(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Extraction, rapid preparation and neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir.

Searching for new anti-ischemic stroke (anti-IS) drugs has always been a hot topic in the pharmaceutical industry. Natural products are an important source of discovering anti-IS drugs. The aim of the present study is to extract, rapidly prepare and explore the neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir., which is a kind of Tibetan medicine with a clear anti-IS effect. The results showed that 95% ethanol was the optimal extraction solvent. A three-step rapid preparation method for texasin was successfully established, with a purity of 99.2%. Texasin at the concentration of 25-100 µM had no effect on the viability of normal cultured PC12 cells; 12.5 and 25 µM texasin could enhance the viability of PC12 cells damaged by oxygen and glucose deprivation/reoxygenation (OGD/R), and their effects are comparable to the positive drug edaravone at the concentration of 50 µM. Compared with the normal group, the expression of Bcl-2 protein in OGD/R-injured PC12 cells was downregulated (p < 0.01), and that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins were upregulated (p < 0.01, p < 0.001). Compared with the OGD/R group, 25 µM texasin could upregulate the expression of Bcl-2 protein (p < 0.01), and downregulate that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins (p < 0.01, p < 0.001). The 7-OH and 1-O of texasin formed H-bonds with residues Cys891 of the hinge ß-strand of PERK, which is crucial for kinase inhibitors. The above results suggest that the method established in the present study achieved rapid preparation of high-purity texasin. Texasin might inhibit neuronal apoptosis via the regulation of endoplasmic reticulum stress PERK/eIF2α/ATF4/CHOP signalling pathway to exert a protective effect on OGD/R-injured PC12 cells. Aiding by molecular docking, texasin was assumed to be a potential PERK inhibitor.

Hyperxylones A and B, two polycyclic polyprenylated acylphloroglucinols with a benzoyl substituted bicyclo[3.2.1]octane core from Hypericum beanii.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs) possessing a rare benzoyl substituted bicyclo[3.2.1]octane core, hyperxylones A (1) and B (2), along with three new dearomatized isoprenylated acylphloroglucinols (DIAPs), hyperxylones C - E (3-5), were isolated from the roots of Hypericum beanii. The structures of 1-5 were determined by high-resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were biomimetically semi-synthesized starting from 5 and 4, respectively, enabling the correct stereochemical assignment of 5 and 4. Moreover, compounds 1 and 2 showed anti-nonalcoholic steatohepatitis (NASH) activity by inhibiting lipid deposition in L02 cells; compounds 3 and 5 exhibited nitric oxide (NO) inhibitory activity in lipopolysaccharides (LPS)-induced RAW264.7 cells.

Diverse polycyclic polyprenylated acylphloroglucinols with anti-neuroinflammatory activity from Hypericum beanii.

A phytochemical investigation on the roots of Hypericum beanii resulted in the isolation of six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperberlones A-F, along with fourteen known analogues. The structural characterization of these compounds was carried out by analyzing the HRESIMS data, 1D and 2D NMR spectroscopic data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations. Hyperberlone A (1) was a caged PPAP with a rare tricyclo[4.3.1.03,8]decane carbon skeleton. It was deduced to be biosynthetically generated from hyperbeanol C (8) through key Paternò-Büchi reaction, radical cascade cyclizations, and retro-aldol reaction. Compounds 4, 6, 7, 9, 14, and 16 exhibited significant nitric oxide (NO) production inhibitory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values of 6.11-25.28 µM. Moreover, compound 4 significantly decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced BV-2 microglia, as well as the phosphorylation of JNK.

The Impostor Phenomenon Among Nursing Students and Nurses: A Scoping Review.

The impostor phenomenon (IP) refers to a false internal experience of low intelligence or ability that is associated with anxiety, depression, psychological distress, and burnout. The emotions associated with the IP affect not only personal mental health but also patient care. To address this issue, we need to completely understand the prevalence of and factors related to the IP and ways to resolve/overcome IP feelings. The aim of this scoping review was to identify the existing evidence regarding the IP among nursing students and nurses and determine gaps that can be addressed in future research. We conducted our study based on the scoping review methodological framework proposed by Arksey and O'Malley (2005) and advanced by Levac et al. (2010). After searching the Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science and ProQuest databases, we identified 11 studies for inclusion in this review. We found that while the IP exists in nursing students and nurses, clinical nurse specialist students and final-year nursing students are at significant risk of impostor behavior. We also found that research in the nursing field has focused on the prevalence of and factors related to the IP, but few studies have addressed ways to resolve/overcome IP feelings. Thus, research in this area should be increased. This scoping review presents research gaps that may serve as a starting point for future work on the IP in the nursing field.

Biodegradation of dibutyl phthalate by a novel endophytic Bacillus subtilis strain HB-T2 under in-vitro and in-vivo conditions.

