Three novel sesquiterpene polyol esters from the root bark of Celastrus angulatus Maxim and their nitric oxide inhibitory activity.

Three new sesquiterpene polyol ester compounds angulatin V [1ß,15-diacetoxy-2ß-(α-methyl)-butanoyloxy-4α,6α-dihydroxy-8α-isobutanoyloxy-9ß-benzoxy-ß-dihydroagarofuran], angulatin W [1ß,2ß-diacetoxy-4α,6α-dihydroxy-8-carbonyl-9ß-benzoxy-15-isobutanoyloxy-ß-dihydroagarofuran], angulatin X [1ß,2ß,8α-triacetoxy-4α, 6α-dihydroxy-9ß-benzoxy-15-nicotinyl-ß-dihydroagarofuran] (1-3), together with one known compound Putterine B (4), were isolated from the root bark of Celastrus angulatus Maxim. The structures of compounds 1-3 were elucidated by NMR, HRESIMS, IR data, and comparison with the literature data. The anti-inflammatory activity of all compounds was evaluated by measuring nitric oxide production in RAW264.7 macrophages. Compounds 1-4 showed no significant nitric oxide inhibitory activity at 2.5 and 5 µM concentrations.

Nutritional and Feeding Adaptability of Clanis bilineata tsingtauica Larvae to Different Cultivars of Soybean, (Glycine max).

The larvae of Clanis bilineata tsingtauica, a special species of Chinese edible insect, are of great nutritional, medicinal and economic value to humans. This study aimed to clarify the effect of different soybean varieties (Guandou-3 (G3), Ruidou-1 (R1), September cold (SC)) on the nutritional quality and feeding selection behavior of C. bilineata tsingtauica larvae. The results showed that soybean isoleucine (Ile) and phenylalanine (Phe) were positively correlated with larval host selection (HS) and protein content. The order of soybean plants selected by C. bilineata tsingtauica larvae was R1 > SC > G3, and they selected R1 significantly higher than SC and G3 by 50.55% and 109.01%, respectively. The protein content of the larvae fed on R1 was also the highest among the three cultivars. In addition, a total of 17 volatiles belonging to 5 classes were detected from soybeans: aldehydes, esters, alcohols, ketones, and heterocyclic compounds. Pearson's analysis showed that soybean methyl salicylate was positively correlated with larval HS and their protein content, and soybean 3-octenol was negatively correlated with larval HS and their palmitic acid content. In conclusion, C. bilineata tsingtauica larvae are more adapted to R1 than to the other two soybean species. This study provides a theoretical basis for the production of more protein-rich C. bilineata tsingtauica in the food industry.

TM7 (Saccharibacteria) regulates the synthesis of linolelaidic acid and tricosanoic acid, and alters the key metabolites in diapause Clanis bilineata tsingtauica.

Good exploitation and utilization of edible insects can effectively alleviate global food security crisis in years. The study on diapause larvae of Clanis bilineata tsingtauica (DLC) was conducted to explore how gut microbiota regulate the nutrients synthesis and metabolism of edible insects. The results showed that C. bilineata tsingtauica maintained a total and stable nutrition levels at early phase of diapause. The activity of instetinal enzymes in DLC fluctuated markedly with diapause time. Additionally, Proteobacteria and Firmicutes were the predominant taxa, and TM7 (Saccharibacteria) was the marker species of gut microbiota in DLC. Combined the gene function prediction analysis with Pearson correlation analysis, TM7 in DLC was mainly involved in the biosynthesis of diapause-induced differential fatty acids, i.e., linolelaidic acid (LA) and tricosanoic acid (TA), which was probably regulated by changing the activity of protease and trehalase, respectively. Moreover, according to the non-target metabolomics, TM7 might regulate the significant differential metabolites, i.e., D-glutamine, N-acetyl-d-glucosamine and trehalose, via the metabolism of amino acid and carbohydrate pathways. These results suggest that TM7 increased LA and decreased TA via the intestinal enzymes, and altered intestinal metabolites via the metabolism pathways, maybe a key mechanism for regulating the nutrients synthesis and metabolisms in DLC.

