Publications by authors named "Sheng Yin"

265 Publications

Hybrid metamaterial absorber for ultra-low and dual-broadband absorption.

Opt Express 2021 Apr;29(9):14078-14086

Developing high-efficiency microwave absorbers remains challenging in the broadband range, particularly in the low-frequency range containing the L band and even lower. To overcome this challenge, a hybrid metamaterial absorber comprising a conventional magnetic absorbing material and a multi-layered meta-structure predesigned with graphene films is proposed to realize wideband absorption performance starting from ultra-low frequencies (0.79-20.9 GHz and 25.1-40.0 GHz). The high absorption ability of the proposed device originates from fundamental resonance modes and their coupling. The experimental results agree well with the simulated ones, proving the effectiveness of our design method. In addition, owing to the use of low-density polymethylacrylimide foam and graphene films with outstanding mechanical properties, our design is lightweight and environmentally adaptable, which reflects its engineering value.
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http://dx.doi.org/10.1364/OE.423245DOI Listing
April 2021

Effect of Tensile Deformation on Residual Stress of GH4169 Alloy.

Materials (Basel) 2021 Apr 3;14(7). Epub 2021 Apr 3.

College of Materials and Metallurgy, Guizhou University, Guiyang 550025, China.

In order to reduce the residual stress of the GH4169 alloy, the effect and micro-mechanism of the tensile deformation were studied. The residual stress, dislocation density, and distribution of the GH4169 alloy were analyzed by X-ray residual stress tester, X-ray diffractometer (XRD), and electron backscatter diffraction (EBSD). The results show that: with the increase of tensile deformation, the residual stress relief first increases and then decreases. When the tensile deformation is 3%, the reduction rate of residual stress reaches the maximum, which is 90%. The mechanism of residual stress relief by the tensile treatment is that the dislocation group in the alloy is activated by tensile treatment, and the dislocation distribution in the alloy is more uniform by dislocation movement, multiplication, and annihilation so that the residual stress can be eliminated.
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http://dx.doi.org/10.3390/ma14071773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038358PMC
April 2021

Jolkinolide B targets thioredoxin and glutathione systems to induce ROS-mediated paraptosis and apoptosis in bladder cancer cells.

Cancer Lett 2021 Jul 6;509:13-25. Epub 2021 Apr 6.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China. Electronic address:

Bladder cancer is a clinically heterogeneous disease with a poor prognosis. In the current study, anti-proliferation assay of a Euphorbiaceae diterpenoid library led to the identification of an anti-bladder cancer agent Jolkinolide B (JB). JB showed significant cytotoxicity against a panel of bladder cancer cell lines and suppressed the growth of cisplatin (CDDP)-resistant bladder cancer xenografts in single or combination treatments. Mechanistic study revealed that, besides inducing mitogen-activated protein kinase (MAPK)-related apoptosis, JB could trigger the paraptosis via activation of reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress and extracellular signal-regulated kinase (ERK) pathway. The excessive production of ROS could be induced by JB via inhibition of thioredoxin reductase 1 (TrxR1) and depletion of glutathione (GSH). Collectively, JB that targets thioredoxin and GSH systems to induce two distinct cell death modes may serve as a promising candidate in future anti-bladder cancer drug development.
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http://dx.doi.org/10.1016/j.canlet.2021.03.030DOI Listing
July 2021

Structurally diverse triterpenoids with cytotoxicity from Euphorbia hypericifolia.

