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(±)-Pyriindolin (1) with a rare molecular backbone formed by fusing a 2,2′-bipyridine nucleus into a spiro[furan-3,3′-indoline] skeleton, was isolated from the Streptomyces albolongus EA12432. The constitution and the relative configuration of (±)-1 were determined by extensive spectroscopic analyses, 13C calculation and DP4+ probability analysis. The absolute configurations of optically pure (+)-1 and (−)-1 which were obtained after a chiral high performance liquid chromatography (HPLC) separation were further identified by electronic circular dichroism (ECD) calculations. (+)- and (−)-Pyriindolins displayed moderate cytotoxicity against HCT-116 cell line with the half-maximal inhibitory concentration (IC50) values of 2.89 ± 0.17 μmol/L and 4.47 ± 0.26 μmol/L, respectively.

Background Although the interaction between gut microbiota and pouchitis after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) has been confirmed, evidence of commensal mycobiota in the etiology of pouchitis is still lacking. This study aimed to investigate the role of fungi in the pathogenesis of pouchitis. Methods Fecal samples were collected from UC patients with or without pouchitis after IPAA. Experimental pouchitis was induced by 5% dextran sulfate sodium for 7 consecutive days in a rat model of IPAA. Fungal dysbiosis was induced by 0.5% fluconazole (Flu), and commensal fungal recognition through dectin-1 was blocked by 5% laminarin. Fecal fungal composition was analyzed using internal transcribed spacer 2 sequencing. Severity of pouchitis and activation of the CARD9-nuclear factor kappa-B pathway was determined among different groups. Results Patients with pouchitis had a lower alpha (α) diversity in mycobiota composition and a higher abundance of Saccharomyces at the genus level compared with those with a normal pouch. In the rat model of pouchitis, Flu treatment decreased fungal burden but induced fungal dysbiosis, characterized by increased α diversity, a decreased relative abundance of Kazachstania, and increased Polythrincium and Saccharomyces. In addition, Flu treatment worsened dextran sulfate sodium pouchitis, as indicated by increased mortality, weight loss, higher histological score, and CD4+ cell infiltration. Laminarin also increased the severity of pouchitis. In the Flu and laminarin groups, the expression of interferon-γ, tumor necrosis factor-α, CARD9, and phosphorylated nuclear factor kappa-B inhibitor alpha was decreased. Conclusions Patients with pouchitis had altered fungal composition. Fungal dysbiosis or recognition deficiency by the host may exacerbate experimental pouchitis. Strategies targeting commensal mycobiota may provide therapeutic potential against pouchitis, especially for antibiotic-refractory patients.

Cyanogramide (1) from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6 features a unique spirooxindole skeleton and exhibits significant bioactivity to efficiently reverse drug resistance in tumor cells. The biosynthetic gene cluster of 1 in A. cyanogriseus WH1-2216-6 was identified and refactored by promoter engineering for heterologous expression in Streptomyces coelicolor YF11, thereby enabling the production of 1 and five new derivatives. Interesting, four of them, including 1, were identified as enantiomeric mixtures in different ratios. The functions of tailoring enzymes, including two methyltransferases (CyaEF), and three cytochrome P450 monooxygenases (CyaGHI) were confirmed by gene inactivation and feeding experiments, leading to the elucidation of a concise biosynthetic pathway for 1. Notably, CyaH was biochemically verified to catalyze the formation of the spirooxindole skeleton in 1 through an unusual carbocation-mediated semipinacol-type rearrangement reaction.

Cyclamenols E (1) and F (2), two bicyclic macrolactams possessing a cyclopentane moiety, were isolated from the Antarctic Streptomyces sp. OUCMDZ-4348. Their structures, including absolute configurations, were determined by spectroscopic analysis, chemical derivatization, and ECD calculation. Treatment of compound 1 with 2,2-dimethoxypropane and pyridinium p-toluenesulfonate in acetone/DMF led to the formation of acetonide 1a with an unexpected skeleton. Compound 1 showed moderate inhibitory activity against the gastric carcinoma cell line N87 with an IC50 value of 9.8 μM, but no cytotoxicity was observed on the other 25 cancer cell lines tested.

Three new p-terphenyl derivatives, nocarterphenyls A-C (1-3), along with three known analogues (4-6) were isolated from the marine-derived actinobacterial strain Nocardiopsis sp. OUCMDZ-4936. Their structures were elucidated on the basis of spectroscopic analysis and a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possess a benzothiazole and benzothiazine moiety, respectively, which are rare in the skeleton of p-terphenyls. Nocarterphenyl A (1) showed potent cytotoxic activity against the HL60 and HCC1954 cancer cell lines with the IC50 values of 0.38 and 0.10 μM among 26 human cancer cell lines.

A site-specific drug delivery system of anticancer agents has been delveloped to enhance the therapeutic efficacy and reduce toxicity to the normal tissue. Semi-synthetic andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide) is one of the potential natural anticancer compounds against many types of cancer including colorectal cancer cells. However, the clinical applications of this compound are limited because of low water solubility and lack of suitable delivery carriers. This study aimed to increase the aqueous solubility and improve the anticancer efficacy of 3A.1 via active targeting approaches. In this study, 3A.1 was loaded into the polymeric micelles self-assembled from N-naphthyl-N,O-succinyl chitosan (NSC). The micelles were conjugated with folate moiety (Fol-NSC) for targeting to the cancer cells. All of the 3A.1-loaded micelles were prepared by dropping method, and the physicochemical properties (size, charge, morphology, encapsulating efficiency, loading capacity), in vitro release behavior and in vitro anticancer activities against HT29 colorectal cancer cells were investigated. The 3A.1-loaded micelles were successfully formulated by dropping method using NSC or Fol-NSC. The micelles loaded with 40% initial 3A.1 showed the maximum encapsulating efficiency and loading capacity. The micelles were in the nanometer range, having a negative surface charge and a spherical structure. The colon site-specific release of the 3A.1 from the 3A.1-loaded micelles was obtained. The release of 3A.1 from the Fol-NSC micelles was slower than that from the NSC micelles. Moreover, the Fol-NSC micelles exhibited superior anticancer efficacy than that of the NSC micelles and free 3A.1. In conclusions, the 3A.1-loaded Fol-NSC micelles developed in the present study had suitable physicochemical properties. These nanocarriers may be a potential delivery system for targeted delivery of the 3A.1 to colorectal cancer cells.