CaMK4 Promotes Acute Lung Injury Through NLRP3 Inflammasome Activation in Type II Alveolar Epithelial Cell.

Background: Type II alveolar epithelial cell (AEC II), in addition to its roles in maintaining lung homeostasis, takes an active role in inflammatory response during acute lung injury (ALI). Ca2+/calmodulin-dependent protein kinase IV (CaMK4) activated by Ca2+/calmodulin signaling, has been implicated in immune responses. This study was to investigate the roles of CaMK4 in the development of ALI and the underlying mechanisms. Methods: CaMK4 inhibitor KN-93 was used to investigate the effects of CaMK4 on NLRP3 inflammasome activation. The effects of KN-93 on disease development of lipopolysaccharide (LPS)-induced ALI were also evaluated. The role of CaMK4 on NLRP3 inflammasome activation was explored in human AEC II cell line A549 using KN-93 or CaMK4 siRNA. NLRP3 inflammasome activation was measured by histology immunofluorescence and Western blot. IL-1ß and IL-18 were measured by ELISA. Results: Phosphorylation of CaMK4 and the expression of NLRP3 and Caspase-1 p20 were increased in the lungs of LPS-induced ALI mice, which was suppressed by KN-93 as measured by Western blot. Further, the activation of NLRP3 inflammasome was detected in AEC II from patients with acute respiratory distress syndrome (ARDS) and LPS-induced ALI mice. In vitro, inhibition or silencing CaMK4 in AEC II significantly inhibited NLRP3 inflammasome activation, resulting in reduced IL-1ß production. The inhibition of NLRP3 inflammasome and decreased IL-1ß/IL-18 production by KN-93 led to reduced inflammatory infiltration and ameliorated lung injury in LPS-induced ALI mice. Conclusion: CaMK4 controls the activation of NLRP3 inflammasome in AEC II during LPS-induced ALI. CaMK4 inhibition could be a novel therapeutic approach for the treatment of ALI.

Universal cooling patterns of the butterfly wing scales hierarchy deduced from the heterogeneous thermal and structural properties of Tirumala limniace (Lepidoptera: Nymphalidae, Danainae).

The radiative cooling of butterfly wing scales hierarchy has great value in understanding how poikilotherms adapt to the environment and developing bionic materials. However, it remains unclear what the cooling system is like and how the variation of hierarchy affects the cooling efficiency. Therefore, the correlation between the variations of the structure and emissivity of scale hierarchy is thoroughly investigated in Tirumala limniace (Cramer, 1775), whose thermal properties are highly heterogeneous among different wings and regions but similar between males and females. Patterns were deduced from the biological and model simulation experiments. The scale hierarchy varies at the micro- to nanolevel on both surface and section, corresponding to the variating emissivity. Scales on wing veins and margins have large nanostructured units with small lumens and are distinctly thickened, which bring extraordinarily high emissivity. The variations of light and dark scales, respectively, lead to the high emissivity of the middle region of wings and the front wings. Generally, the elevation of the inner surface area and the thickness of the chitin is the key to enhancing the cooling efficiency. For the first time, the effects of the variation of hierarchy toward emissivity of the mid-infrared spectrum are systematically clarified. It is demonstrated that wing scales integrally differentiate in coping with the heterogeneous cooling needs, which may benefit in balancing multifunctions and the development toward the adaptation to the abiotic environment. The study provides insights into the comprehensive thermoregulation system of butterflies and the further development of radiative cooling materials.

Three new sesquiterpene polyol esters from Celastrus angulatus.

Three new sesquiterpene polyol ester compounds angulatins S-U, together with three known compounds were isolated from Celastrus angulatus Maxim. According to mainly 1D NMR and 2D NMR analysis, the structures of the new compounds were completely determined as angulatin S (1ß-furoyloxy-2ß,8α-diisobutanoyloxy-9ß-benzoyloxy-15-acetoxy-4α,6α-dihydroxy-ß-dihydroagarofuran), angulatin T (1ß,2ß,6α-triacetoxy-8ß,15-diisobutanoyloxy-9α-benzoyloxy-ß-dihydroagrofuran), and angulatin U (1ß,6α,15-triacetoxy-8ß-isobutanoyloxy-9α-benzoyloxy-ß-dihydroagarofuran).

