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Abstract Background Neonatal health (NH) remains a major problem in many countries. Children dying before 28 days often suffer from conditions that are preventable or treatable with proven, cost-effective interventions. The knowledge gaps are no longer about what should be done, but to understand why guidelines including these interventions are not followed. Using a behaviour change framework, this study explores neonatal health guidelines use and the role of management in supporting effective usage in two rural settings in China and Vietnam. Methods Semi-structured interviews with policy makers, health care managers and providers (n = 49) and focus group discussions with women, husbands and grandmothers who had experienced maternal and NH care services within the last year (n = 7) were conducted. Data were analysed using the framework approach. Results Guidelines are not readily available at county, township and village levels in the study sites in China, whereas, in Vietnam, guidelines are available, accepted and being used at facility level. Improvements in implementation could be made in both settings. Factors influencing guidelines use common to both settings included: lack of equipment and supplies; shortage of staff with NH care experience; and guidelines not in line with patient practices. Factors specific to China included: poor guidelines dissemination; and disagreement with guidelines. There was limited community engagement in NH services in China, whereas in Vietnam, community members were actively involved in decision making and provision of services. Managers have an important role in supporting NH guidelines use through: ensuring guidelines are available; allocating appropriate resources; supporting and monitoring staff in their use; and engaging with local communities to promote effective practices. Conclusions Engaging managers to support implementation is crucial. Management systems that provide the necessary resources, competent staff, and monitoring, regulatory and incentive frameworks as well as community engagement are needed to promote adoption of guidelines. Further research on how best to strengthen local level management so that they tailor interventions to support guideline use to their specific context is needed. This will ensure that proven interventions to address NH problems are used, and that countries move closer to achieving the new Sustainable Development Goal 3 target.

A novel actinobacterium, strain HNM0039T, was isolated from a marine sponge sample collected at the coast of Wenchang, Hainan, China and its polyphasic taxonomy was studied. The isolate had morphological and chemical characteristics consistent with the genus Streptomyces. Based on the 16S rRNA gene sequence analysis, strain HNM0039T was closely related to Streptomyces wuyuanensis CGMCC 4.7042T (99.38%) and Streptomyces spongiicola HNM0071T (99.05%). The organism formed a well-delineated subclade with S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T in the Streptomyces 16S rRNA gene tree. Multi-locus sequence analysis (MLSA) based on five house-keeping gene alleles (atpD, gyrB, rpoB, recA, trpB) further confirmed their relationship. DNA–DNA relatedness between strain HNM0039T and its closest type strains, namely S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T, were 46.5 and 45.1%, respectively. The average nucleotide identity (ANI) between strain HNM0039T and its two neighbor strains were 89.65 and 91.44%, respectively. The complete genome size of strain HNM0039T was 7.2 Mbp, comprising 6226 predicted genes with DNA G+C content of 72.46 mol%. Thirty-one putative secondary metabolite biosynthetic gene clusters were also predicted in the genome of strain HNM0039T. Among them, the tirandamycin biosynthetic gene cluster has been characterized completely. The crude extract of strain HNM0039T exhibited potent antibacterial activity against Streptococcus agalactiae in Nile tilapia. And tirandamycins A and B were further identified as the active components with MIC values of 2.52 and 2.55 μg/ml, respectively. Based on genotypic and phenotypic characteristics, it is concluded that strain HNM0039T represents a novel species of the genus Streptomyces whose name was proposed as Streptomyces tirandamycinicus sp. nov. The type strain is HNM0039T (= CCTCC AA 2018045T = KCTC 49236T).

