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Four new indole-diterpenoids, named penerpenes K-N ( 1 - 4 ), along with twelve known ones ( 5 - 16 ), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds ( 4 , 9, and 15 ) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC 50 value of 5.3 μM. Moreover, six compounds ( 5 , 7 , 10 , 12 , 14 , and 15 ) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

During the course of searching for structurally interesting and bioactive compounds, a further chemical investigation of the leaves of Heynea trijuga Roxburgh was performed, which led to the isolation of a new ergostane derivative, named 3 β , 4 β , 20 S -trihydroxyergosta-5, 24(28)-dien-16-one ( 1 ), together with five known sterides (3 β , 23 S )-ergosta-5, 24(28)-diene-3, 23-diol ( 2 ), ergosta-5, 24(28)-diene-3 β -diol ( 3 ), stigmast-5-ene-3 β , 7 α -diol ( 4 ), sitoindoside I ( 5 ) and stigmast-3 β , 5 α , 6 β -triol ( 6 ). The structure of the new compound was elucidated using a combination of 1 D, 2 D NMR techniques and HR-EI-MS analyses. All the compounds were evaluated for cytotoxic activity against tumor cell line BEL-7402 by MTT method.

Objective: To explore the association between sleep duration, sleep quality and the prevalence of hypertension in the elderly aged 65 years and above. Methods: This study was conducted among the elderly in communities in Yiwu, China from April to July, 2019, and participants were recruited through physical examination in the hospital. Face-to-face interview was performed to obtain basic information. Sleep duration and sleep quality were evaluated by Pittsburgh Sleep Quality Index (PSQI). Associations between sleep duration, sleep quality and hypertension were evaluated by multivariate logistic regression analysis. Results: A total of 3 169 elderly persons, aged ≥65 years old, were included in the study. The overall prevalence of hypertension was 50.8%. The elderly with very poor sleep quality and short sleep duration accounted for 22.4% and 28.5%, respectively. After adjusting for demographic characteristics, socioeconomic status, lifestyle and health status, the OR of hypertension for the elderly with very poor sleep quality was 1.42 (95% CI : 1.12-1.80) compared with those with very good sleep quality. Compared with the elderly with sleep duration of 6-7 h a night, the OR of hypertension for those with sleep duration <6 h was 1.37 (95% CI : 1.15-1.65). As the sleep quality decreased, the risk for hypertension increased. An U-shaped association was found between sleep duration and risk of hypertension. Subgroup analyses showed that this association existed in both men and women, but only significant in the elderly aged <75 years. Conclusion: Poor sleep quality and short sleep duration were associated with risk for hypertension in the elderly.

Agarwood is the resinous portion of Aquilaria trees, and has been widely used as medicine and incense. Sesquiterpenes are the main chemical characteristic constituents of agarwood. Terpene synthase (TPS) is a critical enzyme responsible for biosynthesis of sesquiterpene compounds. However, limited information is available on genome-wide identification and characterization of the TPS family in Aquilaria trees. In this study, TPS gene family was identified and characterized in Aquilaria sinensis by bioinformatics methods. The expression of those genes was analyzed by RNA-seq and quantitative real-time PCR. Transcription factors regulating TPS gene expression were identified by yeast one-hybrid and dual-luciferase assay. In total, 26 AsTPS genes (AsTPS1-AsTPS26) were identified, which were classified into five subgroups. Many putative cis-elements putatively involved in stresses and phytohormones (especially jasmonic acid) were identified in the promoter regions of AsTPSs, suggesting that AsTPSs genes may be regulated by stresses and jasmonic acid. Expression analysis revealed seven TPS genes encoding sesquiterpene synthetases were induced by wounding and methyl jasmonic acid (MeJA), which may be related to sesquiterpene biosynthesis. By yeast one-hybrid screening, a ERF transcription factor AsERF1 was identified to interact with the AsTPS1 promoter. Subcellular localization analysis indicated AsERF1 was a nucleus-localized protein. Transient transfection of AsERF1 in leaves of Nicotiana benthamiana significantly enhanced the promoter activation of AsTPS1, suggesting AsERF1 may participate in sesquiterpene biosynthesis by regulating AsTPS1 expression. These data generated in this study provide a foundation for future studies on functional roles and regulation mechanisms of AsTPS in sesquiterpene biosynthesis and agarwood formation., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Three new 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones and one new dimeric 2-(2-phenylethyl)chromone were isolated from the agarwood of Aquilaria crassna Pierre ex Lecomte in Laos. The structures of the isolates were elucidated by spectroscopic methods, and their configurations were determined via ROESY correlations, 3 J H-H coupling constants analyses, comparisons of chemical shifts and specific rotations with known compounds, and ECD calculation in the case of 1 . Compounds 1 - 4 were evaluated for their cytotoxicity. Compounds 1 and 2 exhibited weak cytotoxicity toward HeLa cell line (IC 50 : 49.8 ± 1.2 μM) and K562 cell line (IC 50 : 42.66 ± 0.47 μM), respectively.