Fitoterapia 2021 Mar 31;151:104888. Epub 2021 Mar 31.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

Extensive phytochemical investigation on the whole herbs of Euphorbia hypericifolia led to the isolation of 18 structurally diverse tetracyclic and pentacyclic triterpenoids, including four 4α,14α-dimethyl-5α-ergostanes (1-4), two seco-adiananes (5 and 6), three dammaranes (7-9), four cycloartanes (10-13), one tirucallane (14), two fernanes (15 and 16), one ursane (17), and one oleanane (18). Among them, euphypenoids A (1) and B (5) were new triterpenoids. Their structures were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and chemical transformation. All isolates were screened for their cytotoxic activities against the colorectal cancer cell line HCT-116, and compounds 1, 12, and 15 showed remarkable activities with IC values of 12.8 ± 1.6, 7.4 ± 0.2, and 10.6 ± 1.2 μM, respectively.
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http://dx.doi.org/10.1016/j.fitote.2021.104888DOI Listing
March 2021

Herbal medicine WangShiBaoChiWan improves gastrointestinal health in mice via modulation of intestinal tight junctions and gut microbiota and inhibition of inflammation.

Biomed Pharmacother 2021 Jun 21;138:111426. Epub 2021 Mar 21.

Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address:

WangShiBoChiWan (WSBCW) is a commonly used Chinese herbal medicine for the treatment of functional gastrointestinal disorders. However, its preclinical efficacy and the mechanisms of action have not been adequately studied. The goals of this study were to evaluate the effects of WSBCW on gastrointestinal health and modulation of related biomarkers. Female C57BL mice were randomly assigned into one of the experimental groups consisting of the control, drug controls, and WSBCW at 40, 120, and 360 mg/kg BW. Whole gut transit, small intestinal motility, and intestinal barrier permeability were determined. The castor oil-induced diarrhea mouse model was used to determine the effect of WSBCW on the diarrhea type of irritable bowel syndrome (IBS-D). WSBCW increased whole gut transit and intestinal motility, improved intestinal permeability in healthy animals and alleviated diarrhea symptoms in IBS-D mice. WSBCW upregulated intestinal junction proteins, increased the abundance of Bifidobacterium genus, Desulfovibrio genus and inhibited Bacteroides fragillis group in the gut microbiota, increased intestinal villi lengths, and decreased blood levels of inflammatory cytokines. Our study provided preclinical evidence to verify the effectiveness of WSBCW in gastrointestinal health and elucidate mechanistic insights. The results warrant further investigations to evaluate the therapeutic efficacy of WSBCW on gastrointestinal disorders, such as IBS and IBD.
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http://dx.doi.org/10.1016/j.biopha.2021.111426DOI Listing
June 2021

Hydrogels for Large-Scale Expansion of Stem Cells.

Authors:
Sheng Yin Yi Cao

Acta Biomater 2021 Mar 19. Epub 2021 Mar 19.

National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, 210093, China; Chemistry and Biomedicine innovation center, Nanjing University, Nanjing, 210093, China; Institute for Brain Sciences, Nanjing University, Nanjing, 210093, China; Shenzhen Research Institute of Nanjing University, Shenzhen, China, 518057. Electronic address:

Stem cells demonstrate considerable promise for various preclinical and clinical applications, including drug screening, disease treatments, and regenerative medicine. Producing high-quality and large amounts of stem cells is in demand for these applications. Despite challenges, as hydrogel-based cell culture technology has developed, tremendous progress has been made in stem cell expansion and directed differentiation. Hydrogels are soft materials with abundant water. Many hydrogel properties, including biodegradability, mechanical strength, and porosity, have been shown to play essential roles in regulating stem cell proliferation and differentiation. The biochemical and physical properties of hydrogels can be specifically tailored to mimic the native microenvironment that various stem cells reside in vivo. A few hydrogel-based systems have been developed for successful stem cell cultures and expansion in vitro. In this review, we summarize various types of hydrogels that have been designed to effectively enhance the proliferation of hematopoietic stem cells (HSCs), mesenchymal stem/stromal cells (MSCs), and pluripotent stem cells (PSCs), respectively. According to each stem cell type's preference, we also discuss strategies for fabricating hydrogels with biochemical and mechanical cues and other characteristics representing microenvironments of stem cells in vivo. STATEMENT OF SIGNIFICANCE: In this review article we summarize current progress on the construction of hydrogel systems for the culture and expansion of various stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem/stromal cells (MSCs), and pluripotent stem cells (PSCs). The Significance includes: (1) Provide detailed discussion on the stem cell niches that should be considered for stem cell in vitro expansion. (2) Summarize various strategies to construct hydrogels that can largely recapture the microenvironment of native stem cells. (3) Suggest a few future directions that can be implemented to improve current in vitro stem cell expansion systems.
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http://dx.doi.org/10.1016/j.actbio.2021.03.026DOI Listing
March 2021

