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Defective coffee beans (DCB) are one of the main reasons for poor coffee quality. In the current research, chemical difference of three common DCB including sour beans (SCB), black beans (BCB), and mold beans (MCB) were clarified using 1 H qNMR method and compared with that of non-defective beans (NDCB). The results indicated that DCB has lower sugar and lipid content compared to NDCB, yet it boasts a higher acetate concentration. The 1 H NMR from water-soluble content was shown to be more effective than that of oil fraction for qualitative of DCB blends, regardless of whether partial least squares discriminant analysis (PLS-DA) or machine learning (ML) algorithms were used. Support vector machine (SVM) was proved to be excellent for distinguishing DCB blends. Finally, a partial least squares regression (PLS) model was built for quantitative analysis of DCB blends. In summary, current research will not only help to reveal the material basis of DCB and their impact on coffee flavor, but also provide feasible strategies for the identification of DCB., Competing Interests: We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2024 The Authors. Published by Elsevier B.V.)

The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. ( qinghao ). Artemisinin and its derivatives share an unusual endoperoxide bridge and are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin and its derivatives have been reported to exhibit promising anticancer effects in recent decades. In this review, we focused on the research progress of artemisinin and its derivatives with potential anticancer activities. The pharmacological effects, potential mechanisms, and clinical trials in cancer therapy of artemisinin and its derivatives were discussed. This review may facilitate the future exploration of artemisinin and its derivatives as effective anticancer agents.

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-β-D-Gal, 1,3,6-β-D-Gal with a few 1,3-β-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-β-D-Gal, T-β-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-β-D-Glc and T-β-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1β, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 μg/mL to 400 μg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two new degrade cycloartane triterpenoids, named buboditones A, B ( 1 , 2 ), together with ten known alkaloids, cyclobuxoviridine ( 3 ), N -dimethylcycloxobuxovircine ( 4 ), cyclovirobuxine C ( 5 ), cyclovirobuxine A ( 6 ), cycloprotobuxine C ( 7 ), cycloprotobuxine A ( 8 ), cyclobuxoxazine ( 9 ), cyclobuxoxazine A ( 10 ), buxruguline B ( 11 ), irehine ( 12 ), were isolated from the leaves and stems of Buxus bodinieri Levl., The structures of compounds 1-2 were elucidated by 1 D and 2 D NMR spectroscopic methods including HSQC, HMBC, 1 H- 1 H COSY, NOESY, as well as HRESIMS spectroscopic analysis.

Obesity, a major public health problem, causes numerous complications that threaten human health and increase the socioeconomic burden. The pathophysiology of obesity is primarily attributed to lipid metabolism disorders. Conventional anti-obesity medications have a high abuse potential and frequently deliver insufficient efficacy and have negative side-effects. Hence, functional foods are regarded as effective alternatives to address obesity. Coffee, tea, and cocoa, three widely consumed beverages, have long been considered to have the potential to prevent obesity, and several studies have focused on their intrinsic molecular mechanisms in past few years. Therefore, in this review, we discuss the mechanisms by which the bioactive ingredients in these three beverages counteract obesity from the aspects of adipogenesis, lipolysis, and energy expenditure (thermogenesis). The future prospects and challenges for coffee, tea, and cocoa as functional products for the treatment of obesity are also discussed, which can be pursued for future drug development and prevention strategies against obesity., Competing Interests: No potential competing interest was reported by the author(s)., (© 2024 The Authors.)

Aims: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear., Method: Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity., Results: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side., Conclusion: Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied., Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI., Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023., Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI., Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively)., Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08)., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% ( P <0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value ( P <0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.

Covering: 2018 to 2022Meroterpenoids found in fungal species of the genus Ganoderma and known as Ganoderma meroterpenoids (GMs) are substances composed of a 1,2,4-trisubstituted benzene and a polyunsaturated side chain. These substances have attracted the attention of chemists and pharmacologists due to their diverse structures and significant bioactivity. In this review, we present the structures and possible biosynthesis of representative GMs newly found from 2018 to 2022, as well as chemical synthesis and biological activity of some interesting GMs. We propose for the first time a plausible biosynthetic pathway for GMs, which will certainly motivate further research on the biosynthetic pathway in Ganoderma species, as well as on chemical synthesis of GMs as important bioactive compounds for the purpose of drug development.

Four undescribed pyrethrins C-F (1-4) as well as four known pyrethrins (5-8) were isolated from seeds of Pyrethrum cinerariifolium Trev. The structures of compounds 1-4 were elucidated by UV, HRESIMS, and NMR ( 1 H and 13 C NMR, 1 H- 1 H COSY, HSQC, HMBC and ROESY), among which the stereostructure of compound 4 was determined by calculated ECD. Furthermore, compounds 1-4 were evaluated for their aphidicidal activities. The insecticidal assay results showed that 1-4 exhibited moderate aphidicidal activities at the concentration of 0.1 mg/mL with the 24 h mortality rates ranging from 10.58 to 52.98%. Among them, pyrethrin D (2) showed the highest aphidicidal activity, with the 24 h mortality rate of 52.98%, which was slightly lower than the positive control (pyrethrin II, 83.52%)., (© 2023. The Author(s).)