Pafuranones A (1) and B (2), a pair of new epimeric polyketide dimers, were isolated from the fungus Paraconiothyrium sp. OUCMDZ-3316 associated with the marine algae Enteromorpha prolifera. Their structures, including absolute configurations, were fully elucidated based on spectroscopic analysis, calculated ECD, and chemical methods. Pafuranones A (1) and B (2) possess a rare dimeric furanone skeleton, which might be formed through a conjugate addition of the monomeric units followed by an intramolecular cyclization.

One new (1) and fifteen known (2–16) p-terphenyls were isolated from a solid culture of the endophytic fungus Aspergillus sp. GZWMJZ-055 by adding the leaves of its host Eucommia ulmoides. Furthermore, nine p-terphenyls (17–25) were synthesized from the main compounds (5–7), among which derivatives 18, 19, 21, 22, and 25 are new p-terphenyls. Compounds 15 and 16 were also, respectively, synthesized from compounds 6 and 7 by oxidative cyclization of air in the presence of silica gel. These p-terphenyls especially those with 4,2′,4″-trihydroxy (4–7, 20, 21) or 4, 4″-dihydroxy-1,2,1′,2′-furan (15, 16) substituted nucleus, exhibited significant antioxidant and α-glucosidase inhibitory activities and lower cytotoxicity to caco-2 cells. The results indicated their potential use as lead compounds or dietary supplements for treating or preventing the diabetes.

The global shrimp industry has suffered bacterial diseases caused mainly by Vibrio species. The typical vibriosis, acute hepatopancreatic necrosis disease (AHPND), has resulted in mass mortality and devastating economic losses. Thus, therapeutic strategies are highly needed to decrease the risk of vibriosis outbreaks. Herein, we initially identified that the growth of the causative agent of AHPND, Vibrio parahaemolyticus (VP AHPND ) and other vibrios in Pacific white shrimp (Litopenaeus vannamei) was inhibited by a Bacillus subtilis strain BSXE-1601. The natural products amicoumacins A, B, and C were purified from the cell-free supernatant from the strain BSXE-1601, but only amicoumacin A was demonstrated to be responsible for this anti-Vibrio activity. Our discovery provided the first evidence that amicoumacin A was highly active against shrimp pathogens, including the representative strain VP AHPND . Furthermore, we elucidated the amicoumacin A biosynthetic gene cluster by whole genome sequencing of the B. subtilis strain BSXE-1601. In addition to amicoumacin A, the strain BSXE-1601 genome harbored other genes encoding bacillibactin, fengycin, surfactin, bacilysin, and subtilosin A, all of which have previously reported antagonistic activities against pathogenic strains. The whole-genome analysis provided unequivocal evidence in support of the huge potential of the strain BSXE-1601 to produce diverse biologically antagonistic natural products, which may facilitate further studies on the effective therapeutics for detrimental diseases in shrimp.

R-Pyrisulfoxin C (1), S-pyrisulfoxin D [(+)-2], R-pyrisulfoxin D [(–)-2], pyrisulfoxin E (13), S-pyrisulfoxin F [(+)-14], and R-pyrisulfoxin F [(–)-14], six new caerulomycin derivatives with a 2,2′-bipyridine skeleton, were obtained from the cultures of the endophytic Streptomyces albolongus EA12432 with Aconitum carmichaeli (Ranunculaceae). Additionally, the racemic pyrisulfoxins A [(±)-3] and B [(±)-4] were further purified as optically pure compounds and identified the configurations for the first time. The racemic pyrisulfoxin D [(±)-2] displayed significant cytotoxicity against a series of cancer cell lines with IC50 values ranging from 0.92 to 9.71 μM. Compounds 7, 8, and (±)-3 showed cytotoxicity against the HCT-116, HT-29, BXPC-3, P6C, and MCF-7 cell lines. Notably, compounds 7 and 8 have a strong inhibition both on the proliferation of human colon cancer cells HCT-116 and HT-29 with IC50 values ranging from 0.048 to 0.2 μM (doxorubicin, 0.21 and 0.16 μM), and compound 1 showed a selective inhibition on the proliferation of the gastric carcinoma cell lines, N87, with an IC50 value of 8.09 μM. Optically pure compounds R(–)-14 and S(+)-14 showed weak cytotoxicity against HCT-116 and MCF-7 cell lines with the IC50 values of 14.7 μM and 10.4 μM, respectively. Interestingly, compounds 1 and (±)-2 didn't show cytotoxic activity against two human normal cell lines, HEK-293F and L02, with IC50 values >100 μM.

Amine compounds biosynthesis using ω-transaminases has received considerable attention in the pharmaceutical industry. However, the application of ω-transaminases was hampered by the fundamental challenge of severe by-product inhibition. Here, we report that ω-transaminase CrmG from Actinoalloteichus cyanogriseus WH1-2216-6 is insensitive to inhibition from by-product α-ketoglutarate or pyruvate. Combined with structural and QM/MM studies, we establish the detailed catalytic mechanism for CrmG. Our structural and biochemical studies reveal that the roof of the active site in PMP-bound CrmG is flexible, which will facilitate the PMP or by-product to dissociate from PMP-bound CrmG. Our results also show that amino acceptor caerulomycin M (CRM M), but not α-ketoglutarate or pyruvate, can form strong interactions with the roof of the active site in PMP-bound CrmG. Based on our results, we propose that the flexible roof of the active site in PMP-bound CrmG may facilitate CrmG to overcome inhibition from the by-product., Xu, Tang et al. show that ω-transaminase CrmG is insensitive to the inhibition from by-products α-ketoglutarate or pyruvate. They find that these by-products cannot interact strongly with the flexible roof of the active site in CrmG. This study provides insights into the rational design of transaminase to eliminate by-product inhibition.

