Two new cyclopentenone metabolites from Streptomyces sp. HU119.

Two previously undescribed cyclopentenone metabolites, (S)-2-(3-acetylamino-2-methyl)propyl-3-butyl-2-cyclopenten-1-one (1) and (S)-2-(3-acetylamino-2-ethyl)propyl-3-butyl-2-cyclopenten-1-one (2), were isolated from the fermentation broth of the strain Streptomyces sp. HU119. The structures of 1 and 2 were determined by the comprehensive spectroscopic analysis, including 1 D, 2 D NMR, MS spectral analysis and the comparison with data from the literature. The absolute configurations were elucidated by experimental and calculated optical rotations (OR). Compounds 1 and 2 displayed weak cytotoxic activity.

Two new compounds from Streptomyces sp. HS-NF-813.

Two new derivatives of cytotoxic substance BE-52211, designed as BE-52211D (1) and BE-52211E (2), were isolated from the fermentation broth of the strain Streptomyces sp. HS-NF-813. Their structures were determined by 1D and 2D NMR techniques, ESI-MS and comparison with data from the literature. The absolute stereochemistry of 1 was elucidated by NMR data of the Mosher ester derivatives. Compounds 1 and 2 showed moderate cytotoxic activity against three human tumor cell lines.

Novel Metabolites from the Endophytic Fungus Chaetomium subaffine L01.

One natural p-terphenyl glycoside, gliocladinin C, and two furano-polyene derivatives, chaetominins A and B, were isolated from potato endophytic fungus Chaetomium subaffine. The absolute configurations of these compounds were elucidated by HR-ESI-MS, NMR, the DP4+ probabilities and electronic circular dichroism (ECD) spectra. Furthermore, gliocladinin C and chaetominin A showed cytotoxic activity against two selected human tumor cell lines (Hep-2 and HepG-2).

Facile Synthesis of Ti3C2Tx-Poly(vinylpyrrolidone) Nanocomposites for Nonvolatile Memory Devices with Low Switching Voltage.

MXenes, an emerging class of two-dimensional (2D) transition-metal carbide materials, have received increasing attention for their interesting physiochemical properties. For not only MXenes but also other 2D materials, delamination is a requisite step for the exploitation of their unique properties. In this work, a facile method for exfoliating Ti3C2Tx MXene to nanosheets of small size with the aid of poly(vinylpyrrolidone) (PVP) is designed, which has never been reported to our knowledge. Since both hydrophobic methylene groups and hydrophilic amide groups are provided with PVP, this method is applicable in a wide range of solvents, such as ethanol, water, and chloroform. Considering the charge detrapping and trapping behavior of 2D transition-metal materials in PVP dielectric, a memory device with the configuration of reduced graphene oxide (rGO)/Ti3C2Tx-PVP/Au is directly fabricated with these well-dispersed Ti3C2Tx-PVP composites by the solution process technique. Interestingly, the resultant device exhibits a typical bistable electrical switching, ultralow switching voltage (∼0.9 V), and a nonvolatile rewritable memory effect with the function of flash. This work might pave the way of using MXenes for future data storage, which is an indispensable field nowadays.

Two new lankacidin-related metabolites from Streptomyces sp. HS-NF-1178.

Two new lankacidin-related metabolites, 2,18-seco-lankacidinol A (1), 2,18-seco-lankacidinol B (2) and a known compound, lankacidinol (3), were isolated from the fermentation broth of Streptomyces sp. HS-NF-1178. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. These two new compounds, especially compound 1, exhibited potent antitumor activity.

A new anthracycline-type metabolite from Streptomyces sp. NEAU-L3.

A new anthracycline-type metabolite, designated as tetracenoquinocin A (1), was isolated from the fermentation broth of Streptomyces sp. NEAU-L3. Its structure was determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. Compound 1 showed potent cytotoxic activity against three cancer cell lines (HepG2, A549, HCT-116) with IC50 values of 5.57, 24.30 and 20.82 µM, respectively.

A new spectinabilin derivative with cytotoxic activity from ant-derived Streptomyces sp. 1H-GS5.

A new spectinabilin derivative (1) was isolated from the fermentation broth of the ant-derived Streptomyces sp. 1H-GS5, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human tumor cell lines A549, HCT-116, and HepG2 with IC50 values of 9.7, 12.8, and 9.1 µg/ml, respectively, which was relative higher than that of spectinabilin.