BackgroundAlthough increasingly studied in high-income countries, there is a paucity of data from the Chinese population on the patterns of cancer among people living with HIV (PLHIV).MethodsWe conducted a nationwide follow-up study using routinely collected data for adult PLHIV diagnosed on or before 31 December 2011 and alive and in care as of 1 January 2008. Participants were observed from 1 January 2008 (study start) to 30 June 2012 (study end). Main outcome measures were gender-stratified age-standardized incidence rates for China (ASIRC) and standardized incidence ratios (SIR) for all malignancy types/sites observed.ResultsAmong 399,451 subjects, a majority was aged 30-44 years (49.3%), male (69.8%), and Han Chinese (67.9%). A total of 3,819 reports of cancer were identified. Overall, ASIRC was 776.4 per 100,000 for males and 486.5 per 100,000 for females. Malignancy sites/types with highest ASIRC among males were lung (226.0 per 100,000), liver (145.7 per 100,000), and lymphoma (63.1 per 100,000), and among females were lung (66.8 per 100,000), lymphoma (48.0 per 100,000), stomach (47.8 per 100,000), and cervix (47.6 per 100,000). Overall SIR for males was 3.4 and for females was 2.6. Highest SIR was observed for Kaposi sarcoma (2,639.8 for males, 1,593.5 for females) and lymphoma (13.9 for males, 16.0 for females).ConclusionsThese results provide evidence of substantial AIDS-defining and non-AIDS-defining cancer burden among adult Chinese PLHIV between 2008 and 2011. Although further study is warranted, China should take action to improve cancer screening, diagnosis, and treatment for this vulnerable population.

Four polyene macrolactams including the previously reported niizalactam C (4), and three new ones, streptolactams A–C (1–3) 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.

Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2′-bipyridyl ring core and 6-aldoxime functional group from Streptomyces caeruleus and recently from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Our previous study revealed that CRM A showed anti-tumor activity against human colorectal cancer (CRC) both in vitro and in vivo. Because some intestinal flora can affect the occurrence and development of CRC, the influence of CRM A on the intestinal flora is worthy of study in Sprague–Dawley (SD) rats. The high throughput sequencing of the V3-V4 hypervariable region in bacterial 16S rDNA gene results showed that the CRM A affected the diversity of intestinal flora of the SD rats treated with CRM A for 2, 3 and 4 weeks. Further analysis indicated that the abundance of genera Prevotella_1, Prevotellaceae_UCG-001, and Lactobacillus were increased while the that of genera Alloprevotella and Ruminiclostridium_1 were decreased. For the CRC related intestinal flora, the abundance of genera Bacteroides, Fusobacterium, Enterococcus, Escherichia-Shigella, Klebsiella, Streptococcus, Ruminococcus_2, and Peptococcus of SD rats treated with CRM A were decreased, while that of abundance of genera Bifidobacterium, Lactobacillus, Faecalibacterium, Blautia, Oscillibacter, and Clostridium were increased. The results indicated that CRM A could influence the intestinal flora by inhibiting some species of harmful flora and improving the beneficial bacteria in intestinal flora in the SD rats. The results may provide a new idea for revealing the mechanism of the anti-CRC activity of CRM A.

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.

This review covers the literature published by chemists from China during the 2015–2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.

Background. Incisional surgical site infection (iSSI) is a frequent postoperative complication of abdominal surgeries in patients with Crohn’s disease (CD). In this study, we investigated the association between thickness of subcutaneous fat (TSF) and iSSI in patients with CD undergoing intestinal resections. Patients and Methods. Patients with CD who had undergone abdominal surgery from January 2014 to January 2017 were included in this retrospective study. Patients’ TSF and other possible predictors of iSSI, including clinical characteristics, preoperative medications, hematological index, surgery-related data, and postoperative outcomes, were collected. Univariate and multivariate statistical analyses were used to examine the potential factors. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of factors. Results. The patient cohort comprised 246 patients (167 male (67.9%); mean age 35.7 ± 12.4 years; mean disease duration 69.6 ± 60.8 months). The incidence of iSSI was 24.8% (61/246). TSF was a significant predictor of iSSI (OR 1.079, 95% CIs (1.020, 1.142), P=0.008), being 13.7 mm in patients with iSSI and 9.9 mm in those without iSSI (P

Metafluidic metamaterial is a metamaterial the optical response of which is dependent on fluid contributed metamolecules. The dependence originates either from a fluid background coupling to the metamolecule or from the resonance in a liquid structured metamolecule. Different liquid materials including water, liquid crystal, and liquid metals are applied to realize the metafluidic metamaterial. Sophisticated technologies like electric bias and microfluidic system have been used for active control of metafluidic metamaterials which provide a new platform for electromagnetic wave manipulation and metadevice realization. The liquid background and significant tunability of the metafluidic metamaterial promise numerous applications, such as material sensing, bio-detection, energy harvesting, and imaging, just to name a few.

