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Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: The plasma uric acid to albumin ratio (UAR) is considered as a novel indicator for Inflammation. However, the association between UAR and coronary slow flow phenomenon (CSFP) remains unclear., Methods: A total of 1328 individuals with chronic coronary syndrome (CCS) receiving coronary angiography (CAG) and found no obvious obstructive stenosis (< 40%) were included in this study. 79 individuals developed CSFP and were divided into CSFP group. The 1:2 age-matched patients with normal coronary blood flow were allocated to the control group (n = 158). The clinical characteristics, laboratory parameters including uric acid, albumin ratio, UAR and the angiographic characteristics were compared between the two groups., Results: Patients with CSFP had a higher level of uric acid (392.3 ± 85.3 vs. 273.8 ± 71.5, P < 0.001), UAR (10.7 ± 2.2 vs. 7.2 ± 1.9, P < 0.001), but a lower level of plasma albumin (36.9 ± 4.2 vs. 38.5 ± 3.6, P = 0.003). Moreover, UAR increased as the numbers of vessels involved in CSFP increased. The logistic regression analysis demonstrated that UAR was independent predictors for CSFP. The Receiver operating characteristic (ROC) curve analysis showed that when UAR was more than 7.9, the AUC was 0.883 (95% CI: 0.840-0.927, p < 0.001), with the sensitivity and specificity were 78.2% and 88.2% respectively., Conclusion: Combined uric acid with plasma albumin, UAR could serve as an independent predictor for CSFP., (© 2024. The Author(s).)

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME., Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma., Results: Treatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma., Conclusion: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first β-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis., 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. Published by Elsevier B.V.)

Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC 50 values from 0.19 ± 0.08 to 1.03 ± 0.25 μM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The incidence of hepatocellular carcinoma (HCC) has been increasing in recent years. With the development of various detection technologies, machine learning is an effective method to screen disease characteristic genes. In this study, weighted gene co-expression network analysis (WGCNA) and machine learning are combined to find potential biomarkers of liver cancer, which provides a new idea for future prediction, prevention, and personalized treatment. In this study, the "limma" software package was used. P < .05 and log2 |fold-change| > 1 is the standard screening differential genes, and then the module genes obtained by WGCNA analysis are crossed to obtain the key module genes. Gene Ontology and Kyoto Gene and Genome Encyclopedia analysis was performed on key module genes, and 3 machine learning methods including lasso, support vector machine-recursive feature elimination, and RandomForest were used to screen feature genes. Finally, the validation set was used to verify the feature genes, the GeneMANIA (http://www.genemania.org) database was used to perform protein-protein interaction networks analysis on the feature genes, and the SPIED3 database was used to find potential small molecule drugs. In this study, 187 genes associated with HCC were screened by using the "limma" software package and WGCNA. After that, 6 feature genes (AADAT, APOF, GPC3, LPA, MASP1, and NAT2) were selected by RandomForest, Absolute Shrinkage and Selection Operator, and support vector machine-recursive feature elimination machine learning algorithms. These genes are also significantly different on the external dataset and follow the same trend as the training set. Finally, our findings may provide new insights into targets for diagnosis, prevention, and treatment of HCC. AADAT, APOF, GPC3, LPA, MASP1, and NAT2 may be potential genes for the prediction, prevention, and treatment of liver cancer in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Percutaneous coronary intervention for in-stent restenosis (ISR) chronic total occlusion (CTO) has been a great challenge. There are occasions when the balloon is uncrossable or undilatable (BUs) even though the guidewire has passed, leading to failure of the procedure. Few studies have focused on the incidence, predictors, and management of BUs during ISR-CTO intervention., Methods: Patients with ISR-CTO were recruited consecutively between January 2017 and January 2022 and divided into two groups based on the presence of BUs. The clinical data of the two groups (BUs group and non-BUs group) were retrospectively analyzed and compared to explore the predictors and clinical management strategies of BUs., Results: A total of 218 patients with ISR-CTO were included in this study, 23.9% (52/218) of whom had BUs. The percentage of ostial stents, stent length, CTO length, the presence of proximal cap ambiguity, moderate to severe calcification, moderate to severe tortuosity, and J-CTO score were higher in the BUs group than in the non-BUs group ( p  < 0.05). The technical success rate and the procedural success rate were lower in the BUs group than in the non-BUs group ( p  < 0.05). Multivariable logistic regression analysis showed that ostial stents (OR: 2.011, 95% CI: 1.112-3.921, p  = 0.031), the presence of moderate to severe calcification (OR: 3.383, 95% CI: 1.628-5.921, p  = 0.024) and moderate to severe tortuosity (OR: 4.816, 95% CI: 2.038-7.772, p  = 0.033) were independent predictors of BUs., Conclusion: The initial rate of BUs in ISR-CTO was 23.9%. Ostial stents, presence of moderate to severe calcification, and moderate to severe tortuosity were independent predictors of BUs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Hou, Luan, Zhang, Li and Pei.)

