Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Dietary l-carnitine regulates liver lipid metabolism via simultaneously activating fatty acid ß-oxidation and suppressing endoplasmic reticulum stress in large yellow croaker fed with high-fat diets.

Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) ß-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial ß-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal ß-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating ß-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA ß-oxidation capability and suppressing the ER stress pathway in fish.

Regulated cell death pathways in cardiomyopathy.

Heart disease is a worldwide health menace. Both intractable primary and secondary cardiomyopathies contribute to malignant cardiac dysfunction and mortality. One of the key cellular processes associated with cardiomyopathy is cardiomyocyte death. Cardiomyocytes are terminally differentiated cells with very limited regenerative capacity. Various insults can lead to irreversible damage of cardiomyocytes, contributing to progression of cardiac dysfunction. Accumulating evidence indicates that majority of cardiomyocyte death is executed by regulating molecular pathways, including apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Importantly, these forms of regulated cell death (RCD) are cardinal features in the pathogenesis of various cardiomyopathies, including dilated cardiomyopathy, diabetic cardiomyopathy, sepsis-induced cardiomyopathy, and drug-induced cardiomyopathy. The relevance between abnormity of RCD with adverse outcome of cardiomyopathy has been unequivocally evident. Therefore, there is an urgent need to uncover the molecular and cellular mechanisms for RCD in order to better understand the pathogenesis of cardiomyopathies. In this review, we summarize the latest progress from studies on RCD pathways in cardiomyocytes in context of the pathogenesis of cardiomyopathies, with particular emphasis on apoptosis, necroptosis, ferroptosis, autophagy, and pyroptosis. We also elaborate the crosstalk among various forms of RCD in pathologically stressed myocardium and the prospects of therapeutic applications targeted to various cell death pathways.

Diagnostic value of multiple b-value diffusion-weighted imaging in discriminating the malignant from benign breast lesions.

OBJECTIVE: The conventional breast Diffusion-weighted imaging (DWI) was subtly influenced by microcirculation owing to the insufficient selection of the b values. However, the multiparameter derived from multiple b-value exhibits more reliable image quality and maximize the diagnostic accuracy. We aim to evaluate the diagnostic performance of stand-alone parameter or in combination with multiparameter derived from multiple b-value DWI in differentiating malignant from benign breast lesions. METHODS: A total of forty-one patients diagnosed with benign breast tumor and thirty-eight patients with malignant breast tumor underwent DWI using thirteen b values and other MRI functional sequence at 3.0 T magnetic resonance. Data were accepted mono-exponential, bi-exponential, stretched-exponential, aquaporins (AQP) model analysis. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of quantitative parameter or multiparametric combination. The Youden index, sensitivity and specificity were used to assess the optimal diagnostic model. T-test, logistic regression analysis, and Z-test were used. P value < 0.05 was considered statistically significant. RESULT: The ADCavg, ADCmax, f, and α value of the malignant group were lower than the benign group, while the ADCfast value was higher instead. The ADCmin, ADCslow, DDC and ADCAQP showed no statistical significance. The combination (ADCavg-ADCfast) yielded the largest area under curve (AUC = 0.807) with sensitivity (68.42%), specificity (87.8%) and highest Youden index, indicating that multiparametric combination (ADCavg-ADCfast) was validated to be a useful model in differentiating the benign from breast malignant lesion. CONCLUSION: The current study based on the multiple b-value diffusion model demonstrated quantitatively multiparametric combination (ADCavg-ADCfast) exhibited the optimal diagnostic efficacy to differentiate malignant from benign breast lesions, suggesting that multiparameter would be a promising non-invasiveness to diagnose breast lesions.

The dualistic model of passion and the service quality of five-star hotel employees during the COVID-19 pandemic.

