Pollution source identification of nitrogen and phosphorus in the lower West Main Canal, the Ganfu Plain irrigation district (South China).

The degradation of surface water quality has been a widespread concern around the world. However, irrigation canal water does not attract much attention although it is important to agriculture and population. In this study, a 5-year water quality monitoring of surface water was conducted in the lower West Main Canal of the Ganfu Plain irrigation district to identify the levels and pollution sources of nitrogen and phosphorus.Over 75% of samples had total phosphorus (TP) concentrations of > 0.02 mg/L, and all samples had total nitrogen (TN) concentrations of > 0.2 mg/L, indicating a risk of eutrophication. The concentrations of NO3--N and NH4+-N averagely occupied 57% and 18% of TN, respectively. PCA analysis showed that phosphorus and nitrogen in canal water were associated with meteorological factors, urban life and surface runoff, agricultural cultivation, livestock-poultry breeding, and water-sediment interaction in the wet season, whereas they were affected by meteorological factors, industrial effluent, urban domestic sewage, and livestock-poultry breeding in the dry season. Absolute principal component score-multiple linear regression (APCS-MLR) model results revealed that (1) agricultural cultivation plus livestock-poultry breeding contributed 43.2% of TP in canal water in the wet season, while livestock-poultry breeding contributed 52.9% in the dry season, and (2) domestic sewage plus surface runoff contributed 29.4% of TN in the wet season, while livestock-poultry breeding contributed 45.9% in the dry season. The unidentified sources had significant contributions of > 20% for almost all variables. So further investigations are required for determining unidentified sources, and anthropogenic pollution control is imperative for canal water quality protection.

Nano Ultrasound Contrast Agent for Synergistic Chemo-photothermal Therapy and Enhanced Immunotherapy Against Liver Cancer and Metastasis.

Advanced liver cancer is the most fatal malignant cancer, and the clinical outcomes of treatment are not very satisfactory due to the complexity and heterogeneity of the tumor. Combination therapy can efficiently enhance tumor treatment by stimulating multiple pathways and regulating the tumor immune microenvironment. Nanodrug delivery systems have become attractive candidates for combined strategies for liver cancer treatment. This study reports a nano ultrasound contrast agent (arsenic trioxide (ATO)/PFH NPs@Au-cRGD) to integrate diagnosis and treatment for efficient ultrasound imaging and liver cancer therapy. This nanodrug delivery system promotes tumor-associated antigens release through ATO-induced ferroptosis and photothermal-induced immunogenic cell death, enhancing the synergistic effects of ATO and photothermal therapy in human Huh7 and mouse Hepa1-6 cells. This drug delivery system successfully activates the antitumor immune response and promotes macrophage M1 polarization in tumor microenvironment with low side effects in subcutaneous and orthotopic liver cancer. Furthermore, tumor metastasis is inhibited and long-term immunological memory is also established in orthotopic liver cancer when the nanodrug delivery system is combined with anti-programmed death-ligand 1 (PD-L1) immunotherapy. This safe nanodrug delivery system can enhance antitumor therapy, inhibit lung metastasis, and achieve visual assessment of therapeutic efficacy, providing substantial potential in clinic applications for liver cancer.

Transcriptome and Metabolome Profiling Provide Insights into Flavonoid Synthesis in Acanthus ilicifolius Linn.

Acanthus ilicifolius is an important medicinal plant in mangrove forests, which is rich in secondary metabolites with various biological activities. In this study, we used transcriptomic analysis to obtain differentially expressed genes in the flavonoid metabolic pathway and metabolomic methods to detect changes in the types and content in the flavonoid metabolic synthesis pathway. The results showed that DEGs were identified in the mature roots vs. leaves comparison (9001 up-regulated and 8910 down-regulated), mature roots vs. stems comparison (5861 up-regulated and 7374 down-regulated), and mature stems vs. leaves comparison (10,837 up-regulated and 11,903 down-regulated). Furthermore, two AiCHS genes and four AiCHI genes were up-regulated in the mature roots vs. stems of mature A. ilicifolius, and were down-regulated in mature stems vs. leaves, which were highly expressed in the A. ilicifolius stems. A total of 215 differential metabolites were found in the roots vs. leaves of mature A. ilicifolius, 173 differential metabolites in the roots vs. stems, and 228 differential metabolites in the stems vs. leaves. The metabolomic results showed that some flavonoids in A. ilicifolius stems were higher than in the roots. A total of 18 flavonoid differential metabolites were detected in the roots, stems, and leaves of mature A. ilicifolius. In mature leaves, quercetin-3-O-glucoside-7-O-rhamnoside, gossypitrin, isoquercitrin, quercetin 3,7-bis-O-ß-D-glucoside, and isorhamnetin 3-O-ß-(2″-O-acetyl-ß-D-glucuronide) were found in a high content, while in mature roots, di-O-methylquercetin and isorhamnetin were the major compounds. The combined analysis of the metabolome and transcriptome revealed that DEGs and differential metabolites were related to flavonoid biosynthesis. This study provides a theoretical basis for analyzing the molecular mechanism of flavonoid synthesis in A. ilicifolius and provides a reference for further research and exploitation of its medicinal value.