By feeding tryptophan to the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis , 3 new quinazoline-containing indole alkaloids, named aspertoryadins H-J ( 1 - 3 ), along with 16 known ones ( 4 - 19 ), were obtained. The structures of the new compounds were elucidated by the analysis of spectroscopic data combined with quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts and electron capture detector (ECD) spectra. Structurally, compound 3 represents the first example of this type of compound, bearing an amide group at C-3. Compounds 10 and 16 showed potent α-glucosidase inhibitory activity with IC 50 values of 7.18 and 5.29 μM, and compounds 13 and 14 showed a clear activation effect on the ryanodine receptor from Spodoptera frugiperda (sfRyR), which reduced the [Ca 2+ ] ER by 37.1 and 36.2%, respectively., 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., (Copyright © 2021 Liu, Yang, Kong, Zhao, Yao, Yuchi, Ma, Xie, Zhou, Guo, Dai, Zhao and Luo.)

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11β-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC&#95;(50) values of 26.55, 11.35, 23.23, 18.66 μmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC&#95;(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 μmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC&#95;(50) value of 42.50 μmol·L~(-1).

Covering: Up to the end of 2019.Agarwood is a resinous portion of Aquilaria trees, which is formed in response to environmental stress factors such as physical injury or microbial attack. It is very sought-after among the natural incenses, as well as for its medicinal properties in traditional Chinese and Ayurvedic medicine. Interestingly, the chemical constituents of agarwood and healthy Aquilaria trees are quite different. Sesquiterpenes and 2-(2-phenethyl)chromones with diverse scaffolds commonly accumulate in agarwood. Similar structures have rarely been reported from the original trees that mainly contain flavonoids, benzophenones, xanthones, lignans, simple phenolic compounds, megastigmanes, diterpenoids, triterpenoids, steroids, alkaloids, etc. This review summarizes the chemical constituents and biological activities both in agarwood and Aquilaria trees, and their biosynthesis is discussed in order to give a comprehensive overview of the research progress on agarwood.

Two new compounds named asperpenes D ( 1 ) and E ( 2 ) were isolated from the marine-derived fungus Aspergillus sp. SCS-KFD66. Their structures were determined on the basis of spectroscopic methods. Compound 2 represents the first natural product bearing a 2-substituted-5-oxo-4-phenyl-2,5-dihydrofuran-3-carboxylic acid skeleton. All the compounds were tested for enzyme inhibitory activity against AChE and α-glucosidase and DPPH radical scavenging activity, respectively. [Formula: see text].

A couple of new cycloheximide epimers, 13(α)-acetoxy-anhydroisoheximide ( 1 ) and 13(β)-acetoxy-anhydroisoheximide ( 2 ), together with six known compounds (3 - 8), were obtained from the cultures of Streptomyces sp. YG7. The structures were elucidated based on a comprehensive spectroscopic data analysis including 1D and 2D NMR, as well as HRESIMS, and by comparison with the literature. The X-ray crystal analysis of 1 further confirmed the structure. All the compounds were tested for antifungal activity. Compounds 1, 2 and 5-8 showed moderate Canidia albicans inhibitory activity, while 5 and 6 presented moderate Pyricularia oryzae inhibitory activity. [Formula: see text].

Recently, cultivated "Qi-Nan" (CQN) agarwood has emerged as a new high-quality agarwood in the agarwood market owing to its similar characteristics, such as high content of resin and richness in two 2-(2-phenylethyl)chromone derivatives, 2-(2-phenylethyl)chromone ( 59 ) and 2-[2-(4-methoxyphenyl)ethyl]chromone ( 60 ), to the wild harvested "Qi-Nan" (WQN) agarwood. In this study, we compared the chemical constituents and fragrant components of two types of WQN agarwood from A. agallocha Roxb. and A. sinensis , respectively, with CQN agarwood and ordinary agarwood varieties. Additionally, we analyzed different samples of WQN agarwood and CQN agarwood by GC-MS, which revealed several noteworthy differences between WQN and CQN agarwood. The chemical diversity of WQN was greater than that of CQN agarwood. The content of ( 59 ) and ( 60 ) was higher in CQN agarwood than in WQN agarwood. For the sesquiterpenes, the richness and diversity of sesquiterpenes in WQN agarwood, particularly guaiane and agarofuran sesquiterpenes, were higher than those in CQN. Moreover, guaiane-furans sesquiterpenes were only detected by GC-MS in WQN agarwood of A. sinensis and could be a chemical marker for the WQN agarwood of A. sinensis . In addition, we summarized the odor descriptions of the constituents and established the correlation of scents and chemical constituents in the agarwood.

