Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Variations of sediment organic phosphorus and organic carbon during the outbreak and decline of algal blooms in Lake Taihu, China.

In this study, sediment organic phosphorus (OP) and organic carbon (OC) in Lake Taihu, China, as well as their relationships, were analyzed during the outbreak and decline of algal blooms (ABs) over a five-month field study. The results showed synchronous temporal changes in the sediment OP and OC contents with the development of ABs. In addition, there was a significant positive correlation between the sediment OP and OC (p < 0.01), suggesting simultaneous deposition and consumption during the ABs outbreak. The sediment OP and OC contents decreased significantly at the early and last stages of the ABs outbreak and increased at the peak of the ABs outbreak and during the ABs decline. These temporal variation patterns suggest that the sediment OC and OP contents did not consistently increase during the ABs outbreak, even though algae are an important source of organic matter in sediments. The depletion or enrichment of OC and OP in sediments may also depend on the scale of the ABs outbreak. The obtained results revealed significant differences in the sediment OC and OP contents between the months (p < 0.05). In addition, OP in the sediments was dominated by orthophosphate diester (phospholipids and DNA-P) and orthophosphate monoester during the ABs outbreak and decline, respectively. The active OC contents and proportions in the sediments in the ABs outbreak were significantly lower than those observed in the ABs decline period, demonstrating the significant impacts of the ABs outbreak and decline on the sediment OC and OP in Lake Taihu.

Oxidation-Resistant Silicon Nanosystem for Intelligent Controlled Ferrous Foliar Delivery to Crops.

Since ferrous (Fe(II)) is the main form of plant absorption, traditional ferrous foliar fertilizers (TFFF) are widely used in modern agriculture. However, TFFF suffer from the shortcomings of weak antioxidant capacity (AC), low foliar adhesion efficiency (FAE), poor fertilizer utilization efficiency (FUE), and noncontrollable slow-release behavior. To overcome these limitations, an oxidation-resistant silicon nanosystem for intelligent controlled ferrous foliar delivery to crops was first developed by using environmentally friendly micro/nano structured hollow silicon as carrier, and combining with vitamin C (in situ antioxidant) to synthesize an oxidation-resistant ferrous foliar fertilizer (ORFFF) for ameliorating Fe-deficiency in crops and increasing crop yield. Compared with TFFF, the ORFFF has excellent ferrous AC (only 11.5% of Fe(II) was oxidized in ORFFF within 72 h), ultrahigh FAE (∼84% of adhesion percentage (%) after two-times simulated rain rinsing), nutrient slow-release ability (720 h gradually release 100.6 mg·g-1), pH-controlled release ability (pH 3-8), and verified high biological safety (100% survival rate for zebrafish and earthworm). The pot experiments showed that ORFFF can correct the Fe-deficiency symptoms of tomato seedlings promptly compared with TFFF, and the FUE of ORFFF is 4.2 times that of TFFF. The specific pH responsiveness of ORFFF can control the slow-release rate of Fe(II) to satisfy the needs of Fe in varying crops and different growing periods of crops. This work provides a feasible way to achieve green and safe Fe supplementation for crops, reduce Fe fertilizer waste, avoid soil pollution caused by Fe fertilizer abuse, and promote the sustainable development of modern nanoagriculture.

Effects of heavy rain on the concentrations and forms of carbon, nitrogen and phosphorus in urban rivers of northern China.

Non-point source pollution caused by rainfall runoff is an important pollution source for river water. To explore the impact of heavy rain on urban river water environments, this paper studied the changes in carbon, nitrogen, and phosphorus levels, composition, and structure in the river water of Kaifeng, China, during the heavy rain in July 2021. The results showed that the concentrations of different forms of carbon, nitrogen, and phosphorus all increased under the effect of the heavy rain. The increase of phosphorus in the river was the largest, and that of carbon was the smallest. The most significant pollution from carbon, nitrogen, and phosphorus occurred in the HJ River. Colored dissolved organic matter (CDOM) was present in the form of macromolecules after the rain, and the degree of humification was deeper compared with before the rain. But heavy rain did not affect the CDOM composition in urban rivers. The spectral slope (SR) and the absorption coefficient at 240 nm to 420 nm (E2/E4) values showed that the CDOM was dominated by exogenous input after the rain, with endogenous pollution again becoming the main factor one week after the rain.

YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6.

BACKGROUND: Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines. METHODS: Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid-liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment. RESULTS: YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors. CONCLUSIONS: Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer-promoter interactions, thereby increasing PCa progression.

Transcriptome analysis reveals the regulatory mode by which NAA promotes the growth of Armillaria gallica.

A symbiotic relationship is observed between Armillaria and the Chinese herbal medicine Gastrodia elata (G. elata). Armillaria is a nutrient source for the growth of G. elata, and its nutrient metabolism efficiency affects the growth and development of G. elata. Auxin has been reported to stimulate Armillaria species, but the molecular mechanism remains unknown. We found that naphthalene acetic acid (NAA) can also promote the growth of A. gallica. Moreover, we identified a total of 2071 differentially expressed genes (DEGs) by analyzing the transcriptome sequencing data of A. gallica at 5 and 10 hour of NAA treatment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these unigenes were significantly enriched in the metabolism pathways of arginine, proline, propanoate, phenylalanine and tryptophan. The expression levels of the general amino acid permease (Gap), ammonium transporter (AMT), glutamate dehydrogenase (GDH), glutamine synthetase (GS), Zn(II) 2Cys6 and C2H2 transcription factor genes were upregulated. Our transcriptome analysis showed that the amino acid and nitrogen metabolism pathways in Armillaria were rapidly induced within hours after NAA treatment. These results provide valuable insights into the molecular mechanisms by which NAA promotes the growth of Armillaria species.

Mechanisms of Intervertebral Disc Degeneration Treatment with Deer Antlers Based on Network Pharmacology and Molecular Docking.

Background: With the aging of the population, the prevalence of IVDD increases preoperatively. How to better treat IVDD has become an important clinical issue. Deer antlers proved to have a great effect on the treatment of IVDD in many studies, but the molecular mechanism has not been clarified. Objective: To investigate the molecular mechanism and target of deer antlers in the treatment of IVDD. Methods: Compounds from deer antlers were collected and targets were predicted using HERB, TCMSP, TCMID, SwissADME, and SwissTargetPrediction. Collection of disease targets for IVDD was done using GeneCards, TTD, DrugBank, DisGeNET, and OMIM. Cytoscape 3.7.2, AutoDock Vina (v1.1.2), and R software were used for data analysis and the construction of network diagrams. Results: A total of 5 active compounds from deer antlers were screened and 104 therapeutic targets were predicted. A total of 1023 IVDD disease targets were collected. Subsequently, PPI network prediction analysis was performed for disease and treatment targets, and 112 core targets were collected after screening. After obtaining the core target, we used the clusterProfiler software package of R software to carry out GO and KEGG enrichment analyses for the core target and plot the bubble maps. According to the GO enrichment results, the main biological processes of IVDD treatment by deer antlers lie in the rhythmic process, mRNA catabolic process, and G1/S transition of the mitotic cell cycle. KEGG results were mainly related to the PI3K-Akt signaling pathway, thyroid hormone signaling pathway, and Notch signaling pathway. Molecular docking results showed that estrone had the best docking results on ESR1. Conclusion: Deer antlers are rich in various compounds that can prevent the development of IVDD by upregulating the PI3K-Akt signaling pathway and Notch signaling pathway. Its key compounds estradiol and estrone can reduce the inflammatory response and oxidative stress in tissues and organs, thus slowing down the progression of IVDD. Estrone, the active compound in deer antlers, was found by molecular docking to have good results against ESR1, the target of the disease, which may be a potential site for drug therapy.

Effect of algal blooms outbreak and decline on phosphorus migration in Lake Taihu, China.

