LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files.

The triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming. Here, we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from variant call format files. It is time and memory saving. In a test dataset with 100 SNPs from 60 000 subjects, it was at least 10.60 times faster and used only 0.03-13.33% of physical memory as compared with other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g. association P-values) and genomic region annotations. It can also compress the SVG files with a large number of SNPs and support subgroup analysis. This fast and convenient tool will facilitate the visualization of LD and haplotype blocks for geneticists.

Arbuscular Mycorrhizal Fungi Compete Asymmetrically for Amino Acids with Native and Invasive Solidago.

Arbuscular mycorrhizal fungi (AMF) and soil amino acids both affect plant performance. However, little is known about how AMF compete for amino acids with native and invasive congeners. We conducted a factorial experiment (inoculation, native and invasive species, and amino acids) to examine the competition for amino acids between soil microbes and both native and invasive congeners. The competition for amino acids between AMF and invasive Solidago canadensis was weaker than that observed between AMF and native S. decurrens. This asymmetric competition increased the growth advantage of S. canadensis over S. decurrens. The efficacy (biomass production per unit of nitrogen supply) of amino acids compared to ammonium was smaller in S. canadensis than in S. decurrens when both species were grown without inoculation, but the opposite was the case when both species were grown with AMF. AMF and all microbes differentially altered four phenotypic traits (plant height, leaf chlorophyll content, leaf number, and root biomass allocation) and the pathways determining the effects of amino acids on growth advantages. These findings suggest that AMF could enhance plant invasiveness through asymmetric competition for amino acids and that amino acid-driven invasiveness might be differentially regulated by different microbial guilds.

Quantitative proteomics reveals arsenic attenuates stem-loop binding protein stability via a chaperone complex containing heat shock proteins and ERp44.

Arsenic pollution impacts health of millions of people in the world. Inorganic arsenic is a carcinogenic agent in skin and lung cancers. The stem-loop binding protein (SLBP) binds to the stem-loop of the canonical histone mRNA and regulates its metabolism during cell cycle. Our previous work has shown arsenic induces ubiquitin-proteasome dependent degradation of SLBP and contributes to lung cancer. In this study, we established the first comprehensive SLBP interaction network by affinity purification-mass spectrometry (AP-MS) analysis, and further demonstrated arsenic enhanced the association between SLBP and a crucial chaperone complex containing heat shock proteins (HSPs) and ERp44. Strikingly, knockdown of these proteins markedly rescued the protein level of SLBP under arsenic exposure conditions, and abolished the increasing migration capacity of BEAS-2B cells induced by arsenic. Taken together, our study provides a potential new mechanism that a chaperone complex containing HSPs and ERp44 attenuates the stability of SLBP under both normal and arsenic exposure conditions, which could be essential for arsenic-induced high cell migration.

The transferrin receptor CD71 regulates type II CD38, revealing tight topological compartmentalization of intracellular cyclic ADP-ribose production.

The CD38 molecule (CD38) catalyzes biogenesis of the calcium-mobilizing messenger cyclic ADP-ribose (cADPR). CD38 has dual membrane orientations, and type III CD38, with its catalytic domain facing the cytosol, has low abundance but is efficient in cyclizing cytosolic NAD to produce cADPR. The role of cell surface type II CD38 in cellular cADPR production is unknown. Here we modulated type II CD38 expression and assessed the effects of this modulation on cADPR levels. We developed a photoactivatable cross-linking probe based on a CD38 nanobody, and, combining it with MS analysis, we discovered that cell surface CD38 interacts with CD71. CD71 knockdown increased CD38 levels, and CD38 knockout reciprocally increased CD71, and both could be cocapped and coimmunoprecipitated. We constructed a chimera comprising the N-terminal segment of CD71 and a CD38 nanobody to mimic CD71's ligand property. Overexpression of this chimera induced a dramatically large decrease in CD38 via lysosomes. Remarkably, cellular cADPR levels did not decrease correspondingly. Bafilomycin-mediated blockade of lysosomal degradation greatly elevated active type II CD38 by trapping it in the lysosomes but also did not increase cADPR levels. Retention of type II CD38 in the endoplasmic reticulum (ER) by expressing an ER construct that prevented its transport to the cell surface likewise did not change cADPR levels. These results provide first and direct evidence that cADPR biogenesis occurs in the cytosol and is catalyzed mainly by type III CD38 and that type II CD38, compartmentalized in the ER or lysosomes or on the cell surface, contributes only minimally to cADPR biogenesis.