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), 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 © 2023 Elsevier Inc. All rights reserved.)

Five undescribed enantiomeric pairs of acylphloroglucinol-monoterpene meroterpenoids ((+)-/(-)-eucateretins A-E) resolved by chiral-phase HPLC were obtained from the leaves of Eucalyptus tereticornis Smith, along with nine known analogues. Their structures were elucidated by spectroscopic methods and ECD calculations. This is the first report of meroterpenoid enantiomers from this plant. Some of the isolates, (-)-eucateretin A, (+)-/(-)-eucateretins E, 7'α-eucalrobusone X, eucalrobusone X, and robustadial B, exhibited inhibitory effects on ATP citrate lyase, and 7'α-eucalrobusone X significantly suppressed the hepatocyte lipogenesis., 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 © 2022 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Fuzheng Xiaoai Decoction 1 (FZXAD1) is a clinical experience prescription for the treatment of cancer patients at an advanced stage. FZXAD1 has been used for more than 10 years in the clinic and can effectively improve the deficiency syndrome of cancer patients. However, its mechanisms need further clarification., Aim of the Study: To check the effects of FZXAD1 in colon 26 (C26) cancer cachexia mice and try to clarify the mechanisms of FZXAD1 in ameliorating cancer cachexia symptoms., Materials and Methods: An animal model of cancer cachexia was constructed with male BALB/c mice bearing C26 tumor cells. Food intake, body weight and tumor size were measured daily during the animal experiment. Tissue samples in different groups including tumor and gastrocnemius muscle, were dissected and weighed at the end of the assay. Serum biochemical indicators such as total protein (TP), glucose (GLU) and alkaline phosphatase (ALP) were also detected. Network pharmacology-based analysis predicted the possible targets and signaling pathways involved in the effects of FZXAD1 on cancer cachexia therapy. Western blotting assays of the gastrocnemius muscle tissues from C26 tumor-bearing mice were then used to confirm the predicted possible targets of FZXAD1., Results: The results of animal experiments showed that FZXAD1 could ameliorate cancer cachexia by alleviating the muscle wasting as well as kidney atrophy and increasing the body weight of cancer cachexia mice. AKT1, MTOR, MAPK3, HIF1A and MAPK1 were predicted as the core targets of FZXAD1. Western blotting confirmed the prediction that FZXAD1 increased the expression levels of phosphorylated Akt and mTOR in the muscle tissues. In addition, FZXAD1 treatment obviously ameliorated the increased levels of HIF-1α and phosphorylated Erk1/2 in C26 tumor-bearing mice., Conclusion: FZXAD1 effectively ameliorated cancer cachexia in an animal model of mice, which is consistent with its efficacy in the treatment of cancer patients. The mechanisms of FZXAD1 might be mainly based on its alleviating effects on muscle atrophy by activating the Akt-mTOR pathway and thus helping to maintain body weight., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP., Methods: We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n = 89 as CSFP group; n = 167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared., Results: SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p < 0.001). A significant positive correlation between SII and the mean thrombolysis in myocardial infarction frame count (mTFC) was found (r = 0.624, p < 0.001). SII increased with the number of coronary arteries involved in CSFP. In multivariate logistic regression analysis, SII/10 was an independent predictor of CSFP (odds ratio: 1.739, p < 0.001). In addition, the SII level > 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity., Conclusions: SII can predict the occurrence of CSFP., (© 2022. The Author(s).)