[Long-term Effect of the Treatment of IgA Nephropathy by Tonifying Shen, Activating Blood Stasis, Dispelling Wind-Dampness Combined with Western Medicine].

Objective To observe the long-term effect of tonifying Shen, activating blood stasis, dispelling wind-dampness (TSABSDWD) combined with Western drugs (WD) for IgA nephropathy. Methods A single center retrospective case-control study was used. The clinical and laboratory examinations, pa- thology of renal biopsy, and treatment programs of IgA nephropathy were obtained from primary IgA ne- phropathy patients (confirmed from renal biopsy at authors' hospital) from Jan 1st, 2008 to Dec 31 , 2008. Patients were assigned to Group A (basic treatment +Chinese herbs) and Group B (basic treatment +Chi- nese herbs + glucocorticoid and/or immune inhibitors). A follow-up visit started from the confirmation of re- nal biopsy to Dec 31, 2008, for at least 12 months. The end point event was defined as entering end stage renal disease (ESRD), estimated glomerular filtration rate (eGFR) decreased by more than 50%, or SCr was doubled. The differences in clinical manifestations, lab indicators and etc. were compared between be- fore treatment and after 1 year of treatment/till the end of follow-ups. The accumulative kidney survival rate was calculated using Kaplan-Meier method. The curve for accumulative kidney survival rate was drawn. Re- sults A total of 219 cases were included, 49 in Group A and 170 in Group B. In Group A, there were 7 pa- tients (14.0%) with Shen deficiency syndrome, 21 cases (43.0%) with Shen deficiency blood stasis syn- drome, 8 (16. 0%) with Shen deficiency wind-dampness syndrome, 13 cases (27. 0%) with Shen deficien- cy blood stasis wind-dampness syndrome. In Group B there were 12 patients (7.1%) with Shen deficiency syndrome, 47 cases (27. 6%) with Shen deficiency blood stasis syndrome, 22 (12.9%) with Shen defi- ciency wind-dampness syndrome, 89 cases (52.4%) with Shen deficiency blood stasis wind-dampness syndrome. No statistical difference in age, sex, or follow-up period between the two groups (P >0.05). Compared with Group A, the disease courser was shorter, 24 h urination increased more, levels of SCr and blood urea nitrogen (BUN) increased higher, plasma albumin decreased lower in Group B (P <0. 05). Compared with before treatment, 24 h urination and counts of urinary red blood cells (RBCs) decreased more in the two groups after 1-year treatment, and decreased further till the end of follow-up (P <0. 05). The total effective rate was 89. 0% (1951219). The total effective rate of Group A was 89. 8% (44/49), with no patient entry into endpoint event. The total effective rate of Group B was 88. 8%(151/170). Totally 5 pa- tients arrived at endpoint event in Group B, 4 in ESRD, 1 with eGFR decreased by more than 50%, or SCr doubled. Compared with Group B, the complete relief rate was higher in Group A (P <0. 01). The accumulative kidney survival rate was 100. 0%, 100. 0%, 98. 0% and 96. 1% in the 219 patients at year 1 , 3, 5, 7, re- spectively using Kaplan-Meier method. Conclusions Programs based on theory of Shen disease wind- dampness in CM and in integrative medicine could be used in treating IgA nephropathy according to differ- ent conditions. Long-term observation showed this program could significantly improve patients' conditions. The 7-year accumulative kidney survival rate was 96. 1%.

Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase.