Calotropis procera fiber (CPF) is the fruit fiber of C. procera and belongs to a typical cellulosic fiber. In this study, Calotropis procera fiber (CPF) was first purified in the pretreatment process including delignification and bleaching before the isolation of cellulose nanocrystal. Chemical composition of Calotropis procera fiber was determined according to TAPPI standard method. It was composed of 64.0 wt% cellulose, 19.5 wt% hemicelluloses, and 9.7 wt% of lignin. The morphology of the Calotropis procera fiber and fiber after each pretreatment process was also investigated. Cellulose nanocrystal was extracted by classical sulfuric acid hydrolysis of the pretreated Calotropis procera fiber. TEM and SEM were used to analyze the morphologies of the obtained CNC. The crystallinity, thermal stability and suspension stability of the CNC were also investigated. The interesting results proved that this under-utilized biomass could be exploited as a new source of cellulose raw material for the production of cellulose nanocrystal.

BACKGROUND AND AIM Patients with inflammatory bowel disease (IBD) have higher incidence of developing nephrolithiasis. Increased uric acid production induced by Saccharomyces cerevisiae exacerbates colitis in mice. We aimed to evaluate the association between serum uric acid level and disease activity in IBD population. METHODS Four hundred and thirty-five patients enrolled in Jinling Hospital from January 1, 2015 to August 31, 2017 were included in the retrospective study. Clinical parameters were collected and compared with non-IBD matched controls (n = 51). Serum uric acid to creatinine ratio (UA/Cr) was used as a biomarker for uric acid metabolism. Sixty-five active IBD patients were longitudinally studied to investigate the UA/Cr before and after therapy. Linear mixed models were estimated for Crohn's disease (CD) group to explore the relationship between UA/Cr and other parameters. RESULTS Uric acid to creatinine ratio was significantly correlated with Crohn's disease activity index (ρ = 0.184, P = 0.002) and Harvey Bradshaw index (ρ = 0.154, P = 0.010) and C-reactive protein (ρ = 0.591, P

Hyperactivation of Wnt/β-catenin signaling implicated in oncogenesis of colorectal cancer (CRC) is a potential molecular target for chemotherapy. An andrographolide analogue, 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) has previously been reported to be potently cytotoxic toward cancer cells by unknown molecular mechanisms. The present study explored the anti-cancer activity of analogue 3A.1 on Wnt/β-catenin signaling in colon cancer cells (HT29 cells) which were more sensitive to the others (HCT116 and SW480 cells). Analogue 3A.1 inhibited viability of HT29 cells with IC50 value of 11.1 ± 1.4 μM at 24 h, which was more potent than that of the parent andrographolide. Analogue 3A.1 also suppressed the proliferation of HT29 cells and induced cell apoptosis in a dose-dependent manner. Its apoptotic activity was accompanied with increased expressions of proteins related to DNA damages; PARP-1 and γ-H2AX. In addition, analogue 3A.1 significantly inhibited T-cell factor and lymphoid enhancer factor (TCF/LEF) promoter activity of Wnt/β-catenin signaling. Accordingly, the expressions of Wnt target genes and β-catenin protein were suppressed. Moreover, analogue 3A.1 increased the activity of GSK-3β kinase, which is a negative regulator responsible for degradation of intracellular β-catenin. This mode of action was further supported by the absence of the effects after treatment with a GSK-3β inhibitor, and over-expression of a mutant β-catenin (S33Y). Our findings reveal, for the first time, an insight into the molecular mechanism of the anti-cancer activity of analogue 3A.1 through the inhibition of Wnt/β-catenin/GSK-3β pathway and provide a therapeutic potential of the andrographolide analogue 3A.1 in CRC treatment.

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide alkaloid (BMA) has been shown to have anti-cancer activities and was thought to suppress tumor cell growth by inhibiting protein kinase C. In this study, we show that a newly synthesized BMA analog, BMA097, is effective in suppressing tumor cell and xenograft growth and in inducing spontaneous apoptosis. We also provide evidence that BMA097 binds directly to the SH2 domain of STAT3 and inhibits STAT3 phosphorylation and activation, leading to reduced expression of STAT3 downstream target genes. Structure activity relationship analysis revealed that the hydroxymethyl group in the 2,5-dihydropyrrole-2,5-dione prohibits STAT3 inhibitory activity of BMA analogs. Altogether, we conclude that the synthetic BMA analogs may be developed as anti-cancer drugs by targeting and binding to the SH2 domain of STAT3 and inhibiting the STAT3 signaling pathway.

Secopaxilline A (1), a new meroditerpenoid derived from indole-diterpenoid by the oxidative cleavage of a carbon–nitrogen bond, was isolated from an aciduric fungus Penicillium camemberti OUCMDZ-1492. Its structure, including absolute configuration, was fully elucidated based on spectroscopic analysis and X-ray single crystal diffraction. Secopaxilline A is the first example of indole-diterpenoid derivatives possessing a carbon–nitrogen bond cleavage skeleton. It was synthesized from paxilline with a 45% overall yield. The one-pot synthesis of the biosynthetic precursor, deacetylsecopaxilline A (4), from paxilline was also developed.

