Nano-pesticide carrier O-Carboxymethyl chitosan is indigestible in Apis cerana cerana and affects intestinal flora.

O-Carboxymethyl chitosan nanoparticles (O-CMC-NPs), which are organic pesticide carriers, have excellent application potential. Exploring the effects of O-CMC-NPs on non-target organisms, such as Apis cerana cerana, is critical for their effective application; however, such studies are limited. This study investigated the stress response of A. cerana Fabricius after O-CMC-NPs ingestion. The administration of high O-CMC-NP concentrations enhanced the activities of antioxidant and detoxifying enzymes in A. cerana, with the activity of glutathione-S-transferase increasing by 54.43 %-64.33 % after one day. The transit of O-CMC-NPs into the A. cerana midgut resulted in their deposition and adherence to the intestinal wall, as they cluster and precipitate in acidic conditions. The population of Gillianella bacteria in the middle intestine was remarkably reduced after 6 d of administration of high O-CMC-NP concentrations. Contrastingly, the abundance of Bifidobacteria and Lactobacillus in the rectum significantly increased. These results indicate that the intake of high concentrations of O-CMC-NPs causes a stress response in A. cerana and affects the relative abundance of crucial intestinal flora, which may pose a potential risk to the colony. This implies that even nanomaterials with favorable biocompatibility should be applied reasonably within a specific range to avoid adverse effects on the environment and non-target organisms in the context of large-scale research and promotion of nanomaterials.

[Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures].

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures / 中国中药杂志

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Interactions Between Body Mass Index and Glomerular Filtration Rate Increase the Identification Ability of Obstructive Sleep Apnea in Patients with Hypertrophic Cardiomyopathy.

Purpose: Obstructive sleep apnea (OSA) is common in hypertrophic cardiomyopathy (HCM) patients and is related to worse adverse prognosis in HCM patients. However, there are no acknowledged warning characteristics to help to identify OSA in HCM patients. Methods: Seventy-one HCM patients and forty-nine hypertensive (HTN) patients as control group underwent polysomnography (PSG) examination at the Second Affiliated Hospital of Nanchang University from January 2015 to December 2019 patients were consecutively enrolled. The characteristics were analyzed and compared between HCM patients with OSA and without OSA. Results: A total of 37 (52%) HCM patients and 25 (51%) HTN patients were diagnosed with OSA. High body mass index (BMI) (OR = 1.228, 95% CI: 1.032,1.461, P = 0.020) and low estimated glomerular filtration rate (eGFR) (OR = 0.959, 95% CI: 0.931,0.989, P = 0.007) independently correlated with the occurrence of OSA in HCM patients, respectively. Multiplicative interaction was shown between high BMI and low eGFR on the risk of OSA in HCM patients (OR: 6.050, 95% CI: 1.598, 22.905, P = 0.008). The additive interaction analysis further suggested that 70.1% of HCM patients developed OSA due to the additive interaction between BMI and eGFR. The identification ability of OSA in HCM patients was significantly enhanced by using both BMI and eGFR (area under receiver-operating characteristic analysis curve 0.785; P = 0.000038) as compared with BMI (area under curve 0.683, P = 0.008) or eGFR (area under curve 0.700, P = 0.004), respectively. Conclusion: High BMI or low eGFR independently related to the occurrence of OSA in HCM patients, and the multiplicative and additive interactions between BMI and eGFR increased the identification ability of OSA in HCM patients.

[Spatiotemporal Distribution and Source Apportionment of Suspended Polycyclic Aromatic Hydrocarbons in Surface Water].

Polycyclic aromatic hydrocarbons (PAHs) are a type of typical environmental pollutant with carcinogenic effects and high ecological risk. With the development of industry, surface water acts as a primary sink for PAHs. Owing to their low solubility, a significant amount of PAHs are adsorbed onto suspended particulate matter in surface water, which presents a serious risk to human health and the ecological environment. To protect human health and aquatic organisms, a systematic assessment of the trends in PAHs exposure risk is essential. Based on long-term monitoring data from 2002 to 2016, this study systematically evaluated the spatiotemporal distribution and source apportionment of PAHs adsorbed on suspended particulate matter in surface water. The results of the Mann-Kendall test indicated that pollution levels of PAHs decreased from 2012 to 2016. The maximum average content was 6239 µg·kg-1, and the minimum was 2760 µg·kg-1. Benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, and benzo(a)anthracene showed significant declines from 2002-2016 (P<0.05). Levels of benzo(a)pyrene, dibenzo(a,h)anthracene, and indeno(1,2,3-cd)pyrene were steady. Wavelet analysis showed that the pollution level of PAHs had significant periodic oscillations for surface water. Midstream and downstream Σ16PAHs showed significant declines from 2002-2016 (P<0.05), whereas upstream Σ16PAHs were steady. ANOVA analysis showed that the spatial difference was significant and occurred in the following order:midstream (6168 µg·kg-1)>upstream (5407 µg·kg-1)>downstream (3412 µg·kg-1). Diagnostic ratio analysis and the positive matrix factorization model suggested that the major sources of PAHs were traffic sources, coal burning sources, and biomass combustion sources, which accounted for 40.9%, 33.7%, and 25.4%, respectively. The contribution of traffic sources decreased by 25.9%. The contributions of coal burning sources and biomass combustion sources increased by 4.8% and 21.1% from 2002-2009 to 2010-2016, respectively. These results provide scientific reference for risk analysis and the control of PAHs pollution in surface water.