PopLDdecay: a fast and effective tool for linkage disequilibrium decay analysis based on variant call format files.

MOTIVATION: Linkage disequilibrium (LD) decay is of great interest in population genetic studies. However, no tool is available now to do LD decay analysis from variant call format (VCF) files directly. In addition, generation of pair-wise LD measurements for whole genome SNPs usually resulting in large storage wasting files. RESULTS: We developed PopLDdecay, an open source software, for LD decay analysis from VCF files. It is fast and is able to handle large number of variants from sequencing data. It is also storage saving by avoiding exporting pair-wise results of LD measurements. Subgroup analyses are also supported. AVAILABILITY AND IMPLEMENTATION: PopLDdecay is freely available at https://github.com/BGI-shenzhen/PopLDdecay.

The relative contributions of climate, soil, diversity and interactions to leaf trait variation and spectrum of invasive Solidago canadensis.

BACKGROUND: Invasive plants commonly occupy diverse habitats and thus must adapt to changing environmental pressures through altering their traits and economics spectra, and addressing these patterns and their drivers has an importantly ecological and/or evolutionary significance. However, few studies have considered the role of multiple biotic and abiotic factors in shaping trait variation and spectra. In this study, we determined seven leaf traits of 66 Solidago canadensis populations, and quantified the relative contributions of climate, soil properties, native plant diversity, and S. canadensis-community interactions (in total 16 factors) to leaf trait variation and spectrum with multimodel inference. RESULTS: Overall, the seven leaf traits had high phenotypic variation, and this variation was highest for leaf dry matter content and lowest for leaf carbon concentration. The per capita contribution of climate to the mean leaf trait variation was highest (7.5%), followed by soil properties (6.2%), S. canadensis-community interactions (6.1%), and native plant diversity (5.4%); the dominant factors underlying trait variation varied with leaf traits. Leaf production potential was negatively associated with leaf stress-tolerance potential, and the relative contributions to this trade-off followed in order: native plant diversity (7.7%), climate (6.9%), S. canadensis-community interactions (6.2%), and soil properties (5.6%). Climate, diversity, soil, and interactions had positive, neutral or negative effects. CONCLUSIONS: Climate, soil, diversity, and interactions contribute differentially to the leaf trait variation and economics spectrum of S. canadensis, and their relative importance and directions depend on plant functional traits.

Autotoxicity of root exudates varies with species identity and soil phosphorus.

Root exudate autotoxicity (i.e. root exudates from a given plant have toxic effects on itself) has been recognized to be widespread. Here we examined how plant species identity and soil phosphorus (P) availability influenced this autotoxicity and the possible stoichiometric mechanisms. We conducted an experiment with three species (Luctuca sativa, Sesbania cannabina, and Solidago canadensis), which were subject to four treatments consisting of activated carbon (AC) and soil P. AC addition increased the whole-plant biomass of each species under high P conditions and this AC effect varied strongly with species identity. For Solidago, the relative increase in whole-plant biomass due to AC addition was larger in the low P than in the high P. Root exudate autotoxicity differed between roots and shoots. AC addition decreased root N:P ratios but failed to influence shoot N:P ratios in three species. These findings suggest that soil P enrichment might mediate root exudate autotoxicity and that this P-mediated autotoxicity might be related to root N and P stoichiometry. These patterns and their implications need to be addressed in the context of plant communities.

[Molecular mechanisms of mycelium of Cordyceps sinensis ameliorating renal tubular epithelial cells aging induced by D-galactose via inhibiting autophagy-related AMPK/ULK1 signaling activation].