Total Synthesis of Mulberry Diels-Alder-Type Adducts Kuwanons G and H.

J Org Chem 2021 Mar 10;86(6):4786-4793. Epub 2021 Mar 10.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.

Mulberry Diels-Alder-type adducts (MDAAs) are a group of rare natural polyphenols biosynthetically derived from [4 + 2]-cycloaddition of chalcones and dehydroprenylphenols. In this study, kuwanons G () and H (), two bioactive MDAAs with unique dehydroprenylflavonoid dienes, were totally synthesized for the first time in a biomimetic manner. The key features of the convergent route include the use of the Baker-Venkataraman rearrangement, alkylation of β-diketone, intramolecular cyclization, and Suzuki-Miyaura coupling to achieve the subunit diene.
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http://dx.doi.org/10.1021/acs.joc.1c00229DOI Listing
March 2021

Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol 2021 04 8;22(4):439-449. Epub 2021 Mar 8.

Ovarian Cancer Program, Department of Gynaecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population.

Methods: This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m] or docetaxel [75 mg/m] combined with intravenous carboplatin [area under the curve of 5 mg/mL per min]; surgery group) or intravenous chemotherapy alone (no surgery group). Primary endpoints were progression-free survival and overall survival, analysed in all participants randomly assigned to treatment, regardless of treatment received (intention-to-treat [ITT] population). Here, we report the final analysis of progression-free survival and the prespecified interim analysis of overall survival. Safety was assessed in all participants who received their assigned treatment and had available adverse event data. This study is registered with ClinicalTrials.gov, NCT01611766, and is ongoing but closed to accrual.

Findings: Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1-58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0-19·8) in the surgery group and 11·9 months (10·0-13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45-0·74; p<0·0001). At the interim overall survival analysis, median overall survival was 58·1 months (95% CI not estimable to not estimable) in the surgery group and 53·9 months (42·2-65·5) in the no surgery group (HR 0·82, 95% CI 0·57-1·19). In the safety population, nine (5%) of 172 patients in the surgery group had grade 3-4 surgical morbidity at 30 days, and no patients in either group had died at 60 days after receiving assigned treatment. The most common grade 3-4 adverse events during chemotherapy were neutropenia (29 [17%] of 166 patients in the surgery group vs 19 [12%] of 156 patients in the no surgery group), leucopenia (14 [8%] vs eight [5%]), and anaemia (ten [6%] vs nine [6%]). Four serious adverse events occurred, all in the surgery group. No treatment-related deaths occurred in either group.

Interpretation: Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival.

Funding: Zhongshan Development Program.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00006-1DOI Listing
April 2021

A Crystalline Three-Dimensional Covalent Organic Framework with Flexible Building Blocks.

J Am Chem Soc 2021 Feb 22;143(4):2123-2129. Epub 2021 Jan 22.

Sauvage Center for Molecular Sciences, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