The mechanism of Bai He Gu Jin Tang against non-small cell lung cancer revealed by network pharmacology and molecular docking.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related burden and deaths, thus effective treatment strategies with lower side effects for NSCLC are urgently needed. To systematically analyze the mechanism of Bai He Gu Jin Tang (BHGJT) against NSCLC by network pharmacology and molecular docking. METHODS: The active compounds of BHGJT were obtained by searching the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Encyclopaedia of Traditional Chinese Medicine. Search tool for interactions of chemicals was used for acquiring the targets of BHGJT. The component-target network was mapped by Cytoscape. NSCLC-related genes were obtained by searching Genecards, DrugBank and Therapeutic Target Database. The protein-protein interaction network of intersection targets was established based on Search Tool for Recurring Instances of Neighboring Genes (STRING), and further, the therapeutic core targets were selected by topological parameters. The hub targets were transmitted to Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, AutoDock Vina and MglTools were employed for molecular docking validation. RESULTS: Two hundred fifty-six compounds and 237 putative targets of BHGJT-related active compounds as well as 1721potential targets of NSCLC were retrieved. Network analysis showed that 8 active compounds of BHGJT including kaempferol, quercetin, luteolin, isorhamnetin, beta-sitosterol, stigmasterol, mairin and liquiritigenin as well as 15 hub targets such as AKR1B10 and AKR1C2 contribute to the treatment of BHGJT against NSCLC. GO functional enrichment analysis shows that BHGJT could regulate many biological processes, such as apoptotic process. Three modules of the endocrine related pathways including the inflammation, hypoxia related pathways as well as the other cancer related pathways based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis might explain the biological mechanisms of BHGJT in treating BHGJT. The results of molecular docking verified that AKR1B10 and AKR1C2 had the strongest binding activity with the 8 key compounds of NSCLC. CONCLUSION: Our study reveals the mechanism of BHGJT in treating NSCLC involving multiple components, multiple targets and multiple pathways. The present study laid an initial foundation for the subsequent research and clinical application of BHGJT and its active compounds against NSCLC.

Current trends in optimal medical therapy after PCI and its influence on clinical outcomes in China.

BACKGROUND: Limited data were available on the current trends in optimal medical therapy (OMT) after PCI and its influence on clinical outcomes in China. We aimed to evaluate the utilization and impact of OMT on the main adverse cardiovascular and cerebrovascular events (MACCEs) in post-PCI patients and analyzed the factors predictive of OMT after discharge. METHODS: We collected data from 3812 individuals from 2016.10 to 2017.09 at TEDA International Cardiovascular Hospital. They were classified into an OMT group and a non-OMT group according to their OMT status, which was defined as the combination of dual antiplatelet therapy, statins, ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after PCI. Multivariable Cox regression models were developed to assess the association between OMT and MACCEs, defined as all-cause mortality, nonfatal myocardial infarction, stroke, and target vessel revascularization. A logistic regression model was established to analyze the factors predictive of OMT. RESULTS: Our results revealed that the proportion of patients receiving OMT and its component drugs decreased over time. A total of 36.0% of patients were still adherent to OMT at the end of follow-up. Binary logistic regression analysis revealed that baseline OMT (P < 0.001, OR = 52.868) was the strongest predictor of OMT after PCI. The Cox hazard model suggested that smoking after PCI was associated with the 1-year risk of MACCE (P = 0.001, HR = 2.060, 95% CI 1.346-3.151), while OMT (P = 0.001, HR = 0.486, 95% CI 0.312-0.756) was an independent protective factor against postoperative MACCEs. CONCLUSIONS: There was still a gap between OMT utilization after PCI and the recommendations in the evidence-based guidelines. Sociodemographic and clinical factors influence the application of OMT. The management of OMT and smoking cessation after PCI should be emphasized.

Distribution and risk of mercury in the sediments of mangroves along South China Coast.