Rationale: Colitis-associated colorectal cancer (CAC) usually exhibits an accelerated disease progression, an increased resistance to therapeutic drugs and a higher mortality rate than sporadic colorectal cancer (CRC). PIAS3 is a member of the protein inhibitor of activated STAT (PIAS) family; however, little is known about the expression and biological functions of PIAS3 in CAC. The aim of our study was to investigate the biological mechanisms of PIAS3 in CAC. Methods: PIAS3 expression was examined in colon tissues of CAC/CRC patients and azoxymethane-dextran sulfate sodium (AOM-DSS)-induced mice. The role of PIAS3 was studied using a series of in vitro, in vivo and clinical approaches. Results: Downregulated PIAS3 expression, upregulated miR-18a expression and highly activated NF-κB and STAT3 were observed in colon tissues of CAC/CRC patients and AOM-DSS-induced mice. In vitro experiments revealed that PIAS3 significantly inhibited the activation of NF-κB and STAT3 and demonstrated that activated NF-κB and STAT3 transcriptionally regulated miR-18a level, and up-regulation of miR-18a expression led to defective PIAS3 expression. Moreover, PIAS3-mediated autoregulatory feedback loops (PIAS3/NF-κB/miR-18a and PIAS3/STAT3/miR-18a) were verified in vitro and were found to regulate cell proliferation. Additionally, modulation of the feedback loops via overexpression of PIAS3 or knockdown of miR-18a significantly inhibited cell proliferation in a mouse CRC xenograft model. Furthermore, upregulation of PIAS3 by intracolonic administration of PIAS3 lentivirus or anti-miR-18a lentivirus in AOM-DSS-induced mice led to dramatically reduced tumor sizes/numbers, whereas knockdown of PIAS3 in CAC mice significantly promoted tumor growth. Conclusion: Our data clearly show that PIAS3-mediated feedback loops control cell proliferation and function as robust driving forces for CAC progression. Targeting these highly activated feedback loops might offer promising therapeutic strategies for CAC.

Four new meroterpenoids identified as (R)-4-((2,2-dimethylchroman-6-yl)methyl)-3-(4-hydroxyphenyl)-5-methoxyfuran-2(5H)-one (1), 1-(2,2-dimethylchroman-6-yl)-3-(4-hydroxyphenyl)propan-2-one (2), (R,E)-3-(2,2-dimethylchroman-6-yl)-4-hydroxy-5-((2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl)methylene)furan-2(5H)-one (3), methyl (R)-2-(2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl) acetate (4), along with nine known compounds (5–13) were isolated from a chemical-epigenetic culture of Aspergillus terreus OUCMDZ-2739 with 10 μM trichostatin A (TSA). Under the same condition without TSA, A. terreus OUCMDZ-2739 produced different compounds (14–20), supporting that the chemical-epigenetic modification of fungi could enrich the chemodiversity of the fungal products. The cytotoxicity was observed for compound 8 against K562 cell, 9 against MCF-7 and K562 cells and 12 against MCF-7 cell with IC50 values of 9.5, 10.1, 13.0 and 8.5 μM, respectively. Compounds 3, 8 and 17 exhibited stronger α-glucosidase inhibition than 1-deoxynojirimycin and acarbose (positive controls) with IC50 values of 24.8, 1.2, 61.6, 191.7 and 555.1 μM, respectively. The enzyme kinetics study further indicated that compound 8 was an anticompetitive inhibitor with Ki value of 1.42 μM.

Seven new ophiobolins (1–5, 12, and 14) along with the 11 known analogues (6–11, 13, 15–18) were isolated from the ethyl acetate extracts of the liquid and solid cultures of the mangrove fungus Aspergillus ustus 094102. The structures including the absolute configurations of the seven new compounds were elucidated by spectroscopic analysis, chemical methods, and quantum ECD calculations. Compounds 4–8 and 11–15 showed cytotoxicities against the G3K, MCF-7, MD-MBA-231, MCF/Adr, A549, and HL-60 human cancer cell lines with the IC50 values ranging from 0.6 to 9.5 μM.

To obtain new bioactive natural products, the effect of acidic stress on the metabolites of an aciduric fungus was investigated. This fungus, Penicillium sp. OUCMDZ-4736, which was isolated from the sediment around roots of mangrove (Acanthus ilicifolius), produced different compounds and higher yields under pH 2.5 than under neutral conditions. Using spectroscopic analyses and calculations, three new anthraquinone derivatives (1-3) were isolated and identified from the acidic fermentation broth (pH 2.5) of OUCMDZ-4736. Compound 1 showed much stronger anti-hepatitis B virus activity than that of the positive control, lamivudine, strongly inhibiting HBsAg and HBeAg secretion from HepG2.2.15 cells. These results show that extremophiles are a valuable resource of bioactive compounds, and that pH regulation is an effective strategy to induce metabolite production in aciduric fungi.

Ochrazepines A−D (1−4), four new conjugates dimerized from 2-hydroxycircumdatin C (5) and aspyrone (6) by a nucleophilic addition to epoxide, were isolated from the fermentation broth of the coral-associated Aspergillus ochraceus strain LCJ11-102. Their structures including absolute configurations were determined based on spectroscopic analysis and chemical methods. Compounds 1−4 were also obtained by the semisynthesis from a nucleophilic addition of 2-hydroxycircumdatin C (5) to aspyrone (6). New compound 1 exhibited cytotoxic activity against 10 human cancer cell lines while new compounds 2 and 4 selectively inhibited U251 (human glioblastoma cell line) and compound 3 was active against A673 (human rhabdomyoma cell line), U87 (human glioblastoma cell line), and Hep3B (human liver cancer cell line) with IC50 (half maximal inhibitory concentration) values of 2.5−11.3 μM among 26 tested human cancer cell lines.

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (‒)-brevianamide R ((‒)-3), (+)-brevianamide Q ((+)-4), (‒)-brevianamide Q ((‒)-4), brevianamide V ((+)-5), brevianamide W ((‒)-5), brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (‒)-brevianamide X ((+)- and (‒)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1–4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-3, (±)-4, and (±)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 μM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC50 values of 117.3 and 255.3 μM, respectively.