Four polysaccharides (MCPa, MCPb, MCPc, MCPd) were obtained from Lepidium meyenii Walp. Their structures were characterized by chemical and instrumental methods including total sugar, uronic acid and protein content determination, UV, IR and NMR spectroscopy, as well as monosaccharide composition determination and methylation analyses. Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa, and shared a similar backbone chain consisting of (1→4)-glucose linkages with branches attached to C-3 and C-6. Furthermore, bioactivity assay showed that MCPs had concentration-dependent inhibitory activity on α-glucosidase. MCPb (Mw = 10.1 kDa) and MCPc (Mw = 5.62 kDa) with moderate molecular weights exhibited higher inhibitory activity compared with MCPa and MCPd., (© 2023. The Author(s).)

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC 50 values of 2.78 and 9.11 μM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: We often experience dreams of strong irrational and negative emotional contents with postural muscle paralysis during rapid eye movement (REM) sleep, but how REM sleep is generated and its function remain unclear. In this study, we investigate whether the dorsal pontine sub-laterodorsal tegmental nucleus (SLD) is necessary and sufficient for REM sleep and whether REM sleep elimination alters fear memory., Methods: To investigate whether activation of SLD neurons is sufficient for REM sleep induction, we expressed channelrhodopsin-2 (ChR2) in SLD neurons by bilaterally injecting AAV1-hSyn-ChR2-YFP in rats. We next selectively ablated either glutamatergic or GABAergic neurons from the SLD in mice in order to identify the neuronal subset crucial for REM sleep. We finally  investigated the role of REM sleep in consolidation of fear memory using rat model with complete SLD lesions., Results: We demonstrate the sufficiency of the SLD for REM sleep by showing that photo-activation of ChR2 transfected SLD neurons selectively promotes transitions from non-REM (NREM) sleep to REM sleep in rats. Diphtheria toxin-A (DTA) induced lesions of the SLD in rats or specific deletion of SLD glutamatergic neurons but not GABAergic neurons in mice completely abolish REM sleep, demonstrating the necessity of SLD glutamatergic neurons for REM sleep. We then show that REM sleep elimination by SLD lesions in rats significantly enhances contextual and cued fear memory consolidation by 2.5 and 1.0 folds, respectively, for at least 9 months. Conversely, fear conditioning and fear memory trigger doubled amounts of REM sleep in the following night, and chemo-activation of SLD neurons projecting to the medial septum (MS) selectively enhances hippocampal theta activity in REM sleep; this stimulation immediately after fear acquisition reduces contextual and cued fear memory consolidation by 60% and 30%, respectively., Conclusion: SLD glutamatergic neurons generate REM sleep and REM sleep and SLD via the hippocampus particularly down-regulate contextual fear memory., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Three new meroterpenoids, cochlearins J-L (1-3) and three known meroterpenoids (4-6) were isolated from the fruiting bodies of Ganoderma cochlear. NMR ( 1 H and 13 C NMR, 1 H -  1 H COSY, HSQC, HMBC and ROESY), and HRESIMS were employed for the structure elucidation of new compounds. The stereostructures of 1-3 were confirmed by calculated ECD and optical rotation methods. Furthermore, compounds (+)-1, (-)-1, (+)-2, (-)-2, (+)-3, (-)-3, and 4-6 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds (+)-1, (-)-1 and (+)-2 exhibited stronger inhibition against α-glucosidase with IC 50 values of 24.18 ± 1.98, 26.49 ± 3.20 and 29.68 ± 2.73 μM, respectively, compared to the positive control ursolic acid (49.65 ± 2.21 μM). The molecular docking experiments reveal that (+)-2 and (-)-2 had different binding mode with α-glucosidase, leading to their different inhibition., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To analyze the predictive value of acute phase proteins (APPs) on the prognosis of patients with acute myeloid leukemia (AML)., Methods: 293 AML patients who met the study requirements from January 2015 to April 2021 were collected, their clinical characteristics and pre-treatment APPs levels ［including albumin (ALB), fibrinogen (FIB), C-reactive protein (CRP), Ferritin (FER)］ were followed up and investigated. Pearson correlation coefficient was used to analyze the correlation between APPs. Logistic regression was used to analyze the risk factors for mortality in AML patients. ROC curve was used to analyze the predictive value of APP for mortality in AML patients, and Kaplan-Meier survival analysis was used to compare the effect of APPs on complete remission (CR) rate, overall survival (OS), disease-free survival (DFS), and progression-free survival rate (PFS) of AML patients., Results: Pearson correlation analysis showed that there were negative correlations between ALB and CRP (r=-0.134, P=0002), as well as ALB and FER (r=-0.148, P=0.001). There were correlations between FER and CRP (r=0361, P＜0.001), as well as FER and FIB (r=0.293, P＜0.001). Logistic regression analysis showed that advanced age (>50 years) (OR=1.87, 95% CI=1.25-2.15, P＜0.001), relapse after treatment (OR=2.11, 95% CI=111-3.18, P=0.003), FLT3-ITD mutation (OR=2.59, 95% CI=1.10-4.12, P＜0.001), CRP≥524 mg/L (OR=1.21, 95% CI=1.02-2.14, P=0.024), CFA (CFA=CRP*FIB/ ALB)≥3 (OR=2.41, 95% CI=1.65-6.47, P＜0.001), and FER≥1145.58 mg/ml (OR=1.67, 95% CI=1.15-3.75, P＜0.001) were the risk factors for the survival of AML patients. ROC curve analysis showed that FER (AUC=0.752, 95% CI=0.681-0823, P＜0.001, the best cut-off value=1220.56 mg/ml) and CFA (AUC=0.804, 95% CI=0.741-0.868, P＜0.001, the best cut-off value=3.00) had higher predictive value for the survival of AML patients. The remission rate, PFS, DFS, and OS in the low CFA group (CFA≤3) were significantly higher than those in the high CFA group (CFA＞3), and the overall mortality rate was lower than that in the high CFA group; the remission rate, PFS, DFS, and OS in the low FER group (FER≤1220.56 mg/ml) were significantly higher than those in the high FER group (FER＞1220.56 mg/ml), while the overall mortality rate was lower than that in the high FER group, and the difference is statistically significant., Conclusion: The CFA value and FER level before treatment in AML patients can independently predict the prognosis of patients, and high levels of CFA and FER are associated with poor prognosis of AML patients.