Aim. Excessive postoperative inflammatory response, which is characterized by overproduction of cytokines, often leads to complications after colorectal surgery. However, the impact of body composition on postoperative inflammatory response is largely unknown. The aim of this study is to elucidate whether body fat amount and its distribution affects postoperative inflammation after colorectal surgery in IBD patients. Methods. Eighty-six patients undergoing colorectal resection for IBD from June 2014 to Jan 2017 were enrolled. Abdominal CT images within one week prior to surgery were assessed for visceral fat, subcutaneous fat, and muscle mass. Postoperative inflammatory response was evaluated using serum CRP, PCT, and IL-6 levels on postoperative days 1, 3, and 5. Univariate analysis was conducted to identify risk factors for infectious complications. The correlation between body composition and postoperative plasma concentration of inflammatory markers was analyzed using a linear regression model. ROC curve was applied to analyze the effect of different body composition parameters on postoperative infectious complications and to determine the relationship between inflammatory markers and infectious complications. Results. Neither volume of fat or muscle was related to postoperative plasma concentrations of CRP, IL-6, and PCT. However, visceral to subcutaneous fat ratio was associated with PCT levels on postoperative days (POD) 1, 3, and 5, with the highest regression coefficient on POD1 (β=0.360; 95% CI, 0.089–0.631; P=0.010). Body composition did not predict postoperative infectious complications, while CRP on POD 3 was predictive of infectious complications. Conclusion. Increased visceral to subcutaneous fat ratio was associated with postoperative inflammatory response in IBD patients undergoing colorectal resection. This may partly explain the increased incidence of postoperative complications in patients with visceral obesity.

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn’s disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn’s disease patients and 10 colon cancer patients. The Crohn’s disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn’s disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn’s disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn’s disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn’s disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn’s disease patients in remission.

Ophiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced G1 phase arrest in human breast cancer MCF-7 cells, and found that ophiobolin O reduced the phosphorylation level of AKT and GSK3β, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK) analysis indicated that ophiobolin O could bind to GSK3β, and GSK3β knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and GSK3β, and blocked ophiobolin O-induced G1 phase arrest. These data suggest that ophiobolin O may induce G1 arrest in MCF-7 cells through interaction with AKT/GSK3β/cyclin D1 signaling. In vivo, ophiobolin O suppressed tumor growth and showed little toxicity in mouse xenograft models. Overall, these findings provide theoretical basis for the therapeutic use of ophiobolin O.

In the process of profiling the secondary metabolites of actinobacteria isolated from the Saudi coastal habitats for production of antibiotics and anti-cancer drugs, the cultures of strain WH1 that was identified as Streptomyces heliomycini exhibited strong antibacterial activity against Staphylococcus aureus. By means of MS and NMR techniques, the active compounds were characterized as actinomycins X0β, X2, and D, respectively. The research on the productivity of this strain for actinomycins revealed that the highest production of actinomycins X0β, X2, and D was reached in the medium MII within 5% salinity and pH 8.5. In this optimized condition, the fermentation titers of actinomycins X0β, X2, and D were 107.6 ± 4.2, 283.4 ± 75.3, and 458.0 ± 76.3 mg/L, respectively. All the three actinomycins X0β, X2, and D showed potent cytotoxicities against the MCF-7, K562, and A549 tumor cell lines, in which actinomycin X2 was the most active against the three tumor cell lines with the IC50 values of 0.8–1.8 nM. Both actinomycins X2 and D showed potent antibacterial activities against S. aureus and the methicillin-resistant S. aureus, Bacillus subtilis, and B. cereus and the actinomycin X2 was more potent.