Nutritional Properties of Larval Epidermis and Meat of the Edible Insect Clanis bilineata tsingtauica (Lepidoptera: Sphingidae).

Insects represent a sustainable, protein-rich food source widely consumed in Asia, Africa, and South America. Eating Clanis bilineata tsingtauica Mell is common in the eastern part of China. A comparative characterization of nutrients in the meat and epidermis of C. bilineata tsingtauica was performed in this study. The results showed this insect to be high in nutrients, particularly in the epidermis where protein total was 71.82%. Sixteen different amino acids were quantified in C. bilineata tsingtauica, and the ratio of essential to nonessential amino acids in the epidermis and meat was 68.14% and 59.27%, respectively. The amino acid composition of C. bilineata tsingtauica is balanced, representing a high-quality protein source. Eight minerals were quantified in C. bilineata tsingtauica, including four macro and four trace elements. Fe in the epidermis and Zn in the meat were abundant at 163.82 and 299.31 µg/g DW, respectively. The presence of phytic acid impacted the absorption of mineral elements in food. We also detected phytic acid in C. bilineata tsingtauica. The molar ratio of phytic acid to zinc (PA/Zn) in C. bilineata tsingtauica was very low (3.28) compared to Glycine max and Cryptotympana atrata, which indicated that mineral utilization was high. In conclusion, this study confirms that C. bilineata tsingtauica is a highly nutritious food source for human consumption, and the results provide a basis for further consumption and industrialization of this edible insect.

Edible Aquatic Insects: Diversities, Nutrition, and Safety.

Edible insects have great potential to be human food; among them, aquatic insects have unique characteristics and deserve special attention. Before consuming these insects, the nutrition and food safety should always be considered. In this review, we summarized the species diversity, nutrition composition, and food safety of edible aquatic insects, and also compared their distinguished characteristics with those of terrestrial insects. Generally, in contrast with the role of plant feeders that most terrestrial edible insect species play, most aquatic edible insects are carnivorous animals. Besides the differences in physiology and metabolism, there are differences in fat, fatty acid, limiting/flavor amino acid, and mineral element contents between terrestrial and aquatic insects. Furthermore, heavy metal, pesticide residue, and uric acid composition, concerning food safety, are also discussed. Combined with the nutritional characteristics of aquatic insects, it is not recommended to eat the wild resources on a large scale. For the aquatic insects with large consumption, it is better to realize the standardized cultivation before they can be safely eaten.

The application of transbronchial cryobiopsy in interstitial lung disease: a prospective, multicenter, real-world study.

BACKGROUND: Transbronchial cryobiopsy (TBCB) has been widely used to diagnose interstitial lung disease (ILD). Existing reports on TBCB in ILD are mostly single-center prospective or retrospective studies but rarely multicenter prospective real-world studies. We explored the diagnostic efficiency and safety of TBCB in ILD in a real world setting. METHODS: A prospective, multicenter, real-world study was conducted to analyze the data of patients with unclarified ILD who underwent TBCB in 20 hospitals in China from October 2018 to October 2019. The results of the pathological and multidisciplinary discussion (MDD) diagnosis and complications related to TBCB were then analyzed. RESULTS: A total of 373 patients were enrolled in this study, including 194 males and 179 females, with an average age of 52.6±12.4 years. None of the patients had severe hemorrhaging, and the incidence of pneumothorax was 4.8%. The proportions of definitive, possible, and unclassified pathological diagnoses were 62.5%, 5.6%, and 31.9%, respectively. The overall diagnostic yield of MDD was 63.5%. There were 237 patients with a definitive diagnosis of MDD and 136 patients with an unclarified MDD diagnosis. The cooling gas pressure, freezing durations, number of specimens, maximum lengths of specimens, and specimen sizes varied significantly between the definitive and unclarified MDD diagnoses. CONCLUSIONS: In China, the application of TBCB in ILD is generally safe, and its diagnostic efficiency is acceptable. Using a 1.9-mm cryoprobe to collect five samples would achieve a better positive diagnostic rate for TBCB in ILD, without a significant increase in complication risk. TRIAL REGISTRATION: ClinicalTrials.gov; date of registration: 09/25/2018; registration number: NCT03704233; URL: clinicaltrials.gov.

