Water and Nitrogen Management at the Booting Stage Affects Yield, Grain Quality, Nutrient Uptake, and Use Efficiency of Fragrant Rice Under the Agro-Climatic Conditions of South China.

The present study was conducted to assess the effects of water and nitrogen applications at the booting stage on yield, grain quality, and nutrient use efficiencies in fragrant rice in the early (March-July) and late (July-November) seasons of 2013. The experiment was comprised of two fragrant rice cultivars, i.e., Nongxiang 18 and Basmati; three nitrogen levels, i.e., 0 kg N ha-1 (N0), 30 kg N ha-1 (N1), and 60 kg N ha-1 (N2); and three water levels, i.e., 2-4 cm water layer well-watered (W0), water with a soil water potential of -15 ± 5 kPa (W1), and water with a soil water potential of -25 ± 5 kPa (W2), which were randomized in a split-split plot design. Results showed that Basmati produced a higher grain yield than Nongxiang 18 (16.20 and 9.61% in the early and late season, respectively), whereas the W1 exhibited the maximum grain yield and harvest index. The moderate application of nitrogen (N1) at the booting stage resulted in higher grain yield, nevertheless, cultivar, water, and nitrogen revealed different trends for some of the grain quality attributes, i.e., brown rice rate, milled rice rate, head milled rice rate, protein content, and amylose content as well as nutrient uptake and use efficiencies in the double rice production system. Basmati had a higher nitrogen harvest index (NHI; 18.28-20.23%) and P harvest index (PHI; 3.95-12.42%) but lower physiological P use efficiency for biomass (PPUEB; 7.66-23.66%) and physiological K use efficiency for biomass (PKUEB; 2.53-7.10%) than Nongxiang 18 in both seasons. Furthermore, the grain number per panicle, biomass yield, grain P uptake, and the whole plant P uptake were significantly related to the grain yield of fragrant rice. In both seasons, the interaction of water and nitrogen (W × N) had a significant effect on panicle number, grain quality attributes, and N, P uptake of straw, as well as the physiological N, P use efficiency for grain and the physiological N, K use efficiency for biomass. Overall, results suggest that moderate nitrogen and irrigation input at the booting stage could be feasible to improve the productivity and quality of the double rice production system with improved nutrient use efficiency under the agro-climatic conditions of South China.

HDL Structure.

HDL has various protein components, including enzymes, complement components, apolipoproteins, protease inhibitors, etc. In addition to proteins, lipids are also a significant component of HDL. These components and their structure determine the function of HDL. HDL is heavily involved in the acute response phase, complement regulation phase, hemostasis phase, immune response phase, and protease inhibition phase. Among the apolipoproteins, the predominant component is Apo A-I, which confers various atherogenic activities to HDL. Apo A-II, Apo-C, Apo-D, Apo-F, Apo-H, Apo-J, and Apo-O, which can bind free fatty acids, regulate the activity of many proteins involved in HDL metabolism, inhibit lipid transfer, and control the endogenous coagulation cascade. A major functional component is the enzyme LCAT, which helps catalyze the conversion of cholesterol to plasma-based lipoproteins and then to cholesteryl esters. Another enzyme associated with HDL is human paraoxonase, calcium-, PON1-, PON2-, and PON3-dependent lactone enzyme with catalytic activity, including reversible binding to substrates. PAF-AH is a phospholipase with lipoprotein properties, and HDL and LDL particles are commonly bound to plasma PAF-AH for circulation. As for lipid components, PC is an essential phospholipid subclass and may be a biomarker for constitutive inflammation. Sphingolipids, such as sphingomyelin and ceramide, also play an indispensable role in HDL function. In different physiological and pathological stages and plasma environments, HDL can exhibit different structural features, such as discoid HDL and spherical rHDL.

HDL and Cholesterol Ester Transfer Protein (CETP).

Cholesterol ester transfer protein (CETP) is important clinically and is one of the major targets in cardiovascular disease studies. With high conformational flexibility, its tunnel structure allows unforced movement of high-density lipoproteins (HDLs), VLDLs, and LDLs. Research in reverse cholesterol transports (RCT) reveals that the regulation of CETP activity can change the concentration of cholesteryl esters (CE) in HDLs, VLDLs, and LDLs. These molecular insights demonstrate the mechanisms of CETP activities and manifest the correlation between CETP and HDL. However, animal and cell experiments focused on CETP give controversial results. Inhibiting CETP is found to be beneficial to anti-atherosclerosis in terms of increasing plasma HDL-C, while it is also claimed that CETP weakens atherosclerosis formation by promoting RCT. Currently, the CETP-related drugs are still immature. Research on CETP inhibitors is targeted at improving efficacy and minimizing adverse reactions. As for CETP agonists, research has proved that they also can be used to resist atherosclerosis.