The environmental prevalence and potential toxicity of dibutyl phthalate (DBP) motivate the attempt to develop feasible strategies to deal with DBP contamination. In this study, a strain of endphytic bacteria HB-T2 was isolated from sorrel roots and identified as Bacillus sp. by analysing its morphology, physiology, biochemistry and 16S rDNA sequence. The degradation efficiency of DBP by HB-T2 was almost identical under the temperature of 30∼40°C, but was significantly enhanced as the culture pH and inoculum size increases from 6.0 to 8.0, and 1% to 5% respectively. The degradation kinetics of DBP could be well described by the first-order kinetic model, with the degradation half-life ranging from 1.59 to 7.61 h when the initial concentrations of DBP were in the range of 5-20 mg/L. LC-MS analysis of the culture samples taken at varying intervals revealed monobutyl phthalate, phthalic acid and protocatechuic acid as the major metabolic intermediates during the degradation process. HB-T2 exhibited an excellent capability to degrade a wide range of phthalate esters (PAEs), especially butyl benzyl phthalate (BBP), dipentyl phthalate (DPP), and diisobutyl phthalate (DIBP). Inoculation of HB-T2 into Chinese cabbage (Brassica chinensis L.) growing in DBP-contaminated soils could significantly reduce the DBP levels in plant tissues and relieve the phytotoxic effects of DBP. Results of this study highlighted the great potential of this novel endophytic Bacillus subtilis strain HB-T2 for bioremediation of PAEs contamination and improvement of agricultural product safety by reducing PAEs accumulation in edible crops.

Dynamic metabolic and transcriptomic profiling reveals the biosynthetic characteristics of hydroxycinnamic acid amides (HCAAs) in sunflower pollen.

Sunflower pollen is a natural nutritious food with a long history and multiple functions, however, the main chemical components apart from flavonoids and their biosynthesis processes have not been thoroughly investigated. In this study, seven hydroxycinnamic acid amides (HCAAs) (1-7) abundant in sunflower pollen were isolated and identified as one type of the pollen's main chemicals. For a comprehensive understanding of HCAA biosynthesis in Helianthus annuus flowers, RNA-seq, metabolomics, and key genes related to biosynthesis in the sunflower were studied. A large number of compounds at different sunflower growth stages (the 7th, 14th, 21st, and 28th days) and high expression levels of related genes in the transcriptome were detected. A molecular network was constructed to clarify the synthetic pathway of HCAAs, which revealed high transcriptional levels of spermidine hydroxycinnamoyl transferase genes (HaSHT2795 and HaSHT2436) in 14-21-days-old flowers. HaSHT2795 enzymes catalyze tri-coumaroylspermidine formation, and virus-induced gene silencing to inhibit HaSHT2795 and HaSHT2436 could significantly reduce the synthesis of hydroxycinnamic acid amides in sunflower pollen. HCAAs were inferred to be related to the formation of pollen walls and the health effects of pollen. Analyzing HCAA biosynthesis and accumulation in H. annuus pollen will be helpful to understand the functions of HCAAs in the development of pollen and its nutritional value.

[Advances in Mechanism and Influencing Factors Affecting Hydrogen Sulfide Adsorption by Biochar].

Hydrogen sulfide(H2S) is one of the most common gas products from modern industrial processes. It is highly toxic, corrosive, and polluting, and poses harm to both the natural environment and human health if it is not properly removed. Biochar has been widely applied for the treatment of environmental pollution due to its excellent adsorption ability, low cost, and wide choice of source materials. Currently, although studies on hydrogen sulfide adsorption by biochar have attracted increasing attention, the factors involved are complex and varied, leading to a necessity to review and summarize the available knowledge and advances. To bridge the research gap, this paper presents the advances in H2S adsorption by biochar, including properties, influencing factors(i.e., biomass feedstock, pyrolysis temperature, residence time, and particle size), control measures(i.e., humidity, adsorption temperature, operating conditions, and modification of biochar by activation), and adsorption mechanism. The work will provide further reference for the preparation and optimization of biochar adsorption conditions to realize a highly efficient removal of H2S.

Loss of UCHL1 rescues the defects related to Parkinson's disease by suppressing glycolysis.

The role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1; also called PARK5) in the pathogenesis of Parkinson's disease (PD) has been controversial. Here, we find that the loss of UCHL1 destabilizes pyruvate kinase (PKM) and mitigates the PD-related phenotypes induced by PTEN-induced kinase 1 (PINK1) or Parkin loss-of-function mutations in Drosophila and mammalian cells. In UCHL1 knockout cells, cellular pyruvate production and ATP levels are diminished, and the activity of AMP-activated protein kinase (AMPK) is highly induced. Consequently, the activated AMPK promotes the mitophagy mediated by Unc-51-like kinase 1 (ULK1) and FUN14 domain-containing 1 (FUNDC1), which underlies the effects of UCHL1 deficiency in rescuing PD-related defects. Furthermore, we identify tripartite motif-containing 63 (TRIM63) as a previously unknown E3 ligase of PKM and demonstrate its antagonistic interaction with UCHL1 to regulate PD-related pathologies. These results suggest that UCHL1 is an integrative factor for connecting glycolysis and PD pathology.