Chylothorax and constrictive pericarditis in a woman due to generalized lymphatic anomaly: a case report.

BACKGROUND: Generalized lymphatic anomaly (GLA) is characterized by diffuse or multicentric proliferation of dilated lymphatic vessels resembling common lymphatic malformations. Compared with soft tissue or bone involvement, thoracic involvement may be associated with a worse prognosis. CASE PRESENTATION: We reported a case of GLA with chylothorax and constrictive pericarditis in a 29-year-old woman. This patient exhibited remarkable features, including a continuously hemorrhagic chylothorax, constrictive pericarditis, and involvement of bone and neck lymph nodes. After attempting to manage her condition with conservative treatment, the patient underwent pericardial stripping surgery. Exploration revealed abundant hyperplasia of tubular tissue in the aortopulmonary window in both pleural cavities. CONCLUSIONS: This case highlights the importance of maintaining the clinical suspicion of GLA during the follow-up of chylothorax patients. Aggressive pericardial surgery, which is important for both diagnosis and treatment, should be performed in patients with GLA with constrictive pericarditis.

Importance of fractional exhaled nitric oxide in diagnosis of bronchiectasis accompanied with bronchial asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measurement is a simple, rapid, highly reproducible, and noninvasive method of airway inflammation assessment. Therefore, FeNO is extensively used for the diagnosis and management of asthma. The feasibility of using FeNO as an alternative to conventional pulmonary function test to differentiate patients with bronchiectasis (BE) and bronchial asthma from those with BE only remains unclear. METHODS: From February 2013 to February 2015, 99 patients diagnosed with BE through high-resolution computed tomography (HRCT) were subjected to FeNO measurement, bronchial challenge test (BCT), or bronchodilator test. Bronchial hyperreactivity and/or reversible airway obstruction was used to define asthma. The receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in the diagnosis of asthmatic patients with BE, and the optimal operating point was also determined. RESULTS: Of 99 patients with BE, 20 patients presented asthma, and 12 of these patients received regular treatment, which were given with budesonide (200 µg, bid) for 12 weeks to evaluate changes in the concentration and assess the role of FeNO in the treatment. The area under the ROC curve was estimated as 0.832 for FeNO. Results also revealed a cut off value of >22.5 part per billion (ppb) FeNO for differentiating asthmatic from non-asthmatic (sensitivity, 90.0%; specificity, 62.5%) patients with BE. FeNO and forced expiratory volume for 1 second significantly improved after the treatment. CONCLUSIONS: Clinical FeNO measurement is a simple, noninvasive, and rapid method used to differentiate asthmatic from nonasthmatic patients with BE. This technique exhibits potential for asthma management.

Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A meta-analysis.

CD133 has been identified as a putative neoplastic stem cell marker in esophageal carcinoma. However, the prognostic value of CD133 overexpression in patients with esophageal carcinoma remains controversial. A meta-analysis of previous studies was performed, in order to assess the association of CD133 overexpression with the clinicopathological characteristics of esophageal carcinoma patients. A total of 7 studies, including 538 patients, were subjected to the final analysis. Our results indicated that a positive CD133 expression was significantly associated with lymph node metastasis [odds ratio (OR)=3.09, 95% confidence interval (CI): 1.93-4.95; P<0.00001], clinical stage (OR=4.26, 95% CI: 1.55-11.73; P=0.005) and histopathological grade (OR=2.40, 95% CI: 1.16-4.94; P=0.02). There was no statistically significant association of CD133 with depth of invasion (OR=1.89, 95% CI: 0.42-8.43; P=0.41). Based on the results of this study, we concluded that CD133 is an efficient prognostic factor in esophageal carcinoma. Higher CD133 expression is significantly associated with lymph node metastasis, clinical stage and histopathological grade.

Single-chain urokinase in empyema induced by Pasturella multocida.