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 electromagnetic (EM) properties of metasurfaces depend on both structural design and material properties. microelectromechanical systems (MEMS) technology offers an approach for tuning metasurface EM properties by structural reconfiguration. In the past 10 years, vast applications have been demonstrated based on MEMS metasurfaces, which proved to have merits including, large tunability, fast speed, small size, light weight, capability of dense integration, and compatibility of cost-effective fabrication process. Here, recent advances in MEMS metasurface applications are reviewed and categorized based on the tuning mechanisms, operation band and tuning speed. As an example, the pros and cons of MEMS metasurfaces for tunable lens applications are discussed and compared with traditional tunable lens technologies followed by the summary and outlook.

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.

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.

Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about 37-fold, compared to the former. However, 0.1 µM Ophiobolin-O (less than 20% inhibition concentration) combined with ADM caused the decreased IC50 of ADM to 6.67 ± 0.98 µM, indicating it reversed ADM resistance of MCF-7/ADR cells (11-fold). Furthermore, Ophiobolin-O increased ADM-induced mitochondrial pathway apoptosis and G2/M phase arrest, which is partly due to the elevation level of ROS in MCF-7/ADR cells. As we described in this paper, the reversal effect of Ophiobolin-O may be due to the reduction of resistance-related protein P-Glycoprotein (P-gp, also known as MDR1) through inhibiting the activity of the multidrug resistance 1 (MDR1) gene promoter, which makes MCF-7/ADR cells more sensitive to ADM treatment. Assays in nude mice also showed that the combination of ADM and Ophiobolin-O significantly improved the effect of ADM.

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 new meroterpenoids 1–4 and four new isocoumarinoids 5–8, along with five known isocoumarinoids (9–13), were isolated from the fungus Myrothecium sp. OUCMDZ-2784 associated with the salt-resistant medicinal plant, Apocynum venetum (Apocynaceae). Their structures were elucidated by means of spectroscopic analysis, X-ray crystallography, ECD spectra and quantum chemical calculations. Compounds 1–5, 7, 9 and 10 showed weak α-glucosidase inhibition with the IC50 values of 0.50, 0.66, 0.058, 0.20, 0.32, 0.036, 0.026 and 0.37 mM, respectively.

Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3- (4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 1–5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher’s, Marfey’s and the C3 Marfey’s methods. Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC50 value of 41.5 ± 4.5 μM. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC50 value of 28.9 ± 2.2 and 6.8 ± 1.5 μM, respectively. Due to the lack of corresponding data in the literature, the 13C NMR data of (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione (6) were also reported here for the first time.

The indolocarbazole (ICZ) alkaloids have attracted much attention due to their unique structures and potential therapeutic applications. A series of ICZs were recently isolated and identified from a marine-derived actinomycete strain, Streptomyces sanyensis FMA. To elucidate the biosynthetic machinery associated with ICZs production in S. sanyensis FMA, PCR using degenerate primers was carried out to clone the FAD-dependent monooxygenase gene fragment for ICZ ring formation, which was used as a probe to isolate the 34.6-kb DNA region containing the spc gene cluster. Sequence analysis revealed genes for ICZ ring formation (spcO, D, P, C), sugar unit formation (spcA, B, E, K, J, I), glycosylation (spcN, G), methylation (spcMA, MB), as well as regulation (spcR). Their involvement in ICZ biosynthesis was confirmed by gene inactivation and heterologous expression in Streptomyces coelicolor M1152. This work represents the first cloning and characterization of an ICZ gene cluster isolated from a marine-derived actinomycete strain and would be helpful for thoroughly understanding the biosynthetic mechanism of ICZ glycosides.

Introduction: Facing the challenges of aging populations, increasing chronic diseases prevalence and health system fragmentation, there have been several pilots of integrated health systems in China. But little is known about their structure, mechanism and effectiveness. The aim of this paper is to analyze health system integration and develop recommendations for achieving integration. Method: Huangzhong and Hualong counties in Qinghai province were studied as study sites, with only Huangzhong having implemented health system integration. Questionnaires, interviews, and health ­insurance records were sources of data. Social network analysis was employed to analyze integration, through structure measurement and effectiveness evaluation. Results: Health system integration in Huangzhong is higher than in Hualong, so is system ­effectiveness. The patient referral network in Hualong has more “leapfrog” referrals. The information sharing ­networks in both counties are larger than the other types of networks. The average distance in the joint ­training network of Huangzhong is less than in Hualong. Meanwhile, there are deficiencies common to both systems. Conclusion: Both county health systems have strengths and limitations regarding system integration. The use of medical consortia in Huangzhong has contributed to system effectiveness. Future research might consider alternative more context specific models of health system integration.

