An innovative way to treat cash crop wastes: The fermentation characteristics and functional microbial community using different substrates to produce Agricultural Jiaosu.

With the increase of global demand for cash crops, a large of cash crop waste was produced and caused severe environmental issues. To produce Agricultural Jiaosu (AJ) using these wastes is a sustainable waste disposal method. However, the fermentation mechanism, metabolites, and microbial characteristics of AJ fermented with different substrates remain unclear. In this study, the effects of different substrates (fruit and vegetable waste and Chinese herbal medicine waste) on the fermentation characteristics of AJ, including metabolites and microbial community properties, were investigated. The results revealed that AJ fermentation was a process of converting organic matter into organic acids and other metabolites, mainly including hydrolysis, acidogenesis, and maturation stages. At the genus level, Lactobacillus, Acetobacter, Hydrogenibacillus, Halomonas, and Prevotella_1 were the dominant bacteria in the fermentation system. The bacterial diversity of composite substrate AJ was higher than that of single substrate AJ. The organic acids and secondary metabolites concentration and the composition of key microorganisms depended on the substrate type. Furthermore, AJ's potential functional genes were mainly concentrated in cofactors and vitamin, carbohydrate, and amino acid metabolism. The findings of this study indicated that AJ is an innovative eco-friendly technology that can convert cash crop wastes into sustainable eco-products, and that its characteristics depend on the substrate type. Therefore, the substrate used to produce AJ should be carefully selected according to the application field.

Agricultural Jiaosu: An Eco-Friendly and Cost-Effective Control Strategy for Suppressing Fusarium Root Rot Disease in Astragalus membranaceus.

Root rot caused by the pathogenic fungi of the Fusarium genus poses a great threat to the yield and quality of medicinal plants. The application of Agricultural Jiaosu (AJ), which contains beneficial microbes and metabolites, represents a promising disease control strategy. However, the action-effect of AJ on Fusarium root rot disease remains unclear. In the present study, we evaluated the characteristics and antifungal activity of AJ fermented using waste leaves and stems of medicinal plants, and elucidated the mechanisms of AJ action by quantitative real-time PCR and redundancy analysis. The effects of AJ and antagonistic microbes isolated from it on disease suppression were further validated through a pot experiment. Our results indicate that the AJ was rich in beneficial microorganisms (Bacillus, Pseudomonas, and Lactobacillus), organic acids (acetic, formic, and butyric acids) and volatile organic compounds (alcohols and esters). It could effectively inhibit Fusarium oxysporum and the half-maximal inhibitory concentration (IC50) was 13.64%. The antifungal contribution rate of the microbial components of AJ reached 46.48%. Notably, the redundancy analysis revealed that the Bacillus and Pseudomonas genera occupied the main niche during the whole inhibition process. Moreover, the abundance of the Bacillus, Pseudomonas, and Lactobacillus genera were positively correlated with the pH-value, lactic, formic and butyric acids. The results showed that the combined effects of beneficial microbes and organic acid metabolites increased the efficacy of the AJ antifungal activity. The isolation and identification of AJ's antagonistic microbes detected 47 isolates that exhibited antagonistic activities against F. oxysporum in vitro. In particular, Bacillus subtilis and Bacillus velezensis presented the strongest antifungal activity. In the pot experiment, the application of AJ and these two Bacillus species significantly reduced the disease incidence of Fusarium root rot and promoted the growth of Astragalus. The present study provides a cost-effective method to control of Fusarium root rot disease, and establishes a whole-plant recycling pattern to promote the sustainable development of medicinal plant cultivation.

JQ1-Loaded Polydopamine Nanoplatform Inhibits c-MYC/Programmed Cell Death Ligand 1 to Enhance Photothermal Therapy for Triple-Negative Breast Cancer.

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy; however, the response of triple-negative breast cancer (TNBC) to PD-L1 antibodies is limited. To address this challenge, we use the bromodomain and extra-terminal inhibitor JQ1 to down-regulate the expression of PD-L1 and thus elicit the immune response to TNBC instead of using antibodies to block PD-L1. JQ1 also inhibits the growth of TNBC as a targeted therapeutic agent by inhibiting the BRD4-c-MYC axis. The polydopamine nanoparticles (PDMNs) are introduced as a biodegradable and adaptable platform to load JQ1 and induce photothermal therapy (PTT) as another synergistic therapeutic modality. Because the JQ1-loaded PDMNs (PDMN-JQ1) are self-degradable and release JQ1 continuously, this synergistic treatment can lead to remarkable activation of cytotoxic T lymphocytes and induce a strong immune-memory effect to protect mice from tumor re-challenge. Taken together, our study demonstrates a compact and simple nanoplatform for triple therapy, including targeted therapy, PTT, and immunotherapy, for TNBC treatment.