Intrapleural fibrin deposition and subsequent fibrosis characterize evolving empyema and contribute to the morbidity associated with this condition. Single-chain urokinase (scuPA) is proenzyme form of the urokinase plasminogen activator, which has recently been shown to effectively clear intrapleural loculation in tetracycline-induced pleurodesis in rabbits. The authors therefore hypothesized that scuPA could likewise improve intrapleural injury associated with empyema. The authors used a rabbit model of empyema induced by intrapleural administration of Pasturella multocida to test this hypothesis and determined the effects of intrapleural scuPA on pleural fluids indices of inflammation and intrapleural fibrosis. The authors found that intrapleural administration of scuPA was well tolerated, generated readily detectable fibrinolytic activity in the empyema fluids and did not induce intrapleural or systemic bleeding. Pleural fluid volume, intrapleural protein, and D-dimer concentrations were increased at 24 and 48 hours (P < .01, respectively) after induction of empyema. Intrapleural loculation did not occur in the scuPA- or vehicle control-treated animals and there was no significant change in the pleural empyema or thickening scores. These findings confirm that intrapleural scuPA generates fibrinolysis in empyema fluids but does not alter fibrotic repair at the pleural surface or the intensity of intrapleural inflammation in this empyema model.

Diagnostic value of pleural fluid N-terminal pro-brain natriuretic peptide levels in patients with cardiovascular diseases.

BACKGROUND AND OBJECTIVE: The diagnosis of the cause of pleural effusions caused by cardiovascular diseases such as congestive heart failure (CHF) and acute pulmonary embolism is sometimes difficult. The purpose of the present study was to evaluate the utility of pleural fluid levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in differentiating pleural effusions due to CHF, pulmonary embolism and post-coronary artery bypass graft (CABG) surgery. METHODS: The levels of pleural fluid NT-proBNP were measured by ELISA in a total of 40 patients: 10 with CHF, 10 with pulmonary embolism, 10 post-CABG and 10 with carcinoma. RESULTS: The median level of NT-proBNP in the pleural fluid of patients with CHF was 5390 pg/mL (25th to 75th percentiles, 4566 to 8158 pg/mL), which was significantly higher than that in patients with post-CABG effusions (424 pg/mL, 352 to 873), with pulmonary embolism (311 pg/mL, 212 to 1159), or with carcinoma (302 pg/mL, 208 to 626) (P < 0.001, CHF group vs all other groups). In receiver-operating curve analysis, an NT-proBNP level of >or=2220 pg/mL demonstrated a sensitivity of 100% and a specificity of 96.7% for the identification of CHF. CONCLUSIONS: Measurement of the NT-proBNP level in pleural fluid is accurate in diagnosing the etiology of the effusion as CHF. Pleural fluid levels above 2220 pg/mL are essentially diagnostic that the pleural effusion is due to CHF.

[Effect of hypertonic medium on expression of aquaporin-1 in pleural mesothelial cells: experiment with rats].

OBJECTIVE: To study the expression of aquaporin-1 (AQP-1) in pleural mesothelial cells (PMCs) and the influence of hypertonic medium thereupon. METHODS: Rat PMCs were isolated, cultured, and divided into 2 groups: hypertonic group, cultured in hypertonic media with NaCl of different concentrations for 24 h and control group, cultured in D-MEM/F-12 medium. The 100 mmol/L NaCI group was examined at the time points 6, 12, 18, and 24 h respectively. RT-PCR and Western blotting were used to analyze the mRNA and protein expression of AQP-1. RESULTS: The A values of AQP-1 protein expression were 24.0 +/- 1.8, 27.8 +/- 2.4, 31.7 +/- 2.5, 89.7 +/- 6.2, and 107.7 +/- 9.3 respectively in the PMCs treated with hypertonic media with NaCl of the concentrations of 25, 50, 75, 100, and 150 mmol/L, all significantly higher than that in the control group (10.8 +/- 1.5, all P < 0.01). The A values of AQP-1 protein expression were 42.1 +/- 2.6, 78.9 +/- 3.6, 109.6 +/- 7.6, and 123.4 +/- 8.7 in the PMCs treated with hypertonic media with NaCl of the concentration of 100 mmol/L after 6 h, 12 h, 18 h, and 24 h, all significantly higher than that in the control group (12.9 +/- 1.9, P < 0. 01). The a values of AQP-1 mRNA expression were 62.6 +/- 6.4, 75.3 +/- 5.5, 122.3 +/- 11.4, 196.2 +/- 18.1, and 223.0 +/- 19.3 respectively in the PMCs treated with hypertonic media with NaCl of the concentrations of 25, 50, 75, 100, and 150 mmol/L, all significantly higher than that in the control group (23.5 +/- 2.7, all P < 0.01). The A values of AQP-1 protein expression were 83.6 +/- 6.1, 159.3 +/- 6.9, 266.2 +/- 24.1, and 196.2 +/- 15.7 in the PMCs treated with hypertonic media with NaCl of the concentration of 100 mmol/L after 6 h, 12 h, 18 h, and 24 h, all significantly higher than that in the control group (26.5 +/- 2.8, P < 0.01). CONCLUSION: Hypertonic medium increases the expression of AQP-1 mRNA and protein. AQP-1 participates in the pleural fluid formation.