BACKGROUND: Avermectin and milbemycin are important 16-membered macrolides that have been widely used as pesticides in agriculture. However, the wide use of these pesticides inevitably causes serious drug resistance, it is therefore imperative to develop new avermectin and milbemycin analogs. The biosynthetic gene clusters of avermectin and milbemycin have been identified and the biosynthetic pathways have been elucidated. Combinatorial biosynthesis by domain swap provides an efficient strategy to generate chemical diversity according to the module polyketide synthase (PKS) assembly line. RESULTS: The substitution of aveDH2-KR2 located in avermectin biosynthetic gene cluster in the industrial avermectin-producing strain Streptomyces avermitilis NA-108 with the DNA regions milDH2-ER2-KR2 located in milbemycin biosynthetic gene cluster in Streptomyces bingchenggensis led to S. avermitilis AVE-T27, which produced ivermectin B1a with high yield of 3450 ± 65 µg/ml. The subsequent replacement of aveLAT-ACP encoding the loading module of avermectin PKS with milLAT-ACP encoding the loading module of milbemycin PKS led to strain S. avermitilis AVE-H39, which produced two new avermectin derivatives 25-ethyl and 25-methyl ivermectin (1 and 2) with yields of 951 ± 46 and 2093 ± 61 µg/ml, respectively. Compared to commercial insecticide ivermectin, the mixture of 25-methyl and 25-ethyl ivermectin (2:1 = 3:7) exhibited 4.6-fold increase in insecticidal activity against Caenorhabditis elegans. Moreover, the insecticidal activity of the mixture of 25-methyl and 25-ethyl ivermectin was 2.5-fold and 5.7-fold higher than that of milbemycin A3/A4 against C. elegans and the second-instar larva of Mythimna separate, respectively. CONCLUSIONS: Two new avermectin derivatives 25-methyl and 25-ethyl ivermectin were generated by the domain swap of avermectin PKS. The enhanced insecticidal activity of 25-methyl and 25-ethyl ivermectin implied the potential use as insecticide in agriculture. Furthermore, the high yield and genetic stability of the engineered strains S. avermitilis AVE-T27 and AVE-H39 suggested the enormous potential in industrial production of the commercial insecticide ivermectin and 25-methyl/25-ethyl ivermectins, respectively.

Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces bingchenggensis.

Milbemycin oxime has been commercialized as effective anthelmintics in the fields of animal health, agriculture, and human infections. Currently, milbemycin oxime is synthesized by a two-step chemical reaction, which involves the ketonization of milbemycins A3/A4 to yield the intermediates 5-oxomilbemycins A3/A4 using CrO3 as catalyst. Due to the low efficiency and environmental unfriendliness of the ketonization of milbemycins A3/A4, it is imperative to develop alternative strategies to produce 5-oxomilbemycins A3/A4. In this study, the atmospheric and room temperature plasma (ARTP) mutation system was first employed to treat milbemycin-producing strain Streptomyces bingchenggensis, and a mutant strain BC-120-4 producing milbemycins A3, A4, B2, and B3 as main components was obtained, which favors the construction of genetically engineered strains producing 5-oxomilbemycins. Importantly, the milbemycins A3/A4 yield of BC-120-4 reached 3,890 ± 52 g/l, which was approximately two times higher than that of the initial strain BC-109-6 (1,326 ± 37 g/l). The subsequent interruption of the gene milF encoding a C5-ketoreductase responsible for the ketonization of milbemycins led to strain BCJ60 (∆milF) with the production of 5-oxomilbemycins A3/A4 and the elimination of milbemycins A3, A4, B2, and B3. The high 5-oxomilbemycins A3/A4 yield (3,470 ± 147 g/l) and genetic stability of BCJ60 implied the potential use in industry to prepare 5-oxomilbemycins A3/A4 for the semisynthesis of milbemycins oxime.

Three new cyclopentenone derivatives from Actinoalloteichus nanshanensis NEAU 119.

Three new cyclopentenone derivatives (1-3) were isolated from the rare actinomycete Actinoalloteichus nanshanensis NEAU 119. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 showed moderate cytotoxic activity against human lung adenocarcinoma cell line A549, human leukemia cell line K562, and human renal carcinoma cell line ACHN with an IC50 of 14.67, 11.87, and 23.36 µg ml(-1), respectively.

A new prenylated indole derivative from endophytic actinobacteria Streptomyces sp. neau-D50.

A new prenylated indole derivative 3-acetonylidene-7-prenylindolin-2-one (1) was isolated from the endophytic actinobacterium Streptomyces sp. neau-D50, together with four known hybrid isoprenoids, 7-isoprenylindole-3-carboxylic acid (2), 3-cyanomethyl-6-prenylindole (3), 6-isoprenylindole-3-carboxylic acid (4) and 7,4'-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (5). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compounds 1 and 2 demonstrated strong cytotoxic activities against human lung adenocarcinoma cell line A549 with an IC50 of 3.3 and 5.1 µg mL(- 1), respectively, which are comparable to that of the positive control doxorubicin (4.2 µg mL(- 1)). Furthermore, compounds 1-4 exhibited potent antifungal activity against phytopathogenic fungi Colletotrichum orbiculare, Phytophthora capsici, Corynespora cassiicola and Fusarium oxysporum.

Characterization and analysis of an industrial strain of Streptomyces bingchenggensis by genome sequencing and gene microarray.