Atmospheric particulate matter aggravates cns demyelination through involvement of TLR-4/NF-kB signaling and microglial activation.

Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-kB signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders.

Role of Plant-Derived Natural Compounds in Experimental Autoimmune Encephalomyelitis: A Review of the Treatment Potential and Development Strategy.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is mainly mediated by pathological T-cells. Experimental autoimmune encephalomyelitis (EAE) is a well-known animal model of MS that is used to study the underlying mechanism and offers a theoretical basis for developing a novel therapy for MS. Good therapeutic effects have been observed after the administration of natural compounds and their derivatives as treatments for EAE. However, there has been a severe lag in the research and development of drug mechanisms related to MS. This review examines natural products that have the potential to effectively treat MS. The relevant data were consulted in order to elucidate the regulated mechanisms acting upon EAE by the flavonoids, glycosides, and triterpenoids derived from natural products. In addition, novel technologies such as network pharmacology, molecular docking, and high-throughput screening have been gradually applied in natural product development. The information provided herein can help improve targeting and timeliness for determining the specific mechanisms involved in natural medicine treatment and lay a foundation for further study.

Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor.

BACKGROUND: Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. METHODS: Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. FINDINGS: Oral URA (25 mg/kg/d) suppressed disease progression at prevention, induction, and effector phases of preclinical EAE. Histological evaluation showed that significantly fewer inflammatory cells, decreased demyelination, lower numbers of M1-type microglia and activated DCs, as well as reduced infiltrating Th1/Th17 cells were present in the central nervous system (CNS) of the URA-treated group. URA treatment at 25 µM inhibited the activation of BM-DCs in vitro, restrained Th17 cell differentiation in T cell polarization conditions, and in a DC-CD4+ T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. INTERPRETATION: Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.

Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.

Molecular engineering of L-aspartate-α-decarboxylase for improved activity and catalytic stability.

ß-Alanine is an important precursor for the production of food additives, pharmaceuticals, and nitrogen-containing chemicals. Compared with the conventional chemical routes for ß-alanine production, the biocatalytic routes using L-aspartate-α-decarboxylase (ADC) are more attractive when energy and environment are concerned. However, ADC's poorly understood properties and its inherent mechanism-based inactivation significantly limited the application of this enzyme. In this study, three genes encoding the ADC enzymes from Escherichia coli, Corynebacterium glutamicum, and Bacillus subtilis were overexpressed in E. coli. Their properties including specific activity, thermostability, and mechanism-based inactivation were characterized. The ADC enzyme from B. subtilis, which had higher specific activity and thermostability than the others, was selected for further study. In order to improve its activity and relieve its mechanism-based inactivation by molecular engineering so as to improve its catalytic stability, a high-throughput fluorometric assay of ß-alanine was developed. From a library of 4000 mutated enzymes, two variants with 18-22% higher specific activity and 29-64% higher catalytic stability were obtained. The best variant showed 50% higher ß-alanine production than the wild type after 8 h of conversion of L-aspartate, showing great potential for industrial biocatalytic production of ß-alanine.

[Characterization of L-aspartate-α-decarboxylase from Bacillus subtilis].

As an important material in pharmaceutical and chemical industry, ß-alanine was mainly produced by chemical methods. L-aspartate-α-decarboxylase could catalyze the α-decarboxylation from L-aspartate to ß-alanine. Determinations for specific activities of PanDs from Escherichia coli, Corynebacterium glutamicum and Bacillus subtilis were performed in this study (0.98 U/mg, 7.52 U/mg and 8.4 U/mg respectively). The optimal temperature and pH of PanDs from C. glutamicum and B. subtilis were 65 degrees C, pH 6.5 and 60 degrees C, pH 6.5 respectively. According to our research, PanD from B. subtilis could be more appropriate for industrial application because of the higher activity and thermostability when compared to PanDs from E. coli and C. glutamicum which had been the most studied. We also analyzed and discussed the special post-translation self-cleavage phenomenon and the mechanism based inactivation.