The short-term administration of Ketoprofen does not decrease the effect of Pleurodesis induced by talc or Doxycycline in rabbits.

OBJECTIVE: To determine whether the concomitant administration of ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) has any effect on the pleurodesis induced by talc or doxycycline in rabbits. METHODS: Four groups of seven New Zealand rabbits were assigned to receive the following treatments: 400mg/kg of talc intrapleurally only (group 1), 400mg/kg of talc plus 1mg/kg of ketoprofen intramuscularly (group 2), 10mg/kg of doxycycline intrapleurally only (group 3) and 10mg/kg of doxycycline plus 1mg/kg of ketoprofen intramuscularly (group 4). Intramuscular administration of ketoprofen began 4h before the intrapleural administration of the sclerosing agents, followed by twice daily administrations for 1 week. Pleural fluid was collected 24, 48 and 72h after intrapleural injections. Pleurodesis was evaluated macroscopically and microscopically after 14 days. RESULTS: The concomitant use of ketoprofen at 1mg/kg does not decrease the WBC, LDH, and protein in pleural fluid at 24h following intrapleural injection of talc or doxycycline. There were no significant differences in the macroscopic pleurodesis scores, the degree of microscopic pleural fibrosis, the thickness of the pleura or the percent of the pleura occupied with angiogenesis. CONCLUSIONS: The study shows that the short-term systemic administration of NSAIDs does not affect the efficacy of pleurodesis induced by talc or doxycycline in rabbits.

Intrapleural heparin or heparin combined with human recombinant DNase is not effective in the treatment of empyema in a rabbit model.

OBJECTIVE AND BACKGROUND: The aim of this study was to investigate the effectiveness of intrapleural heparin or heparin combined with human recombinant DNase in the treatment of empyema. METHODS: Empyema was induced in rabbits with an intrapleural injection of 10(9)Pasteurella multicoda organisms in infusion agar via a surgically placed chest tube. Once empyema was verified, a blinded investigator administered drugs via the chest tube. There were three treatment groups each with six rabbits. One group was given 1000 IU heparin, a second group was given 1000 IU heparin plus 1 mg of human recombinant DNase via chest tube and the control group received saline. The rabbits received treatment every 12 h for a total of six treatments and the volume of each treatment was 3 mL. The animals were sacrificed at day 10 and the amount of empyema and pleural thickening was scored macroscopically on a scale of 0-6. RESULTS: The total volume of pleural effusion aspirated was significantly higher in the heparin group (25.8+/-10.7 mL) compared with either saline (8+/-8.9) or heparin plus human recombinant DNase (6.8+/-6.1) groups (P=0.003). The mean empyema and pleural thickening scores did not differ significantly between the groups (P=0.8, P=0.5 respectively). A weak correlation was found between total volume of aspirated pleural fluid and pleural parameters of white blood cell counts and LDH levels (r=0.546 and P=0.02, r=0.631 and P=0.02 respectively). CONCLUSION: The intrapleural administration of 1000 IU heparin alone or in combination with 1 mg of human recombinant DNase is no more effective than saline in the treatment of empyema in rabbits. Intrapleural heparin significantly increased the drainage of pleural fluid compared with the combination and saline group.