Twelve undescribed 2-(2-phenylethyl)chromone derivatives, including one pair of enantiomers, together with eleven known ones, were isolated from the EtOAc extract of agarwood originating from Aquilaria filaria. All structures were elucidated by spectroscopic (NMR, UV, IR, MS) methods and compared with reported data in literatures. Twenty-one compounds were assessed for α-glucosidase inhibitory activity, which showed inhibition of α-glucosidase with IC 50 values ranging between 7.8 ± 0.3 to 137.7 ± 3.0 μM (Acarbose, 743.4 ± 3.3 μM; Genistein, 8.3 ± 0.1 μM). Our results expanded the structural diversity of 2-(2-phenylethyl)chromones from agarwood, and revealed the potential of 2-(2-phenylethyl)chromones as α-glucosidase inhibitors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Patchouli is a tropical medicinal and spice crop with high economic value, and the endophytic microorganism is also one of its important components and can provide new active compounds with medicinal use. In the present study, four new biphenyl compounds named 3-O-demethylaltenuisol (1), (-)-dialtenuisol (5) and (+)-dialtenuisol (6), and altertoxin VII (9), as well as six known related compounds, were isolated from the patchouli (Pogostemon cablin) endophytic fungus Alternaria sp. PfuH1. The structures of the new compounds were elucidated from spectroscopic data, ECD spectra analysis, and ECD calculations. Compounds 5 and 6 are a pair of dimeric axially chiral enantiomers. Compounds 2, 4, and 9 showed antibacterial activities against S. agalactiae with MIC values of 9.3, 85.3, and 17.3 μg/mL, respectively, and compound 4 also showed weak antibacterial activity against E. coli with MIC value of 128 μg/mL., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The metabolites of the genus Marasmius are diverse, showing good research prospects for finding new bioactive molecules. In order to explore the active metabolites of the fungi Marasmius berteroi , the deep chemical investigation on the bioactive compounds from its cultures was undertaken, which led to the isolation of three new naphthalene compounds dipolynaphthalenes A-B ( 1 , 2 ) and naphthone C ( 3 ), as well as 12 known compounds ( 4 - 15 ). Compounds 1 , 2 , and 4 are dimeric naphthalene compounds. Their structures were elucidated by MS, 1D and 2D NMR spectroscopic data, as well as ECD calculations. Compounds 2 - 4 and 7 exhibited acetylcholinesterase (AChE) inhibitory activities at the concentration of 50 μg/mL with inhibition ratios of 42.74%, 44.63%, 39.50% and 51.49%, respectively. Compounds 5 and 7 , 8 showed weak inhibitory activities towards two tumor cell lines, with IC 50 of 0.10, 0.076 and 0.058 mM (K562) and 0.13, 0.18, and 0.15 mM (SGC-7901), respectively.

Objective: To explore the influencing factors of job burnout of medical staff and provide reference for the formulation of intervention measures. Methods: From November to December, 2018, a questionnaire survey was conducted among medical staff in a general hospital by using the research design of the current situation survey. A total of 1193 questionnaires were distributed and 939 questionnaires were returned, with a recovery rate of 78.7%, including 891 valid questionnaires and an effective recovery rate of 94.9%. Social support rating scale (SSRs) was used to evaluate social support, and Maslach Burnout Scale (MBI-GS) was used to evaluate job burnout. Single factor analysis was performed by chi square test and Fisher exact probability method. To explore the influencing factors of job burnout by using disordered multi classification logistic. Results: The average age was (27.47 ± 4.22) years old, female accounted for 71.5% (637/891) . The total physical examination rate of job burnout was 46.6%. The scores of emotional exhaustion, cynicism and decreased sense of achievement were (10.10±3.75) , (6.14±3.43) , (17.91±4.13) respectively. Multiple logistic regression analysis showed that, compared with the non detected job burnout, the young, working for 1-3 years, average sleep ≤6 hours, and poor social support were more likely to have mild job burnout ( OR =0.91, 0.40, 2.25, 2.38, P <0.05) ; female, high night shift frequency in the past year, average sleep ≤6 h. Those with poor social support were more likely to have moderate to severe job burnout ( OR =1.59, 2.94, 4.01, 2.40, 3.66, P <0.05) . Conclusion: Corresponding measures should be taken to reduce job burnout and improve work efficiency.

Two new sesquiterpenoids ( 1 and 2 ), together with two known sesquiterpenoids ( 3 and 4 ), were isolated from agarwood originated from Aquilaria sp. Their structures were elucidated by extensive spectroscopic methods including 1D and 2D NMR, IR, HRESIMS, and comparison with the literatures. All compounds were evaluated for cytotoxicity against five human cancer cell lines, but none of them displayed significant activity. [Formula: see text].

