GOSpel for tiny allies.

Infant formulas are often supplemented to foster the development of a healthy gut microbiota. In this issue of Cell Host & Microbe, Heppner et al. present an elaborate clinical trial examining the impact of formula supplementation on the development and circadian rhythmicity of the microbiota during the first year of life.

Lignite-steel slag constructed wetland with multi-functionality and effluent reuse.

Constructed wetlands (CWs) are widely used to treat wastewater, while innovative studies are needed to support resource conservation, enhance multi-functionality, and improve the effectiveness of effluent usage. This study assessed the potential of CW's multiple functions by combining low-rank coal (lignite) and industrial waste (steel slag) in different configurations as CW substrates. The results of scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and metagenomic sequencing showed that the experimental treatment with lignite and steel slag mixtures had the highest multi-functionality, including efficient nutrient removal and carbon sequestration, as well as hydroponic crop production. Lignite and steel slag were mixed to form lignite-steel slag particle clusters, where Ca2+ dissolved on the surface of steel slag was combined with PO43- in wastewater to form Ca3(PO4)2 precipitation for phosphorus removal. A biofilm grew on the surface of lignite in this cluster, and OH- released from steel slag promoted lignite to release fulvic acid, which provided a carbon source for heterotrophic microorganisms and promoted denitrification. Moreover, fulvic acid enhanced carbon sequestration in CWs by increasing the biomass of Phragmites australis. The effluent from lignite-steel slag CW increased cherry tomato yield and quality while saving N and P applications. These results provide new ideas for the "green" and economic development of CW technology.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Potential in paleoclimate reconstruction of modern pollen assemblages from natural and human-induced vegetation along the Heilongjiang River basin, NE China.

The relationships among modern pollen, vegetation, climate and human activities can help improving the reliability of reconstruction of past vegetation, regional climate and human activities based on fossil pollen records. We used a dataset of 114 surface soil pollen samples from natural vegetation (wetlands, forests and grasslands) and human-induced vegetation (farmlands and residences) along the Heilongjiang River basin in northeast China to explore the relationships among modern pollen, vegetation, climate and human activities. The results indicated that surface pollen assemblages differentiated modern vegetation well in natural and human-induced vegetation types. The wetlands were mainly composed of Cyperaceae, along with Artemisia, weeds Poaceae (<35 µm) and Sanguisorba. The forests were predominated by Pinus and Betula. Artemisia, weeds Poaceae (<35 µm) and Chenopodiaceae were the most important pollen taxa in grasslands. The farmlands were characterized by Artemisia, Aster, Chenopodiaceae, cereal Poaceae (>35 µm) and Taraxacum. The pollen assemblages of residences were composed of weeds Poaceae (<35 µm), Chenopodiaceae and Salix. Ordination analyses based on main pollen taxa and climatic variables were used to determine the relationships between pollen and climate, suggesting the surface pollen assemblages were primarily influenced by the mean annual temperature (Tann) in northeast China. The statistical performance of transfer function between pollen and Tann were well indicating the modern pollen assemblages could be reliably used in paleoclimate reconstruction in our study area. Furthermore, human-induced vegetation had high frequencies of human-companion pollen taxa, such as Chenopodiaceae, Aster, Taraxacum and cereal Poaceae (>35 µm). Pollen concentrations of human-induced vegetation were lower than natural vegetation types, which could be used as an indicator of human influence intensity.

Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation.

The resistances of matrix protein 2 (M2) protein inhibitors and neuraminidase inhibitors for influenza virus have attracted much attention and there is an urgent need for new drug. The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient. Therefore, there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase. Three natural compounds were found by using molecular docking-based virtual screening, which could bind tightly within the polymerase acidic protein-polymerase basic protein 1 (PA-PB1) subunit of influenza virus polymerase. Firstly, their drug likeness properties were evaluated, which showed that the hepatotoxicity values of all the three compounds indicating they had less or no hepatotoxicity, and did not have the plasma protein biding (PPB) ability, the three compounds needed to be modified in some aspects, like bulky molecular size. The stability of the complexes of PA-hits was validated through molecular dynamics (MD) simulation, revealing compound 2 could form more stable complex with PA subunit. The torsional conformations of each rotatable bond of the ligands in PA subunit were also monitored, to investigate variation in the ligand properties during the simulation, compound 3 had fewer rotatable bonds, indicating that the molecule had stronger rigidity. The bar charts of protein-ligand contacts and contacts over the course of trajectory showed that four key residues (Glu623, Lys643, Asn703 and Trp706) of PA subunit that participated in hydrogen-bond, water bridge and hydrophobic interactions with the hit compounds. Finally, the binding free energy and contributed energies were calculated by using MM-GBSA method. Out of the three compounds, compound 1 showed the lowest total binding free energy. Among all the interactions, the contribution of the covalent binding and the van der Waals energy were more than other items, compound 1 formed more stable hydrogen bonds with the residues of PA subunit binding pocket. This study smoothed the path for the development of novel lead compounds with improved binding properties, high drug likeness, and low toxicity to humans for the treatment of influenza, which provided a good basis for further research on novel and effective influenza virus PA-PB1 interaction inhibitors.