Two new maytansinoids, N -methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora , together with three known congeners (3:  - 5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1:  - 5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 - 11, and MCF-7, with IC 50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC 50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC 50 values of 3.6 and 3.2 µM, respectively., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To investigate the feasibility and accuracy of the Euro CTO (CASTLE) CTA score obtained on coronary computed tomography angiography (CCTA) for predicting the success of percutaneous coronary intervention (PCI) and the 30-min wire crossing in chronic total occlusions (CTO)., Method: One hundred and fifty patients (154 CTO cases; median age, 61 (interquartile range [IQR], 54-68) years; 75.3% male) received CCTA at the People's Hospital of Liaoning Provincce within 1 month before the procedure. The Euro CTO (CASTLE) score obtained on CCTA(CASTLE CTA ) was calculated and compared with the Euro CTO (CASTLE) score obtained based on coronary angiography (CASTLE CAG ) for the predictive value of 30-min wire crossing and CTO procedural success., Results: In our study, the CTO-PCI success rate was 89.0%, with guidewires of 65 cases (42.2%) crossing within 30 min. There were no significant differences in the median CASTLE CTA and CASTLE CAG scores in the procedure success group (3 [IQR, 2-4] vs 3 (IQR, 2-3]; p = 0.126). However, the median CASTLE CTA score was significantly higher than the median CASTLE CAG score in the procedure failure group (4 [IQR, 3-5.5] vs 4 [IQR, 2.5-5.5]; p = 0.021). There was no significant difference between the median CASTLE CTA score and the median CASTLE CAG score in the 30-min wire crossing failure group (3 [IQR, 3-4] vs 3 [IQR, 2-4]; p = 0.254). However, the median CASTLE CTA score was significantly higher than the median CASTLE CAG score in the 30-min wire crossing group (3 [IQR, 2-3] vs 2 [IQR, 2-3]; p < 0.001). The CASTLE CTA score described higher levels of calcification than the CASTLE CAG score (48.1% vs 33.8%; p = 0.015). There was no significant difference between the CASTLE CTA score (area under the curve [AUC], 0.643; 95% confidence interval [CI], 0.561-0.718) and the CASTLE CAG score (AUC, 0.685; 95% CI, 0.606-0.758) for predicting procedural success (p = 0.488). The CASTLE CTA score (AUC, 0.744; 95% CI, 0.667-0.811) was significantly better than the CASTLE CAG score (AUC, 0.681; 95% CI, 0.601-0.754; p = 0.046) for predicting 30-min wire crossing with the best cut-off value being CASTLE CTA  ≤ 3. The sensitivity, specificity, positive predictive value, and negative predictive value were 90.8%, 55.2%, 54.6%, and 87.0%, respectively., Conclusion: The CASTLE CTA scores obtained from noninvasive CCTA perform better for the prediction of the 30-min wire crossing than the CASTLE CAG score., (© 2022. The Author(s).)

Background: Soluble growth stimulator gene 2 protein (sST2) is associated with heart failure and myocardial infarction; however, the predictive value of plasma sST2 level for coronary slow flow/no-reflow (CSF/NRF) is unclear. This study aimed to explore the predictive value of plasma sST2 levels for CSF/NRF in patients with ST-elevation myocardial infarction (STEMI) who underwent emergency percutaneous coronary intervention (PCI)., Methods: A total of 242 STEMI patients who underwent emergency PCI at our hospital between November 2020 and July 2021 were enrolled in this study. According to the postprocedural procedure, these patients were divided into the CSF/NRF and control groups. Clinical data were collected from both groups and were used to explore the predictive value of serum sST2 levels for CSF/NRF., Results: Of the total 242 patients, CSF/NRF was observed in 50 patients (20.7%). Statistically significant differences ( P < 0.05) were observed in age, diabetes mellitus, sST2 level, neutrophil-to-lymphocyte ratio (NLR), fasting blood sugar, preprocedural blood pressure, intraprocedural hypotension, N-terminal pro-B-type natriuretic peptide, MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTNI). Multivariate analysis showed that the sST2 level, NLR, and intraoperative hypotension were independent risk factors for CSF/NRF. ROC curve analysis showed that the sensitivity and specificity of the sST2 level for predicting CSF/NRF were 68.0% and 75.5%, respectively, when the sST2 level was more than 64.6 ng/mL (AUC = 0.780, 95% CI: 1.003-1.020, P =0.009)., Conclusion: For STEMI patients, preprocedural sST2 levels significantly correlated with CSF/NRF occurring in PCI. sST2 level is a potential predictor for CSF/NRF occurrence., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Shu-min Chang et al.)

Two new oleanane-triterpenoid saponins, clinograsaponins A (1) and B (2), together with twelve known ones (3-14), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF-κB)., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg -1  d -1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg -1  d -1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI., (© 2021 Federation of American Societies for Experimental Biology.)

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC 50 values from 6.63 ± 2.40 to 14.21 ± 3.51 μM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Although remarkably successful against liquid tumors, chimeric antigen receptor (CAR)-T cell therapy has been stymied by solid tumors, limited by inadequate specificity and poor efficacy. Pairing synthetic Notch (synNotch) receptors with CARs, Choe et al. and Hyrenius-Wittsten et al. engineer T cells that more precisely and potently combat solid tumors., Competing Interests: Declaration of interests Y.Y.C. and A.J.H. are inventors on patent applications that are unrelated to the work discussed here but whose value may be affected by the publication of this work. L.C.C. declares no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The adoptive transfer of T cells that are engineered to express chimeric antigen receptors (CARs) has shown remarkable success in treating B cell malignancies but only limited efficacy against other cancer types, especially solid tumours. Compared with haematological diseases, solid tumours present a unique set of challenges, including a lack of robustly expressed, tumour-exclusive antigen targets as well as highly immunosuppressive and metabolically challenging tumour microenvironments that limit treatment safety and efficacy. Here, we review protein- and cell-engineering strategies that seek to overcome these obstacles and produce next-generation T cells with enhanced tumour specificity and sustained effector function for the treatment of solid malignancies.