The construction of three-dimensional covalent organic frameworks (3D COFs) has proven to be very challenging, as their synthetic driving force mainly comes from the formation of covalent bonds. To facilitate the synthesis, rigid building blocks are always the first choice for designing 3D COFs. In principle, it should be very appealing to construct 3D COFs from flexible building blocks, but there are some obstacles blocking the development of such systems, especially for the designed synthesis and structure determination. Herein, we reported a novel highly crystalline 3D COF (FCOF-5) with flexible C-O single bonds in the building block backbone. By merging 17 continuous rotation electron diffraction data sets, we successfully determined the crystal structure of FCOF-5 to be a 6-fold interpenetrated topology. Interestingly, FCOF-5 is flexible and can undergo reversible expansion/contraction upon vapor adsorption/desorption, indicating a breathing motion. Moreover, a smart soft polymer composite film with FCOF-5 was fabricated, which can show a reversible vapor-triggered shape transformation. Therefore, 3D COFs constructed from flexible building blocks can exhibit interesting breathing behavior, and finally, a totally new type of soft porous crystals made of pure organic framework was announced.
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http://dx.doi.org/10.1021/jacs.0c12505DOI Listing
February 2021

Stenotrophomonas-maltophilia inhibits host cellular immunity by activating PD-1/PD-L1 signaling pathway to induce T-cell exhaustion.

Mol Immunol 2021 02 21;130:37-48. Epub 2020 Dec 21.

Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China. Electronic address:

Background: Smalotrophomonas maltophilia(S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ.

Materials And Methods: S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells.

Results: T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells.

Conclusions: These indicates that T cells are inhibited after being stimulated by S. maltophilia, and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered.
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http://dx.doi.org/10.1016/j.molimm.2020.12.019DOI Listing
February 2021

Significance of the ratio interferon-γ/interleukin-4 in early diagnosis and immune mechanism of unexplained recurrent spontaneous abortion.

Int J Gynaecol Obstet 2020 Nov 23. Epub 2020 Nov 23.

Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, China.

Objective: To investigate the significance of T helper type 1 (Th1)/Th2 cytokines in the pathogenesis of unexplained recurrent spontaneous abortion (URSA), and reveal the value of single cytokines and their proportions in early diagnosis.

Methods: A total of 44 URSA patients (URSA group), 51 patients with adverse pregnancy history (ad-pregnancy group), and 42 healthy volunteers with normal pregnancy (pregnancy group) were recruited for a cross-sectional study from July 2018 to April 2019 in the Second Xiangya Hospital. Pregnancies involving chromosomal abnormalities, infection, autoimmune diseases, and anatomical abnormalities were excluded. Flow cytometry was used to determine the level of Th1/Th2 cytokines in peripheral blood.

Results: The level of interleukin-6 (IL-6) in the peripheral blood of the ad-pregnancy group was significantly higher than in the other two groups. The ratio of interferon-γ (IFN-γ)/IL-4 in the URSA group was significantly higher than that of the pregnancy group. The area under the curve for IFN-γ/IL-4 was 0.821, with high diagnostic efficiency, and sensitivity as high as 84.09%.

Conclusion: Laboratory testing for IL-6 is not recommended for the diagnosis or monitoring of URSA. The variable IFN-γ/IL-4 can be used for the initial diagnosis of URSA to reduce the rate of missed diagnosis. This ratio was more important than the expression of a single cytokine in the Th1/Th2 immune response.
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http://dx.doi.org/10.1002/ijgo.13494DOI Listing
November 2020

Stereoselective Construction of the Methylcyclopentane Core of Peditithins B-H with Five Continuous Stereocenters.

Org Lett 2020 12 20;22(23):9360-9364. Epub 2020 Nov 20.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.

A stereoselective construction of the methylcyclopentane core () of jatrophane diterpenoids peditithins B-H was achieved in 14 steps from commercially available d-(+)-ribono-1,4-lactone (). The linear 5-ene-heptanal derived from was cyclized to the five-membered ring by an intramolecular carbonyl ene reaction, and five continuous stereocenters on were stereoselectively introduced via a successive substrate-controlled manner, involving diastereoselective 1,4-addition, MoOPH-induced hydroxylation, and stereospecific epoxidation.
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http://dx.doi.org/10.1021/acs.orglett.0c03615DOI Listing
December 2020

Selaginellins from the genus : isolation, structure, biological activity, and synthesis.

Nat Prod Rep 2021 04;38(4):822-842

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. China.