Sheng-Di-Da-Huang Decoction Inhibited Inflammation Expressed in Microglia after Intracerebral Hemorrhage in Rats.

OBJECTS: Sheng-Di-Da-Huang Decoction was used as an effective hemostatic agent in ancient China. However, its therapeutic mechanism is still not clear. Inflammatory injury plays a critical role in ICH-induced secondary brain injury. After hemolysis, hematoma components are released, inducing microglial activation via TLR4, which initiates the activation of transcription factors (such as NF-κB) to regulate expression of proinflammatory cytokine genes. This study aimed to verify the anti-inflammatory effects of Sheng-Di-Da-Huang Decoction on ICH rats. MATERIALS AND METHODS: Intracerebral hemorrhage was induced by injection of bacterial collagenase (0.2 U) in rats. Neurological deficits, brain water content, Evans blue extravasation, expression of TLR4, NF-κB, Iba-1 positive cells (activated microglia), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were examined 1, 3, 7, and 14 days after collagenase injection. MR images were also studied. RESULTS: Sheng-Di-Da-Huang Decoction remarkably improved neurological function, reduced brain water content as well as Evans blue extravasation, downregulated expression of TLR4, NF-κB, TNF-α, and IL-1ß, and inhibited microglial activation. CONCLUSIONS: Sheng-Di-Da-Huang Decoction reduced inflammation reaction after ICH through inhibited inflammation expressed in microglia.

Thin ferrihydrite sediment capping sequestrates phosphorus experiencing redox conditions in a shallow temperate lacustrine wetland.

Synthesized ferrihydrite (Fh) with the dosages of 0.3, 0.6 and 0.9 cm thickness (labeled as Fh, 2Fh and 3Fh respectively, equivalent to 248-774 g/m2) were deployed to serve as the reactive capping layer covering the Ornamental Lake sediments, the Royal Botanic Garden of Melbourne. The sediments were exposed to an alternating regime of oxic/anoxic conditions using laboratory reactors for 45 days. Dynamics of dissolved oxygen (DO), pH, filterable reactive phosphorus (FRP), filterable ammonium (NH4+), nitrate and nitrite (NOx), total dissolved nitrogen (TDN) and dissolved iron (Fe) of overlying water were examined. After incubation, O2 and H2S profiles across the water-sediment interface were observed with microelectrodes. The element distributions in the upper sediments were tested as well. Results showed that DO and pH kept relatively stable during oxic period, while decreased significantly during anoxic period. Fh cappings decreased both DO and pH, and inhibited the release of FRP. No significant increments of FRP in overlying waters were observedduring anoxic period. Fh cappings prompted the releases of NH4+ and TDN, while inhibited that of NOx.NH4+increased while NOx decreased during anoxic period. Fe(II) and TFe increased only in 3Fh, especially during anoxic conditions. Fh cappings increased O2 and H2S concentrations across the water-sediment interfaces. TP and TN in the sediments decreased after capping, while TFe increased significantly. We concluded that 0.6 cm thickness of (496 g/m2) Fh capping could sequestrate P, even experiencing redox conditions.

[Effects of Canalization on the Iron Deposition in Sanjiang Plain].