The nectar of Camellia reticulata Lindl. contains sugar, amino acids and other nutritional components, suggesting that it could be developed for food and food additives. To understand the effects of the nectar on human health, we investigated its chemical constituents. Two new flavonoid glycosides, cameretiins A and B (1 and 2) , and two known flavonoid glycosides, kaempferol 3- O -(2''- O - E - p -coumaroyl)- β -D-glucopyranoside (3) and tiliroside (4) were obtained from the nectar of Camellia reticulata Lindl. Their structures were determined based on analysis of their spectroscopic data and by comparison with 1D NMR spectroscopic data of known compounds reported in the literature. Compounds (1-4) were first isolated from the nectar of Camellia reticulata Lindl.

Our previous research has shown that lanostane triterpenoids from Ganoderma applanatum exhibit significant anti-adipogenesis effects. In order to obtain more structurally diverse lanostane triterpenoids to establish a structure-activity relationship, we continued the study of lanostane triterpenoids from the fruiting bodies of G. applanatum , and forty highly oxygenated lanostane-type triterpenoinds ( 1 - 40 ), including sixteen new compounds ( 1 - 16 ), were isolated. Their structures were elucidated using NMR spectra, X-ray crystallographic analysis, and Mosher's method. In addition, some of their parts were evaluated to determine their anti-adipogenesis activities in the 3T3-L1 cell model. The results showed that compounds 16 , 22 , 28 , and 32 exhibited stronger anti-adipogenesis effects than the positive control (LiCl, 20 mM) at the concentration of 20 μM. Compounds 15 and 20 could significantly reduce the lipid accumulation during the differentiation process of 3T3-L1 cells, comparable to the untreated group. Their IC 50 values were 6.42 and 5.39 μM, respectively. The combined results of our previous and present studies allow us to establish a structure-activity relationship of lanostane triterpenoids, indicating that the A- seco -23→26 lactone skeleton could play a key role in anti-adipogenesis activity.

A total of 11 new ( 1 - 11 ) and 2 known ( 12 and 13 ) ent -kaurane diterpene derivatives were identified from the roasted beans of Coffea cultivar S288. Their structures were established by extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance (heteronuclear single-quantum correlation, heteronuclear multiple-bond correlation, correlation spectroscopy, and rotating-frame Overhauser enhancement spectroscopy), high-resolution electrospray ionization mass spectrometry, and X-ray analyses. Cafespirone acid A ( 1 ) represents the first example of diterpene featuring a spirocyclic skeleton constructed from a 6/6/5 tricyclic system. Cafeane acid A ( 2 ) possesses a 6/6/6/5 tetracyclic system as a result of the C/D ring rearrangement. Furthermore, compounds 1 - 12 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds 2 , 4 , 5 , 6 , 7 , 10 , and 11 had a moderate inhibitory effect on α-glucosidase, and half-maximal inhibitory concentration values of compounds 4 , 6 , 7 , and 10 were 18.76 ± 1.46, 4.88 ± 0.03, 12.35 ± 0.91, and 12.64 ± 0.59 μM, respectively, compared to the positive control acarbose (60.71 ± 16.45 μM). Additionally, the molecular docking experiments showed that the carbonyl group at C-19 of compounds 4 , 6 , and 7 formed strong hydrogen bonds with ARG315, which may make them have moderate inhibitory activity.

Two new triterpenoid-chromone hybrids, cimitriteromones H ( 1 ) and I ( 2 ), along with two known analogues ( 3 , 4 ) were isolated from the phytochemical research on the n- butyl alcohol extracts of Actaea cimicifuga rhizomes. The new compounds were elucidated by spectroscopic experiments and chemical method. The cytotoxic activities of the isolated compounds were tested on A-549/Taxol cell line. Cimitriteromone I ( 2 ) showed cytotoxicity with IC 50 value of 27.14 ± 1.38  μ M comparable to positive control group cisplatin (IC 50 value of 25.80 ± 1.15  μ M).

