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Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Astrocytes (AST) play an important role in the pathogenesis of neurological disorders, and their activation is involved in the progression of multiple sclerosis (MS). (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits vast pharmacological activities, such as anti-tumor, anti-fibrosis and immune regulation. In this study, we demonstrate that MASM is a promising agent for the treatment of experimental autoimmune encephalomyelitis (EAE). MASM not only inhibited inflammatory responses in LPS-stimulated astrocytes, but also suppressed the formation of reactive A1 astrocyte and maintained astrocytic functions, including the ability to promote synapse formation and phagocytose synapses and myelin debris. Importantly, MASM could significantly alleviate the development of EAE, with significant inhibition of inflammation, demyelination, axon loss and the body weight loss. Meanwhile, MASM also inhibited the activation of astrocytes and improved the function of BBB in vivo. These findings provide novel insights into the protective effect of MASM on EAE, which may be a promising drug candidate for treatment of EAE.

The Arctic fungus Eutypella sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (1-4), along with the known biogenetically related compound cytosporin D (5). The structures of the new compounds were elucidated by their detailed spectroscopic analysis and modified Mosher's method. Compounds 1-4 may be formed by the 12,32-ester linkage of two moieties, cytosporin D (5) and decipienolide A or B. All isolated compounds, except 5, showed weak cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cell lines with IC50 values ranging from 4.9 to 17.1 μM.

Ulcerative colitis (UC) is a chronically relapsing inflammatory disease in the intestinal tract. Current unsatisfactory treatments prompt people to seek for alternative therapies and drug candidates. Cryptotanshinone (CTS), a diterpene quinoneextractedfromthe roots ofSalviamiltiorrhiza, has recently been shown to inhibit acute colitis by reducing pro-inflammatory mediators. However, whether CTS can protect against chronic UC and its effect on T lymphocytes remain unknown. In this study, CTS (20, 60 mg/kg) showed potent inhibitory activity against dextran sulfate sodium (DSS)-induced acute UC, as determined by weight loss, disease activity, colon length and histology. Similarly, in a model of DSS-induced chronic colitis, the administration of CTS prevented the disease progression with longer colon length, lower histological scores, and less expression of fibrosis-related collagen and α-smooth muscle actin in the colon. CTS also reduced the proportion of CD4

The Arctic fungus

(6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits better anti-inflammatory activity. This study was designed to evaluate the protective effect of MASM on acute and chronic liver injuries and explore the possible mechanisms.Acute and chronic liver injury models were established by the CCl4 intraperitoneal injection and the protective effect of MASM was assessed by biochemical and histological examination. The infiltration of different monocyte subsets into the liver was characterized and analyzed by flow cytometry. The in vitro effect of MASM on liver nonparenchymal cells was evaluated by real-time PCR and transwell chemotaxis assays.Administration of MASM markedly attenuated acute liver injury and liver fibrosis induced by CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in injured livers and induced hepatic expression of monocyte chemoattractant protein-1 (MCP-1) were greatly inhibited. Cellular experiments demonstrated that MASM not only decreased the expression of MCP-1 but also inhibited its chemotactic activity.This study demonstrates that the protective effect of MASM on liver injury could be contributed to the suppression of Gr1hi monocyte infiltration to the liver and the inhibition of MCP-1 production and activity. These findings provide new insights into the protective role of MASM in liver injury.

Three new pimarane diterpenes, eutypellenoids A–C (1–3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1–3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 μg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candida parapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 μg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 μM.

Seven new pimarane-type diterpene derivatives, libertellenones O–S (1–5) and eutypellenones A and B (6 and 7), together with two known compounds (8 and 9), were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures were elucidated from spectroscopic data, as well as experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 1–5 possess a cyclopropyl-fused pimarane diterpene moiety, whereas compounds 6 and 7 share an unusual cyclobutyl-fused pimarane diterpene skeleton. Compounds 1–9 exhibited cytotoxicities against HeLa, MCF-7, HCT-116, PANC-1, and SW1990 cells, with IC50 values in the range of 0.3 to 29.4 μM. Compounds 6 and 7 could dose-dependently inhibit the activity of NF-κB and exhibited significantly inhibitory effects on nitric oxide production induced by lipopolysaccharide.

Tree crown projection area and crown volume are the important parameters for the estimation of biomass and other forestry science applications. However, it is difficult to validate their accuracy. In this research, measurement errors were quantified based on the 3D virtual LiDAR dataset of 22 common tree species in Beijing, China, which were derived from high-resolution terrestrial laser scanner. The hypotheses include that: (1) primary sources of height measurement are the violations of Total station based on the triangulation theory; (2) approximation of tree crown projections with 4-point fixed angles are not precise enough for irregular crown silhouettes; and (3) tree crown volumes obtained by conventional method with a taper's formula (V"C) are not corresponding to the need of accurate measurement. The relative accuracies derived from total station measurements between crown base height (B"T) and tree height (H"T) were compared. Meanwhile, different methods for tree crown projections and crown volumes were researched. The results show that the measurement errors of H"T (RMSE=4.56m) is higher than that of B"T (RMSE=3.35m), V"C (RMSE=45.0243m^3) is 8.03% on average smaller than V"V"C (RMSE=48.56094m^3), A"4 is 25.5% on average larger than A"V. The deviations between filed investigation method and virtual 3D LiDAR data could be attributed to irregularity of the crowns' silhouettes. Based on the results, we propose that: (1) the use of 8-point or 16-point projection with fixed angles to estimate crown projections and (2) different regular volume formula to simulate crown volume according to the tree crown shapes.