Three unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nine undescribed acylphloroglucinol derivatives, oblatones A-I, along with three known ones, were isolated from Syzygium oblatum. Their structures were determined on the basis of extensive spectroscopic analysis, including NMR and MS data interpretation. Oblatones A and B possess an alkylated chromanone scaffold featuring a hemiketal moiety. Oblatones C and D are the first acylphloroglucinol derivatives with an α,β-unsaturated ketone lipid chain. Some of the isolates showed inhibitory effects on ATP citrate lyase in vitro. The binding mode of oblatone A was predicted by molecular docking., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Three maytansinoids with strong cytotoxicities, dehydrotrewiasine, maytanbutine, and trewiasine, were isolated and identified from Trewia nudiflora, and maytanbutine was obtained from this plant for the first time. A quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction combined with high-performance liquid chromatography (HPLC) was established to determine the three maytansinoids in T. nudiflora. The effects of major factors on the extraction efficiency of the QuEChERS method were evaluated and the optimal conditions using acetonitrile-ethyl acetate (1:1, v/v) as the extraction solvent and PestiCarb as the clean-up sorbents were established. Compared with Soxhlet extraction (SE) and ultrasonic-assisted extraction (UAE), the QuEChERS method was easy-to-operate and afforded a cleaner extract. A phenomenex HyperClone BDS C 18 column was used for HPLC analysis. Methanol-acetonitrile-water was chosen as mobile phase for gradient elution. Method validation showed that all analytes showed good linearity (r > 0.999) over the investigated ranges and satisfactory recoveries ranging from 95.0% to 105.0%. The developed QuEChERS-HPLC method was simple, efficient, and applicable to the determination of maytansinoids in T. nudiflora., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Six undescribed clerodane diterpenoids, dodovisins A-F, together with nine known ones, were isolated from the aerial parts of Dodonaea viscosa (L.) Jacq. Their structures were elucidated by extensive spectroscopic techniques, X-ray crystallographic analysis, and ECD calculation. Dodovisins A and B possess a rare carbon skeleton featuring a bicyclo[6.2.0]decane motif. Dodovisins C-E represent the first clerodane diterpenoids with a 4(5 → 19)-abeo-2,4,10(1)-triene moiety. Dodovisins A, E, and strictic acid showed potent inhibitory activities against ATP citrate lyase., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients., Background: Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (<2 mm) is one of the challenges physicians are facing during the coronary intervention. In cases where the antegrade wire passed the occluded segment reaching the branch vessel, but could not access the main vessel through various adjustments, application of active antegrade reverse wire technique (ARW) could be considered. Patients and Methods . A total of 301 consecutive CTO patients who received the antegrade percutaneous coronary intervention (PCI) between December 2015 and December 2019 at our institution were included, of whom 11 were treated with ARW (10 successfully) for vascular recanalization. The applicability and safety of ARW were assessed., Results: Among the 301 CTO patients who received antegrade vascular recanalization, 11 were treated with ARW. ARW was successful in 10 patients as follows: from the diagonal branch (D) to anterior descending branch (LAD) in 4 patients; from the septal branch (S) to LAD in 1 patient; from D to S and LAD in 1 patient; from the circumflex branch (LCX) to obtuse marginal branch (OM) in 1 patient; from OM to LCX in 1 patient; from a posterior descending artery (PDA) to the posterior lateral vein (PLV) in 2 patients. Yet, ARW in patient with RCAm CTO failed, while the consequent retrograde PCI succeeded. The mean J-CTO score of the 11 patients was 2.7 ± 0.65, among whom eight were accompanied with calcifications. Sion Black and Fielder XTR reverse wires were used in 9 and 2 patients, respectively. No loss of side branches or severe procedure-related complications occurred in 11 patients., Conclusion: Therefore, ARW can improve procedural efficiency and should be popularized for further application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xiao-jiao Zhang et al.)