Objective: To compare the efficacy and safety of ticagrelor and clopidogrel in elderly Chinese patients with acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI) in the real world. Methods: This study is a post-hoc analysis of a single center, retrospective cohort study. Between March 2016 and March 2018, elderly (age≥65) ACS patients who underwent PCI in the General Hospital of Northern Theater Command were included in the study. The patients were grouped according to P2Y 12 receptor inhibitor. The primary endpoints of this study were ischemic events during the 2-year follow-up, which were defined as the composite of cardiac death, myocardial or stroke. The secondary efficiency endpoints included all-cause death and BARC 2, 3, 5 bleeding events. Results: A total of 4 022 elderly (mean age: (71.5±5.3) years) ACS patients were included in this study. Based on the choice of P2Y 12 receptor inhibitor, patients were divided into clopidogrel ( n =3 201) and ticagrelor ( n =821) groups. Incidences of ischemic events (3.2% (26/821) vs. 5.6% (179/3 201), P =0.005) at 2 years were significantly lower in ticagrelor group compared to clopidogrel group. BARC 2, 3, 5 bleeding events (1.7% (14/821) vs. 1.6% (52/3 201), P =0.818) were comparable between the two groups. The incidence of all-cause death (1.5% (12/821) vs. 4.1% (132/3 201), P =0.005) were also lower in the ticagrelor group compared to the clopidogrel group. Clinical outcomes were consistent after adjusting for confounding factors, the incidence of ischemic events ( HR = 0.637, 95% CI 0.409-0.991, P =0.046) and all-cause mortality ( HR =0.402, 95% CI 0.213-0.758, P =0.005) was significantly lower in the ticagrelor group compared with the clopidogrel group. Risk of BARC 2, 3, 5 bleeding events were similar between the two groups ( HR= 0.957 , 95% CI 0.496-1.848 , P= 0.897). Conclusion: In real-world clinical practice, for elderly patients with ACS undergoing PCI, ticagrelor use might reduce the incidence of long-term ischemic events and all-cause death without increasing the risk of bleeding.

Objective: To develop a set of data elements and standardized definitions of Coronary Artery Disease and Creative Antithrombotic Clinical Research Collaboration (CardiaCare), aiming to facilitate the exchange of disparate data sources, enhance the abilities to support multicenter researches, and subsequently ensure the databases use under standardized process and criteria. Methods: The Cardiacare writing committee members reviewed data elements and definitions from published guidelines, clinical trials, databases, and standardized documents, then determined the data elements and standardized definitions, which should be included in CardiaCare. The writing committee also considered the specific domestic clinical management strategies during the establishment of Cardiacare. The resulting documents provide a series of key data elements and standardized definitions used in the management of coronary artery disease patients. Key data elements from CardiaCare could be sorted by clinical management flowsheet and outcome from hospitalization to long-term follow-up. Results: The Cardiacare standardized set comprised 864 data elements from admission to post-hospital follow-up visit. There were 8 tables in the documents, including demographic and admission information (23 elements), medical history and risk factors (102 elements), clinical presentations and diagnosis (22 elements), diagnostic and laboratory tests (111 elements), interventional diagnosis and treatment (118 elements), pharmacological therapy (213 elements), clinical outcomes (161 elements), and special subpopulations (114 elements: 87 elements for transcatheter valve replacement and 27 elements with cardiac rehabilitation). Conclusions: The Cardiacare standardized data elements set could provide support for real-world clinical research in consecutive data collection and databases mining. A wider applicability in various settings of CardiaCare needs to be explored further.

Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13 C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC 50 value of 7.93 μM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 μM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-β (C/EBP-β), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sleep disorders are highly prevalent among stroke survivors and impede stroke recovery. It is well established that melatonin has neuroprotective effects in animal models of ischemic stroke. However, as a modulator of endogenous physiological circadian rhythms, the effects of melatonin on poststroke sleep disorders remain unclear. In the present study, we investigated how melatonin delivered intraperitoneally once daily in the subacute phase after stroke onset, influencing neuronal survival, motor recovery, and sleep-wake profiles in rats., Methods: Transient ischemic stroke in male Sprague-Dawley rats was induced with 30 min occlusion of the middle cerebral artery. Melatonin or vehicle was delivered intraperitoneally once daily in the subacute phase, from 2 to 7 days after stroke. Electroencephalogram and electromyogram recordings were obtained simultaneously., Results: Compared to the effects observed in the vehicle-treated ischemic group, after 6 daily consecutive treatment of melatonin at 10 mg/kg starting at ischemic/reperfusion day 2, the infarct volume was significantly decreased (from 39.6 to 26.2%), and the degeneration of axons in the ipsilateral striatum and the contralateral corpus callosum were significantly alleviated. Sensorimotor performances were obviously improved as evidenced by significant increases in the latency to falling off the wire and in the use of the impaired forelimb. In addition to those predictable results of reducing brain tissue damage and mitigating behavioral deficits, repeated melatonin treatment during the subacute phase of stroke also alleviated sleep fragmentation through reducing sleep-wake stage transitions and stage bouts, together with increasing stage durations. Furthermore, daily administration of melatonin at 9 a.m. significantly increased the nonrapid eye movement sleep delta power during both the light and dark periods and decreased the degree of reduction of the circadian index., Conclusions: Melatonin promptly reversed ischemia-induced sleep disturbances. The neuroprotective effects of melatonin on ischemic injury may be partially associated with its role in sleep modulation., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: There are scarce real-world data on the long-term efficacy and safety of cardiopulmonary exercise testing (CPET) combined with the systematic education of cardiac rehabilitation (CR) approach for patients post-coronary stenting, which is, therefore, the subject of this study., Methods: Data collected between 1 April 2015 and 20 May 2017 from 11,345 patients in the rehabilitation center database at our hospital were retrospectively analyzed. Five hundred thirty-six patients with incomplete information, or unable to cooperate with telephone follow-up, were excluded; 4001 patients received the combined CR approach; and 6808 patients received only routine post-procedure education (controls). Of these, 2805 CR participants (CR group) were matched 1:1 to controls (control group) using propensity scores. The main outcome was quality of life in Seattle Angina Questionnaire (SAQ) scores. SAQ was measured in hospital and at follow-up; meanwhile, volume/type of habitual exercise, major adverse cardiovascular event (MACE), and its components of target vessel revascularization, myocardial infarction, and cardiac death were recorded and analyzed., Results: At median 583 (range 184-963) day follow-up, compared with controls, the CR group showed fewer patients not engaging in physical exercise (22 vs. 956, p < 0.05); more cumulative exercise time (h/week) (8.22 ± 6.17 h vs. 3.00 ± 1.65 h, p < 0.05); higher SAQ scores (physical limitation, 69.59 ± 10.96 vs. 57.49 ± 7.19; anginal stability, 80.50 ± 18.21 vs. 58.82 ± 11.95; anginal frequency, 78.58 ± 11.07 vs. 67.14 ± 22.41; treatment satisfaction, 82.33 ± 13.21 vs. 56.84 ± 21.61; quality of life, 68.69 ± 18.33 vs. 60.26 ± 17.13, all p < 0.01), but a similar MACE rate (log-rank p = 0.621)., Conclusion: Compared with only routine post-procedure education, CR combining at least one-time CPET with a systematic cardiac education program before discharge improved engagement in physical activity and quality of life for patients after percutaneous coronary intervention (PCI) without increasing clinical adverse events., (© 2021. The Author(s).)