Algal blooms (ABs) can affect the migration of phosphorus (P) among sediments, interstitial water and overlying water. It is important to analyze the characteristics of P and their interactions in the three media during ABs. A 5-month field study (June to October in 2016) was conducted in Zhushan Bay of Lake Taihu. P fractions, P adsorption characteristics and P diffusion fluxes at the sediment-water interface (SWI) were investigated. During the outbreak period of ABs from June to August, labile P concentrations in the sediment measured by diffusive gradients in thin films (DGT-labile P) and its diffusion fluxes across the SWI increased significantly. The equilibrium P concentration (EPC0) of the sediment was higher than the PO43--P concentration in the overlying water. During the period of decline of ABs from September to October, the concentrations and diffusion fluxes of DGT-labile P sharply decreased. However, the sediment total P (TP), overlying water TP, total dissolved P (TDP) and PO43--P concentrations increased. These results show that the ability of sediment solids to supplement interstitial water labile P was significantly enhanced by the outbreak of ABs. Labile P was then intensively released into the overlying water by interstitial water. Degraded algae became a crucial P source during the period of decline of ABs. P from the degraded algae was re-released to the sediment and overlying water. The observed DGT-labile P and DGT-labile Fe coupling in June, September and October confirmed the Fe redox-driven P release mechanism in sediment during these periods. The decoupling of DGT-labile P and DGT-labile Fe was observed in July and August and was probably caused by algal decomposition, labile organic P degradation and/or sulfate reduction in sediment stimulated by the ABs outbreak.

Identifying causality, genetic correlation, priority and pathways of large-scale complex exposures of breast and ovarian cancers.

BACKGROUND: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. METHODS: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. RESULTS: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. CONCLUSIONS: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

Discovery of Novel and Potent N-Methyl-d-aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models.

N-Methyl-d-aspartate receptors (NMDARs) are glutamate-gated Na+ and Ca2+-permeable ion channels involved in excitatory synaptic transmission and synaptic plasticity. NMDAR hypofunction has long been implicated in the pathophysiology including major depressive disorders (MDDs). Herein, we report a series of furan-2-carboxamide analogues as novel NMDAR-positive allosteric modulators (PAMs). Through structure-based virtual screen and electrophysiological tests, FS2921 was identified as a novel NMDAR PAM with potential antidepressant effects. Further structure-activity relationship studies led to the discovery of novel analogues with increased potentiation. Compound 32h caused a significant increase in NMDAR excitability in vitro and impressive activity in the forced swimming test. Moreover, compound 32h showed no significant inhibition of hERG or cell viability and possessed a favorable PK/PD profile. Our study presented a series of novel NMDAR PAMs and provided potential opportunities for discovering of new antidepressants.

Knockdown of the DUF647 family member RUS4 impairs stamen development and pollen maturation in Arabidopsis.

ROOT UV-B SENSITIVE4 (RUS4) encodes a Domain of Unknown Function647 (DUF647) protein, whose function is poorly understood. We have previously shown the artificial microRNA knockdown Arabidopsis RUS4 plants, referred to as amiR-RUS4, have severely reduced male fertility with a defect in anther dehiscence. Here, we show that amiR-RUS4 plants are also defective in pollen maturation and germination. Promoter-reporter analysis shows that RUS4 is highly expressed in tapetal layer, developing microspores, mature and germinating pollen, strongly suggesting its role in the process of pollen maturation. As the translational RUS4-GFP fusion protein has been localized to the chloroplasts where the first step of jasmonic acid (JA) biosynthesis takes place, leading to the hypothesis that RUS4 may be involved in JA-mediated stamen development. We show that expression of several JA metabolic genes increased markedly in flower buds of the amiR-RUS4 plants compared to that of the wild-type. We further show that transcript abundance of a clade of the JA-responsive MYB transcript factor genes, especially MYB108, reduced significantly in stamens of amiR-RUS4 plants relative to the wild-type; these MYB transcript factors have been shown to be required for JA-mediated stamen and pollen maturation. Our data suggest that RUS4 may play a role in coordinating anther dehiscence and pollen maturation by affecting the expression of JA-related genes.

Roles for circulating polyunsaturated fatty acids in ischemic stroke and modifiable factors: a Mendelian randomization study.