Five new sesquiterpenoids (1-5), together with a known compound 6 was isolated from ethyl ether extract of agarwood. Their structures were elucidated on the basis of spectroscopic techniques (UV, IR, MS, 1D and 2D NMR), as well as by comparison with literature data. Compound 5 exhibited inhibitory activity against acetylcholinesterase with inhibition ratio of 48.33 ± 0.17% at the concentration of 50 μg/mL., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fourteen compounds were isolated from the ethanol extract of Dalbergiae Odoriferae Lignum by various chromatographic techniques, including column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were determined by spectroscopic techniques as S-3'-hydroxy-7,2',4'-trimethoxyisoxane(1), 2-(2',4'-dimethoxyphenyl)-6-hydroxybenzofuran(2), 2-(2'-hydroxy-4'-methoxyphenyl)-6-methoxybenzofuran(3), 7,2',4'-trimethoxydihydroisoflavone(4), sativanone(5), 3,9-dimethoxy-6H-benzofuro[3,2-c]chromen-6-one(6),(6 aS,11 aS)-homopterocarpin(7),(6 aS,11 aS)-8-hydroxy-3,9-dimethoxypterocarpan(8),(6 aS,11 aS)-3,8,9-trimethoxypterocarpan(9), isodalbergin(10), isoliquiritigenin(11), butein(12), butin(13) and 3,7,4'-trihydroxyflavone(14). Among them, compound 1 was a new compound, while 2 and 3 were new natural products, 6, 8, 9 and 14 were isolated for the first time from Dalbergiae Odoriferae Lignum. Compounds 1-14 were tested for their cytotoxic activity against human hepatoma cell line BEL-7402, human gastric cancer cell line SCG-7901, human lung cancer cell line A549, human chronic myeloid leukemia cell line K562 and HeLa human cervical cancer cellline by MTT method. Compound 1 exhibited significant cytotoxicity with IC&#95;(50) values ranging from 2.85 to 11.62 μg·mL~(-1). In addition, 2, 11 and 12 showed weak cytotoxic activities.

Seven new quinazoline-containing indole alkaloids ( 1 - 7 ) named aspertoryadins A-G, along with nine known ones ( 8 - 16 ), were isolated from the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis . The structures of the new compounds were elucidated from spectroscopic data, X-ray diffraction analysis, ECD spectra analysis, and ECD calculations. Compound 1 bears an aminosulfonyl group in the structure, which is rarely encountered in natural products. Compounds 6 , 7 , and 13 exhibited quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with MIC values of 32, 32, and 16 μg/well, respectively.

Objective: To explore the difference of personality characteristics of physicians, nurses, medical skills and administrative personnel in a general hospital and its influence on job burnout. Methods: Employee entered the hospital before 2018 were enrolled in the current study and the position was classified as physicians, nurses, medical technician and administrative staff. Minnesota Multiphasic Personality Inventory (MMPI) was completed by the employee at the time of entering the hospital. Status of job burnout was assessed in 2018 using the Maslach Burnout Inventory-General Survey (MBI-GS) . Results: Physicians have a higher rate of paranoia than others ( P <0.05) , and administrative staff and medical technician have a slightly higher score than the other two categories of people ( P <0.05) , and administrators lie at a higher rate than others ( P <0.05) . Further analysis found that personality traits did not have a significant association with job burnout at the time of entry. Conclusion: The administrative and medical staff is slightly more irritable, the administrative staff lying slightly higher score, the staff after the entry of job burnout is not affected by the personality characteristics of the onboarding.

The ethyl ether extract of agarwood from an Aquilaria plant afforded six new sesquiterpenoids, Agarozizanol A - F (1-6), together with four known sesquiterpenoids and six known 2-(2-phenylethyl)chromones. Their structures were elucidated via detailed spectroscopic analysis, X-ray diffraction, and comparisons with the published data. All the isolates were evaluated for the α-glucosidase and tyrosinase inhibitory activities in vitro. Compounds 5, 7, 8, and 10 showed significant inhibition of α-glucosidase with IC 50 values ranging between 112.3 ± 4.5 and 524.5 ± 2.7 µM (acarbose, 743. 4 ± 3.3 µM). Compounds 13 and 14 exhibited tyrosinase inhibitory effect with IC 50 values of 89.0 ± 1.7 and 51.5 ± 0.6 µM, respectively (kojic acid, 46.1 ± 1.3). In the kinetic studies, compounds 5 and 14 were found to be uncompetitive inhibitors for α-glucosidase and mixed type inhibitors for tyrosinase, respectively. Furthermore, molecular docking simulations revealed the binding sites and interactions of the most active compounds with α-glucosidase and tyrosinase.

Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman's Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.

Ten new tricyclic prezizaane types sesquiterpenoids (1-10) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp. Their structures were unambiguously elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of the new prezizaenes 1, 2 and 4 was determined by single-crystal X-ray diffraction, while TDDFT-ECD method was applied for 6. Compounds 4 and 5 displayed significant inhibitory activities toward α-glucosidase with IC 50 values of 0.22 and 1.99 mM, respectively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Phytochemical investigation on the roots of Swietenia macrophylla yielded one new pharagmalin-type limonoid named 2-dehydroxyl-swietephragmin C ( 1 ) and one new xanthone, 1,5-dihydroxy-6-methoxy-6',6'-dimethyl-2 H -pyrano[2',3':3,2]xanthone ( 2 ), in addition to three known compounds. The structures of the new compounds were unambiguously determined by comprehensive spectroscopic methods (NMR, UV, IR, MS), as well as by comparison with the reported data in the literature. Xanthones were reported from Swietenia genus for the first time.