Nuclear magnetic resonance (NMR) spectroscopy was used for the qualitative and quantitative analysis of aqueous extracts of unroasted and roasted coffee silverskin (CS). Twenty compounds were identified from 1D and 2D NMR spectra, including caffeine, chlorogenic acid (CGA), trigonelline, fructose, glucose, sucrose, etc. For the first time, the presence of trigonelline was detected in CS. Results of the quantitative analysis showed that the total amount of the main components after roasting was reduced by 45.6% compared with values before roasting. Sugars in the water extracts were the main components in CS, and fructose was the most abundant sugar, its relative content accounting for 38.7% and 38.4% in unroasted and roasted CS, respectively. Moreover, 1D NMR combined with 2D NMR technology shows application prospects in the rapid, non-destructive detection of CS. In addition, it was observed by optical microscopy and scanning electron microscopy (SEM) that the morphology of CS changed obviously before and after roasting.

Previously, we have demonstrated the antiadipogenic benefits of Ganoderma triterpenoids (GTs), which indicated GTs have potential therapeutic implications for obesity. In this study, the EtOAc extract of Ganoderma applanatum was further phytochemically investigated for searching new antiadipogenic agents, which led to the isolation of a total of 15 highly oxygenated lanostane triterpenoids, including 9 new compounds (1-9) and 6 known analogues (10-15). Structurally, ganodapplanoic acids A and B (1, 2) are two rearranged 6/6/5/6-fused lanostane-type triterpenoids with an unusual C-13/C-15 oxygen bridge moiety. In addition, the EtOAc extract (GAE) and isolates (1-4,6-15) were assayed for their antiadipogenic effects in 3T3-L1 adipocytes. The results revealed that compound 9 effectively repressed adipogenesis through down-regulating the expression of major proteins (PPARγ, CEBPβ and FAS) involving differentiation and adipogenesis in 3T3-L1 adipocytes. Thus, the present study further demonstrated the antiadipogenic potential of GTs and provided a possible perspective for obesity treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2‑carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC 50 value of 16.78 ± 0.49 μM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Two new pyrrolizidine alkaloids, sclerwalins A and B ( 1 and 2 ), and one known 9-O-E-hydroxysenecioylretronecine ( 3 ) were first isolated from the seeds of Scleropyrum wallichianum . Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].

The seed oil of Prinsepia utilis is extensively used as an edible oil by the nationalities of Naxi, Tibetan, and Mosuo in China, which is particularly good for beauty care and has a health protection function. A large amount of industrial waste is thrown away during the production process of seed oil. Therefore, to recover bioactive compounds from the oil residue of P. utilis is environmentally friendly and economically important. For this purpose, the chemical constituents of the P. utilis oil residue were investigated in our research, and five new compounds, prinsepicyanosides F-I ( 1 - 4 ) and prinamoside A ( 5 ), together with 16 known compounds ( 6 - 21 ) were isolated. The structures of the new compounds ( 1 - 5 ) were unambiguously confirmed by extensive spectroscopic techniques. Preliminary in vitro pharmacological studies showed that the hydroxynitrile glucosides ( 3 , 9 , and 10 ) exhibited weak α-glucosidase inhibitory activity. To a certain extent, our research provides some evidence for the pharmacological function of γ-hydroxynitrile glucosides and proposes new ideas for recycling of the oil residue of P. utilis .