Background. The rate of anastomotic leakage is high in surgeries for Crohn’s disease, and therefore a temporary diverting stoma is often needed. We conducted this study to investigate whether preoperative nutritional therapy could reduce the risk of anastomotic leakage while decreasing the frequency of temporary stoma formation. Methods. This was a retrospective study. Patients requiring bowel resections due to Crohn’s disease were reviewed. The rate of anastomotic leakage and temporary diverting stoma was compared between patients who received preoperative nutritional therapy and those on a normal diet before surgery. Possible predictive factors for anastomotic leakage were also analyzed. Results. One hundred and fourteen patients undergoing 123 surgeries were included. Patients in nutritional therapy (NT) group had a significantly lower level of C-reactive protein on the day before surgery. Patients in NT group suffered less anastomotic leakage (2.3% versus 17.9%, P=0.023) and less temporary diverting stoma (22.8% versus 40.9%, P=0.036). Serum albumin of the day before surgery ≤35 g/L and preoperative nutritional therapy were identified as factors which independently affected the rate of anastomotic leakage. Conclusion. Preoperative nutritional therapy reduced the risk of anastomotic leakage and the frequency of temporary diverting stoma formation in patients with Crohn’s disease requiring resections.

Aim. The study aimed to investigate the impact of laparoscopic surgery and open surgery on postoperative edema in Crohn’s disease. Methods. Patients who required enterectomy were divided into open group (Group O) and laparoscopic group (Group L). Edema was measured using bioelectrical impedance analysis preoperatively (PRE) and on postoperative day 3 (POD3) and postoperative day 5 (POD5). The postoperative edema was divided into slight edema and edema by an edema index, defined as the ratio of total extracellular water to total body water. Results. Patients who underwent laparoscopic surgery had better clinical outcomes and lower levels of inflammatory and stress markers. A total of 31 patients (26.05%) developed slight edema and 53 patients (44.54%) developed edema on POD3. More patients developed postoperative edema in Group O than in Group L on POD3 (p=0.006). The value of the edema index of Group O was higher than that of Group L on POD3 and POD5 (0.402±0.010 versus 0.397±0.008, p=0.001; 0.401±0.009 versus 0.395±0.007, p=0.039, resp.). Conclusions. Compared with open surgery, laparoscopic surgery can reduce postoperative edema, which may contribute to the better outcomes of laparoscopic surgery over open surgery.

To investigate the structurally novel and bioactive natural compounds from marine-derived microorganisms under high salinity, the fungus Aspergillus terreus PT06-2 was isolated from the sediment of the Putian Sea Saltern, Fujian, China. Three new compounds, terremides A (1) and B (2) and terrelactone A (3), along with twelve known compounds (4–15) were isolated and identified from the fermentation broth of A. terreus PT06-2 at 10% salinity. Among these metabolites, compounds 4 and 15 only produced in the 10% salinity culture, were identified as methyl 3,4,5-trimethoxy-2-(2-(nicotinamido) benzamido) benzoate, and (+)-terrein, respectively. The new compounds 1 and 2 exhibited antibacterial activity against Pseudomonas aeruginosa and Enterobacter aerogenes with MIC values of 63.9 and 33.5 μM, respectively. Compounds 5 showed moderate anti-H1N1 activity and lower cytotoxicity with IC50 and CC50 values of and 143.1 and 976.4 μM, respectively.