Streptomyces bingchenggensis is a soil bacterium that produces milbemycins, a family of macrolide antibiotics that are commercially important in crop protection and veterinary medicine. In addition, S. bingchenggensis produces many other natural products including the polyether nanchangmycin and novel cyclic pentapeptides. To identify the gene clusters involved in the biosynthesis of these compounds, and better clarify the biochemical pathways of these gene clusters, the whole genome of S. bingchenggensis was sequenced, and the transcriptome profile was subsequently investigated by microarray. In comparison with other sequenced genomes in Streptomyces, S. bingchenggensis has the largest linear chromosome consisting of 11 936 683 base pairs (bp), with an average GC content of 70.8%. The 10 023 predicted protein-coding sequences include at least 47 gene clusters correlated with the biosynthesis of known or predicted secondary metabolites. Transcriptional analysis demonstrated an extremely high expression level of the milbemycin gene cluster during the entire growth period and a moderately high expression level of the nanchangmycin gene cluster during the initial hours that subsequently decreased. However, other gene clusters appear to be silent. The genome-wide analysis of the secondary metabolite gene clusters in S. bingchenggensis, coupled with transcriptional analysis, will facilitate the rational development of high milbemycins-producing strains as well as the discovery of new natural products.

Genetic engineering of Streptomyces bingchenggensis to produce milbemycins A3/A4 as main components and eliminate the biosynthesis of nanchangmycin.

Milbemycins A3/A4 are important 16-membered macrolides which have been commercialized and widely used as pesticide and veterinary medicine. However, similar to other milbemycin producers, the production of milbemycins A3/A4 in Streptomyces bingchenggensis is usually accompanied with undesired by-products such as C5-O - methylmilbemycins B2/B3 (α-class) and ß1/ß2 (ß-class) together with nanchangmycin. In order to obtain high yield milbemycins A3/A4-producing strains that produce milbemycins A3/A4 as main components, milD, a putative C5-O-methyltransferase gene of S. bingchenggensis , was biofunctionally investigated by heterologous expression in Escherichia coli . Enzymatic analysis indicated that MilD can catalyze both α-class (A3/A4) and ß-class milbemycins (ß11) into C5-O-methylmilbemycins B2/B3 and ß1, respectively, suggesting little effect of furan ring formed between C6 and C8a on the C5-O-methylation catalyzed by MilD. Deletion of milD gene resulted in the elimination of C5-Omethylmilbemycins B2/B3 and ß1/ß2 together with an increased yield of milbemycins A3/A4 in disruption strain BCJ13. Further disruption of the gene nanLD encoding loading module of polyketide synthase responsible for the biosynthesis of nanchangmycin led to strain BCJ36 that abolished the production of nanchangmycin. Importantly, mutant strain BCJ36 (ΔmilDΔnanLD) produced milbemycins A3/A4 as main secondary metabolites with a yield of 2312 ± 47 µg/ml, which was approximately 74 % higher than that of the initial strain S. bingchenggensis BC-109-6 (1326 ± 37 µg/ml).

New nemadectin congeners with acaricidal and nematocidal activity from Streptomyces microflavus neau3 Y-3.

Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is unprecedented among known milbemycins and avermectins. Both compounds 1 and 2 exhibited potent acaricidal activity and nematocidal activity. Especially, compound 2 demonstrated impressive acaricidal activity against adult mites with an IC50 of 2.3±0.9 µg/mL and mite eggs with an IC50 of 17.5±2.1 µg/mL and nematocidal activity against Caenorhabditis elegans with an IC50 of 0.7±0.2 µg/mL, which are higher than those of nemadectin and the known commercial acaricide and nematocide milbemycin A3/A4.

Minimization of excess sludge production by in-situ activated sludge treatment processes--a comprehensive review.

The widespread application of conventional activated sludge treatment process has been employed to deal with a variety of municipal and industrial sewage. While the generation of waste activated sludge (WAS) was considerably huge, the management and disposal expenses were substantially costly. A promising process aimed for WAS reduction during the operation process is urgently needed. Thus, increasing attentions emphasizing on the improved or novel sludge reduction processes should be intensively recommended in the future. This review presents the current and emerging technologies for excess sludge minimization within the process of sewage treatment. The ultimate purpose of this paper is to guide or inspire researchers who are seeking feasible and promising technologies (or processes) to tackle the severe WAS problem.