BACKGROUND: Available data about the effects of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its main risk factors remains limited and conflicting. Therefore, we conducted Mendelian randomization (MR) to assess whether genetically predicted PUFA affected IS, lipids and blood pressure (BP). METHODS: Genetic instruments associated with IS were derived from ISGC Consortium (n = 29,633), with lipids were derived from GLGC(n = 188,577), with BP were derived from Neale Lab(n = 337,000). The inverse-variance weighted method was the main analysis to estimate the effect of exposure on outcome. Sensitivity analyses included principal components analysis, MR-Egger, weighted median, and weighted mode. RESULTS: Per SD increases in serum α-linolenic acid (ALA) were associated with lower IS risk, with odd ratio (OR) of 0.867(0.782,0.961), arachidonic acid (AA) were associated with higher IS risk (OR: 1.053(1.014,1.094)). Likewise, Per SD increases in ALA were associated with the lower-level low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) (ß:-0.122(- 0.144, - 0.101), - 0.159(- 0.182, - 0.135), - 0.148(- 0.171, - 0.126), respectively), AA were associated with the higher-level of LDL-C, HDL-C and TC (ß:0.045(0.034,0.056), 0.059(0.050,0.067), 0.055(0.046,0.063), respectively). Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) had little or no association with IS, lipids or BP at Bonferroni-corrected significance. Different analytic methods supported these findings. The intercept test of MR-Egger implied no pleiotropy. CONCLUSIONS: High-level plasma ALA was protective for IS but AA was the opposite. LA, EPA, DHA, and DPA had no effects on IS.

Synthesis and biological evaluation of panaxatriol derivatives against myocardial ischemia/reperfusion injury in the rat.

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18, was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents.

Investigation of watershed nutrient export affected by extreme events and the corresponding sampling frequency.

Although the real-time monitoring technique has been widely applied due to the improvement of sensors, development of traditional sampling methods is still worth of being discussed due to the economically feasibility. Currently, extreme events (e.g. extreme rainfall caused by climate change) play a relatively important role in nutrient export. However, impacts of extreme events on the optimization of sampling strategy is still not well addressed despite the uncertainty of different frequency sampling programs has been sufficiently discussed in previous studies. Therefore, the corresponding impact of extreme events impact on the optimization of sampling strategy was investigated by examining temporal (i.e., inter-annual and seasonal) variations of available data. Uncertainty of nutrient flux estimates under different sampling frequencies was explored by subsampling daily monitoring data. Results showed that uncertainty in flux estimates differed between nitrogen and phosphorus. The relative error (RE) in annual TN flux estimates ranged from -4.2% to 2.4% (once per three-day) to -21.4-31.1% (monthly sampling), while the RE in annual TP flux estimates varied from -14.1% to 8.2% (once per three-day) to -65.9%-163.4% (monthly sampling). Biweekly and weekly sampling routines are considered the optimal sampling program for total nitrogen (TN) and for total phosphorus (TP) when the extreme events impact were not been considered. The uncertainty of flux estimates with different sampling frequencies increased with the increasing extreme events. High level of uncertainty occurred in years with the most extreme events in 2012 (RE: 21.4-69.0% for TN, 33.3-96.6% for TP), while the lowest can be found in 2011 (RE: 0-20.7% for TN, 0-48.3% for TP) (with the fewest extreme events). In addition, uncertainty in TN and TP flux estimates was generally greater during summer season than during other seasons. These results highlighted the important role of extreme events in nutrient export. Approximately half of the annual TN and TP flux occurred in some extreme days that only accounted for less than 20% in the same year. The onset of these extremes of nutrient export was likely due to the stormflow with addition of external fertilizer and the direct discharge of surface ponding water from paddy fields during special periods of time. These results would be helpful for the optimization of sampling strategy.

Enhanced Photoacoustic and Photothermal Effect of Functionalized Polypyrrole Nanoparticles for Near-Infrared Theranostic Treatment of Tumor.

Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that this designed PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.

Research on the interaction between tubeimoside 1 and HepG2 cells using the microscopic imaging and fluorescent spectra method.