De Novo Transcriptome Assembly and EST-SSR Marker Development and Application in Chrysosplenium macrophyllum.

Chrysosplenium macrophyllum Oliv., belonging to the family Saxifragaceae, is a traditional and unique Chinese herbal medicine. However, the lack of adequate molecular markers has hampered the progress regarding population genetics and evolution within this species. In this research, we used the DNBSEQ-T7 Sequencer (MGI) sequencing assay to analyze the transcriptome profiles of C. macrophyllum. SSR markers were developed on the basis of transcriptomic sequences and further validated on C. macrophyllum and other Chrysosplenium species. The genetic diversity and structure of the 12 populations were analyzed by using polymorphic expressed sequence tag simple sequence repeat (EST-SSR) markers. A potential pool of 3127 non-redundant EST-SSR markers were identified for C. macrophyllum in this study. The developed EST-SSR markers had high amplification rates and cross-species transferability in Chrysosplenium. Our results also showed that the natural populations of C. macrophyllum had a high level of genetic diversity. Genetic distance, principal component analysis, and popular structure analysis revealed that all 60 samples clustered into two major groups that were consistent with their geographical origins. This study provided a batch of highly polymorphic EST-SSR molecular markers that were developed via transcriptome sequencing. These markers will be of great significance for the study of the genetic diversity and evolutionary history of C. macrophyllum and other Chrysosplenium species.

Genome-wide analysis of R2R3-MYB transcription factors reveals their differential responses to drought stress and ABA treatment in desert poplar (Populus euphratica).

The R2R3-MYB transcription factors are widely involved in the regulation of plant growth, biotic and abiotic stress responses. Meanwhile, seed germination, which is stimulated by internal and external environments, is a critical stage in the plant life cycle. However, the identification, characterization, and expression profiling of the Populus euphratica R2R3-MYB family in drought response during seed germination have been unknown. Our study attempted to identify and characterize the R2R3-MYB genes in P. euphratica (PeR2R3-MYBs) and explore how R2R3-MYBs trigger the drought and abscisic acid (ABA) response mechanism in its seedlings. Based on the analysis of comparative genomics, 174 PeR2R3-MYBs were identified and expanded driven by whole genome duplication or segment duplication events. The analysis of Ka/Ks ratios showed that, in contrast to most PeR2R3-MYBs, the other PeR2R3-MYBs were subjected to positive selection in P. euphratica. Further, the expression data of PeR2R3-MYBs under drought stress and ABA treatment, together with available functional data for Arabidopsis thaliana MYB genes, supported the hypothesis that PeR2R3-MYBs involved in response to drought are dependent or independent on ABA signaling pathway during seed germination, especially PeR2R3-MYBs with MYB binding sites (MBS) cis-element and/or tandem duplication. This study is the first report on the genome-wide analysis of PeR2R3-MYBs, as well as the other two Salicaceae species. The duplication events and differential expressions of PeR2R3-MYBs play important roles in enhancing the adaptation to drought desert environment. Our results provide a reference for prospective functional studies of R2R3-MYBs of poplars and lay the foundation for new breeding strategies to improve the drought tolerance of P. euphratica.

Regulatory effects mediated by ulvan oligosaccharide and its zinc complex on lipid metabolism in high-fat diet-fed mice.