Covering: 2007 to 2020 Selaginellins are a small group of pigments exclusively found in the ancient genus Selaginella. Since the first report of selaginellin from S. sinensis in 2007, more than 110 selaginellins with diverse polyphenolic skeletons have been reported. This review provides extensive coverage of the selaginellins discovered from 2007 to 2020, including 61 natural ones and 52 synthetic analogues. The isolation, chemical structures, plausible biosynthetic pathways, bioactivity, and total synthesis of these selaginellins have been summarized for the first time, and this highlights the fact that the vast uninvestigated Selaginella species may serve as a potential treasure trove of chemically diverse selaginellins waiting to be discovered.
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http://dx.doi.org/10.1039/d0np00065eDOI Listing
April 2021

Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF-κB and Nrf2 signaling pathways.

Phytother Res 2021 Mar 23;35(3):1559-1571. Epub 2020 Oct 23.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.
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http://dx.doi.org/10.1002/ptr.6922DOI Listing
March 2021

Redox-triggered switching in three-dimensional covalent organic frameworks.

Nat Commun 2020 Oct 1;11(1):4919. Epub 2020 Oct 1.

Sauvage Center for Molecular Sciences and Key Laboratory of Biomedical Polymers (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.

The tuning of molecular switches in solid state toward stimuli-responsive materials has attracted more and more attention in recent years. Herein, we report a switchable three-dimensional covalent organic framework (3D COF), which can undergo a reversible transformation through a hydroquinone/quinone redox reaction while retaining the crystallinity and porosity. Our results clearly show that the switching process gradually happened through the COF framework, with an almost quantitative conversion yield. In addition, the redox-triggered transformation will form different functional groups on the pore surface and modify the shape of pore channel, which can result in tunable gas separation property. This study strongly demonstrates 3D COFs can provide robust platforms for efficient tuning of molecular switches in solid state. More importantly, switching of these moieties in 3D COFs can remarkably modify the internal pore environment, which will thus enable the resulting materials with interesting stimuli-responsive properties.
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http://dx.doi.org/10.1038/s41467-020-18588-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531008PMC
October 2020

Enzymatic Plasticity Inspired by the Diterpene Cyclase CotB2.

ACS Chem Biol 2020 10 5;15(10):2820-2832. Epub 2020 Oct 5.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functions drastically. Many efforts have been made to disclose the mysteries of CotB2 enzyme catalysis. However, the catalytic details and regulatory mechanism toward the precise chemo- and stereoselectivity are still elusive. In this work, multiscale simulations are employed to illuminate the biocyclization mechanisms of the linear substrate into the final product cyclooctat-9-en-7-ol with a 5-8-5 fused ring scaffold, and the derailment products arising from the premature quenching of reactive carbocation intermediates are also discussed. The two major regulatory factors, local electrostatic stabilization effects from aromatic residues or polar residue in pocket and global features of active site including pocket-contour and pocket-hydrophobicity, are responsible for the enzymatic plasticity of CotB2. Further comparative studies of representative Euphorbiaceae and fungal diterpene cyclase (RcCS and PaFS) show a correlation between pocket plasticity and product diversity, which inspires a tentative enzyme product prediction and the rational diterpene cyclases' reengineering in the future.
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http://dx.doi.org/10.1021/acschembio.0c00645DOI Listing
October 2020

Extracellular vesicles of bacteria as potential targets for immune interventions.

Hum Vaccin Immunother 2021 Mar 1;17(3):897-903. Epub 2020 Sep 1.

Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Bacterial infection is one of the most common and serious diseases. Extracellular vesicles (EVs) expressed by bacterial cells during infection and their biological functions have been a growing field in recent years. The study of the immune interaction mechanism between EVs and bacteria has become more significant. EVs are released into the extracellular microenvironment during bacterial infection. EVs carry various lipids, proteins, nucleic acids, and other substances of host bacteria and participate in various physiological and pathological processes. EV-based vaccines against bacterial infection are also being evaluated. This review focuses on the biological characteristics of EVs, the interaction between EVs and the host immune system, and the potential of EVs as new vaccines. A deeper understanding of the interaction between EVs and the immune system informs on the biological function and heterogeneity of EVs. This knowledge also can facilitate the development and application of EVs and their potential as vaccines.
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http://dx.doi.org/10.1080/21645515.2020.1799667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993133PMC
March 2021

Global Exponential Stability of Memristive Neural Networks With Mixed Time-Varying Delays.

IEEE Trans Neural Netw Learn Syst 2020 Aug 28;PP. Epub 2020 Aug 28.

This article investigates the Lagrange exponential stability and the Lyapunov exponential stability of memristive neural networks with discrete and distributed time-varying delays (DMNNs). By means of inequality techniques, theories of the M-matrix, and the comparison strategy, the Lagrange exponential stability of the underlying DMNNs is considered in the sense of Filippov, and the globally exponentially attractive set is estimated through employing the M-matrix and external input. Especially, when the external input is not concerned, the Lyapunov exponential stability of the corresponding DMNNs is developed immediately in the form of an M-matrix, which contains some published outcomes as special cases. Furthermore, by constructing an M-matrix-based differential system, the Lyapunov exponential stability of the DMNNs is studied, which is less conservative than some existing ones. Finally, three simulation examples are carried out to examine the validness of the theories.
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http://dx.doi.org/10.1109/TNNLS.2020.3015944DOI Listing
August 2020

Study of upfront surgery versus neoadjuvant chemotherapy followed by interval debulking surgery for patients with stage IIIC and IV ovarian cancer, SGOG SUNNY (SOC-2) trial concept.

J Gynecol Oncol 2020 Sep;31(5):e86

Shanghai Gynecologic Oncology Group and Ovarian Cancer Program, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice.

Methods: The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT02859038.
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http://dx.doi.org/10.3802/jgo.2020.31.e86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440987PMC
September 2020

Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.

Nutrients 2020 Aug 8;12(8). Epub 2020 Aug 8.

Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Chronic kidney disease (CKD) is a global epidemic with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study aimed to investigate the effect of nutraceutical components, a fermented soybean product (ImmuBalance, IMB) and an oligo-lactic acid product (LAP), on the prevention of adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into following experimental groups: negative control; model control; and models treated with IMB at 250 or 1000 mg/kg body weight (BW), LAP at 1000 or 2000 mg/kg BW, and IMB/LAP combinations. The CKD model was established by intraperitoneal injection of adenine daily for 4 weeks, and treatments started 2 weeks before adenine injection and ended after 10 weeks. Compared with the model control, the treatments did not significantly alter the body weight or food intake. Both IMB and LAP, especially their combination, significantly inhibited tubular dilation, tubulointerstitial degeneration or atrophy, interstitial chronic inflammation and acute inflammation in the kidneys of CKD mice, and significantly decreased serum cystatin C levels. IMB or LAP significantly reversed CKD-associated increases of circulating and kidney levels of inflammatory cytokines, circulating levels of kidney injury biomarkers, and kidney levels of stem cell biomarkers, and significantly reversed CKD-associated reduction of cecum group. Our results suggest that dietary supplementation of IMB or LAP may significantly delay the development and/or progression of CKD.
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http://dx.doi.org/10.3390/nu12082376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468970PMC
August 2020

Global Stability of Bidirectional Associative Memory Neural Networks With Multiple Time-Varying Delays.

IEEE Trans Cybern 2020 Aug 12;PP. Epub 2020 Aug 12.