Enhancing naked oat (Avena nuda L.) productivity with minimal indirect nitrogen loss and maximum nitrogen use efficiency through integrated use of different nitrogen sources.

Oat (Avena nuda L.) is a nutritious grain crop, rich in dietary fibers and phytochemicals. Application of efficient nitrogen (N) sources and dose is very important to obtain higher crop productivity and to achieve environmental sustainability. The exploitation of natural beneficial microbes and organic nitrogen in combination with chemical nitrogen would be effective to boost soil N for plant uptake. Hence, a field experiment was conducted during 2016 and 2017 with the aim to ameliorate the use of chemical N (CN) with organic nitrogen (ON) and microbial fertilizer (MBF) without compromising the productivity of oat. T1 = control, T2 = 100% CN, T3 = 100% CN+MBF, T4 = 75% CN+ 25% ON+MBF, T5 = 50% CN+ 50% ON+MBF, T6 = 100% ON+MBF, T7 = 100% ON were the treatments. 50% CN + 50% ON + MBF treatment proved to be an efficient combination regarding enhanced biomass and grain yield, nitrogen uptake and NUE as compared to rest of the treatments in both years. During the critical stages of the crop, when most of the applied CN was leached from the top 20 cm soil depth, a substantial N came from the PM mineralization through enhanced microbial activity by the addition of MBF. Lastly, the application of ON supplemented with MBF improved the rhizosphere soil properties, i.e. mineral N concentration, total N (TN), soil organic carbon (SOC), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), soil respiration rate and enzymatic activity. A balanced and source conscious application of CN, ON and MBF reduced N losses and added a substantial amount of N into the soil N pool. We concluded that organic N combined with chemical N and MBF proved to be effective in improving soil properties ensuring less N loss and increasing oat production in the semi-arid region.

Effects of molybdenum, selenium and manganese supplementation on the performance of anaerobic digestion and the characteristics of bacterial community in acidogenic stage.

The addition of trace elements to aid anaerobic digestion has already been widely studied. However, the effects of rare trace elements on anaerobic digestion remain unclear. In this study, the effects of Mo, Se and Mn on anaerobic digestion of rice straw were explored. The results showed the methane yield increased by 59.3%, 47.1% and 48.9% in the first 10 days following addition of Mo (0.01 mg/L), Se (0.1 mg/L) and Mn (1.0 mg/L), respectively. Toxic effects and the accumulation of volatile fatty acids (VFAs) were observed when the Se, Mo and Mn concentrations were greater than 100, 1000 and 1000 mg/L, respectively. The half-maximal inhibitory concentrations (IC50) for Se, Mn and Mo were 79.9 mg/L, 773.9 mg/L and 792.3 mg/L, respectively. The addition of trace elements has changed the bacterial structure of the bacteria, which in turn has affected the digestion performance.

Anti-EGFR Peptide-Conjugated Triangular Gold Nanoplates for Computed Tomography/Photoacoustic Imaging-Guided Photothermal Therapy of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is difficult to cure because of the high recurrence rate and the side effects of current treatments. It is urgent to develop a new treatment that is safer and more effective than current treatments against NSCLC. Herein, we constructed anti-epidermal growth factor receptor (EGFR) peptide-conjugated PEGylated triangular gold nanoplates (TGN-PEG-P75) as a targeting photothermal therapy (PTT) agent to treat NSCLC under the guidance of computed tomography (CT) and photoacoustic (PA) imaging. The surface of TGNs is successfully conjugated with a novel peptide P75 that has the specific affinity to epidermal growth factor receptor (EGFR). It is found that the EGFR is overexpressed in NSCLC cells. The TGN-PEG-P75 has uniform edge length (77.9 ± 7.0 nm) and neutrally charged surface. The cell uptake experiments demonstrate remarkable affinity of the TGN-PEG-P75 to high EGFR expression cells than low EGFR expression cells (5.1-fold). Thanks to the strong near-infrared absorbance, high photothermal conversion efficiency, and the increased accumulation in tumor cells via the interaction of P75 and EGFR, TGN-PEG-P75 exhibits 3.8-fold superior therapeutic efficacy on HCC827 cells than TGN-PEG. The in vivo CT/PA dual-modal imaging of the TGN-PEG-P75 is helpful in selecting the optimal treatment time and providing real-time visual guidance of PTT. Furthermore, treatments on HCC827 tumor-bearing mouse model demonstrate that the growth of NSCLC cells can be effectively inhibited by the TGN-PEG-P75 through PTT, indicating the great promise of the nanoplatform for treating NSCLC in vivo.

Optimization of Fe2+ supplement in anaerobic digestion accounting for the Fe-bioavailability.