Objective: To explore the medication compliance for secondary prevention drugs and long-term prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) between hospitals in different regions of China. Methods: The Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study was a prospective, multi-center and registered study. Patients diagnosed as ACS and underwent PCI in OPT-CAD study were selected. Taking the Yangtze River as the dividing line between the south and the north of China, these patients were divided into two groups according to the hospitals where the patients visited, namely the southerns region group ( n =1 958) and the northerns region group ( n =5 091). In order to reduce selection bias and potential confounding factors, the patients in the two groups were matched by the tendency score, and the patients in the two groups were matched by the 1: 1 nearest match method according to the tendency score. The main endpoint of this study was the major adverse cardiovascular and cerebrovascular events (MACCE) occurring within 5 years after discharge, namely the composite endpoint of cardiac death, myocardial infarction, and/or ischemic stroke. Secondary endpoints were all-cause death, cardiac death, myocardial infarction, ischemic stroke, and type 2, 3, and 5 bleeding events defined by the Academic Research Consortium on Hemorrhage (BARC) within 5 years. The secondary preventive drugs was recorded, including antiplatelet drugs, statins, beta blockers, angiotensin converting enzyme inhibitors/angiotensinⅡreceptor blockers (ACEI/ARB), etc. Before and after the matching, the secondary preventive medication and the incidence of clinical events of the two groups were compared. Results: A total of 7 049 ACS patients, including 1 958 patients in the southern region group and 5 091 patients in the northern region group were enrolled in this study. There were 5 319 males (37.9%), and the aged was (60.7±6.7) years. After propensity score matching, there were 1 324 cases in each group. Before matching, in the northern region group, the proportion of smoking, hypertension and diabetes, previous history (myocardial infarction, PCI and stroke) and family history of coronary heart disease were higher (all P <0.05). The proportion of complex lesions, diffuse lesions, small vessel lesions and thrombotic lesions in the northern region group was higher than that in the southern region group (all P <0.05). Sixty months after discharge, the antiplatelet patterns were quite different between patients in the northern and southern region group ( P <0.001). The proportion of clopidogrel monotherapy in the southern region group was higher than that in the northern region group (9.8% (130/1324) vs. 1.1% (14/1324)), while the proportion of aspirin monotherapy in the northern region group was higher than that in the southern region group (67.4% (893/1324) vs. 46.5% (616/1324)). As for the use of other secondary prophylactic drugs, the proportion of patients in southern region group receiving beta blockers (24.5% (325/1324) vs. 16.8% (222/1324), P <0.001) and ACEI/ARB (19.4% (257/1324) vs. 10.0% (133/1324), P <0.001) was higher than that in northern region group. After matching, the incidence of MACCE (8.4%(111/1 324) vs.6.2% (82/1 324), P =0.030) and BARC 2, 3 and 5 bleeding (6.0% (80/1 324) vs. 4.0% (53/1 324), P =0.020) was higher in patients in northern region group. Conclusions: ACS patients who undergo PCI in northern area hospital is at higher prevalence of comorbidities and complicated coronary artery lesions compared to patients in the southern area hospital, and the drug compliance is worse than that in southern area, and the prognosis is also relatively poor.

Ganoderma triterpenoids (GTs), a class of major active constituents in Ganoderma species, play an important role in the anti-obesity effect of Ganoderma fungi. In the study, seventeen new highly oxygenated lanostane triterpenoids, ganoapplanoids A-Q (1-17), together with five previously reported compounds (18-22), were isolated from the fruiting bodies of Ganoderma applanatum. Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction and Mo 2 (OAc) 4 induced CD cotton effect. Structurally, compound 6 represents the first example of 2-norlanostane triterpenoid possessing an unusual semiacetal moiety. Furthermore, isolates (1-5, 7-11, 13-22, 3a) were evaluated for regulatory effects on lipid accumulation by 3T3-L1 adipocytes model. Among them, compounds 11 and 17 exhibited significant potency in blunted adipogenesis activities dose-dependently. Meanwhile, compounds 11 and 17 reduced triglyceride (TG) and total cholesterol (TC) levels in the adipocytes. These results supported that the highly oxygenated lanostane triterpenoids from G. applanatum may serve as agents for inhibiting the lipid accumulation in adipocytes and the G. applanatum provided an important source for searching new drugs to treat obesity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ganoderma resinaceum is a multi-purpose herbal medicine that is homologous to functional food that has long been used for enhancing health and treating chronic hepatopathy in Traditional Chinese Medicine. In a search program to discover the key bioactive composition of G. resinaceum, sixteen new lanostane-type triterpenoids (1-16), and twenty known analogues (17-36) were isolated from the fruiting bodies of G. resinaceum. Spectroscopic analyses and X-ray crystallography were used to determine the new structures. Furthermore, the spectroscopic properties of 15β-hydroxy-4,4,14α- trimethyl-3,7,11,20-tetraoxo-5α-pregn-8-ene (15) and 15α-hydroxy-4,4,14α-trimethyl- 3,7,11,20-tetraoxo-5α-pregn-8-ene (34) indicated a potential structural misassignment of their analogues, lucidone E and lucidone H, reported previously. To probe this hypothesis, ROESY experiments and single-crystal X-ray diffraction analysis were conducted. These results undoubtedly reassigned the structure of lucidone E and lucidone H. Biological evaluation of the selected compounds disclosed that compounds 3, 4, 7/21, 11, 12, 13/14, 17, 18, 24/25, 27, 30, 31, and 35 had significant hepatoprotective activities, due to their remarkable in vitro inhibitory activities against the increase of ALT and AST levels in HepG2 cells induced by H 2 O 2 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Meroapplanins A-E ( 1 - 5 ) with a 2,3,4,5-tetrahydropyridine fragment were isolated from the fruiting bodies of Ganoderma applanatum . Their structures were elucidated by comprehensive spectroscopic analyses. Their absolute configurations were established based on the X-ray diffraction, electronic circular dichroism (ECD), and calculated nuclear magnetic resonance (NMR) with DP4+ analysis. A plausible biosynthetic pathway for 1 - 5 was proposed. Furthermore, compounds 1 - 5 , together with optically pure compounds 1a - 4a and 1b - 4b , were evaluated for their protective effects in PC12 cells damaged by H 2 O 2 . The results showed that 3b had protective activity with a cell viability of 82.58 ± 1.31%, compared with the model group (cell viability: 65.27 ± 1.48%).