Obesity-induced lipid metabolism disorders are risk factors for hyperlipidemia, atherosclerosis, and non-alcoholic fatty liver disease. Seaweed oligosaccharides and Zn supplements are potential alternatives to alleviate obesity. Herein, ulvan oligosaccharide (UO) was used as a ligand to prepare a novel Zn supplement (UO-Zn). Subsequently, we explored potential mechanisms underlying UO- and UO-Zn-mediated improvements in lipid metabolism in mice fed a high-fat diet. We found that UO enhanced the abundance of key species (Blautia and Turicibacter) and functions (glycolytic, pentose phosphate, and histidine/lysine biosynthesis pathways) in the gut microbiota, thereby increasing the production of short-chain fatty acids and activating AMPK. Accordingly, UO treatment regulated the transcription of lipid metabolism genes, including ACOX1, ACC, and FASN, thereby reducing blood lipid levels and hepatic lipid accumulation. Zn could act synergistically with UO, enhancing the reversal of cholesterol transport and fatty acid ß-oxidation via the MTF1/PPARα pathway, markedly reducing body and adipose tissue weights.

Prospects of Probiotic Adjuvant Drugs in Clinical Treatment.

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.

Biocontrol mechanism of Myxococcus xanthus B25-I-1 against Phytophthora infestans.

Phytophthora infestans is the pathogen causing potato late blight, one of the most serious diseases of potato. Myxobacteria have become a valuable biological control resource due to their preponderant abilities to produce various secondary metabolites with novel structure and remarkable biological activity. In this study, Myxococcus xanthus strain B25-I-1, which exhibited strong antagonistic activity against P. infestans, was isolated from soil sample and identified by 16S rRNA sequence analysis. The strain exhibited antagonistic activity against several species of fungus and bacteria. Analysis of the biocontrol mechanism showed that the active extract produced by strain B25-I-1 had strong inhibitory effects on mycelium and the asexual and sexual reproductive structures of P. infestans. Furthermore, these active extract decreased the content of soluble proteins and activity of the protective enzymes (PPO, POD, PAL, and SOD), increased the oxidative damage and the permeability of the cell membrane in P. infestans. All of these mechanisms might be the biocontrol mechanism of B25-I-1 against P. infestans. The active extract of strain B25-I-1 was separated by TLC and HPLC, and the components with antibiotic activity were detected by HPLC-MS. It was found that the antagonistic components of B25-I-1 contained methyl (2R)-2-azido-3-hydroxyl-2-methylpropanoate and N-(3-Amino-2-hydroxypropyl)-N-methylsulfuric diamide. The active extract significantly inhibited the infection on detached potato leaves by P. infestans, and these substances did not cause damage to the potato leaves. In conclusion, M. xanthus B25-I-1 produced active extract against P. infestans and might potentially be a candidate to develop into biological pesticides for the control of potato late blight. This study adds to the literature on the isolation and identification of active extracts from myxobacteria, and B25-I-1 in particular, for cures or treatments to potato late blight.

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 µM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.

Transcriptome analyses reveals the dynamic nature of oil accumulation during seed development of Plukenetia volubilis L.

Sacha inchi (Plukenetia volubilis L.) is a shrub native to Amazon rainforests that's of commercial interest as its seeds contain 35-60% edible oil (dry weight). This oil is one of the healthiest vegetable oils due to its high polyunsaturated fatty acid content and favourable ratio of omega-6 to omega-3 fatty acids. De novo transcriptome assembly and comparative analyses were performed on sacha inchi seeds from five stages of seed development in order to identifying genes associated with oil accumulation and fatty acid production. Of 30,189 unigenes that could be annotated in public databases, 20,446 were differentially expressed unigenes. A total of 14 KEGG pathways related to lipid metabolism were found, and 86 unigenes encoding enzymes involved in α-linolenic acid (ALA) biosynthesis were obtained including five unigenes encoding FATA (Unigene0008403), SAD (Unigene0012943), DHLAT (Unigene0014324), α-CT (Unigene0022151) and KAS II (Unigene0024371) that were significantly up-regulated in the final stage of seed development. A total of 66 unigenes encoding key enzymes involved in the synthesis of triacylglycerols (TAGs) were found, along with seven unigenes encoding PDCT (Unigene0000909), LPCAT (Unigene0007846), Oleosin3 (Unigene0010027), PDAT1 (Unigene0016056), GPDH (Unigene0022660), FAD2 (Unigene0037808) and FAD3 (Unigene0044238); these also proved to be up-regulated in the final stage of seed development.

