing the clinical outcome in patients suffering from anSAH. Methods: A retrospective cohort of 75 patients with anSAH [26 perimesencephalic (pmSAH) and 49 non-perimesencephalic SAH (npmSAH)] admitted between January 2016 and June 2022 was included. We analyzed demographic, clinical data and 6-month functional outcomes. Enter regression analysis was performed to identify factors associated with outcomes. Results: Unfavorable outcome was achieved in 10 of 75 patients (13.3%). Unfavorable outcome was associated with senior adults (p = 0.008), Hijdra cistern score (HCS) elevation (p = 0.015), long-time lumbar cistern continuous drainage (LCFD; p = 0.029) and hydrocephalus (p = 0.046). The only significant risk factor for unfavorable outcome after npmSAH was the HCS (OR 1.213 (95%CI 1.007-1.462), p = 0.042). Conclusion: Our study provides valuable information on both SAH patterns and functional outcome in patients suffering from anSAH and should be taken into consideration during management of these patients.

The Application of "Stilted Building" Technique in the Embolization of Aneurysms with Secondary Branches.

OBJECTIVE: Many intracranial aneurysms often have branch arteries, and it is especially important to protect them during embolization. The purpose of the present study was to evaluate the curative effect and safety of the "stilted building" technique. METHODS: 25 patients with intracranial aneurysms with branch arteries that have been treated by coil embolization with the "stilted building" technique were retrospectively reviewed. Clinical follow-up was performed after endovascular treatment. RESULTS: All 25 patients successfully underwent aneurysm embolization. During the operation, the ruptured sac and most of the body of the aneurysm were embolized using the "stilted building" technique. Immediate imaging showed that the blood flow to the branch arteries from the neck or sidewall of the aneurysm was unobstructed. The mRS scores of the 25 patients during the follow-up period were mRS 0 for twenty-one patients, mRS 1 for three patients, and mRS 6 for one patient. No aneurysms recurred among the patients who completed the follow-up. CONCLUSIONS: In an aneurysm with a branch artery, when a balloon or stent cannot be effectively used to protect the branch artery, the use of "stilted building" embolization can achieve good therapeutic effects, and the short-term follow-up results are satisfactory; the technique can effectively protect branch arteries originating from aneurysms.

Severe bleeding following off-pump coronary artery bypass grafting: predictive factors and risk model.

BACKGROUND: Severe bleeding following cardiac surgery remains a troublesome complication, but to date, there is a lack of comprehensive predictive models for the risk of severe bleeding following off-pump coronary artery bypass grafting (OPCABG). This study aims to analyze relevant indicators of severe bleeding after isolated OPCABG and establish a corresponding risk assessment model. METHODS: The clinical data of 584 patients who underwent OPCABG from January 2018 to April 2020 were retrospectively analyzed. We gathered the preoperative baseline data and postoperative data immediately after intensive care unit admission and used multifactor logistic regression to screen the potential predictors of severe bleeding, upon which we established a predictive model. Using the consistency index and calibration curve, decision curve, and clinical impact curve analysis, we evaluated the performance of the model. RESULTS: This study is the first to establish a risk assessment and prediction model for severe bleeding following isolated OPCABG. Eight independent risk factors were identified: male sex, aspirin/clopidogrel withdrawal time, platelet count, fibrinogen level, C-reactive protein, serum creatinine, and total bilirubin. Among the 483 patients in the training group, 138 patients (28.6%) had severe bleeding; among the 101 patients in the verification group, 25 patients (24.8%) had severe bleeding. Receiver operating characteristic (ROC) curve analysis for the internal training group revealed a convincing performance with a concordance index (C-index) of 0.859, while the area under the ROC curve for the external validation data was 0.807. Decision curve analysis showed that the model was useful for both groups. CONCLUSIONS: Although there are some limitations, the model can effectively predict the probability of severe bleeding following isolated OPCABG and is therefore worthy of further exploration and verification.