Fe is widely used as an additive in anaerobic digestion, but its bioavailability and the mechanism by which it enhances digestion are unclear. In this study, sequential extraction was used to measure Fe bioavailability, while biochemical parameters, kinetics model and Q-PCR (fluorescence quantitative PCR) were used to explore its mechanism of stimulation. The results showed that sequential extraction is a suitable method to assess the anaerobic system bioavailability of Fe, which is low and fluctuates to a limited extent (1.7 to -3.1wt%), indicating that it would be easy for Fe levels to be insufficient. Methane yield increased when the added Fe2+ was 10-500mg/L. Appropriate amounts of Fe2+ accelerated the decomposition of rice straw and facilitated methanogen metabolism, thereby improving reactor performance. The modified Gompertz model better fitted the results than the first-order kinetic model. Feasibility analysis showed that addition of Fe2+ at ≤50mg/L was suitable.

Development and assessment of a complete-detoxication strategy for Fuzi (lateral root of Aconitum carmichaeli) and its application in rheumatoid arthritis therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi (lateral root of Aconitum carmichaeli) is a popular traditional Chinese medicine well known for its both therapeutic and high-toxic activities. Its toxic alkaloid ingredients, mainly aconitine, mesaconitine, and hypaconitine, are responsible for the high toxicity. However, to date, no detoxication strategy is available to completely eliminate Fuzi's toxicity, and, whether Fuzi's efficacy could be kept after detoxication, remain unknown and debatable. MATERIALS AND METHODS: The purpose of this study was to establish and validate a complete-detoxication strategy for Fuzi via acute toxicity test, to clarify the detoxication mechanism by HPLC and titrimetric analyses, and to evaluate the therapeutic effect of detoxicated Fuzi on adjuvant arthritis (AA). Three processed Fuzi (Bai-fu-pian) with 30-min, 60-min, and 120-min decoctions, respectively, named dBfp-30, dBfp-60, and dBfp-120, were prepared for this study. For the acute toxicity test, their oral doses to male and female Kunming mice were up to 70-190g/kg body weight, and their toxicological profiles were evaluated by median lethal dose (LD50), maximal tolerance dose (MTD), minimal lethal dose (MLD), no-observed-adverse-effect-level (NOAEL), and time-concentration-mortality (TCM) modeling methods using a 14-day schedule with up to five doses. The HPLC analysis was performed to determine the detoxication-induced changes in composition and amount of aconitine, mesaconitine and hypaconitine in Fuzi, whilst the titrimetric method was adopted to estimate the amount changes of Fuzi's total alkaloids. AA model was established by incomplete Freund's adjuvant injection in Wistar rats, and the animal's physiological (body weight, food intake, etc.), clinical (hind paw volume), and immunological (IL-1 and TNF-α) parameters were assessed as markers of inflammation and arthritis. RESULTS: With increasing decoction time, the acute toxicity of detoxicated Fuzi became decreased in the following order: dBfp-30 (LD50 of 145.1g/kg; MTD of 70g/kg; MLD of 100g/kg; NOAEL of 70g/kg) >dBfp-60 (too large LD50; MTD of 160g/kg; MLD of 190g/kg; NOAEL of 100g/kg) >dBfp-120 (no LD50; unlimited MTD; unlimited MLD; NOAEL of 130g/kg). dBfp-30 and dBfp-60 displayed the toxicity at a dose-dependent manner with maximum mortalities reaching 100% and 50% respectively, whereas no mortality or signs of intoxication was induced by dBfp-120. The chemical analyses revealed a dramatic reduction of the toxic alkaloids as well as total alkaloids in Fuzi after the detoxication, from which no level of aconitine and only minimum residual of mesaconitine (0.56±0.02µg/g) and hypaconitine (8.73±0.13µg/g) were detected in dBfp-120. However, no significant difference of total alkaloid amount was found among dBfp-30, dBfp-60, and dBfp-120 (P>0.05), suggesting an equivalent conversion from toxic alkaloids to its non-toxic derivants in dBfp-120. Further, also no significant differences were seen among dBfp-30, dBfp-60, and dBfp-120 for the therapeutic effects on physiological, clinical, and immunological parameters in AA rat, indicating that dBfp-120 is of non-toxicity and efficacy. CONCLUSIONS: A complete-detoxication strategy has been developed successfully for ensuring the safe and effective use of Fuzi. The detoxication mechanism associated with elimination of toxic alkaloids has kept Fuzi's efficacy, indicating a non-interdependent relationship between its efficacy and toxicity. This is the first report on such an optimal detoxication strategy and on the application of detoxicated Fuzi in AA. It may provide in depth understanding to the toxicological and pharmacological profiles of Fuzi and further benefit the herbal drug development with safety and efficacy for disease especially RA therapy.