Background: Sex differences in the long-term prognosis of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing alcohol septal ablation (ASA) remain unclear, especially in the Chinese Han population., Method: This cohort study included 320 HOCM Chinese Han patients who underwent ASA because of symptomatic left ventricular outflow tract (LVOT) obstruction. Patients were grouped according to sex: females (mean±standard deviation age [SD] 50.7±6.8 years) and males (mean±SD age 52.6±7.3 years). Individuals were followed over the long term., Results: Pre-procedure, women had more symptoms (New York Heart Association [NYHA] class III-IV 67.3% vs 56.3%, p=0.03), more atrial fibrillation (23.5% vs 14.6%, p=0.047) than men. Transient complete atrioventricular block after ASA was more common in woman than in men (34.0 vs 23.4%; p=0.048). Residual LVOT gradient, post-procedural residual left ventricular wall thickness, NYHA functional class, and adverse arrhythmic events were comparable between the two groups. The 10-year survival rate (77% vs 89%, p=0.037) and the annual adverse arrhythmic event rate (1.3% vs 0.4%, p<0.01) following ASA were significantly worse in women compared with men. Kaplan-Meier analysis showed a significantly lower survival in women compared with men (p=0.023). In multivariable modelling, female sex remained independently associated with higher all-cause mortality (hazard ratio, 1.12; 95% confidence interval, 1.08-1.27; p=0.03) when adjusted for age, NYHA class III-IV symptoms, and other cardiovascular comorbidities., Conclusions: Female patients with HOCM undergoing ASA tended to have more severe symptoms and adverse arrhythmic events. The 10-year survival rate after ASA was significantly worse in women compared with men with HOCM. Sex may need to be considered as an important factor in the clinical management of patients with symptomatic HOCM., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Eight pairs of meroterpenoid enantiomers and four achiral meroterpenoids were isolated from Rhododendron anthopogonoides Maxim. Seventeen of them, named (+)-/(-)-anthoponoids A-G, (+)-daurichromene D, and anthoponoids H and I, are undescribed compounds with structural diversity. Their structures were characterized herein by a combined application of spectroscopic techniques, X-ray crystallographic analysis, ECD calculation, and the modified Mosher's method. (+)-/(-)-Anthoponoid A and anthoponoid I are the first Rhododendron meroterpenoids found to possess a hexahydroxanthene motif and a diterpene unit, respectively. Some isolates were identified as NF-κB pathway inhibitors, and (+)-anthoponoid E, (-)-anthoponoid G, and anthoponoid H showed suppressive effects on LPS-induced inflammatory responses in RAW 264.7 macrophages., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To explore the feasibility and safety of the active retrograde backup (ARB) for treatment of chronic total occlusion (CTO) during retrograde percutaneous coronary intervention (PCI)., Background: Guiding support plays an important role in guidewire and microcatheter coronary channel (CC) tracking in retrograde PCI therapy for patients with CTO. However, the feasibility and safety of retrograde active use of a mother-and-child catheter are still unclear. Patients and Methods. A total of 271 consecutive patients with CTO who underwent retrograde PCI between January 2015 and January 2020 were retrospectively analyzed. Clinical data of two groups were compared to evaluate the feasibility and safety of ARB., Results: Of the 271 patients, 69.0% (187/271) underwent therapy through the septal branch, 31.0% (84/271) through the epicardial collateral channel, and 47.6% (129/271) through active retrograde extra backup with a mother-and-child catheter to facilitate retrograde microcatheter collateral CC tracking. The time of wire CC tracking was shorter in the ARB group than that in the non-ARB group (25.4 ± 8.5 vs 26.4 ± 9.7, p =0.348), but there was no significant difference. The duration of the retrograde microcatheter tracking (10.2 ± 3.8 vs 15.5 ± 6.8, p =0.012) and the retrograde approach (62.8 ± 20.3 vs 70.4 ± 24.3, p =0.026) in the ARB group was significantly shorter than that in the non-ARB group. The radiation dose (223.6 ± 112.7 vs. 295.2 ± 129.3, p =0.028), fluoroscopy time (50.6 ± 21.3 vs 62.3 ± 32.1, p =0.030), and contrast volume (301.8 ± 146.7 vs 352.2 ± 179.5, p =0.032) in the ARB group were significantly lower than that in the non-ARB group. There were no life-threatening procedural complications in either group. Complications unrelated to ARB included two cases of donor-vessel dissection, one case of CC perforation, and two cases of target-vessel perforation. There was no statistically significant difference in major adverse cardiac and cerebrovascular events between the groups during hospitalization ( p > 0.05)., Conclusion: ARB is feasible, safe, and conducive to guidewire and microcatheter CC tracking in the recanalization of coronary CTO. It improves procedural efficiency and is worthy of further promotion., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yong Wang et al.)

Chimeric antigen receptor (CAR) T cells use re-engineered cell surface receptors to specifically bind to and lyse oncogenic cells. Two clinically approved CAR-T-cell therapies have significant clinical efficacy in treating CD19-positive B cell cancers. With widespread interest to deploy this immunotherapy to other cancers, there has been great research activity to design new CAR structures to increase the range of targeted cancers and anti-tumor efficacy. However, several obstacles must be addressed before CAR-T-cell therapies can be more widely deployed. These include limiting the frequency of lethal cytokine storms, enhancing T-cell persistence and signaling, and improving target antigen specificity. We provide a comprehensive review of recent research on CAR design and systematically evaluate design aspects of the four major modules of CAR structure: the ligand-binding, spacer, transmembrane, and cytoplasmic domains, elucidating design strategies and principles to guide future immunotherapeutic discovery., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Six compounds including three new polyketide ones named eleubosas A-C ( 1 - 3) were isolated from the active frations of Eleutherine bulbosa . Their structures were elucidated by extensive spectroscopic methods, including NMR, MS and IR spectroscopic analyses data. All the isolates were evaluated against three pathogenic bacteria, Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa , and the results showed that compounds 1 and 2 displayed moderate inhibitory activities against E. coli with MIC values both 12.5 μg/mL, which are consistent with the clinical applications and need further studies.