Canalization is the representative process and landscape of wetland reclamation. A typical ditch system of four levels near the Honghe National Nature Reserve in Sanjiang Plain was selected. Deposition plates were set on the sediments along the ditch level and the remained natural wetland nearby was quantitatively sampled for two years as the control. The deposition fluxes, total iron concentration, iron oxides and their components, as well as biogenic elements in the sediments collected by deposition plates were measured. The results showed that the litter, mud/sand and total deposition fluxes showed no significant differences between different ditch levels, with the means of (57.00 ± 16.90) g x (m2 x a)(-1), (3 997.57 ± 798.98) g x (m2 x a)(-1) and (4054.57 ± 792.91) g x (m2 x a)(-1), respectively. The litter flux decreased with the increase of ditch level, and the flux in the natural wetland [ (120.26 ± 19.42) g x (m2 x a)(-1) ] was significantly greater than that of the ditches. The mud/sand [ (35.41 ± 11.15 ) g x (m2 x a)(-1)] and total deposition fluxes [ (155.67 ± 20.75) g x ( m2 x a](-1) ] were significantly smaller than those of the ditches. There were no significant differences in the total iron between different ditches and natural wetland, while the free iron oxide content in the ditch sediments was significantly lower than that of natural wetland sediment. Except for the main ditch, the amorphous and complex iron oxides in the other ditch and natural wetland sediments showed no significant differences. The free degree of the iron oxide in ditch sediments was 60.2% of that in the natural wetland, while the differences in the complex degree and the activated degree were insignificant. The differences in the total organic carbon, total nitrogen and total phosphorus were insignificant, and all were smaller than those of the natural wetland, with the percentages of 14.6%, 31.6% and 41.0%, respectively. It could be concluded that the effects of canalization on iron and biogenic elements were significant. Consequently, rational agricultural water managements are strongly recommended to avoid the potential environmental and ecological risks caused by canalization in Sanjiang Plain.

Small molecule inhibits activity of scavenger receptor A: Lead identification and preliminary studies.

Scavenger receptor A (SRA) has been implicated in the processes of tumor invasion and acts as an immunosuppressor during therapeutic cancer vaccination. Pharmacological inhibition of SRA function thus holds a great potential to improve treatment outcome of cancer therapy. Macromolecular natural product sennoside B was recently shown to block SRA function. Here we report the identification and characterization of a small molecule SRA inhibitor rhein. Rhein, a deconstructed analog of sennoside B, reversed the suppressive activity of SRA in dendritic cell-primed T cell activation, indicated by transcription activation of il2 gene and production of IL-2. Rhein also inhibited SRA ligand polyinosinic:polycytidylic acid (poly(I:C)) induced activation of transcriptional factors, including interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1). Additionally, this newly identified lead compound was docked into the homology models of the SRA cysteine rich domain to gain insights into its interaction with the receptor. It was then found that rhein can favorably interact with SRA cysteine rich domain. Collectively, rhein, being the first identified small molecule inhibitors for SRA, warrants further structure-activity relationship studies, which may lead to development of novel pharmacological intervention for cancer therapy.

Effect of fire on phosphorus forms in Sphagnum moss and peat soils of ombrotrophic bogs.

The effect of burning Sphagnum moss and peat on phosphorus forms was studied with controlled combustion in the laboratory. Two fire treatments, a light fire (250 °C) and a severe fire (600 °C), were performed in a muffle furnace with 1-h residence time to simulate the effects of different forest fire conditions. The results showed that fire burning Sphagnum moss and peat soils resulted in losses of organic phosphorus (Po), while inorganic phosphorus (Pi) concentrations increased. Burning significantly changed detailed phosphorus composition and availability, with severe fires destroying over 90% of organic phosphorus and increasing the availability of inorganic P by more than twofold. Our study suggest that, while decomposition processes in ombrotrophic bogs occur very slowly, rapid changes in the form and availability of phosphorus in vegetation and litter may occur as the result of forest fires on peat soils.

Enhanced endoplasmic reticulum entry of tumor antigen is crucial for cross-presentation induced by dendritic cell-targeted vaccination.

Efficient cross-presentation of protein Ags to CTLs by dendritic cells (DCs) is essential for the success of prophylactic and therapeutic vaccines. In this study, we report a previously underappreciated pathway involving Ag entry into the endoplasmic reticulum (ER) critically needed for T cell cross-priming induced by a DC-targeted vaccine. Directing the clinically relevant, melanoma Ag gp100 to mouse-derived DCs by molecular adjuvant and chaperone Grp170 substantially facilitates Ag access to the ER. Grp170 also strengthens the interaction of internalized protein Ag with molecular components involved in ER-associated protein dislocation and/or degradation, which culminates in cytosolic translocation for proteasome-dependent degradation and processing. Targeted disruption of protein retrotranslocation causes exclusive ER retention of tumor Ag in mouse bone marrow-derived DCs and splenic CD8(+) DCs. This results in the blockade of Ag ubiquitination and processing, which abrogates the priming of Ag-specific CD8(+) T cells in vitro and in vivo. Therefore, the improved ER entry of tumor Ag serves as a molecular basis for the superior cross-presenting capacity of Grp170-based vaccine platform. The ER access and retrotranslocation represents a distinct pathway that operates within DCs for cross-presentation and is required for the activation of Ag-specific CTLs by certain vaccines. These results also reinforce the importance of the ER-associated protein quality control machinery and the mode of the Ag delivery in regulating DC-elicited immune outcomes.