Tree crown projection area and crown volume are the important parameters for the estimation of biomass, tridimensional green biomass and other forestry science applications. Using conventional measurements of tree crown projection area and crown volume will produce a large area of errors in the view of practical situations referring to complicated tree crown structures or different morphological characteristics. However, it is difficult to measure and validate their accuracy through conventional measurement methods. In view of practical problems which include complicated tree crown structure, different morphological characteristics, so as to implement the objective that tree crown projection and crown volume can be extracted by computer program automatically. This paper proposes an automatic untouched measurement based on terrestrial three-dimensional laser scanner named FARO Photon120 using plane scattered data point convex hull algorithm and slice segmentation and accumulation algorithm to calculate the tree crown projection area. It is exploited on VC+6.0 and Matlab7.0. The experiments are exploited on 22 common tree species of Beijing, China. The results show that the correlation coefficient of the crown projection between Av calculated by new method and conventional method A4 reaches 0.964 (p0.01); and the correlation coefficient of tree crown volume between V(VC) derived from new method and V(C) by the formula of a regular body is 0.960 (p0.001). The results also show that the average of V(C) is smaller than that of V(VC) at the rate of 8.03%, and the average of A4 is larger than that of A(V) at the rate of 25.5%. Assumed Av and V(VC) as ture values, the deviations of the new method could be attributed to irregularity of the crowns' silhouettes. Different morphological characteristics of tree crown led to measurement error in forest simple plot survey. Based on the results, the paper proposes that: (1) the use of eight-point or sixteen-point projection with fixed angles to estimate crown projections, and (2) different regular volume formula to simulate crown volume according to the tree crown shapes. Based on the high-resolution 3D LIDAR point cloud data of individual tree, tree crown structure was reconstructed at a high rate of speed with high accuracy, and crown projection and volume of individual tree were extracted by this automatical untouched method, which can provide a reference for tree crown structure studies and be worth to popularize in the field of precision forestry.

In order to establish volume model,living trees have to be fallen and be divided into many sections, which is a kind of destructive experiment. So hundreds of thousands of trees have been fallen down each year in China. To solve this problem, a new method called living tree volume accurate measurement without falling tree was proposed in the present paper. In the method, new measuring methods and calculation ways are used by using photoelectric theodolite and auxiliary artificial measurement. The diameter at breast height and diameter at ground was measured manually, and diameters at other heights were obtained by photoelectric theodolite. Tree volume and height of each tree was calculated by a special software that was programmed by the authors. Zhonglin aspens No. 107 were selected as experiment object, and 400 data records were obtained. Based on these data, a nonlinear intelligent living tree volume prediction model with Particle Swarm Optimization algorithm based on support vector machines (PSO-SVM) was established. Three hundred data records including tree height and diameter at breast height were randomly selected form a total of 400 data records as input data, tree volume as output data, using PSO-SVM tool box of Matlab7.11, thus a tree volume model was obtained. One hundred data records were used to test the volume model. The results show that the complex correlation coefficient (R2) between predicted and measured values is 0. 91, which is 2% higher than the value calculated by classic Spurr binary volume model, and the mean absolute error rates were reduced by 0.44%. Compared with Spurr binary volume model, PSO-SVM model has self-learning and self-adaption ability,moreover, with the characteristics of high prediction accuracy, fast learning speed,and a small sample size requirement, PSO-SVM model with well prospect is worth popularization and application.

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

The controlled aldol condensation between an aliph. ketone and an acetaldehyde equiv. remains a challenge. One soln. to this evergreen problem consists of the nucleophilic addn. of acetylene to the ketone and the subsequent isomerization of the resulting 3-hydroxy-1-alkyne to the corresponding 2-alkenal. So far, however, the latter step could only be executed with acid-insensitive substrates. The authors now present a milder, three-step method which extends the scope of the procedure considerably. In the first step, the 3-hydroxy-1-alkynes RCMeOHC.tplbond.CH (R = Me, Ph, Me2CH:CHCH2CH2, Q, CH2:CH, HC.tplbond.C) are converted into 2-propynyl ethylene glycol monoethers RCMe(OCH2CH2OH)C.tplbond.CH; these then undergo base-catalyzed cyclization to give the dihydro-1,4-dioxepins (I and II; R = same as above), which are hydrolyzed in acidic medium in the third and final step to give ketones RCMeOHCOMe (R = same as above) and a,b-unsatd. aldehydes RCMe:CHCHO (R = same as above), resp. Thus, RCMe(OCH2CH2OH)C.tplbond.CH (R = Q) (prepn. given) was treated with Me3COK in Me3COH for 12 h at 85 Deg to give a 4:96 mixt. of I (R = Q) and II (R = Q) in 95% yield. II (R = Q) was hydrolyzed by 6 M HCl in THF under reflux for 5 h to give 90% RCMe:CHCHO (R = Q). [on SciFinder (R)]