To obtain structurally novel and bioactive natural compounds from marine-derived microorganisms, the effect of high salt stress on secondary metabolite production in the marine-derived fungal strain, Spicaria elegans KLA-03, was investigated. The organism, which was isolated from marine sediment, produced different secondary metabolites when cultured in 3% and 10% saline conditions. Four characteristic metabolites, only produced in the 10% salinity culture, were isolated, and their structures were identified as (2E,2'Z)-3,3'-(6,6'-dihydroxybiphenyl-3,3'-diyl)diacrylic acid (1), aspulvinone E (2), aspochalasin E (3) and trichodermamide B (6), according to their 1D and 2D NMR spectra. Compound 1 is a new compound. High salt stress may therefore be a promising means to induce the production of new and chlorinated compounds in halotolerant fungi. Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa and Escherichia coli with minimum inhibitory concentration (MIC) values of 0.038 and 0.767 mM, respectively.

Two new ansamycins, trienomycins H (1) and I (2), together with the known trienomycinol (3), were isolated from the fermentation broth of the deep-sea-derived bacterium Ochrobactrum sp. OUCMDZ-2164. Their structures, including their absolute configurations, were elucidated based on spectroscopic analyses, ECD spectra, and Marfey’s method. Compound 1 exhibited cytotoxic effects on A549 and K562 cell lines with IC50 values of 15 and 23 μM, respectively.

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.

Introduction. To determine the effect of fecal microbiota transplantation (FMT) on quality of life (QoL) in patients with inflammatory bowel disease (IBD). Methods. Fourteen IBD patients, including 11 Ulcerative colitis (UC) and 3 Crohn’s disease (CD), were treated with FMT via colonoscopy or nasojejunal tube infusion. QoL was measured by IBD Questionnaire (IBDQ). Disease activity and IBDQ were evaluated at enrollment and four weeks after treatment. Patients’ attitude concerning the treatment was also investigated. Results. One patient was excluded due to intolerance. All the other patients finished the study well. Mean Mayo score in UC patients decreased significantly (5.80 ± 1.87 versus 1.50 ± 1.35, P

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.

ObjectiveTo describe changes in sexual behaviors among HIV-infected individuals after their HIV diagnosis.MethodsAll HIV-infected individuals diagnosed by the end of 2009 in Taizhou Prefecture were invited to participate in this 12-month prospective study. Assessments including the total number and types of sexual contacts, and condom use details for up to their most familiar eight sexual contacts were collected both at enrollment and 12-month follow-up.Results262 HIV-infected individuals were eligible for analysis. The total number of sexual contacts reported by participants was 4,017, 1,496 and 356 during the 12- month period prior to HIV diagnosis (T1), the 12-month period prior to the baseline survey (T2), and the 12-month follow-up period (T3), respectively. The difference in the number of sexual contacts between T2 and T1 was -5 in median (IQR -1, -14), and the difference between T3 and T2 was 0 in median (IQR: 0, -6). A larger proportion of spousal or long-term heterosexual contact was reported from T1(27.7%) to T2(42.5%) to T3(76.1%), whereas a smaller proportion of commercial heterosexual contacts was reported from T1 (48.6%) to T2 (33.2%) to T3 (7.0%) as well as a smaller proportion of non-commercial casual homosexual contacts was reported from T2 (8.4%) to T3 (3.8%).The proportion of consistent condom use increased significantly from T1 (9.3%) to T2 (35.3%) to T3 (91.5%).ConclusionSexual behaviors did not change in a uniform manner for the participants in our study. Sexual behaviors and sexual networks vis-à-vis HIV diagnosis and follow-up were associated with the participant's characteristics and HIV infection and treatment status. The overall lesson is that individuals who are unaware of their HIV infection are the main drivers of secondary transmission. Early identification of HIV infection and access to antiretroviral therapy (ART) are both key strategies to the control and prevention.

ObjectiveInflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.MethodsWe performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.ResultsNine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54-0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I(2)=68.0%, pConclusionThe current meta-analysis revealed that thiopurines had a chemopreventive effect of colorectal neoplasms and a tendency of reducing advanced colorectal neoplasms in IBD. Due to the heterogeneity of included studies, these results should be interpreted with caution.