Five new indole-terpenoids named penerpenes E-I ( 1 - 5 ), along with seven known ones ( 6 - 12 ), were isolated from the marine-derived fungus Penicillium sp. KFD28 from a bivalve mollusk, Meretrix lusoria . The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. Compound 1 was assigned as an indole-diterpenoid with a unique 6/5/5/6/6/5/5 heptacyclic ring system. Compound 2 represents an indole-diterpenoid with a new carbon skeleton derived from paxilline by the loss of three carbons (C-23/24/25). Compound 3 contains an additional oxygen atom between C-21 and C-22 compared to paxilline to form an unusual 6/5/5/6/6/7 hexacyclic ring system bearing a 1,3-dioxepane ring, which is rarely encountered in natural products. Compounds 1 , 2 , 4 , and 6 showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC 50 values of 14, 27, 23, and 13 μM, respectively.

A new phenolic derivative ( 1 ) and a new dihydrophenanthrene ( 2 ) were isolated from the aerial part of Dendrobium hainanense rofe, along with 12 known compounds. The structures of the new compounds were elucidated by spectroscopic analysis，and the relative configuration of compound 1 was determined by J -based configuration analysis (JBCA) method. Bioassay result indicated that compound 1 exhibited weak antibacterial activity against Canidia albicans and Ralstonia solanaceanum .

Four unusual indole-terpenoids, penerpenes A-D (1-4), along with two known ones paxilline (5) and emindole SB (6), were isolated from the marine-derived fungus Penicillium sp. KFD28. The absolute structures of 1-4 were elucidated on the basis of spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Compounds 1 and 2 showed potent inhibitory activity toward protein tyrosine phosphatases (PTP1B and TCPTP). Plausible biosynthetic pathways of compounds 1-4 are proposed.

Granulocyte colony stimulating factor (GCSF) is a key regulator of neutrophil production, and plays a vital role in immune response of mammals and teleost against pathogen. Sequences of GCSF were identified in several teleost species, however, the function and activity of GCSF in teleost remain largely unknown. In this study, we examined the biological activity and the immunomodulatory property of a GCSF homologue, PoGCSF, from Japanese flounder (Paralichthys olivaceus). Structural analysis showed that PoGCSF possesses conserved structural characteristics of GCSF proteins, including a signal peptide and a typical IL-6 domain. The expression of PoGCSF was upregulated in a time-dependent manner by extracellular and intracellular bacterial pathogens and viral pathogen. Different expression patterns were exhibited in response to the infection of different types of microbial pathogens in different immune tissues. Recombinant PoGCSF increased the capability of host cells to defense against pathogen infection and enhanced the expression of immune related genes. The knockdown of PoGCSF attenuated the ability of host cells to eliminate pathogenic bacteria. In vivo results showed that overexpression of PoGCSF promoted the host defense against invading pathogenic microorganism. Collectively, this study is the first report about the immunoregulatory property and anti-infectious immunity of GCSF in teleost. These findings suggested that PoGCSF serves as an immune-related cytokine and plays an important role in the immune defense system of Japanese flounder., (Copyright © 2019. Published by Elsevier Ltd.)

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4β,5β,7β-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC&#95;(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC&#95;(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].

Six 8,12-epoxyguaiane sesquiterpenes (1-6), together with two known 2-(2-phenylethyl)chromone derivatives (7-8) were isolated from agarwood originating from Aquilaria filaria. Their structures were established by spectroscopic methods including IR, HRESIMS, 1D, and 2D NMR, and comparison with the published data. The absolute configuration of compound 1 was unambiguously determined by quantum chemical calculation of the electronic circular dichroism (ECD) spectrum. All compounds were tested for their α-glucosidase inhibitory activity and cytotoxicity. Compound 5 showed significant α-glucosidase inhibitory activity with IC 50 value of 253.2 ± 9.7 μM (Acarbose, 743. 4 ± 3.3 μM). Compounds 2-4 displayed weak cytotoxicity against K562 tumor cell lines., (Copyright © 2019. Published by Elsevier B.V.)

Eleven novel uncommon single ether linkage dimeric 2-(2-phenylethyl)chromones (aquilasinenones A-K) were isolated by a UPLC-MS guided method from artificial hole-induced agarwood originating from Aquilaria sinensis . Their structures were unambiguously deduced using HRESIMS data, detailed 1D and 2D NMR spectroscopic analysis, and experimental ECD spectra. All the compounds were tested for acetylcholinesterase (AChE) inhibitory activity by Ellman's colorimetric method, and compounds 9-11 displayed weak AChE inhibitory activity with the inhibition ranging from 15.6% to 16.8% at a concentration of 50 μg mL -1 ., Competing Interests: The authors declare that they have no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Thioredoxins (Trxs) play an important role in defending against oxidative stress and keeping disulfide bonding correct to maintain protein function. Edwardsiella piscicida, a severe fish pathogen, has been shown to encode several thioredoxins including TrxA, TrxC, and TrxH, but their biological roles remain unknown. In this study, we characterized TrxH of E. piscicida (named TrxH Ep ) and examined its expression and function. TrxH Ep is composed of 125 residues and possesses typical thioredoxin H motifs. Expression of trxH Ep was upregulated under conditions of oxidative stress, iron starvation, low pH, and during infection of host cells. trxH Ep expression was also regulated by ferric uptake regulator (Fur), an important global regulatory of E. piscicida. Compared to the wild type TX01, a markerless trxH Ep in-frame mutant strain TX01∆trxH exhibited markedly compromised tolerance of the pathogen to hydrogen peroxide, acid stress, and iron deficiency. Deletion of trxH Ep significantly retarded bacterial biofilm growth and decreased resistance against serum killing. Pathogenicity analysis shows that the inactivation of trxH Ep significantly impaired the ability of E. piscicida to invade host cells, reproduce in macrophages, and infect host tissues. Introduction of a trans-expressed trxH gene restored the lost virulence of TX01∆trxH. There is likely to be a complex relationship of functional complementation or expression regulation between TrxH and another two thioredoxins, TrxA and TrxC, of E. piscicida. This is the first functional report of TrxH in fish pathogens, and the findings suggest that TrxH Ep is essential for coping with adverse circumstances and contributes to host infection of E. piscicida.