Hyperprins A ( 1 ) and B ( 2 ), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii . Compound 1 possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.0 3,8 .0 8,12 ]hexadecane motif. Compound 2 features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1 showed antiproliferation activity against the MV-4-11 cell line, and the p -bromobenzoate derivative of 2 displayed PTP1B inhibition.

The expression of synthetic receptors in primary T cells enables the programming of user-defined responses when designing T-cell therapies. Chimeric antigen receptors (CARs) are synthetic receptors that have demonstrated efficacy in cancer therapy by targeting immobilized antigens on the surface of malignant cells. Recently, we showed they can also rewire T-cell responses to soluble ligands. In contrast to other synthetic receptors, CARs are not only readily engineered by rational design, but also clinically translatable, with robust function in primary human T cells. This protocol discusses design principles for CARs responsive to soluble ligands and delineates steps for producing T cells expressing synthetic receptors. Functional assays for quantifying the ability of CAR T cells to sense and respond to soluble ligands are also presented. This protocol provides a framework for proficient immune-cell researchers to test novel T-cell therapies targeting soluble ligands in <2 weeks.

Background: Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear., Method: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI., Results: The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan-Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group., Conclusion: In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.

Seven undescribed cycloartane triterpenoids, pseudolarnoids A-G, together with ten known ones, were isolated from the seeds of Pseudolarix amabilis (J. Nelson) Rehder. Their structures were elucidated on the basis of spectroscopic analysis, X-ray crystallography, and ECD data. Pseudolarnoids A-C are cycloartane triterpenoids with a unique 16S, 23R-spirolactone moiety. Pseudolarnoids F, G, and pseudolarolide C demonstrated potent antiviral effects on HSV-1 in vitro., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear., Methods: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes., Results: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p =0.002) and hypertension (50.6% vs 37.1%, p =0.018) and a lower incidence of retrograde filling grade >2 (34.8% vs 47.1%, p =0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6±19.4 vs 52.4±18.3, p =0.038) and levels of low-density lipoprotein (LDL; 3.0±0.8 vs 2.8±0.6, p =0.029), fasting glucose (FG; 8.3±1.3 vs 6.8±1.1, p =0.005), uric acid (332.6±82.9 vs 308.2±62.8, p =0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8±4.8 vs 7.3±3.9, p =0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198-2.721; p =0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108-1.895; p =0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105-2.491; p =0.036), FG (OR, 2.095; 95% CI, 1.495-2.899; p =0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556-3.519; p =0.029), and retrograde filling of grade >2 (OR, 0.822; 95% CI, 0.622-0.907; p =0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group ( p <0.0001)., Conclusion: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade >2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wang et al.)

Nine ursane-type triterpenoids including three new ones 2 α , 19 α- dihydroxyurs-3 -O- acetyltormentic acid ( 1 ), 1 α , 2 α , 3 α , 20 β -tetrahydroxyurs -13(18)-en-28-oic acid ( 2 ), and 2 α , 3 α , 20 β , 24-tetrahydroxyurs-13(18)-en-28-oic acid ( 3 ) were isolated from the roots of Rosa multiflora . Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and IR spectroscopic analyses data. All the isolates were evaluated for their anti-inflammatory activity in vitro and the results showed that compounds 1 - 9 displayed moderate inhibitory activity with IC 50 values ranging from 24.7 to 86.2 μM compared with the postitive control Amino guanidine (IC 50 4.3 μM).[Formula: see text].

Four new alkaloids, ficuhismines A-D (1-4), together with three known ones, were isolated from Ficus hispida. Their structures were elucidated by spectroscopic analysis and chemical method. The new compounds represent the first amine alkaloids with a rhamnosyl moiety (1-2) or with a N-oxide motif (2-4) from the genus Ficus. Compound 2 showed potent inhibitory effect in nuclear factor-κB (NF-κB) pathway luciferase assay with IC 50 value of 0.52 ± 0.11 μM.