Evaluation of atherogenic lipoprotein-cholesterol to HDL cholesterol ratio as a prognostic test for ST-segment elevation myocardial infarction.

Background: The detectable component of triglyceride-rich lipoproteins (TGRLs), remnant lipoprotein cholesterol (RLP-c), has been proven being correlated with the progression of atherosclerosis and myocardial infarction. However, when taken as a risk predictor, the prognostic and diagnostic potential of RLP-c remains controversial in studies. In this study, we evaluated the hypothesis that atherogenic lipoprotein-cholesterol (AL-c), representing the sum of RLP-c and the sd-LDL-c, to the HDL-c ratio, could represent a better predictive indicator than RLP-c alone in ST-segment elevation myocardial infarction (STEMI). Methods: The 316 consecutive patients suffering from persistent chest discomfort admitted to the Shanghai General Hospital between January 2018 and June 2018 were enrolled. 149 STEMI patients (62% men, mean age 69.6 ± 13.3 years) were included as the study cohort. The AL-c/HDL-c ratio was calculated on admission in a cohort of electrocardiogram-confirmed STEMI patients and compared to other lipid profiles as a predictive indicator. Results: The AL-c/HDL-c ratio was significantly increased in STEMI patients compared with apparently healthy adults (0.93; IQR [0.71-1.18] vs 0.70; IQR [0.45-1.04]; p < 0.001). Gender dependency existed, and the male and female patients had median AL-c/HDL-c ratios of 1.01 and 0.79, respectively (p < 0.001). Compared to RLP-c, the AL-c/HDL-c ratio had a better prognostic value to predict STEMI risk in both sexes (AUC of 0.672 with a sensitivity of 0.794 in males and 0.613 with a sensitivity of 0.684 in females). Conclusions: The AL-c/HDL-c ratio could represent a convenient and sensitive biomarker for screening and predicting STEMI risk.

Impact of corrected sinus node recovery time in predicting recurrence in patients with paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and sinus node dysfunction (SND) have common underlying pathophysiological mechanisms. As an index of SND, corrected sinus node recovery time (CSNRT) may also reflect atrial function. The aim of the present study was to determine whether CSNRT predicts AF recurrence in patients undergoing AF ablation. METHODS: Consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent radiofrequency catheter ablation between January 2017 and December 2018 were enrolled. Clinical data, CSNRT, and other electrophysiology indices were collected and analysed between patients with or without AF recurrence. RESULTS: A total of 159 patients with PAF who underwent the same radiofrequency catheter ablation procedure were enrolled, including 25 patients with SND. During the one-year follow-up period, 22 patients experienced AF recurrence. Patients with recurrence had a significantly longer CSNRT and a larger left atrial volume index (LAVI) than patients without AF recurrence. SND (CSNRT > 550 ms) and a larger LAVI were independently associated with AF recurrence after ablation. A statistically significant CSNRT cut-off value of 550 ms predicted AF recurrence with 73% sensitivity and 85% specificity. CONCLUSION: CSNRT and LAVI are independent predictors of PAF recurrence following ablation.

Type B polycyclic polyprenylated acylphloroglucinols from the roots of Hypericum beanii.

Two new type B polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2) and a known biogenetic precursor hyperbeanol Q (3) were isolated from the root extract of Hypericum beanii, a medicinal plant widespread in southwest China. Their chemical structures were elucidated by 1D/2D NMR and HRESIMS data analysis, and absolute configurations were determined through detailed electric circular dichroism (ECD) analysis including ECD exciton chirality, Mo2(OAc)4-induced ECD, and ECD comparison. Of these compounds, hyperbeone A (1) is a typical [3.3.1]-type B PPAP with an unusual C-1 geranyl side chain, and hyperberin C (2) possesses a rare bicyclo[5.3.1]hendecane core. Taking compound 3 as a starting point, a plausible biosynthetic pathway to the bicyclic type B frameworks of 1 and 2 was proposed.

Diverse Polycyclic Polyprenylated Acylphloroglucinol Congeners with Anti-Nonalcoholic Steatohepatitis Activity from Hypericum forrestii.

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.

Cajuputones A-C, ß-Triketone Flavanone Hybrids from the Branches and Leaves of Melaleuca cajuputi.