Using Thromboelastography to Predict Blood Loss After Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE: This study aims to investigate the value of thromboelastography (TEG) in predicting blood loss, and its relationship with blood transfusion demand, during the perioperative period in off-pump coronary artery bypass grafting (OPCABG). METHODS: The data of 398 patients undergoing OPCABG were retrospectively analyzed. Blood was drawn before anesthesia induction (T1) and at 10 minutes after heparin neutralization (T2) for further TEG detection. The patients were divided into two groups based on the results at T2: a TEG normal group and a TEG abnormal group. Logistic regression analysis was used to predict the related factors contributing to the significant increase in perioperative blood loss (more than 20% of the estimated blood volume). RESULTS: There were 277 (69.6%) patients in the TEG normal group and 121 (30.4%) in the TEG abnormal group. Compared with the TEG normal group, the volume of blood loss, red blood cell count, and volume of plasma transfusion in the TEG abnormal group significantly increased within 24 hours after surgery. The results of the logistic regression analysis identified the use of clopidogrel, platelet count at T2, fibrinogen level at T2, and abnormality in TEG value as independent predictors for the significant increase in perioperative blood loss (P < 0.001). CONCLUSION: The abnormality in TEG value after heparin neutralization is correlated with massive hemorrhage and blood transfusion during the perioperative period in OPCABG. TEG detection can assist in clinical treatment and reduce the volume of blood lost in a hemorrhage and the volume of blood required in a transfusion during OPCABG.

Efficient and regioselective synthesis of 5-hydroxy-2-isoxazolines: versatile synthons for isoxazoles, beta-lactams, and gamma-amino alcohols.

An efficient and highly regioselective protocol was developed for the preparation of 5-hydroxy-2-isoxazolines, which have been proved to be versatile synthons for isoxazles, beta-hydroxy oximes, and gamma-amino alcohols. Beta-lactams, commonly embedded in the skeletons of bioactive natural products, were also synthesized in two steps from beta-hydroxy oximes, providing a new strategy for the synthesis of this kind of compounds.

Stereoselective syntheses of four diastereomers of 3,9,12-trihydroxycalamenene via a benzobicyclo[3.3.1] intermediate.

The highly stereoselective syntheses of four diastereomers of natural 3,9,12-trihydroxycalamenene are described. The syntheses highlight the utility of an unusual framework of benzobicyclo[3.3.1] lactones, which were accomplished via an intramolecular Friedel-Crafts-type Michael addition of alpha,beta-unsaturated lactones.

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Methanol, ethyl acetate, and water were used to extract the continuous cropping soils of Panax notoginseng, with the solution/soil ratios of 3:1, 6:1, and 9:1. We investigated the effects of those soil extracts on the growth and population of root-rot pathogens of P. notoginseng. Results showed that the methanol, ethyl acetate and water extracts all promoted mycelial growth of Fusarium oxysporum and Fusarium solani after 72 h of plate culture. The response indices of methanol and ethyl acetate extracts on the growth of F. oxysporum were 14.0%-19.8% and 16.2%-20.2%, being higher than that of water extract (8.9%-14.2%), but without significant difference between diffe-rent extraction ratios. However, methanol extract inhibited the mycelial growth of Alternaria spp. The inhibitory effect was highest at the extraction ratio of 3:1, reaching -33.2% to -38.5%. Ethyl acetate and water extracts did not affect the mycelial growth of Alternaria spp. After four weeks of soil culture, methanol, ethyl acetate and water extracts all increased the F. oxysporum populations. The positive effect of water extract was higher than that of methanol (1.68×104-6.73×104 copies·g-1 dry soil) and ethyl acetate (1.77×104-3.72×104 copies·g-1 dry soil) extracts, being 3.49×106-9.56×106 copies·g-1 dry soil. This increment was weakened along with the increase of extraction ratio. Both water extract and methanol extract with low extraction ratio could increase the F. solani populations, while there were no significant effects of methanol, ethyl acetate and water extracts on the population of Alternaria spp. Therefore, the extracts from continuous P. notoginseng cropping soil showed allopathically promoting effects on the growth and population of root-rot pathogens, F. oxysporum and F. solani, which may be one of the reasons for the occurrence of root rot and other soil-borne diseases in replanted P. notoginseng gardens.

Temperature effects on N2O production pathways in temperate forest soils.

Nitrous oxide (N2O) is an important greenhouse gas and contributes to stratospheric ozone depletion. Increasing temperature generally exerts a positive effect on soil N2O production. However, not much is known on the temperature influence on individual N2O production pathways. In this study, both laboratory 15N labelling experiments with an incubation temperature gradient (35 °C, 25 °C, 15 °C, 5 °C) and field 15N labelling experiments carried out in different seasons were conducted in Korean pine forest (KF) and Redwood coniferous forest (RF) soils. The results showed that the contribution of denitrification was positively correlated with temperature in KF and negatively correlated with temperature in RF, while their N2O production rates via denitrification (N2Od) all declined with decreasing temperature. The contribution of autotrophic nitrification in KF ranged from 11% to 21%, while the contribution in RF significantly increased with decreasing temperature (P < 0.05). However, the N2O production rates via autotrophic nitrification process (N2Oa) were significantly and positively correlated with incubation temperature (P < 0.05). In addition, the contribution of heterotrophic nitrification to N2O production showed a negative and positive relation with increasing temperature in KF and RF, respectively. Whereas, the N2O production rates via heterotrophic nitrification (N2Oh) showed a significantly positive correlation with temperature (P < 0.05), but a negative relation with gross heterotrophic nitrification rates. The results in the field experiments corresponded to the laboratory results, indicating that the methods applied in field experiments were suitable for the estimation and prediction of in situ N2O production. The response of calculated N2O production rates to seasonal temperature in KF during the year of 2015-2017 also confirmed the suitability of the field research methods. This novel in situ technique to determine N2O production in temperate forest soils should be validated for other ecosystems.