Four polyene macrolactams including the previously reported niizalactam C (4), and three new ones, streptolactams A&ndash, C (1&ndash, 3) with a 26-membered monocyclic, [4,6,20]-fused tricyclic and 11,23-oxygen bridged [14,16]-bicyclic skeletons, respectively, were isolated from the fermentation broth of the deep-sea sediment-derived Streptomyces sp. OUCMDZ-3159. Their structures were determined based on spectroscopic analysis, X-ray diffraction analysis, and chemical methods. The abiotic formation of compounds 2 and 4 from compound 1 were confirmed by a series of chemical reactions under heat and light conditions. Compounds 1 and 3 showed a selective antifungal activity against Candida albicans ATCC 10231.

Improving electrochemical performance of cathode materials for lithium-ion batteries requires comprehensive understanding of their structural properties which could facilitate or impede the diffusion of lithium during charge-discharge. In order to optimize the structure and improve the electrochemical performance of layered cathode material, the detailed structural evolution as a function of heat treatment temperature in LiNi0.8Co0.1Mn0.1O2 was investigated by in-situ and ex-situ neutron powder diffraction methods. We show that both cycling stability and rate performance of LiNi0.8Co0.1Mn0.1O2 can be improved by performing heat treatment at 400 °C, which is attributed to the optimization of surface structure and the enlargement of c/a ratio. Heat treatment of LiNi0.8Co0.1Mn0.1O2 at higher temperature induces a layered-to-rock-salt structure phase transition accompanied with the precipitation of lithium oxide. A 3D phase diagram, which correlates the high temperature phases and room temperature phases, is constructed. The presentation of comprehensive phase diagrams up to 1000 °C could provide the basis for further research on not only synthesis strategy but also thermal stability in Ni-rich layered cathode materials.

Background The traditional Chinese medicine, Tripterygium wilfordii Hook F (TwHF) is widely used to treat Crohn's disease (CD) in China. Methods The authors compared different doses of TwHF with mesalazine in 198 patients with CD over a 52-week period. Subjects were randomized to receive mesalazine (3 g/d), low-dose TwHF (1.5 mg·kg −1 ·d −1 ), or high-dose TwHF (2.0 mg·kg −1 ·d −1 ). Results A total of 137 patients completed the study. At week 52, a significant lower proportion of patients in the high-dose TwHF group (7/71) had clinical recurrence compared with patients in the low-dose TwHF (15/68, P = 0.047) or mesalazine group (17/59, P = 0.006), whereas the difference between the low-dose TwHF group and the mesalazine group was not significant ( P = 0.503). Patients receiving mesalazine experienced less adverse events than those receiving high-dose TwHF ( P = 0.029) and those receiving low-dose TwHF ( P = 0.048), but no significant difference was found about drug adverse events resulted withdrawal in the 3 groups ( P > 0.05). In addition, compared with low-dose TwHF and mesalazine, the authors also detected significant superiority of high-dose TwHF arm in the decrease of CDAI and SESCD ( P Conclusion A 2.0 mg/kg daily TwHF was well tolerated and prolonged remission in patients with CD.

Fabrication of multifunctional hydrogel with excellent mechanical property, self-healing and shape memory ability is still a challenging issue. In this study, a mechanical robust multifunctional hydrogel based on PVA reinforced by cellulose nanocrystal using nanofiller reinforcement strategy was reported. Owing to the hydrogen bonding and supramolecular interaction between PVA and CNC, the prepared hydrogel exhibited satisfying mechanical property. The obtained multifunctional PVA hydrogel could be potentially applied in biomedical or artificial skins fields.

Grain boundary engineering is considered an effective approach to improve the performance of thermoelectric materials. Herein, by introducing KOH into the grain boundary of Bi2[Formula: see text][Formula: see text] (BTS) via liquid phase sintering strategy, the thermoelectric performances are improved significantly. The melting KOH spreads over the grain boundaries during the high temperature sintering process, which could be used to optimize the carrier/phonon transport behavior. The maximum ZT reaches up to 0.97 for the sample incorporated with 0.5%[Formula: see text]Wt of KOH at 425[Formula: see text]K, which achieves 30% improvement over the pure BTS. The homogeneous distribution of KOH layer on the grain boundaries forms efficient potential barrier scattering, which increases power factor and reduces thermal conductivity simultaneously. Particularly, it is found that the maximum ZT can be tuned gradually in the temperature range from 450[Formula: see text]K to 375[Formula: see text]K by tuning the weight percent of KOH, demonstrating a possibility in adjusting the thermoelectric properties of BTS using a relatively simple method.

Five new polyketides (2–6) and ten known compounds (1 and 7–15) were obtained from the fermentation products of the endophytic fungus Cladosporium sp. OUCMDZ-302 with the mangrove plant, Excoecaria agallocha (Euphorbiaceae). The new structures of 2–6 were established on the basis of ECD, specific rotation and spectroscopic data as well as the chemical calculation. Compound 7 showed cytotoxicity against H1975 cell line with an IC50 value of 10.0 μM. Compounds 4 and 8–10 showed radical scavenging activity against DPPH with the IC50 values of 2.65, 0.24, 5.66, and 6.67 μM, respectively. In addition, the absolute configuration of compound 1 was solidly determined by X-ray and sugar analysis of the acidic hydrolysates for the first time as well as those of compounds 8–10 in this paper.

One new indolocarbazole, 3-hydroxy-K252d (3), together with the recently reported 3-hydroxyholyrine A (1) and 3′-N-acetyl-3-hydroxyholyrine A (2), were obtained by feeding a culture of the marine-derived Streptomyces strain OUCMDZ-3118 with 5-hydroxy-l-tryptophan. Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 potently induced apoptosis of gastric cancer cells by inhibiting topoisomerase IIα enzyme activity and reducing the expression of antiapoptosis protein level. Compound 3 displayed moderate cytotoxicity against the A549 and MCF-7 cell lines with IC50 values of 1.2 ± 0.05 μM, 1.6 ± 0.09 μM, respectively.