Three new ß-triketone flavanone hybrids, cajuputones A-C were obtained from Melaleuca cajuputi (the Australian 'tea tree'). The structures of cajuputones A-C were elucidated by 1D/2D NMR spectroscopy and HR-ESI-MS analyses; and their absolute configurations were established by electric circular dichroism (ECD) calculations using TDDFT method. Structurally, cajuputones A-C feature a rare 6/6/6/6 oxatetracyclic ring system fused between an acylphloroglucinol-derived ß-triketone and a pinocembrin or strobopinin moiety via an angle-type pyran-like motif. DFT-based conformational optimization in chloroform explained the similarity of the 1D NMR data of cajuputones B and C (C-2 epimers).

Dimethylated acylphloroglucinol meroterpenoids with anti-oral-bacterial and anti-inflammatory activities from Hypericum elodeoides.

Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum, the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(-)-elodeoidols A-F (1-6)), along with three biogenetical homologues (7-9) were isolated from the herbaceous plant of Hypericum elodeoides. Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1-6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5, 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)-5 was 6.25 µg/ml; Compounds 3, 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC50: 10.39 ± 0.49 ~ 34.25 ± 2.32 µM).

Histidine decarboxylase-expressing PMN-MDSC-derived TGF-ß1 promotes the epithelial-mesenchymal transition of metastatic lung adenocarcinoma.

Metastasis is a major risk for lung adenocarcinoma-related mortality. Accumulating evidence raises the possibility that anticancer therapies might be more sensitive by targeting premetastatic niches in addition to the cancer cells themselves. Here, we identified a subpopulation of metastatic lung adenocarcinoma, which was characterized by EMT-related markers such as E-cadherin, Twist, SMAD, and ß-catenin. EMT+ cases exhibited poorer prognosis than EMT- patients, reflecting the pro-metastatic features of EMT. Immunohistochemical staining decorated CD15+ PMN-MDSCs surrounding EMT+ cancer cells in lymph nodes. Metastatic tissues secreted high levels of chemokines, including CXCL1, CXCL5, and CCL2, into the circulation to recruit histidine decarboxylase (Hdc)-positive PMN-MDSCs into metastatic colonies through upregulated CXCR2. The percentage of Hdc+ PMN-MDSCs increased in the setting of metastasis. Hdc+ PMN-MDSCs obtained from EMT+ metastatic masses expressed a higher level of TGF-ß1, rather than TGF-ß2 and TGF-ß3, compared to EMT- counterparts. The depletion of Hdc+ PMN-MDSCs or downregulation of TGF-ß1 significantly decreased EMT+ percentage and, thus, hampered the metastasis process in murine models. Together, our findings suggest that metastatic tumor secretes high levels of chemokines to recruit Hdc+ PMN-MDSCs, which, in turn, express TGF-ß1 to induce cancer cells to undergo EMT at metastatic sites.

Toonasindiynes A-F, new polyacetylenes from Toona sinensis with cytotoxic and anti-inflammatory activities.

The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.

Hyperberins A and B, Type B Polycyclic Polyprenylated Acylphloroglucinols with Bicyclo[5.3.1]hendecane Core from Hypericum beanii.

The first examples of type B polycyclic polyprenylated acylphloroglucinols with a bicyclo[5.3.1]hendecane core, hyperberins A (1) and B (2), were isolated from Hypericum beanii, together with three biosynthetic congeners. Their structures were established by a combination of NMR, electric circular dichroism (ECD), and X-ray diffraction analyses. These isolates indicated divergent cationic cyclization as key steps in the biosynthesis of PPAPs with diverse architectures. Compounds 1 and 2 were moderately cytotoxic and exhibited significant anti-inflammatory activities.

Hyperbeanols F-Q, diverse monoterpenoid polyprenylated acylphloroglucinols from the flowers of Hypericum beanii.

Hyperbeanols F-Q, which are twelve undescribed monoterpenoid polyprenylated acylphloroglucinols, and four known analogues were isolated from the dried flowers of Hypericum beanii. Their structures were elucidated by detailed HRESIMS and 1D and 2D NMR data analyses. The absolute configurations of hyperbeanols FH were established by the circular dichroism (CD) exciton chirality method. The plausible biosynthetic pathway speculation of hyperbeanols F-Q indicated that diverse reactions, including prenylation, 1,6-ene reaction, rearrangement, epoxidation and dehydration, contributed to their diverse skeletons. Hyperbeanols FI, O and hypercalin B exhibited moderate nitric oxide (NO) inhibitory activities in LPS-induced RAW 264.7 macrophages, with IC50 values in the range of 17.11-28.74 µM.

Identification of Potential Therapeutic Targets in the Liver of Pioglitazone-Treated Type 2 Diabetes Sprague-Dawley Rats via Expression Profile Chip and iTRAQ Assay.

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.