Risk factors for vasovagal reaction associated with cerebral angiography via femoral catheterisation.

Objective To analyse the related risk factors for vasovagal reaction associated with cerebral angiography via femoral catheterisation and discuss treatment measures and prevention and control methods. Methods The data of 3107 patients on whom cerebral angiography was performed in two high-volume interventional neuroradiology centres within 8 years were retrospectively analysed. Patients were divided into the vasovagal reaction and non-vasovagal reaction groups according to whether vasovagal reaction developed. The two groups' clinical data were analysed using univariate and multivariate logistic regression analysis to examine vasovagal reaction-related factors. Results Of the 3107 patients included, 127 developed vasovagal reaction (4.09%). Of the 127 patients who developed vasovagal reaction, 123, three and one had vasovagal reaction after sheath removal, during cerebral angiography and upon femoral artery compression device removal, respectively. Differences in age, body mass index, sex ratios, proportions of patients with hypertension, diabetes and hyperlipemia, and adoption rate of femoral artery compression device were not statistically significant between the two groups ( P > 0.05). Compared with the control group, the vasovagal reaction group had a significantly longer preoperative fasting time ( P < 0.05). Multivariate logistic regression analysis revealed preoperative fasting time as the only risk factor for vasovagal reaction that was associated with cerebral angiography ( P < 0.001). Conclusion Excessive fasting time before cerebral angiography is the most important risk factor for vasovagal reaction associated with cerebral angiography.

Efficient and regioselective one-pot synthesis of 3-substituted and 3,5-disubstituted isoxazoles.

A series of 3-substituted and 3,5-disubstituted isoxazoles have been efficiently synthesized in moderate to excellent yields by the reaction of N-hydroxyl-4-toluenesulfonamide with alpha,beta-unsaturated aldehydes/ketones. This novel strategy is associated with readily available starting materials, mild conditions, high regioselectivity, and wide scope.

First total syntheses and spectral data corrections of 11-alpha-methoxycurvularin and 11-beta-methoxycurvularin.

Concise and efficient total syntheses of 11-alpha-methoxycurvularin and 11-beta-methoxycurvularin were accomplished for the first time. The three-component linchpin coupling and intramolecular acylation reactions were key steps, in which we found the spectral data of 11-alpha-methoxycurvularin and 11-beta-methoxycurvularin, reported in the literature, were reversed with each other.

The first asymmetric total syntheses and determination of absolute configurations of xestodecalactones B and C.

The first efficient asymmetric total syntheses of xestodecalactones B and C have been accomplished in 10 steps with an overall yield of 22 and 20.2%, respectively. The key steps involve the utility of Evans oxazolidinone-mediated syn-aldol condensations to establish the C-9 configuration and the macrolide ring formation by intramolecular acylation. The absolute configurations of xestodecalactones B and C have been determined via these syntheses.

Status and fuzzy comprehensive assessment of combined heavy metal and organo-chlorine pesticide pollution in the Taihu Lake region of China.

The status of combined heavy metal and organo-chlorine pesticide (OCPs; i.e. HCH and DDT) pollution was investigated and the soil environmental quality of the Taihu Lake watershed, one of the most developed regions in China, was evaluated using a fuzzy comprehensive assessment. Statistical analyses showed the presence of combined pollution in the soil. At many sampling sites, heavy metal concentrations were above corresponding background values, indicating the effects of extraneous pollutants. It has been over 20 years since China banned the use of OCPs, but they can still be found in soil samples of this region. HCH levels at all investigated sites were below the Chinese Environmental Quality Standard for Soils. Fuzzy comprehensive assessment showed that the overall soil quality in this region could be categorized as class I. Nevertheless, the high coefficients of variation for levels of DDT, Cd and Hg indicated the existence of some point-source pollution. Continuous monitoring and further studies of the region are recommended to prevent pollution of farmland from these sources.