This article investigates the global stability of bidirectional associative memory neural networks with discrete and distributed time-varying delays (DBAMNNs). By employing the comparison strategy and inequality techniques, global asymptotic stability (GAS) and global exponential stability (GES) of the underlying DBAMNNs are of concern in terms of p-norm (p≥ 2). Meanwhile, GES of the addressed DBAMNNs is also analyzed in terms of 1-norm. When distributed time delay is neglected, the GES of the corresponding bidirectional associative memory neural networks is presented as an M-matrix, which includes certain existing outcomes as special cases. Two examples are finally provided to substantiate the validity of theories.
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http://dx.doi.org/10.1109/TCYB.2020.3011581DOI Listing
August 2020

A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression.

Cancer Cell Int 2020 5;20:372. Epub 2020 Aug 5.

Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan China.

Background: Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated.

Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2-AS1 or SMAD3 and miR-143-3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis.

Results: ACTA2-AS1 was significantly increased in CC tissues and cells and miR-143-3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells.

Conclusions: In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.
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http://dx.doi.org/10.1186/s12935-020-01471-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409411PMC
August 2020

Crotonpenoids A and B, Two Highly Modified Clerodane Diterpenoids with a Tricyclo[7.2.1.0]dodecane Core from : Isolation, Structural Elucidation, and Biomimetic Semisynthesis.

Org Lett 2020 06 26;22(11):4435-4439. Epub 2020 May 26.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.

Crotonpenoids A () and B (), two highly modified clerodane diterpenoids featuring a new 10-(butan-2-yl)-1,6,12-trimethyltricyclo[7.2.1.0]dodecane skeleton, were isolated from the leaves and twigs of . Their structures including the absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, and biomimetic semisynthesis. Compounds and exhibited an agonistic effect on pregnane X receptor at 10 μM.
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http://dx.doi.org/10.1021/acs.orglett.0c01443DOI Listing
June 2020

Euphopanes A-C, three new diterpenoids from .

Nat Prod Res 2020 May 13:1-8. Epub 2020 May 13.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

Three new diterpenoids, euphopanes A-C (-), including one -isopimarane (), one -abietane () and one cembrane (), along with five known compounds (-) were isolated from the roots of . Their structures were elucidated by extensive spectroscopic analysis, and the absolute configurations of compounds - were determined by ECD calculations. All the isolates were screened for the cytotoxicity against three cancer cell lines (C4-2B, C42B/ENZR, and MDA-MB-231), and compounds , , and showed significant cytotoxicity against human prostate cancer cells C4-2B with IC values of 14.3, 16.9, and 15.3 μM, respectively.
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http://dx.doi.org/10.1080/14786419.2020.1765342DOI Listing
May 2020

The implications of preliminary screening and diagnosis: Clinical characteristics of 33 mild patients with SARS-CoV-2 infection in Hunan, China.

J Clin Virol 2020 07 30;128:104397. Epub 2020 Apr 30.

Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Electronic address:

Background: In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions.

Objectives: To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020.

Study Design: From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed.

Results: There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2.

Conclusions: The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic.
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http://dx.doi.org/10.1016/j.jcv.2020.104397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192082PMC
July 2020

Diterpenoids from Euphorbia royleana reverse P-glycoprotein-mediated multidrug resistance in cancer cells.

Phytochemistry 2020 Aug 27;176:112395. Epub 2020 Apr 27.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China. Electronic address:

Eight previously undescribed diterpenoids, euphoroyleans A-H, including two cembranes, three ingenanes, two ent-atisanes, and one ent-kaurane, along with 22 known analogues were isolated from the whole plants of Euphorbia royleana. The structures of euphoroyleans A-H, including the absolute configurations, were elucidated by extensive spectroscopic analyses, chemical transformation, and single crystal X-ray diffractions. All the isolates were screened for their chemoreversal abilities on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) cancer cell line HepG2/DOX, and eight compounds exhibited significant activities. Among them, ingol-3,7,12-triacetate-8-benzoate, the most active MDR modulator with no obvious cytotoxicity, could enhance the efficacy of anticancer drug DOX to ca. 105 folds at 10 μM, being stronger than the positive drug verapamil. Mechanistic study revealed that ingol-3,7,12-triacetate-8-benzoate could inhibit the transport activity of P-gp rather than its expression, and the possible recognition mechanism between compounds and P-gp was predicted by molecular docking.
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http://dx.doi.org/10.1016/j.phytochem.2020.112395DOI Listing
August 2020

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study.