The importance of mangrove was widely reported. However, the potential risks of pollutants (e.g., Hg) accumulated in the mangroves are often ignored. Thus, the present study aimed to explore the distribution and risk of mercury (Hg) in the sediments of mangroves along South China Coast. Results showed that concentrations of total Hg ranged from 0.0815 to 0.6377 mg/kg, with an arithmetic mean value of 0.2503 mg/kg. The contamination index (Pi) showed mild pollution toxicity risks in NS, slight toxicity risks in DZG, QZ, SY, ND, GQ, TLG, and free pollutions in BMW, SJ, ZJK and BLHK. NS, DZG and SY scored the highest values of Igeo among the eleven mangrove regions studied, indicating moderate to heavy pollution inputs in these regions. As for the distribution of Hg in the sediments along tidal gradient, concentrations of Hg in the sediments sharply increased from seaward mudflat to landward mangrove, corresponding with the increases of TOC. In summary, the present data indicated that mangrove ecosystem is efficient in Hg reservoir. However, the potential ecological risks of Hg, especially in some mangrove regions easily affected by human activities, should be noted.

Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology.

Systemic lupus erythematosus (SLE) is a refractory autoimmune disease. Zhibai Dihuang Wan (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we collected putative targets of ZDW based on TCMSP, GeneCards, and STITCH databases and built a network containing the interactions between the putative targets of ZDW and known therapeutic targets of SLE. Then, the key hubs were imported to DAVID Bioinformatics Resources 6.7 to perform gene ontology biological process (GOBP) and pathway enrichment analysis. A total of 95 nodes including 73 putative targets of ZDW were determined as major hubs in terms of their node degree. The results of GOBP and pathway enrichment analysis indicated that putative targets of ZDW mostly were involved in various pathways associated with inflammatory response and apoptosis. More importantly, eleven putative targets of ZDW (CASP3, BCL2, BAX, CYCS, NFKB1, NFKBIA, IL-6, IL-1ß, PTGS2, CCL2, and TNF-α) were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZDW acting on SLE. This study provides novel insights into the mechanisms of ZDW in SLE, from the molecular level to the pathway level.

Alashanoids K-M, bioactive eremophilane sesquiterpenoids from Syringa pinnatifolia.

Three new eremophilane-type sesquiterpenoids, alashanoids K-M (1-3), and one known analogue (4) were isolated from the peeled stems of Syringa pinnatifolia. All the compounds were isolated from the genus Syringa for the first time. Structures of these compounds were established using 1D and 2D NMR and MS data. The absolute configurations were determined by experimental and calculated electronic circular dichroism analysis, a modification of Mosher's method, and X-ray diffraction. Compounds 2 and 3 inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC50 values of 14.23 and 12.20 µM, respectively, and showed cytotoxic activities against HepG2 cells with the IC50 values of 34.41 and 40.86 µM, respectively.

[Phytochemical and pharmacological progress on humulane-type sesquiterpenoids].

Humulane-type sesquiterpenoids, widely distributed in plants and microbes, include three types: α-humulene, ß-humulene, and γ-humulene. Up to now, 98 humulane-type sesquiterpenoids have been reported, which possessed anti-tumor, anti-inflammatory, antibacterial, and antiviral activities. Herein, this paper describes their chemical constituents and pharmacological activities, hoping to bring benefits for further research and lay a foundation for investigating the structure-activity relationships.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

Phytochemical and pharmacological progress on humulane-type sesquiterpenoids / 中国中药杂志

Humulane-type sesquiterpenoids, widely distributed in plants and microbes, include three types: α-humulene, β-humulene, and γ-humulene. Up to now, 98 humulane-type sesquiterpenoids have been reported, which possessed anti-tumor, anti-inflammatory, antibacterial, and antiviral activities. Herein, this paper describes their chemical constituents and pharmacological activities, hoping to bring benefits for further research and lay a foundation for investigating the structure-activity relationships.

[Chemical constituents from stems of Ilex asprella].

Phytochemical investigation on the stems of Ilex asprella by using various chromatographic techniques led to the isolation of 13 compounds. By spectroscopic analyses and comparisons the spectral data with those in literatures, these compounds were identified as salicifoneoliganol(1), rel-(7R,8S)-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan-4,9,9'-triol 9-ß-D-glucopyranoside(2),(+)-cycloolivil(3),(+)-syringaresinol-4'-O-ß-D-monoglucoside(4), liriodendrin(5), caffeic acid (6), 3,4-dihydroxy-5-methoxybenzaldehyde(7), benzene-1,2,4-triol(8), 3,4,5-trimethoxyphenyl-1-O-ß-D-apiofuranosyl(1″→6')-glucopyranoside(9), aeculetin(10), cryptochlorogenic acid ethyl ester(11), chlorogenic acid ethyl ester(12), and rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo [3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(13). Among them, compounds 7, 8, 11, and 13 were isolated from genus Ilex for the first time, and 1-3, 9, 10, and 12 were isolated from this speciesfor the first time. The anti-inflammatory assay results of these compounds showed that compounds 1 and 9 showed moderate inhibitory effect against NO production in RAW 267. 4 cells with IC50 values of 35.7 and 50.6 µmol•L⁻¹, in vitro respectively, whereas compound 10 showed weak inhibition(IC50 value 98.7 µmol•L⁻¹).