A phytochemical investigation of the roots of Swietenia macrophylla led to the isolation of seven polyacetylenes, including five new compounds ( 1 - 5 ) and two known ones ( 6 - 7 ). Their structures were elucidated by extensive spectroscopic analysis and detailed comparison with reported data. All the isolates were tested for their cytotoxicity against the human hepatocellular carcinoma cell line BEL-7402, human myeloid leukemia cell line K562, and human gastric carcinoma cell line SGC-7901. Compounds 1 and 6 showed moderate cytotoxicity against the above three human cancer cell lines with IC 50 values ranging from 14.3 to 45.4 μM. Compound 4 displayed cytotoxicity against the K562 and SGC-7901 cancer cell lines with IC 50 values of 26.2 ± 0.4 and 21.9 ± 0.3 μM, respectively.

Five optically active epoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone derivatives (1-5) with four chirality centers in the condensed cyclohexene ring were isolated from artificial holing agarwood originating from Aquilaria sinensis (Lour.) Gilg. Their structures were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The absolute configuration of 2 was elucidated by TDDFT-ECD calculations and ECD spectra of 1, 3-5 allowed their configurational assignment as well. All of the new compounds contained a condensed oxirane ring, and compound 1 was the only 6,7-epoxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromone derivative that has ever been found in agarwood. AChE inhibitory activity was tested for the first time of these new compounds by using modified Ellman's colorimetric method. Compounds 3 and 5 exhibited inhibitory activity against AChE with IC 50 value of 441.6, and 155.6 μM, respectively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Twelve undescribed compounds including six phenanthrene derivatives (parviphenanthrines A-F), two stilbene derivatives (parvistilbines A-B), three esters (parviesters A-C), and one sesquiterpenoid (parvidiol A) were isolated from the roots of Stemona parviflora, together with twenty-two known ones. The structures of the undescribed compounds were elucidated based on the analyses of their spectroscopic data. The absolute configuration of parviphenanthrine A was determined by the quantum ECD calculations. Parviphenanthrines A and E, stemanthrene A, stilbostenin E, 4-hydroxy-benzenepropanol-α-benzoate, and (E)-4-hydroxycinnamic acid methyl ester showed nematocidal activity against Meloidogyne incognita with IC 50 values of 14.02 ± 0.32, 2.51 ± 0.13, 17.10 ± 0.65, 2.05 ± 0.07, 4.22 ± 0.31, and 1.07 ± 0.05 μM, respectively., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To observe the effect of anti-osteoporosis drugs on the curative effect of femoral head replacement in the elderly patients with proximal humerus fracture., Methods: From November 2012 to June 2016, 38 patients with proximal humeral fractures received humeral head replacement were divided into the treatment group and the control group according to whether the anti-osteoporosis drugs were used after the operation. The treatment group included 19 cases, of which 11 cases were three part fractures, 18 cases were four part fractures, and bone density was(0.58±0.14) g/cm²; the control group involved 19 cases, of which 10 cases were the three part fractures, 9 cases were four part fractures, and bone density was(0.58±0.11) g/cm². Periprosthetic bone mineral density(BMD) was measured at 4, 8, 12, 24 and 48 weeks after operation, and visual analogue scale(VAS) was used to evaluate the pain and Neer score was used to evaluate the function of the shoulder joint., Results: The incisions of all patients were healed with grade A and no complications occurred. Thirty-five patients were followed up for 1 year. The bone density around the prosthesis of treatment group was higher than that of control group, the difference was statistically significant( P <0.05);VAS in two groups had no statistical significance( P >0.05). The total score and functional score of Neer in the treatment group were better than those in the control group, the difference was statistically significant( P <0.05), and there was no significant difference in pain and activity score between the two groups( P >0.05). According to the Neer score, the results of treatment group was excellent in 10 cases, good in 5 cases, fair in 3 cases;in the control group, 3 cases were excellent, 9 cases were good, and 5 cases were fair;the difference between the two groups was statistically significant( P <0.05)., Conclusions: Artificial humeral head replacement combined with anti-osteoporosis drugs in the treatment of proximal humeral fractures in elderly patients can effectively improve the bone density around the prosthesis and restore shoulder function. The early clinical effect is satisfactory., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Two new 2-(2-phenylethyl)chromone derivatives ( 1 ⁻ 2 ), comprising 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and benzylacetone moieties, together with one new 2-(2-phenylethenyl)chromone ( 3 ) were isolated from the ethyl acetate extraction of agarwood originated from Gyrinops salicifolia Ridl. All structures were unambiguously elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. All isolated compounds were tested for acetylcholinesterase (AChE) inhibitory activity and cytotoxic activity against human myeloid leukemia cell line (K562). However, none of the compounds displayed AChE inhibitory activity at a concentration of 50 µg mL -1 or cytotoxic activity against K562 cell line.