J Gynecol Oncol 2020 05;31(3):e61

Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence.

Methods: SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate.

Trial Registration: ClinicalTrials.gov Identifier: NCT03983226.
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http://dx.doi.org/10.3802/jgo.2020.31.e61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189080PMC
May 2020

Dual-energy CT to differentiate gallbladder polyps: cholesterol versus adenomatous.

Acta Radiol 2021 Feb 15;62(2):147-154. Epub 2020 Apr 15.

Department of Medical Imaging, Suzhou Ninth People's Hospital, Wujiang, Jiangsu, PR China.

Background: Dual-energy computed tomography (DE-CT) scans were acquired to identify cholesterol and adenomatous gallbladder (GB) polyps, which have not been well evaluated before surgery.

Purpose: To evaluate the DE-CT findings of GB polyps 1.0-2.0 cm in size and differentiate between cholesterol and adenomatous polyps.

Material And Methods: Forty-six patients with GB polyps were surgically treated from December 2017 to December 2019 and divided into two groups according to their postoperative pathologic results: a cholesterol group with 26 patients and an adenomatous group with 20 patients. All of these patients underwent DE-CT imaging with tube voltages of 80 kVp and 140 kVp within two weeks before surgery. Mean attenuation values were measured for every GB polyp at 80/140 kVp and at 40/140 keV. The mean attenuation value changes between 140 kVp and 80 kVp (MAVC) and mean attenuation value changes between 100 keV and 40 keV (MAVC) were calculated.

Results: The CT image parameters of all 46 patients with GB polyps were analyzed. There were significant differences in MAVC and MAVC between cholesterol and adenomatous polyps ( <0.05); these values were positive for cholesterol polyps and negative for adenomatous polyps.

Conclusion: The unique energy spectrum information provided by DE-CT scans is helpful in differentiating between cholesterol and adenomatous polyps 1.0-2.0 cm in size.
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http://dx.doi.org/10.1177/0284185120916202DOI Listing
February 2021

Two highly oxygenated -clerodane diterpenoids from .

J Asian Nat Prod Res 2020 Oct 15;22(10):927-934. Epub 2020 Apr 15.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Two highly oxygenated -clerodane diterpenoids, crocleropenes A and B ( and ), together with four known compounds () were isolated from the leaves and twigs of . Their structures were elucidated by combination of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. and represent the first examples of -clerodane-3,5(10)-diene diterpenoids. Compounds and exhibited weak cytotoxicity against MCF-7 cancer cells with IC values of 35.8 and 40.2 μM, respectively. [Formula: see text].
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http://dx.doi.org/10.1080/10286020.2020.1751618DOI Listing
October 2020

Euphane- and 19(10 → 9)abeo-euphane-type triterpenoids from Jatropha gossypiifolia.

Fitoterapia 2020 Jun 28;143:104582. Epub 2020 Mar 28.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address:

Four new tetracyclic triterpenoids (1-4) were isolated from the leaves and twigs of Jatropha gossypiifolia. Their structures were elucidated by MS and NMR data analysis, together with the Mo(OAc)-induced CD data. Jagabeoeuphols A-C (1-3) are rare 19(10 → 9)abeo-euphane-type triterpenoids possessing a Δ group and a 7,8-epoxide moiety, and jagoseuphone A (4) is a typical euphane-type triterpenoid. The inhibitory effects of 1-4 on nitric oxide production induced by lipopolysaccharide in RAW264.7 cells were evaluated, and 4 exhibited moderate inhibitory activity with an IC value of 20.1 μM.
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http://dx.doi.org/10.1016/j.fitote.2020.104582DOI Listing
June 2020