Five pairs of optically pure meroterpenoid enantiomers (1a/1b-5a/5b) and two known compounds (6 and 7) were isolated from Rhododendron fastigiatum. Compounds 1a/1b-5a/5b were resolved from naturally scalemic mixtures by chiral HPLC. Their structures were elucidated by spectroscopic methods, X-ray crystallographic experiments, and ECD analyses. Compounds 1a/1b, 2a/2b, 3b, 4a/4b, and 5a/5b were new meroterpenoids with different polycyclic systems. Two enantiomeric pairs (2a/2b and 3a/3b), 6, and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) in vitro., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Six new triterpenoids, pseudolarins A-F (1-6), were isolated from the twigs of Pseudolarix amabilis, together with four known triterpenoids (7-10) and five known diterpenoids (11-15). Their structures were determined by extensive spectroscopic analysis, and the absolute configuration of 1 was assigned by single-crystal X-ray diffraction. Compound 1 is a 3,4:9,10-diseco-cycloartane triterpenoid possessing an unprecedented 5/5/7/6/5/6/5 ring system. Compounds 1, 5, 7, 9-11, and 13 showed inhibition against protein tyrosine phosphatase 1B (PTP1B) in vitro., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate whether ginsenoside-Rb1 (Gs-Rb1) improves the CoCl-induced autophagy of cardiomyocytes via upregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway., Methods: Ventricles from 1- to 3-day-old Wistar rats were sequentially digested, separated and incubated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 3 days followed by synchronization. Neonatal rat cardiomyocytes were randomly divided into 7 groups: control group (normal level oxygen), hypoxia group (500 μmol/L CoCl 2 ), Gs-Rb1 group (200 μmol/L Gs-Rb1 + 500 μmol/L CoCl 2 ), Ara A group (500 μmol/L Ara A + 500 μmol/L CoCl 2 ), Ara A+ Gs-Rb1 group (500 μmol/L Ara A + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl 2 ), AICAR group [1 mmol/L 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) + 500 μmol/L CoCl 2 ], and AICAR+Gs-Rb1 group (1 mmol/L AICAR + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl 2 ). Cells were treated for 12 h and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cardiac troponin I (cTnI) levels were detected by enzyme-linked immunosorbent assay (ELISA). AMPK activity was assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) ELISA assay. The protein expressions of Atg4B, Atg5, Atg6, Atg7, microtubule-associated protein 1A/1B-light chain 3 (LC3), P62, and active-cathepsin B were measured by Western blot., Results: Gs-Rb1 significantly improved the cell viability of hypoxia cardiomyocytes (P<0.01). However, the viability of hypoxia-treated cardiomyocytes was significantly inhibited by Ara A (P<0.01). Gs-Rb1 increased the AMPK activity of hypoxia-treated cardiomyocytes. The AMPK activity of hypoxia-treated cadiomyocytes was inhibited by Ara A (P<0.01) and was not affected by AICAR =0.983). Gs-Rb1 up-regulated Atg4B, Atg5, Beclin-1, Atg7, LC3B II, the LC3B II/I ratio and cathepsin B activity of hypoxia cardiomyocytes (P<0.05), each of these protein levels was significantly enhanced by Ara A (all P<0.01), but was not affected by AICAR (all P>0.05). Gs-Rb1 significantly down-regulated P62 levels of hypoxic cardiomyocytes (P<0.05). The P62 levels of hypoxic cardiomyocytes were inhibited by Ara A (P<0.05) and were not affected by AICAR (P=0.871)., Conclusion: Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

Background: The usefulness of the CHA2DS2-VASC risk score (CVRS) in predicting the occurrence of contrast-induced nephropathy (CIN) among patients with chronic total occlusion (CTO) undergoing percutaneous coronary intervention (PCI) remains unclear., Method: A total of 239 patients with CTO who underwent PCI were included in this study. They were divided into 3 groups according to the CVRS: low-risk group (1 point, n = 64), intermediate-risk group (2 points, n = 135), and high-risk group (≥3 points, n = 40). Baseline serum creatinine was determined upon admission before the procedure. The serum creatinine level was monitored for 72 h post-procedure to determine the occurrence of CIN., Results: The total incidence of CIN in patients with CTO who underwent PCI was 16.3%. The average CVRS in the CIN group was significantly higher than that in the non-CIN group (3.1 ± 1.2 VS 2.1 ± 1.1, P < 0.001). The incidence of CIN in the high-risk group was 5.6 times higher than that in the low-risk group (37.5% VS 6.3%, P < 0.001). Similar to the Mehran risk score (AUC, 0.754; 95% CI, 0.698-0.810; P < 0.001), the receiver operating characteristic curve analysis showed a good diagnostic value of the CVRS in predicting CIN among patients with CTO who underwent interventional therapy for having CVRS≥3 (sensitivity, 69.2%; specificity, 78.0%; AUC, 0.742; 95% CI, 0.682-0.797; P < 0.001). The multivariate analysis showed that the higher pulse pressure and contrast volume, lower baseline glomerular filtration rate, and CVRS ≥3 were independent predictors of CIN., Conclusions: The CVRS can be used as a simple pre-procedural predictor of CIN among patients with CTO undergoing PCI.