The treatment of cancer draws interest from researchers worldwide. Of the different extracts from traditional Chinese medicines, Tubeimoside 1 (TBMS 1) is regarded as an effective treatment for cancer. To determine the mechanism of TBMS 1, the shape/pattern of HepG2 cells based on the microscopic imaging technology was determined to analyze experimental results; then the fluorescent spectra method was designed to investigate whether TBMS 1 affected HepG2 cells. A three-dimensional (3D) fluorescent spectra sweep was performed to determine the characteristic wave peak of HepG2 cells. A 2D fluorescent spectra method was then used to show the florescence change in HepG2 cells following treatment with TBMS 1. Finally, flow cytometry was employed to analyze the cell cycle of HepG2 cells. It was shown that TBMS 1 accelerated the death of HepG2 cells and had a strong dose- and time-dependent growth inhibitory effect on HepG2 cells, especially at the G2/M phase. These results indicate that the fluorescent spectra method is a promising substitute for flow cytometry as it is rapid and cost-effective in HepG2 cells.

Giardia intestinalis: effects of Pulsatilla chinensis extracts on trophozoites.

Pulsatilla chinensis is a medicinal root plant that has been used to treat a wide range of disease conditions. Our study determined the antiprotozoal activity of various P. chinensis extracts and fractions against Giardia intestinalis including their effects on parasite growth, cell viability, adherence, and morphology. Ethyl acetate extracts (IC50 = 257.081 µg/ml) were the most active to inhibit the growth of G. intestinalis followed by aqueous extract (PWE), saponins, and n-butanol extract. The PWE and ethyl acetate extract inhibited G. intestinalis trophozoites adherence after 3 h of incubation and killed almost 50 % of the parasite population in a time-dependent manner. Changes in morphology, presence of precipitates in the cytoplasm, dissolved cytoplasm with large vacuole, break of flagella and ventral disk, membrane blebs, and intracellular and nuclear clearance of the treated trophozoites were observed by scanning and transmission electron microscopy. We demonstrated that P. chinensis induced these changes in G. intestinalis morphology and consequently has potential therapeutic use against giardiasis.

[Phosphorus threshold for the shift between grass- and algae-stable states in Dahong Harbor of Gehu Lake].

Taking the macrophytes remaining area in Dahong Harbor of Gehu Lake as test object, this paper studied the phosphorus threshold for the shift between grass- and algae-stable states under natural conditions. The correlation analysis on the environmental factors showed that the total phosphorous in water body had better liner relationships with phytoplankton chlorophyll a and Secchi depth, and principal component analysis indicated that total phosphorous and nitrogen in the water body were the two main components affecting the water quality, among which, total phosphorous was the maximum weight source and played a determinant role in the shift between grass- and algae-stable states. The Harbor was in grass-stable state in winter, shifted to grass-algae intermediate state in spring, and kept the intermediate state in summer and autumn. The total phosphorous threshold for grass-stable state shifting to grass-algae intermediate state was 61 microg x L(-1), and that for grass-algae intermediate state shifting to algae-stable state was 115 microg x L(-1). In order to make the ecosystem shift from algae-stable state to grass-stable state, some measures such as cutting and controlling the Lake's nutrient sources, removing the sediment rich in organic matter, and constructing submerged macrophytes areas should be adopted to make the total phosphorous threshold in the water body dropped to below 61 microg x L(-1).

Tanshinone IIA and tanshinone I production by Trichoderma atroviride D16, an endophytic fungus in Salvia miltiorrhiza.

In this study the isolation of an endophytic fungus from the root of the medicinal herb Salvia miltiorrhiza Bunge is reported for the first time. The fungus produced tanshinone I and tanshinone IIA in rich mycological medium (potato dextrose broth) under shake flask and bench scale fermentation conditions. The fungus was identified as Trichoderma atroviride by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Tanshinone I and tanshinone IIA were identified by HPLC and LC-HRMS/MS and confirmed through comparison with authentic standards. This endophytic fungus has significant scientific and industrial potential to meet the pharmaceutical demands for tanshinone I and tanshinone IIA in a cost-effective, easily accessible and reproducible way.

Trichodermanin A, a novel diterpenoid from endophytic fungus culture.

Trichodermanin A, a structurally unique diterpenoid with skeletal carbons arranged compactly in a fused 6-5-6-6 ring system, has been isolated from cultures of Trichoderma atroviride (strain no. S361), an endophytic fungus isolate in Cephalotaxus fortunei. The structure of this compound was elucidated based on extensive spectroscopic methods and confirmed by X-ray diffraction analysis.