The first synthesis of fradcarbazole A ( 1 ) has been accomplished by using a biomimetic intramolecular cyclization/dehydration to construct the staurosporine-thiazole-indole skeleton. The phenyl and oxazole analogues of fradcarbazole A ( 2 – 4 ) were also synthesized using the same strategy. Compounds 1 – 4 displayed cytotoxicity against A549 cell line with IC 50 values of 0.4–3.6 μM, induction of G 0 /G 1 arrest of A549 cell cycle at 10 μM, and inhibition of PKC-β kinase with IC 50 values of 0.5–0.9 μM.

Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10(-)/(-) mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease.

Ethnopharmacological relevance Curcuma comosa Roxb. (C. comosa) or Wan chak motluk Zingiberaceae family, is widely used in Thai traditional medicine for treatment of gynecological problems as well as relief of postmenopausal symptoms. Since C. comosa contains phytoestrogen and causes lipid lowering effect by an unknown mechanism, we investigated its effect on adiposity and lipid metabolism in estrogen-deprived rats. Materials and methods Adult female rats were ovariectomized (OVX) and received daily doses of either a phytoestrogen from C. comosa [(3R)–1,7-diphenyl-(4E,6E)–4,6-heptadien-3-ol; DPHD], C. comosa extract, or estrogen (17β-estradiol; E2) for 12 weeks. Adipose tissue mass, serum levels of lipids and adipokines were determined. In addition, genes and proteins involved in lipid synthesis and fatty acid oxidation in visceral adipose tissue were analyzed. Results Ovariectomy for 12 weeks elevated level of serum lipids and increased visceral fat mass and adipocyte size. These alterations were accompanied with the up-regulation of lipogenic mRNA and protein expressions including LXR-α, SREBP1c and their downstream targets. OVX rats showed decrease in proteins involved in fatty acid oxidation including AMPK-α and PPAR-α in adipose tissue, as well as alteration of adipokines; leptin and adiponectin. Treatments with E2, DPHD or C. comosa extract in OVX rats prevented an increase in adiposity, down-regulated lipogenic genes and proteins with marked increases in the protein levels of AMPK-α and PPAR-α. These findings indicated that their lipid lowering effects were mediated via the suppression of lipid synthesis in concert with an increase in fatty acid oxidation. Conclusions C. comosa exerts a lipid lowering effect in the estrogen deficient rats through the modulations of lipid synthesis and AMPK-α activity in adipose tissues, supporting the use of this plant for health promotion in the post-menopausal women.

Metasurfaces enable flat optical components with predesigned functionalities, including the polarization conversion using subwavelength elements. However, switching between different functionalities of the metasurface-based optical components is extremely difficult because subwavelength elements have to be finely addressed to change the spatial phase gradient for desired functionality. Here, it is demonstrated, for the first time, a broadband wide-angle multifunctional polarization converter via galinstan-based metasurface with each element array actively addressed. The switching between different functionalities is realized by controlling L-shaped galinstan resonator using microfluidic channels, which maintain the optical performances, that is, broadband and large angular tolerance, of the polarization converter. Furthermore, the galinstan-based metasurface is also demonstrated to function as a broadband optical attenuator, which provides prospects for various applications, such as smart radar, stealth technology, and light manipulation for quantum communication. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

Summary Background & aims Mesenteric adipose tissue hypertrophy is a hallmark of Crohn's disease and can express various adipokines. Exclusive enteral nutrition could effectively induce remission in Crohn's disease with mechanisms largely unknown. We investigated whether exclusive enteral nutrition could modify mesenteric fat in patients with active Crohn's disease. Methods Sixteen patients who underwent resection for ileum Crohn's disease were studied. As a control group, eight patients without inflammatory bowel disease were enrolled. Before operation, eight Crohn's disease patients received exclusive enteral nutrition for four weeks, and the other patients had no nutritional therapy. The mesenteric fat samples were obtained during operation. Adipocyte size, adipokine production and topical C-reactive protein level were assessed. Results The adipocyte size from patients treated with exclusive enteral nutrition was much larger than that from Crohn's disease patients without nutritional therapy. Furthermore, protein levels of proinflammatory adipokines such as TNF-alpha and leptin were lower while protein level of adiponectin was higher in these patients. As to mRNA level, the expression of adiponctin was up-regulated and leptin was down-regulated in the patients received enteral nutrition. Conclusions Exclusive enteral nutrition could ameliorate mesenteric fat alterations which are associated with intestinal injury in patients with Crohn's disease by restoring adipocyte morphology and diminishing the inflammatory environment of mesenteric fat.

Cyanogramide (1), an unprecedented alkaloid bearing a novel spirocyclic pyrrolo[1,2-c]imidazole skeleton, was identified from the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. The structure was fully determined by spectroscopic analysis, an exciton chirality CD method, and quantum mechanical calculations. Cyanogramide (1) could efficiently reverse the adriamycin-induced resistance of K562/A02 and MCF-7/Adr cells, and the vincristine-induced resistance of KB/VCR cells at a concentration of 5 μM, with the reversal fold values of 15.5, 41.5, and 9.7, respectively.

Two new indole-diterpenoids (1 and 2) and a new isocoumarin (3), along with the known β-aflatrem (4), paspalinine (5), leporin B (6), α-cyclopiazonic acid (7), iso-α-cyclopiazonic acid (8), ditryptophenaline (9), aflatoxin B1 (10), 7-O-acetylkojic acid (11) and kojic acid (12), were isolated from the fermentation broth of the marine-derived fungus, Aspergillus flavus OUCMDZ-2205. The structures of Compounds 1–12 were elucidated by spectroscopic analyses, quantum ECD calculations and the chemical method. New Compound 1 exhibited antibacterial activity against Staphylococcus aureus with a MIC value of 20.5 μM. Both new Compounds 1 and 2 could arrest the A549 cell cycle in the S phase at a concentration of 10 μM. Compound 1 showed PKC-beta inhibition with an IC50 value of 15.6 μM. In addition, the absolute configurations of the known compounds, 4–6 and leporin A (6a), were also determined for the first time.