Objectives: To assess the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in high-bleeding-risk elderly patients., Background: Bivalirudin reduces PCI-related bleeding; however, its efficacy and safety in patients with CTO, especially elderly patients with a high bleeding risk, remain unclear., Methods: This single-center prospective randomized controlled trial assigned 123 high-bleeding-risk elderly patients with CTO to either the unfractionated heparin (UFH) group (n = 55) or the bivalirudin group (n = 68). The primary efficacy endpoint was the incidence of major adverse cardiac events (MACEs) during hospitalization and at the 6-month follow-up. The safety endpoint was bleeding or procedure (access)-related complications after PCI., Results: MACE incidence was 17.6% and 20.0% in the bivalirudin and UFH groups, respectively (P = 0.82). Bleeding Academic Research Consortium (BARC) type 1-2 bleeding events during hospitalization were comparable between the groups (UFH: 10.9% vs. bivalirudin: 8.8%, P = 0.77). No BARC type 3-5 bleeding events or severe procedure (access)-related complications (subcutaneous hematoma >5 cm) occurred in either group. At the 6-month follow-up, MACE incidence was comparable between the groups (UFH: 3.6% vs. bivalirudin: 1.5%, P = 0.59). The Kaplan-Meier analysis revealed that MACE-free survival rates were comparable between the groups (P = 0.43). One case of BARC type 3-5 bleeding (fatal intracranial hemorrhage) was observed in the UFH group at the 6-month follow-up., Conclusions: Bivalirudin and UFH showed comparable efficacy and safety in elderly patients with a high bleeding risk, undergoing PCI for CTO lesions., (© 2019 Wiley Periodicals, Inc.)

Twelve alkaloids were isolated from the bulbs of Fritillaria yuminensis by column chromatography over silica gel, ODS, and Sephadex LH-20, as well as RP-HPLC. Their structures were identified mainly by NMR and MS analyses as yubeinine(1), imperialine(2), delavinone(3), tortifoline(4), hupehenizioiside(5), imperialine-β-D-glucoside(6), kuroyurinidine(7), pengbeisine A(8), walujewine A(9), peimisine-3-O-β-D-glucopyranoside(10), solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(11), and solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-glucopyranoside(12). Compounds 4-12 were obtained from F. yuminensis for the first time.

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.

Two new triterpenoids, vistriterpenoids A (1) and B (2), and four known ones, were acquired from Dodonaea viscosa. Compounds 1 and 2 represent the 24-nor-oleanane triterpenoids isolated from the genus Dodonaea for the first time. Their structures were identified based on extensive spectroscopic methods. Compounds 1, 2, 5, and 6 exerted inhibitory activities against PTP1B in vitro., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Three new isosteroidal alkaloids, frititorines A-C (1-3), were isolated from the bulbs of Fritillaria tortifolia, together with ten known ones (4-13). Their structures were elucidated by extensive spectroscopic analyses, chemical methods, and single-crystal X-ray crystallographic analysis. Compound 1 is the first 5β-cevanine alkaloid with a cis A/B ring junction from the Fritillaria genus. Compound 2 is the first example of glycosylated isosteroidal alkaloid N-oxide. Compound 1 showed significant relaxant effect on Ach-induced tracheal contraction with pA 2 and EC 50 values equivalent to those of aminophylline., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three new (1a/1b and 2b) and five known flavans (2a, 6a/6b, 7, and 8), one new flavan glycoside (3), and two new (4 and 5) and six known 1,3-diphenylpropanes (9-14) were isolated from the twigs of Broussonetia kazinoki. Compounds 1, 2, and 6 are scalemic mixtures, and were resolved by chiral HPLC to provide 1a/1b, 2a/2b, and 6a/6b. The structures of these compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD analyses. Compounds 1, 2, 5, 8, 9, 11, and 12 showed in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Eight enantiomeric pairs of new meromonoterpenoids (1a/1b-8a/8b) and four known compounds (9-12) were isolated from Rhododendron nyingchiense. Their structures were established by spectroscopic methods, quantum chemical calculations, and X-ray crystallography. The enantiomeric pairs were acquired from scalemic mixtures by chiral-phase HPLC and showed diverse heterocyclic frameworks. Compounds 1a/1b possess a rare 6/7/5/5 heterocyclic system, and 2a/2b incorporate a new 6/6/3/5 heterocyclic system featuring a quinone motif. Compounds 3a/3b represent the first meroterpenoids with a 6/6/5 ring system from the Rhododendron genus. Putative biosynthetic pathways of these compounds are proposed. Compounds 1b, 2a-4a, 8a, 8b, and 11 exhibited weak inhibitory effects on PTP1B, with IC 50 values ranging from 5.7 ± 0.5 to 61.0 ± 4.8 μM.