Given the generally stressful job demands of the hospitality industry during the COVID-19 pandemic, understanding the work passion and emotions of hotel employees is particularly important. Based on the conservation of resources theory and the job demands-resources model, this study develops a multiple mediation model to investigate how frontline hotel employees with different types of work passion choose emotional labor strategies under the effects of the COVID-19 pandemic and the impact of different choices on their service quality. A two-stage survey using data from 206 frontline employees of five-star hotels in China explored how work passion influences emotional labor and thereby affects emotional expression as well as service quality. The results showed emotional labor partially mediates the relationship between work passion and emotional expression, which in turn mediates the relationship between emotional labor and service quality during the COVID-19 pandemic. The theoretical and practical implications of this study are discussed.

Soluble Klotho-integrin ß1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). METHODS: A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1-4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. RESULTS: A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05-1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00-1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00-1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453]. CONCLUSIONS: NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%. Trial registration NCT02803294, 16/06/2016.

Role of interleukin-15 in cardiovascular diseases.

Interleukin (IL)-15 is a recently identified cytokine, which belongs to the interleukin-2(IL-2) family, and plays an important role in innate and adaptive immunoreaction. Given the fact that the structure of IL-15 is partially similar to IL-2, they share some common biological effects, including immunoregulation. IL-2 was proven to protect cardiac function in mouse myocardial infarction models. Cardiovascular diseases (CVDs) dominate the cause of mortality worldwide. Besides atherosclerosis, inflammation is also widely involved in the pathogenesis of many CVDs including hypertension, heart failure (HF) and aneurysm. IL-15, as a pro-inflammatory cytokine, is up-regulated in some cardiovascular diseases, such as myocardial infarction and atherosclerosis. The current understanding of IL-15, including its signal pathway and cellular function, was described. Furthermore, IL-15 has a protective effect in myocardial infarction and myocarditis by decreasing cardiomyocyte death and improving heart function. The inhibited effect of IL-15 in ductus arteriosus (DA) should be focused on. IL-15 promoted atherogenesis. IL-15 may be a good target in treatment of cardiovascular diabetology. Finally, future research direction of IL-15 deserves attention. Since IL-15 plays several roles in CVDs, understanding the role of the IL-15/IL-15R system may provide a scientific basis for the development of new approaches that use IL-15 for the treatment of CVDs.

Mitochondrial Fatty Acid ß-Oxidation Inhibition Promotes Glucose Utilization and Protein Deposition through Energy Homeostasis Remodeling in Fish.

BACKGROUND: Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid ß-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied. OBJECTIVES: This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish. METHODS: Carnitine-depleted male Nile tilapia (initial weight: 4.29 ± 0.12 g; 3 mo old) were established by feeding them with mildronate diets (1000 mg/kg/d) for 6 wk. Zebrafish deficient in the carnitine palmitoyltransferase 1b gene (cpt1b) were produced by using CRISPR/Cas9 gene-editing technology, and their males (154 ± 3.52 mg; 3 mo old) were used for experiments. Normal Nile tilapia and wildtype zebrafish were used as controls. We assessed nutrient metabolism and energy homeostasis-related biochemical and molecular parameters, and performed 14C-labeled nutrient tracking and transcriptomic analyses. RESULTS: The mitochondrial FAO decreased by 33.1-88.9% (liver) and 55.6-68.8% (muscle) in carnitine-depleted Nile tilapia and cpt1b-deficient zebrafish compared with their controls (P < 0.05). Notably, glucose oxidation and muscle protein deposition increased by 20.5-24.4% and 6.40-8.54%, respectively, in the 2 fish models compared with their corresponding controls (P < 0.05). Accordingly, the adenosine 5'-monophosphate-activated protein kinase/protein kinase B-mechanistic target of rapamycin (AMPK/AKT-mTOR) signaling was significantly activated in the 2 fish models with inhibited mitochondrial FAO (P < 0.05). CONCLUSIONS: These data show that inhibited mitochondrial FAO in fish induces energy homeostasis remodeling and enhances glucose utilization and protein deposition. Therefore, fish with inhibited mitochondrial FAO could have high potential to utilize carbohydrate. Our results demonstrate a potentially new approach for increasing protein deposition through energy homeostasis regulation in cultured animals.

Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model.

l-Carnitine is essential for mitochondrial ß-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in ß-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal ß-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.

Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus).

Although the key metabolic regulatory functions of mammalian peroxisome proliferator-activated receptor α (PPARα) have been thoroughly studied, the molecular mechanisms and metabolic regulation of PPARα activation in fish are less known. In the first part of the present study, Nile tilapia (Nt)PPARα was cloned and identified, and high mRNA expression levels were detected in the brain, liver, and heart. NtPPARα was activated by an agonist (fenofibrate) and by fasting and was verified in primary hepatocytes and living fish by decreased phosphorylation of NtPPARα and/or increased NtPPARα mRNA and protein expression. In the second part of the present work, fenofibrate was fed to fish or fish were fasted for 4weeks to investigate the metabolic regulatory effects of NtPPARα. A transcriptomic study was also performed. The results indicated that fenofibrate decreased hepatic triglyceride and 18C-series fatty acid contents but increased the catabolic rate of intraperitoneally injected [1-(14)C] palmitate in vivo, hepatic mitochondrial ß-oxidation efficiency, the quantity of cytochrome b DNA, and carnitine palmitoyltransferase-1a mRNA expression. Fenofibrate also increased serum glucose, insulin, and lactate concentrations. Fasting had stronger hypolipidemic and gene regulatory effects than those of fenofibrate. Taken together, we conclude that: 1) liver is one of the main target tissues of the metabolic regulation of NtPPARα activation; 2) dephosphorylation is the basal NtPPARα activation mechanism rather than enhanced mRNA and protein expression; 3) activated NtPPARα has a hypolipidemic effect by increasing activity and the number of hepatic mitochondria; and 4) PPARα activation affects carbohydrate metabolism by altering energy homeostasis among nutrients.

Inhibited fatty acid ß-oxidation impairs stress resistance ability in Nile tilapia (Oreochromis niloticus).

Energy metabolism plays important roles in stress resistance and immunity in mammals, however, such functions have not been established in fish. In the present study, Nile tilapia (Oreochromis niloticus) was fed with mildronate, an inhibitor of mitochondrial fatty acid (FA) ß-oxidation, for six weeks subsequently challenged with Aeromonas hydrophila and ammonia nitrogen exposure. Mildronate treatment reduced significantly l-carnitine concentration and mitochondrial FA ß-oxidation efficiency, while it increased lipid accumulation in liver. The fish with inhibited hepatic FA catabolism had lower survival rate when exposed to Aeromonas hydrophila and ammonia nitrogen. Moreover, fish fed mildronate supplemented diet had lower immune enzymes activities and anti-inflammatory cytokine genes expressions, but had higher pro-inflammatory cytokine genes expressions. However, the oxidative stress-related biochemical indexes were not significantly affected by mildronate treatment. Taken together, inhibited mitochondrial FA ß-oxidation impaired stress resistance ability in Nile tilapia mainly through inhibiting immune functions and triggering inflammation. This is the first study showing the regulatory effects of lipid catabolism on stress resistance and immune functions in fish.

Size-segregated characteristics of water-soluble oxidative potential in urban Xiamen: Potential driving factors and implications for human health.