Six compounds were isolated from the aerial part of cultivated Clerodendranthus spicatus in Hainan with various chromatographic techniques,and their structures were determined as:1-dehydroxy-1-oxo-rupestrinol(1),N-trans-feruloyltyramine(2),methyl 3,4-dihydroxyphenyllactate(3),caffein acid(4),methyl caffeate(5) and ethyl caffeate(6),via analysis of physicochemical properties and spectroscopic evidence.Compound 1 was a new compound,while compounds 2 and 3 were isolated from C.spicatus for the first time.Biological activity results showed that compounds 2-4 exhibited α-glucosidase inhibitory activity with different inhibition ratio.

Six new compounds (1-4, 8, 10), along with six known limonoids (5-7, 9, 11, 12), were isolated from the roots of Trichilia sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including 1 H NMR, 13 C NMR, DEPT, HSQC, HMBC, 1 H- 1 H COSY and ROESY experiments, as well as by comparison with the literature. All the compounds were evaluated for cytotoxicities against K562, SGC-7901 and BEL-7402 cell lines. Compounds 2, 7, 10, 11, and 12 showed weak inhibitory activity to the selected cell lines.

One new havanensin-type limonoid ( 1 ) named trisinlin A with two known compounds (4 E ,8 E )-2-[2'-hydroxyhexadecanoyl amino]-4,8-octadecadiene-1,3-diol ( 2 ), 9-octadecenoic acid-2',3'-dihydroxypropyl ester ( 3 ) were isolated from the roots of Trichilia sinensis . The structure of the new compound was unambiguously determined through comprehensive spectroscopic analyses including 1D and 2D NMR, and mass spectrometry, as well as by comparison with the literature. Trisinlin A showed significant insecticidal activity against newly hatched larvae of Spodoptera litura .

Five new compounds named asperpenes A-C ( 1 ⁻ 3 ), 12,13-dedihydroversiol ( 4 ), and methyl 6-oxo-3,6-dihydro-2 H -pyran-4-carboxylate ( 5 ), along with 10 known compounds ( 6 ⁻ 15 ), were isolated from the fermentation broth of Aspergillus sp. SCS-KFD66 associated with a bivalve mollusk, Sanguinolaria chinensis , collected from Haikou Bay, China. The structures of the compounds, including the absolute configurations of their stereogenic carbons, were unambiguously determined by spectroscopic data, single-crystal X-ray diffraction analysis, and electronic circular dichroism (ECD) spectral analysis, along with quantum ECD calculations. The growth inhibitory activity of the compounds against four pathogenic bacterial ( Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538, Listeria monocytogenes ATCC 1911, and Bacillus subtilis ATCC 6633), their enzyme inhibitory activities against acetylcholinesterase and α-glucosidase, and their DPPH radical scavenging activity were evaluated.

Six new phragmalin limonoids, named moluccensin Z1 ( 1 ), moluccensin Z2 ( 2 ), carapanolide Y ( 3 ), tabulalin N ( 4 ), chukvelutilide A1 ( 5 ), and velutinasin J ( 6 ), as well as two known compounds, chukvelutilide A ( 7 ) and velutinasin D ( 8 ) were isolated from the stems of Chukrasia tabularis A. Juss. The structures of the new compounds 1 ⁻ 6 were confirmed by spectroscopic methods, including IR and HRESIMS, as well as 1D and 2D NMR, and by comparisons with the data of known analogues. All compounds were tested for α-glucosidase and acetylcholinesterase inhibitory activities. However, none of the compounds was active against α-glucosidase and acetylcholinesterase in vitro.

A new cytochalasin derivative xylarisin B (1), together with four known compounds astropyrone (2), guaidiol (3), xylaropyrone B (4), and xylaropyrone C (5), were isolated from the fermentation broth of Xylaria sp. HNWSW-2. Their structures were elucidated by spectroscopic data. Among them, compounds 2 and 3 at a concentration of 50 μg/ml showed weak inhibitory activity against AChE with inhibition rates of 10.4 and 12.9%, respectively. In addition, compound 2 also exhibited inhibitory activity against α-glycosidase with inhibition rate of 77.0% at a concentration of 0.25 mg/ml.

A novel pyrone derivative (1) bearing two fused five-member rings, together with two new naphthalenone derivatives (2, 3), as well as two known compounds (4, 5) were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from "Qi-Nan" agarwood. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR, and by HRESIMS spectra, as well as by comparison with the literature. Bioactivity results indicated that compound 3 showed weak acetylcholinesterase inhibitory activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.