Iron-induced chelation alleviates the potential allergenicity of ovotransferrin in a BALB/c mouse model.

Ovotransferrin (OVT) is one of the main egg allergens with 2 iron-binding sites. Several studies have demonstrated that iron-chelation decreased the allergenicity of milk allergen and birch pollen allergens. Therefore, we hypothesized that iron-chelation could also reduce the allergenicity of OVT. Apo-OVT (iron-free OVT, the natural state in egg white) and Holo-OVT (iron-chelated OVT) were prepared, and the allergenicity of them were assessed and compared using a BALB/c mouse model as well as dendritic cells (DCs) based on antigen uptake. Mice were orally sensitized with Apo-OVT or Holo-OVT using cholera toxin as adjuvant. Clinical signs of allergy, morphological structure of jejunum, specific antibody levels, mast cell protease-1 (mMCP-1) concentrations, cytokines and antigen uptake by DCs were determined after the mice were challenged with Apo-OVT or Holo-OVT. Results showed that both Apo-OVT and Holo-OVT induced intestinal allergy, but no systematic allergic symbols were observed. Serum levels of mouse mast cell protease-1 (mMCP-1) and specific IgE in Apo-OVT group were lower than in control group, and no significant difference between Apo-OVT group and Holo-OVT group (P>.05). The levels of OVT-specific IgG and IgG1, as well as the Th-1 cytokine interferon gamma and Th2-type cytokine interleukin-13 in Holo-OVT sensitized mice were significantly decreased compared to Apo-OVT group (P<.05), while no significant difference with control group (P>.05). However, DCs took in less Apo-OVT than Holo-OVT. Overall, iron-induced chelation could alleviate the potential allergenicity of OVT in vivo.

[Evaluation of Amberlite XAD-1600 resin-based purification of the bioactive components from Radix Paeoniae Alba and Rhizoma Curcumae Longae extracts by pharmacodynamic and toxicological models].

OBJECTIVE: To evaluate the pharmacodynamics and toxicicity of the major bioactive components extracted and purified from Radix Paeoniae Alba and Rhizoma Curcumae Longae using Amberlite XAD-1600 resin. METHODS: Amberlite XAD-1600 was used to purify the bioactive components from the crude 75% ethanol extracts of the two herbs. The pharmacodynamic and toxic effects of the crude extracts and extract purified using XAD-1600 resin were comparatively examined with two acute inflammatory models, two pain models and acute toxicity test in vivo. RESULTS: The anti-inflammatory and analgesic effects of the purified extract were significant stronger with lower toxicity than those of the crude ethanol extract. CONCLUSION: Amberlite XAD-1600 resin allows efficient extraction and purification of the bioactive components from the two herbs.

Identification of inhibitors of the HIV-1 gp41 six-helix bundle formation from extracts of Chinese medicinal herbs Prunella vulgaris and Rhizoma cibotte.

An increasing portion of patients with HIV infection and/or AIDS cannot use currently FDA-approved anti-HIV drugs, including the reverse transcriptase and protease inhibitors, due to the adverse effects and the emergence of drug resistance. Thus, it is essential to develop new anti-HIV agents with a target different from the HIV reverse transcriptase and protease. Using a conformation-specific monoclonal antibody NC-1, we previously established a high throughput screening assay for identification of small molecular organic compounds that disrupt the HIV-1 gp41 six-helix bundle formation, a critical step of membrane fusion between the HIV and the target cell. In the present study, we used this assay to screen for inhibitors of the gp41 six-helix bundle formation from aqueous extracts of nine Chinese medicinal herbs with antiviral activity. We found that the extracts of two herbs, Prunella vulgaris and Rhizoma cibotte, showed potent inhibitory activity. The inhibitory activity of these two herb extracts significantly decreased after they were passed through polyamide resin mini-columns, which are able to bind polyphenols including tannin, an HIV-1 inhibitor with multiple mechanisms of action. The bound polyphenols were eluted from the polyamide columns and also showed potent inhibitory activity on the gp41 six-helix bundle formation. Tannin purchased from different commercial sources inhibited the gp41 six-helix bundle formation in a manner similar to the polyphenols isolated from the herb extracts. These results suggest that tannin may be one of major inhibitors of the HIV-1 gp41 six-helix bundle formation in the herb extracts and that tannin may inhibit HIV-1 entry by disrupting the gp41 six-helix bundle formation.