Penicillium sp. WC-29-5 was co-cultured with Streptomyces fradiae 007 to produce five natural products (1–3, 4a and 4b) that were isolated and characterized by spectroscopic analysis. Interestingly, these compounds were found to be different from those produced in discrete fungal and bacterial controls. Among these compounds, the absolute configurations of compounds 4a and 4b were determined for the first time by X-ray single crystal diffraction experiments and electronic circular dichroism (ECD) calculations. An evaluation of the cytotoxic activities of these compounds revealed that 4b was moderately cytotoxic towards HL-60 and H1975 tumor cells with IC50 values of 3.73 and 5.73 µM, respectively, whereas compound 4a was only moderately cytotoxic towards H1975 cells with an IC50 value of 3.97 µM.

A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-β-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2–6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8–11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/ 39.7(±5.6)/45.9(±2.1) μg/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(±1.7) μg/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2–5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3–6 were also reported here for the first time.

The diversity and ecological function of microorganisms associated with Euphausia superba, still remain unknown. This study identified 75 microbial isolates from E. superba, that is 42 fungi and 33 bacteria including eight actinobacteria. And all the isolates showed NaF tolerance in conformity with the nature of the fluoride krill. The maximum concentration was 10%, 3% and 0.5% NaF for actinobacteria, bacteria and fungi, respectively. The results demonstrated that 82.4% bacteria, 81.3% actinobacteria and 12.3% fungi produced antibacterial metabolites against pathogenic bacteria without NaF; the MIC value reached to 3.9 μg/mL. In addition, more than 60% fungi produced cytotoxic metabolites against A549, MCF-7 or K562 cell lines. The presence of NaF led to a reduction in the producing antimicrobial compounds, but stimulated the production of cytotoxic compounds. Furthermore, seven cytotoxic compounds were identified from the metabolites of Penicillium citrinum OUCMDZ4136 under 0.5% NaF, with the IC50 values of 3.6–13.1 μM for MCF-7, 2.2–19.8 μM for A549 and 5.4–15.4 μM for K562, respectively. These results indicated that the krill microbes exert their chemical defense by producing cytotoxic compounds to the mammalians and antibacterial compounds to inhibiting the pathogenic bacteria.

High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving inflammatory bowel disease (IBD). We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL)-10−/− mice. At 8 weeks of age, mice were allocated into three groups (n = 4/group): normal (C57BL/6), IL-10−/−, and IL-10−/− treated with sodium butyrate (100 mM). Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF)-α and IL-6 in IL-10−/− mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10−/− mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10−/− mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10−/− mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10−/− mice.

Four new azaphilones, sclerotiorins A−D (1−4), as well as the dimeric sclerotiorin E (5) of which we first determined its absolute configuration, and 12 known analogues (5−16) were isolated from the fermentation broth of Penicillium sclerotiorum OUCMDZ-3839 associated with a marine sponge Paratetilla sp.. The new structures, including absolute configurations, were elucidated by spectroscopic analyses, optical rotation, ECD spectra, X-ray single-crystal diffraction, and chemical transformations. Compounds 11 and 14 displayed significant inhibitory activity against α-glycosidase, with IC50 values of 17.3 and 166.1 μM, respectively. In addition, compounds 5, 7, 10, 12−14, and 16 showed moderate bioactivity against H1N1 virus.

Two new rubrolides, rubrolides R (1) and S (2), were isolated from the fermentation broth of the marine-derived fungus Aspergillus terreus OUCMDZ-1925. Their structures were elucidated on the basis of spectroscopic analysis and X-ray single crystal diffraction. Compound 1 showed comparable or superior antioxidation against 2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals to those of trolox and ascorbic acid with an IC₅₀ value of 1.33 mM. Compound 2 showed comparable or superior anti-influenza A (H1N1) virus activity to that of ribavirin with an IC₅₀ value of 87.1 μM. Both compounds 1 and 2 showed weak cytotoxicity against the K562 cell line with IC₅₀ values of 12.8 and 10.9 μM, respectively.

A new cytotoxic pyrrolidinoindoline diketopiperazine dimer, cristatumin E (1), was isolated from the fermentation broth of the algal fungus Eurotium herbariorum HT-2 associated with the marine algae, Enteromorpha prolifera. The structure was determined by spectroscopic analyses and Marfey's amino acid analysis. Cristatumin E (1) showed cytotoxicity against K562 tumor cell line and antibacterial activity against Enterobacter aerogenes and Escherichia coli with IC50 and MIC values of 8.3, 44.0 and 44.0 μmol/L, respectively.

One new kojic acid dimer, dikojiacid A (1), one new naturally occurring kojic acid dimer, dikojiacid B (2), one new sesquiterpene, 12-hydroxy-8-ene-3-oxodrimenol (6), as well as three known kojic acid derivatives (3–5) and five sesquiterpenes (7–11) were isolated from a solid culture of the endophytic fungus Aspergillus flavus GZWMJZ-288 with Garcinia multiflora. The structures of the new compounds were determined on the basis of spectroscopic data and ECD calculation. This is the first report for the natural kojic acid dimers by which Aspergillus flavus GZWMJZ-288 avoids the injury from acetaldehyde.

Two new solid hybrid molecular materials [PyPS]H6P2W17VO62 and [PyPS]H8P2W15V3O62 have been synthesized from 1-(3-sulfonic group) propyl-pyridine ionic liquid cation and tungstovanadophosphoric anion with the Dawson structure. They were characterized by element analysis, impedance spectroscopy (IS), IR- and UV-spectroscopy. The formation of the hybrid molecular compounds with the Dawson structure was showed. Ion conductivity of [PyPS]H6P2W17VO62 and [PyPS]H8P2W15V3O62 are 3.99 × 10−3 and 7.37 × 10−3 S cm−1 at 18°C and 55% relative humidity respectively. The activation energies of proton conductivity are 28.2 and 26.7 kJ mol−1 respectively.