Oxidative potential (OP), defined as the ability of particulate matter (PM) to generate reactive oxygen species (ROS), has been considered as a potential health-related metric for PM. Particles with different sizes have different OP and deposition efficiencies in the respiratory tract and pose different health risks. In this study, size-segregated PM samples were collected at a coastal urban site in Xiamen, a port city in southeastern China, between August 2020 and September 2021. The water-soluble constituents, including inorganic ions, elements and organic carbon, were determined. Total volume-normalized OP based on the dithiothreitol assay was highest in spring (0.241 ± 0.033 nmol min-1 m-3) and lowest in summer (0.073 ± 0.006 nmol min-1 m-3). OP had a biomodal distribution with peaks at 0.25-0.44 µm and 1.0-1.4 µm in spring, summer, and winter and a unimodal pattern with peak at 0.25-0.44 µm in fall, which were different from the patterns of redox-active species. Variations in the seasonality of fine and coarse mode OP and their correlations with water-soluble constituents showed that the size distribution patterns of OP could be attributed to the combined effects of the size distributions of transition metals and redox-active organics and the interactions between them which varied with emissions, meteorological conditions and atmospheric processes. Respiratory tract deposition model indicated that the deposited OP and the toxic elements accounted for 47.9 % and 36.8 % of their measured concentrations, respectively. The highest OP doses and the excess lifetime carcinogenic risk (ELCR) were found in the head airway (>70 %). However, the size distributions of OP deposition and ELCR in the respiratory tract were different, with 63.9 % and 49.4 % of deposited ELCR and OP, respectively, coming from PM2.5. Therefore, attention must be paid to coarse particles from non-exhaust emissions and road dust resuspension.

Therapeutic Potential of Kaempferol against Sleep Deprivation-Induced Cognitive Impairment: Modulation of Neuroinflammation and Synaptic Plasticity Disruption in Mice.

Sleep deprivation (SD) has led to a rise in cognitive impairment (CI) cases. Kaempferol (KMP), known for its anti-inflammatory and antiapoptotic properties, holds promise in countering SD-induced CI. Experimental validation using a sleep-deprived CI model confirmed KMP's efficacy in mitigating CI. Immunofluorescence investigations emphasized diminished activation of astrocytes and reduced the proliferation of microglia in the hippocampus of mice subjected to SD. Subsequently, network pharmacological analyses were conducted and found that KMP may be closely related to the mitogen-activated protein kinase (MAPK) pathway in SD-induced CI. The influence of KMP on the MAPK pathway was verified by the observed decrease in the expression of phosphorylated JNK (p-JNK) and p38 (p-p38). Analyzing hippocampal AMPARS and NMDARS expression indicated KMP's ability to enhance GluA1 phosphorylation (Ser831 and Ser845) and GluN2A levels. Patch clamp assays demonstrated heightened excitatory transmitter transmission in the hippocampus, suggesting KMP's positive influence. Overall, KMP combats neuroinflammation via MAPK inhibition, augments synaptic function, and addresses learning and memory dysfunction in sleep-deprived mice.

Circulating Irisin Level as a Biomarker for Pure Aortic Stenosis and Aortic Valve Calcification.

Irisin, a myokine mainly secreted by skeletal and cardiac muscles, is actively involved in cardiovascular diseases. However, whether irisin is associated with aortic stenosis remains unknown. Two hundred ninety-three severe AS patients who underwent transcatheter aortic valve implantation were enrolled and followed-up for 35 months on average. Enzyme-linked immunosorbent assay (ELISA) was applied to measure circulating irisin levels. Patients were divided into two groups based on the median plasma irisin level. We found that high plasma irisin levels were independently associated with pure aortic stenosis (PAS) after adjusting for age, body mass index, history of peripheral vascular disease, and creatinine (OR = 3.015, 95% CI 1.775-5.119, P < 0.001). ROC curve analysis showed a significant predictive value of irisin for PAS (AUC = 0.647, 95% CI 0.583-0.711, P < 0.001). The severity of aortic valve calcification was negatively associated with plasma irisin levels (P < 0.05). In conclusion, irisin is an independent predictor for PAS and is negatively associated with the severity of aortic valve calcification.

The associations of particulate matter short-term exposure and serum lipids are modified by vitamin D status: A panel study of young healthy adults.