Daphnauranins C⁻E (compounds 1 ⁻ 3 ), two sesquiterpenoids and one monoterpenoid were isolated from the roots of Daphne aurantiaca Diels. Daphnauranin C is a 9- O -13 etherified and hydroperoxy-substituted guaiane sesquiterpenoid, daphnauranin D is a guaiane sesquiterpenoid ketal, and daphnauranin E is a monoterpenoid lactone. Their structures were elucidated by comprehensive analyses of MS, 1D NMR, and 2D NMR spectroscopic data. In an anti-feeding activities test, daphnauranins C⁻E showed activity against male fruit fly with anti-feeding indexes (AI) up to 39.1, 39.2, and 27.8% respectively, at 1 mM., Competing Interests: The authors declare no conflict of interest.

Streptococcus agalactiae is a hazardous pathogen that can cause great harm to humans and fish. In the present study, the known fungal metabolite helvolic acid (10), seven new helvolic acid derivatives named 16- O-deacetylhelvolic acid 21,16-lactone (2), 6- O-propionyl-6,16- O-dideacetylhelvolic acid 21,16-lactone (3), 1,2-dihydro-6,16- O-dideacetylhelvolic acid 21,16-lactone (4), 1,2-dihydro-16- O-deacetylhelvolic acid 21,16-lactone (5), 16- O-propionyl-16- O-deacetylhelvolic acid (6), 6- O-propionyl-6- O-deacetylhelvolic acid (7), and 24- epi-6β,16β-diacetoxy-25-hydroxy-3,7-dioxo-29-nordammara-1,17(20)-diene-21,24-lactone (9), and two known ones (1 and 8) were isolated from the marine-derived fungus Aspergillus fumigatus HNMF0047 obtained from an unidentified sponge from Wenchang Beach, Hainan Province, China. The structures and the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and electronic circular dichroism (ECD) spectroscopic analyses along with quantum ECD calculations. In addition, the spectroscopic data of compound 1 are reported here for the first time, the configuration of C-24 of known compound 8 was revised based on comparison of its ROESY data with its C-24 epimer 9, and the absolute configuration of 8 was also determined for the first time. Compounds 6, 7, and 10 showed stronger antibacterial activity than a tobramycin control against S. agalactiae with MIC values of 16, 2, and 8 μg/mL, respectively.

Objectives: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood., Materials and Methods: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-β-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy. Western blotting, siRNA transfection and coimmunoprecipitation were carried out to investigate the mechanisms of CGN-induced senescence and autophagy. The anti-tumour activities of combination therapy with CGN and chloroquine were observed in mice tumour models., Results: We demonstrated that CGN inhibits the proliferation of colorectal cancer cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by CGN is independent of apoptosis, but is associated with cell-cycle arrest and senescence in colorectal cancer cells. Notably, CGN induces protective autophagy that attenuates CGN-mediated cell proliferation. Functional studies revealed that CGN disrupts the association of Hsp90 with both CDK4 and Akt, leading to CDK4 degradation and Akt dephosphorylation, eventually resulting in senescence and autophagy, respectively. Combination therapy with CGN and chloroquine resulted in enhanced anti-tumour effects in vivo., Conclusions: Our results demonstrate that CGN induces senescence and autophagy in colorectal cancer cells and indicate that combining it with an autophagy inhibitor may be a novel strategy suitable for CGN-mediated anti-cancer therapy., (© 2018 John Wiley & Sons Ltd.)

The cyclic depsipeptide FR900359 (FR), isolated from the traditional Chinese medicine plant Ardisia crenata, is a potent Gq protein inhibitor and thus a valuable tool to study Gq-mediated signaling of G protein-coupled receptors. Two new FR analogues (3 and 4) were isolated from A. crenata together with the known analogues 1 and 2. The structures of compounds 3 and 4 were established by NMR spectroscopic data and MS-based molecular networking followed by in-depth LCMS 2 analysis. The latter approach led to the annotation of further FR analogues 5-9. Comparative bioactivity tests of compounds 1-4 along with the parent molecule FR showed high-affinity binding to Gq proteins in the low nanomolar range (IC 50 = 2.3-16.8 nM) for all analogues as well as equipotent inhibition of Gq signaling, which gives important SAR insights into this valuable natural product. Additionally, FR was detected from leaves of five other Ardisia species, among them the non-nodulated leaves of Ardisia lucida, implying a much broader distribution of FR than originally anticipated.

Five new amide alkaloids (1-3, 5-6) were isolated from the seeds of Clausena lansium together with one new natural product (4) and four known analogues (7-10). The structures of the new amide alkaloids were elucidated based on a comprehensive spectroscopic data analysis including 1D and 2D NMR as well as HRESIMS, and by comparison with the literature. The bioactivity results showed that compound 8 expressed potent nematicidal activity against Panagrellus redivevus, with IC 50 value of 0.12 mM, while compounds 3 and 5 presented moderate nematicidal activity with IC 50 values of 2.75 and 3.93 mM, respectively (abamectin as the positive control with IC 50 value of 1.05 mM)., (Copyright © 2018. Published by Elsevier B.V.)