The marine fungus Aspergillus terreus produces an extracellular polysaccharide, YSS, when grown in potato dextrose-agar medium. YSS was isolated from the fermented liquids using ethanol precipitation, anion-exchange and size-exclusion chromatography. YSS was mainly composed of mannose and galactose in a molar ratio of 7.68:1.00, its average molecular weight was estimated to be about 18.6 kDa. On the basis of chemical and spectroscopic analyses, including one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopy, structure of YSS may be represented, at an average, as a backbone of mannan with two types of branches. The mannan backbone is mainly composed of (1→2)-linked α-mannopyranose with small amounts of (1→6)-linked α-mannopyranose residues. The branches consist of terminal β-galactofuranose residues, and disaccharide units of (1→6)-linked α-mannopyranose. The branches are linked to C-6 of (1→2)-linked α-mannopyranose residues of backbone. The antioxidant activity of YSS was evaluated with the scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals in vitro, and the results indicated that YSS had good antioxidant activity, especially scavenging ability on DPPH radicals. The investigation demonstrated that YSS is a novel branched galactomannan with antioxidant activity, and differs from previously described extracellular polysaccharides.

The coral-associated fungus Penicillium commune produces an extracellular polysaccharide, FP2-1, when grown in potato dextrose-agar medium. FP2-1 was isolated from the fermented broth using anion-exchange and size-exclusion chromatography, and its structure was elucidated by chemical and spectroscopic analyses, including detailed nuclear magnetic resonance spectroscopy. The results showed that FP2-1 was a glucomannogalactan with a molar ratio of galactose, mannose and glucose of 3.9:1.9:1.0. Structure of FP2-1 may be represented, at an average, as a backbone of (1→2)-linked α-mannopyranose with the every second residue substituted at position 6 by a pentasaccharide branch. The branches consist of four (1→6)-linked β-galactofuranose residues with terminal α-glucopyranose residue attached to the last galactofuranose residue at position 2. FP2-1 was a novel galactofuranose-containing extracellular polysaccharide differing from previously described extracellular polysaccharides.

Background IL-6/STAT3/SOCS3 signaling pathway plays an important role in the pathogenesis of Crohn's disease by induction of the antiapoptotic factors Bcl-2 and Bcl-xl in lamina propria mononuclear cells (LPMCs). We previously reported that triptolide showed therapeutic activity in mouse colitis by mechanisms involving suppression of IL-6 trans-signaling. IL-10 gene-deficient mice with established colitis were used for the experiments with triptolide administration. Methods This study further investigates the mechanism by which triptolide attenuates Crohn's colitis. IL-10 gene-deficient mice (IL-10−/−) of 10–12 weeks with established colitis were used for the experiments with chronic triptolide administration. Apoptosis of lamina propria mononuclear cells (LPMCs) were measured by flow cytometry. SOCS, Bcl-2, Bcl-xl and Bax were determined by Western blot. Furthermore, an in vitro study was performed by using cultured intestine from CD patients to observe the direct effects of triptolide. Results Our data indicated triptolide promoted apoptosis in LPMCs in vivo. Interestingly, triptolide significantly induced the apoptosis of LP-CD4-positive but not LP-CD4-negative cells. Triptolide significantly induced SOCS3 protein and reduced STAT3 target anti-apoptotic genes Bcl-2 and Bcl-xl in LPMCs. The results were confirmed by an in vitro study using colonic explants cultured with triptolide. Conclusions Our results indicated that triptolide therapy may restore the homeostatic balance of LP-T cell apoptosis within the gut, and demonstrate a novel mechanism of action of triptolide therapy mediated through regulation IL-6/STAT3/SOCS3 signaling pathway.

Tungstovanadophosphoric heteropoly acid H6PW9V3O40·(13.81 ± 0.13)H2O (abbreviated as PW9V3) has been synthesized by the stepwise acidification and the stepwise addition of element solutions. The crystal structure was determined from single crystal X-ray diffraction. The complex crystallizes in the space group R3m, with a = 16.4374 (9) A, b = 16.4374 (9) A, c = 25.3866 (14) A, α = 90°, β = 90°, γ = 120°, V = 5940.20 A, and Z = 6. The product possesses Keggin structure, and its conductivity was 1.730 × 10–2 S·cm–1 at 26 °C and 75% relative humidity by electrochemical impedance spectroscopy (EIS) measurement. Two conducting systems were prepared with a mixture of as-synthesized PW9V3 and organic polymers [polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG)] at the weight ratio 80:20. The hybrid materials exhibit high proton conductivities with 7.110 × 10–3 and 1.050 × 10–2 S·cm–1 (PW9V3/PEG) at 26 °C and 75% relative humidity, respectively. Their activation energies of proton conduction are 15.23 and 13...

Two new pyran-2-ones, nocardiopyrones A and B (1 and 2, resp.), along with four known compounds, pyridinols 3-5, and 1-acetyl-β-carboline (6) were isolated from the alkalophilic actinomycete Nocardiopsis alkaliphila sp. nov. YIM-80379. Their structures were established on the basis of spectroscopic analysis, CD spectra, and the quantum-chemical ECD calculation. Pyridinols 3-5 were isolated from a natural source for the first time. Compounds 1 and 2 showed weak antibacterial activities against Pseudomonas aeruginosa, Enterobacter aerogenes, and Escherichia coli with MIC values of 20-48 μM. Compound 2 showed weak antimicrobial activities against Candida albicans and Staphylococcus aureus with MIC values of 24 and 48 μM, respectively.