Particulate matter (PM) exposure is associated to the adverse change in blood lipids. Vitamin D is beneficial to lipid metabolism, but whether vitamin D levels modifies the impact of air pollutants on lipids is unclear. The purpose of the study was to investigate if vitamin D modifies the associations of PM and serum lipids in young healthy people. From December 2017 to January 2018, a panel study with five once weekly follow-ups was conducted on 88 healthy adults aged 21.09 (1.08) (mean (SD)) years on average in Guangzhou, China. We measured serum lipids, serum 25-hydroxyvitamin D (25(OH)D) concentrations (440 blood samples in total), mass concentrations of particulate matter with diameters ≤2.5 µm (PM2.5), ≤1.0 µm (PM1.0), and ≤0.5 µm (PM0.5), and number concentrations of particulate matter with diameters ≤0.2 µm (PN0.2) and ≤0.1 µm (PN0.1) at each follow-up. Linear mixed-effect models were applied to assess the interaction of vitamin D and size-fractionated PM short-term exposure on four lipid metrics. We found the interactions between 25(OH)D and size-fractionated PM exposure on blood lipids in different lags (lag 3 days and 4 days). An interquartile range increase in PM2.5, PM1.0, PM0.5 were significantly associated with increments of 12.30%, 12.99%, and 13.66% in triglycerides (TGs) at lag 4 days at vitamin D levels <15 ng/mL group, respectively. Similar results were found for PN0.2, PN0.1 and low-density lipoprotein cholesterol (LDL-C). All the associations between size-fractionated PM and blood lipids were found null statistically significant in vitamin D levels ≥15 ng/mL group.

Crosstalk between PML and p53 in response to TGF-ß1: A new mechanism of cardiac fibroblast activation.

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.

Development of microsatellite markers in Parakmeria nitida (Magnoliaceae).

PREMISE OF THE STUDY: We developed microsatellite makers for Parakmeria nitida to investigate its population structure and conservation genetics. METHODS AND RESULTS: A total of 25 microsatellite primer pairs were developed using the Fast Isolation by AFLP of Sequences COntaining repeats (FIASCO) protocol, and polymorphism was assessed in three natural populations of P. nitida. Among these markers, 11 were monomorphic and 14 showed polymorphism. CONCLUSIONS: These markers are potentially useful for future population genetic analyses of P. nitida and will serve as an important tool for conservation efforts.

(4Z)-4-[(2-Chloro-anilino)(phen-yl)methyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

The title compound, C(23)H(18)ClN(3)O, exists in an enamine-keto form with the amino group involved in an intra-molecular N-H⋯O hydrogen bond. The five-membered ring is nearly planar, the largest deviation being 0.0004 (7) Å, and makes dihedral angles of 16.62 (6), 41.89 (5) and 71.27 (4)° with the phenyl rings. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into supra-molecular chains along the b axis.

A hybrid variable selection and modeling strategy for the determination of target compounds in different spectral datasets.

In this paper, a hybrid technique is proposed to establish quantitative models for the determination of target compounds in different spectral datasets. The proposed hybrid method is the hybridization of interval partial least squares (iPLS) method with gradient descent (GD) algorithm. Here, the novelty of the proposed method is that the iPLS method is applied to variable selection and the GD algorithm is employed to establish quantitative models based on the selected optimal variables. In the application of the hybrid iPLS-GD method, the factors, i.e., the number of the interval for the iPLS method and the learning rate, the number of iterations for the GD method, that affect the quantitative accuracy of the method are optimized and determined. Then three spectral datasets, including the near-infrared spectroscopy (NIR) dataset, nuclear magnetic resonance (1H NMR) dataset and excitation-emission matrix fluorescence (EEM) dataset, are used to test and verify the performance of the iPLS-GD method. We compare the hybrid iPLS-GD method with the PLS and iPLS methods from the aspects of modeling ability and predictive ability. The results demonstrated that the iPLS-GD method can be used as an effective and promising tool for the determination of target compounds in complex samples in practice.