Shewanella oneidensis is a facultative anaerobic γ-proteobacterium possessing remarkably diverse respiratory capacities for reducing various organic and inorganic substrates. As a veteran research model for investigating redox transformations of environmental contaminants the bacterium is well known to be a naturally ampicillin-resistant microorganism. However, in this study we discovered that ampicillin has a significant impact on growth of S. oneidensis. Particularly, cell lysis occurred only with ampicillin at levels ranging from 0.49 to 6.25 µg/ml but not at 50 µg/ml. This phenotype is attributable to insufficient expression of the β-lactamase BlaA. The subsequent analysis revealed that the blaA gene is strongly induced by ampicillin at high (50 µg/ml), but not at low levels (2.5 µg/ml). In addition, we demonstrated that penicillin binding protein 5 (PBP5), the most abundant low molecular weight PBP (LMW PBP), is the only one relevant to β-lactam resistance under the tested conditions. This nonessential PBP, largely resembling its Escherichia coli counterpart in functionality, mediates expression of the blaA gene.

BACKGROUND: Transplantation of bone marrow mesenchymal stem cells (MSCs) provides a promising therapeutic efficiency for a variety of disorders caused by ischemia or reperfusion impairment. We have previously demonstrated the efficacy of MSCs in mitigating intestinal ischemia/reperfusion (I/R) injuries in rats, but the mechanism by which MSCs engraft ameliorates I/R injuries has largely been unknown. The present study aimed at investigating probable mechanisms by which MSCs exert their function. METHODS: Male donor derived rat MSCs were implanted into intestine of female recipient rat by direct submucosal injection after superior mesenteric artery clamping and unclamping. The homed MSCs were detected by Y chromosome in situ hybridization probe, and the tumor necrosis factor-α (TNF-α) content in intestinal mucosa was determined by ELISA. Expression of proliferative cell nuclear antigen (PCNA) in bowel mucosa was assayed by real-time PCR and intestinal mucosa expression of phosphorylation extracellular signal-regulated kinase (pERK1/2) and nuclear factor-κB (NF-κB) were evaluated by western blot. RESULTS: Four and seven days after MSCs transplantation, the TNF-α content of bowel mucosa in MSCs group was significantly lower than that in saline group. The PCNA in bowel mucosa showed higher expression in MSCs treated group than the saline group, both at 4 and 7 days after cell transplantation. The expression of intestinal mucosal pERK1/2 in MSCs treated group was markedly higher than that in saline group, and the expression of NF-κB in MSCs treated group was noticeably decreased than that in saline group at 4 and 7 days post MSCs transplantation. CONCLUSION: The present investigation provides novel evidence that MSCs have the potential to reduce intestinal I/R injuries probably due to their ability to accelerate cell proliferation and decrease the inflammatory response within intestinal mucosa after ischemia and reperfusion.

Synbiotic intake may efficiently restore the balance of gut microbiota and improve gastrointestinal functions. The aim of the study was to evaluate the efficacy of a synbiotic in patients with slow transit constipation. A total of 100 patients with slow transit constipation were randomized to receive either a synbiotic or placebo twice daily for 12 weeks. The primary efficacy endpoints were the clinical remission and improvement rates at weeks 4 and 12. Stool frequency and consistency, colonic transit time (CTT), evacuation and abdominal symptoms, patient assessment of constipation symptoms, gastrointestinal quality-of-life index scores, satisfaction scores, and adverse events were also monitored. The clinical remission rates reached 37.5% at week 4 and 45.8% at week 12 in the treatment group, compared to 13.3% at week 4 and 16.7% at week 12 in the placebo group (p < 0.01 for both comparisons). Over 12 weeks, 64.6% of the patients who received the synbiotic experienced clinical improvement, compared to 29.2% of the patients in the placebo group (p < 0.01). During the intervention period, patients who were treated with the synbiotic exhibited increased stool frequency, improved stool consistency, decreased CTT, and improved constipation-related symptoms. This randomized, placebo-controlled trial suggested that dietary supplementation with a synbiotic improved evacuation-parameters-associated symptoms and colonic motility in patients with slow transit constipation (STC).

MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn’s disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C–reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = −0.518, p = 0.008, and r = −0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD.

Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy’s fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H2S, neutrophil elastase inhibitor and phophatidyl choline.