Seven new lactam ent -kaurane diterpenoids, cafemides A-G ( 1 - 7 ), were isolated from roasted beans of Coffea arabica . Their structures were elucidated by extensive spectroscopic analysis including 1D, 2D NMR (heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), 1 H- 1 H correlation spectroscopy (COSY), and rotating frame Overhauser effect spectroscopy (ROESY)), high-resolution electrospray ionization mass spectrometry (HRESIMS), and IR spectra. They were divided into subtype I-III according to the structure. Further, with the aid of liquid chromatography-tandem mass spectrometry (LC-MS/MS) based molecular network, seven ( 8 - 14 ) subtype II diterpenoids were successfully identified. In addition, a variety of other subtypes of N-containing diterpenoids have been proven in roasted coffee. Compounds 1 , 2 , 3 , 5 , and 7 showed a moderate inhibitory effect on α-glucosidase with an IC 50 value of 8.28 ± 0.62 μM, 38.23 ± 8.87 μM, 28.94 ± 1.42 μM, 12.44 ± 1.37 μM, and 22.2 ± 5.34 μM, respectively. To the best of our knowledge, this is the first time that N-containing diterpenoids have been reported in coffee.

Ten cucurbitane-type triterpene glycosides, including five new compounds named charantosides H (1), J (2), K (3), momorcharacoside A (4), goyaglycoside-L (5), and five known compounds (6-10), were isolated from the EtOAc extract of Momordica charantia fruits. The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses. Configurations of new compounds were determined by ROESY correlations and comparison of their 13 C NMR data with literature reported values. All compounds were evaluated for their inhibition against α-glucosidase, in which compounds 2, 5, 7, 8, 9 showed moderate inhibitory activities with IC 50 values ranging from 28.40 to 63.26 μM comparing with the positive control (acarbose, IC 50 87.65 ± 6.51 μM).

HER2-positive breast cancer accounts for 15-20% in breast cancer and 50% of the metastatic HER2-positive breast cancer patients died of central nervous system progression. The present study investigated the effects of actein (a natural cycloartane triterpene) on cells adhesion, migration, proliferation and matrix degradation, and its underlying mechanism in HER2-positive breast cancer cells. The in vivo effect of actein on tumor growth and metastasis in MDA-MB-361 tumor-bearing mice as well as the anti-brain metastasis in tail vein injection mice model were also investigated. Our results showed that actein inhibited HER2-positive breast cancer cells viability, proliferation and migration. Actein also induced MDA-MB-361 cells G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. For intracellular mechanisms, actein inhibited the expressions of molecules in AKT/mTOR and Ras/Raf/MAPK signaling pathways. Furthermore, actein (15 mg/kg) was shown to exhibit anti-tumor and anti-metastatic activities in MDA-MB-361 breast tumor-bearing mice, and reduced brain metastasis in tail vein injection mice model. All these findings strongly suggested that actein is a potential anti-metastatic agent for HER2-positive breast cancer., (Copyright © 2020 Wu, Yue, Dong, Lam, Wong, Qiu and Lau.)

Six previously undescribed benzolactone constituents, ganodumones A-F (1-6), a new type of Ganoderma meroterpenoids (GMs) fused with 1,2,3,4,5-pentasubstituted phenyl and 1',2'-dioxy-3'-methyl-pentyl chain were isolated from the fruiting bodies of Ganoderma lucidum. Their structures were determined by spectroscopic analysis, X-ray crystal diffraction, and ECD computational methods. Meanwhile, bioactive evaluation showed that compounds 3 and 5 have antibacterial activities against Microsporum gypseum with MIC 90 56.86 ± 3.98 and 18.48 ± 0.47 μg/mL, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ganoderma lucidum is one of the most famous medicinal fungi and is traditional Chinese medicine with various biological activities in Asian countries. To clarify its pharmacodynamic material basis, 15 lanostane triterpenoidswere obtained from the fruiting bodies of G. lucidum, including 8 previously undescribed lanostanoids. Their structures, including absolute configuration, were established based on ultraviolet, infrared, high-resolution electrospray ionisation mass spectrometry, 1D and 2D nuclear magnetic resonance, and X-ray crystallographic analysis. Ganoluciduone A was an unusual octonorlanostane, which was isolated from Ganoderma for the first time. In addition, the anti-inflammatory activities of all isolates were evaluated by observing their inhibitory effects on nitric oxide production in RAW264.7 cells activated by a lipopolysaccharide. Ganoluciduone B exhibited moderate inhibitory activity on nitric oxide production, with an inhibition rate of 45.5% at a concentration of 12.5 μM., (Copyright © 2019. Published by Elsevier Ltd.)