[A new lignan from stem bark of Syringa pinnatifolia].

One new lignan, named Z-pinnatifolin A, along with ten known analogues, were isolated from the stem bark of Syringa pinnatifolia by various chromatographic methods. Their structures were extensively determined on basis of MS and NMR spectroscopic data analyses, and comparison with those in literature. Among them, compounds 3,4, and 8-11 were isolated from this genus for the first time, and 5-7 were isolated from the specie for the first time. Compound 1 showed a moderate inhibition on NO production in BV-2 cells. The present study provides a preliminary data for clarification of bioactive ingredients of S.pinnatifolia with anti-myocardial ischemic effect.

NCAM affects directional lamellipodia formation of BMSCs via ß1 integrin signal-mediated cofilin activity.

The neural cell adhesion molecule (NCAM), a key member of the immunoglobulin-like CAM family, was reported to regulate the migration of bone marrow-derived mesenchymal stem cells (BMSCs). However, the detailed cellular behaviors including lamellipodia formation in the initial step of directional migration remain largely unknown. In the present study, we reported that NCAM affects the lamellipodia formation of BMSCs. Using BMSCs from Ncam knockout mice we found that Ncam deficiency significantly impaired the migration and the directional lamellipodia formation of BMSCs. Further studies revealed that Ncam knockout decreased the activity of cofilin, an actin-cleaving protein, which was involved in directional protrusions. To explore the molecular mechanisms involved, we examined protein tyrosine phosphorylation levels in Ncam knockout BMSCs by phosphotyrosine peptide array analyses, and found that the tyrosine phosphorylation level of ß1 integrin, a protein upstream of cofilin, was greatly upregulated in Ncam-deficient BMSCs. Notably, by blocking the function of ß1 integrin with RGD peptide or ROCK inhibitor, the cofilin activity and directional lamellipodia formation of Ncam knockout BMSCs could be rescued. Finally, we found that the effect of NCAM on tyrosine phosphorylation of ß1 integrin was independent of the fibroblast growth factor receptor. These results indicated that NCAM regulates directional lamellipodia formation of BMSCs through ß1 integrin signal-mediated cofilin activity.

Noralashinol B, a norlignan with cytotoxicity from stem barks of Syringa pinnatifolia.

One new norlignan, noralashinol B (1), and one new natural product, proposed noralashinol C (2), were isolated in a continuous phytochemical investigation on the stem barks of Syringa pinnatifolia. Their structures were elucidated based on the analysis of spectroscopic data, including mass spectrometry and 1D and 2D NMR spectroscopies, and the absolute configuration was determined by experimental and calculated electronic circular dichroism. Compound 1 showed a weak cytotoxicity against HepG2 hepatic cancer cells with its IC50 value of 31.7 µM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-80.0 µM.

[AMP-activated kinase activation inhibits transforming growth factor-ß1 production in cardiac fibroblasts via targeting C/EBPß].

AMP-activated protein kinase (AMPK) activation has been shown to protect against fibrosis. However, the underlying mechanism remains unclear. Here we explored the effect of AMPK activation on transforming growth factor-ß1 (TGFß1) production induced by angiotensin II (AngII) in cardiac fibroblasts and the underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFß1 and AMPK activity were determined by ELISA and Western blots, respectively. Pretreatment of AMPK activator AICAR inhibited TGFß1 production induced by AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C. Furthermore, bioinformatics predicted a potential CCAAT/enhancer-binding protein ß (C/EBPß) binding site in the promoter region of the mouse Tgfb1 gene. Luciferase reporter with wild type, but not deleted, C/EBPß binding sites transfection in mouse embryonic fibroblasts showed increased TGFß1 transcriptional activity induced by AngII, indicating that C/EBPß mediates AngII-induced TGFß1 transcript expression. Pretreatment of AICAR inhibited C/EBPß expression induced by AngII. In conclusion, AMPK activation inhibited TGFß1 production induced by AngII in cardiac fibroblasts through targeting C/EBPß. This finding provides a new mechanism underlying the anti-fibrogenic effects of AMPK activation.