Background: P53 is the most frequently mutated gene in most tumour types, and the mutant p53 protein accumulates at high levels in tumours to promote tumour development and progression. Thus, targeting mutant p53 for degradation is one of the therapeutic strategies used to manage tumours that depend on mutant p53 for survival. Buxus alkaloids are traditionally used in the treatment of cardiovascular diseases. We found that triterpenoid alkaloids extracted from Buxus sinica found in the Yunnan Province exhibit anticancer activity by depleting mutant p53 levels in colon cancer cells., Purpose: To explore the anticancer mechanism of action of the triterpenoid alkaloid KBA01 compound by targeting mutant p53 degradation., Study Design and Methods: Different mutant p53 cell lines were used to evaluate the anticancer activity of KBA01. MTT assay, colony formation assay and cell cycle analysis were performed to examine the effect of KBA01 on cancer cell proliferation. Western blotting and qPCR were used to investigate effects of depleting mutant p53, and a ubiquitination assay was used to determine mutant p53 ubiquitin levels after cells were treated with the compound. Co-IP and small interfering RNA assays were used to explore the effects of KBA01 on the interaction of Hsp90 with mutant p53., Results: The triterpenoid alkaloid KBA01 can induce G2/M cell cycle arrest and the apoptosis of HT29 colon cancer cells. KBA01 decreases the stability of DNA contact mutant p53 proteins through the proteasomal pathway with minimal effects on p53 mutant protein conformation. Moreover, KBA01 enhances the interaction of mutant p53 with Hsp70, CHIP and MDM2, and knocking down CHIP and MDM2 stabilizes mutant p53 levels in KBA01-treated cells. In addition, KBA01 disrupts the HSF1-mutant p53-Hsp90 complex and releases mutant p53 to enable its MDM2- and CHIP-mediated degradation., Conclusion: Our study reveals that KBA01 depletes mutant p53 protein in a chaperone-assisted ubiquitin/proteasome degradation pathway in cancer cells, providing insights into potential strategies to target mutant p53 tumours., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group ( n= 184), type B2 lesion group ( n= 457) and type C lesion group ( n= 614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P< 0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P< 0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE ( HR= 1.59, 95 %CI 1.21-2.08, P< 0.001) and TLF ( HR= 2.31, 95 %CI 1.53-3.49, P< 0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95 %CI 1.25-2.92, P= 0.003) and 1.64 (95 %CI 1.23-2.20, P< 0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95% CI 1.29-4.64, P =0.006) and 2.55 (95% CI 1.62-4.02, P= 0.001), respectively. Conclusions: The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

A new alkaloid, ( E )-3-(3-methyl-1-oxo-2-butenyl)-6-methoxy-1 H - indole ( 1 ), along with two known ones, was isolated from the aerial parts of Cimicifuga heracleifolia . The structure of 1 was elucidated on the basis of extensive spectroscopic data analysis. The structures of known compounds were determined by comparison with the literature data.

Objective: To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients. Methods: Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group ( n= 963), 50%≤SRI<100% group ( n= 527) and SRI<50% group ( n= 339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months. Results: Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P< 0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P< 0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P< 0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P< 0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P< 0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P< 0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality ( HR =2.06, 95 %CI 1.25-3.38) and PoCE ( HR =1.34, 95 %CI 1.09-1.66). Conclusions: SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Background: Most allelochemicals are secondary products released from root excretions or plant residues that accumulate in continuous cropping systems and cause severe decline in peanut yield. Resveratrol is a plant-derived stilbene that is released from peanut residues and accumulates in the soil; however, its allelopathic effects on peanut production are overlooked. Effective management solutions need to be developed to relieve allelopathy caused by soil resveratrol. Here, the biodegradation of resveratrol by the fungal endophyte Phomopsis liquidambari was investigated in a mineral salt medium and a soil trial. Resveratrol and its metabolites (produced by degradation by P. liquidambari) were detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS)., Results: Resveratrol released from peanut residues reached a maximum concentration of 0.18 μg g -1 soil in litterbag experiments. Exogenous resveratrol inhibited peanut growth, nodule formation, and soil dehydrogenase activity, and reduced the soil microbial biomass carbon content and bacterial abundance, indicating an allelopathic role in peanut growth. More than 97% of the resveratrol was degraded within 72 and 168 h by P. liquidambari in pure culture and soil conditions, respectively. Resveratrol was first cleaved to 3,5-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde, which were subsequently oxidized into 3,5-dihydroxybenzoic acid and 4-hydroxybenzoic acid, respectively. Fungal resveratrol cleavage oxygenase and the related gene expression were enhanced when P. liquidambari was induced by the resveratrol during the incubation., Conclusion: Our results indicate that the practical application of the fungal endophyte P. liquidambari has strong potential for biodegrading soil resveratrol, which can cause allelopathy in peanut continuous cropping systems. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)