To explore the effects and molecular mechanisms of mycelium of Cordyceps sinensis(MCs)improving renal tubular epithelial cells aging induced by D-galactose,the renal proximal tubular epithelial cells(NRK-52E cells)of rats in vitro were divided into the normal group(N),the D-gal model group(D),the low dose of MCs group(L-MCs),the medium dose of MCs group(M-MCs)and the high dose of MCs group(H-MCs),and treated by the different measures,respectively.More specifically,the NRK-52E cells in each group were separately treated by 1%fetal bovine serum(FBS)or D-galactose(D-gal,100 mmol·L~(-1))or D-gal(100 mmol·L~(-1))+MCs(20 mg·L~(-1))or D-gal(100 mmol·L~(-1))+MCs(40 mg·L~(-1))or D-gal(100 mmol·L~(-1))+MCs(80 mg·L~(-1)).After the intervention for24 h or 48 h,firstly,the effects of D-gal on the protein expression levels of klotho,P27 and P16,the staining of senescence-associatedß-galactosidase(SA-ß-gal)and the activation of adenosine monophosphate activated protein kinase(AMPK)/uncoordinated 51-like kinase 1(ULK1)signaling in the NRK-52E cells were detected,respectively.Secondly,the effects of MCs on the activation of the NRK-52E cells proliferation were investigated,respectively.Finally,the effects of MCs on the protein expression levels of klotho,P27,P16and microtubule-associated protein 1 light chain 3(LC3),the staining of SA-ß-gal and the activation of AMPK/ULK1 signaling in the NRK-52E cells exposed to D-gal were examined severally.The results indicated that,for the NRK-52E cells,D-gal could cause aging,induce the protein over-expression levels of the phosphorylated AMPK(p-AMPK)and the phosphorylated ULK1(p-ULK1)and activate AMPK/ULK1 signaling pathway.The co-treatment of MCs at the medium and high doses and D-gal could significantly ameliorate the protein expression levels of klotho,P27,P16 and the staining of SA-ß-gal,suggesting the anti-cell aging actions.In addition,the cotreatment of MCs at the medium and high doses and D-gal could obviously improve the protein expression levels of LC3,p-AMPK,and p-ULK1,inhibit the activation of AMPK/ULK1 signaling and increase autophagy.On the whole,for the renal tubular epithelial cells aging models induced by D-gal,MCs not only has the in vitro actions of anti-aging,but also intervenes aging process by inhibiting autophagy-related AMPK/ULK1 signaling activation,which may be the novel molecular mechanisms of MCs protecting against aging of the renal tubular epithelial cells.

Oleanolic acid attenuates TGF-ß1-induced epithelial-mesenchymal transition in NRK-52E cells.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Oleanolic acid (OA), an activator of NF-E2-related factor 2 (Nrf2), is reported to attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, the role of OA in the regulation of EMT and the underlying mechanisms remain to be investigated. This study aimed to evaluate the effects of OA on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-ß1, and to elucidate its underlying mechanism. METHODS: Cells were incubated with TGF-ß1 in the presence or absence of OA. The epithelial marker E-cadherin, the mesenchymal markers, α-smooth muscle actin (α-SMA), fibronectin, Nrf2, klotho, the signal transducer (p-Smad2/3), EMT initiator (Snail), and ILK were assayed by western blotting. RESULTS: Our results showed that the NRK-52E cells incubated with TGF-ß1 induced EMT with transition to the spindle-like morphology, down-regulated the expression of E-cadherin but up-regulated the expression of α-SMA and fibronectin. However, the treatment with OA reversed all EMT markers in a dose-dependent manner. OA also restored the expression of Nrf2 and klotho, decreased the phosphorylation of Smad2/3, ILK, and Snail in cells which was initiated by TGF-ß1. CONCLUSION: OA can attenuate TGF-ß1 mediate EMT in renal tubular epithelial cells and may be a promising therapeutic agent in the treatment of renal fibrosis.

[Low dose of triptolide ameliorates podocyte epithelial-mesenchymal transition induced by high dose of D-glucose via inhibiting Wnt3α/ß-catenin signaling pathway activation].

To explore the effects and molecular mechanisms of triptolide（TP）on improving podocyte epithelial-mesenchymal transition（EMT）induced by high dose of D-glucose（HG）, the immortalized podocytes of mice in vitro were divided into the normal group（N）, the high dose of D-glucose group（HG）, the low dose of TP group（L-TP）, the high dose of TP group（H-TP）and the mannitol group（MNT）, and treated by the different measures respectively. More specifically, the podocytes in each group were separately treated by D-glucose（DG, 5 mmol·L⁻¹ï¼‰or HG（25 mmol·L⁻¹ï¼‰or HG（25 mmol·L⁻¹ï¼‰+ TP（3 µg·L⁻¹ï¼‰or HG（25 mmol·L⁻¹ï¼‰+ TP（10 µg·L⁻¹ï¼‰or DG（5 mmol·L⁻¹ï¼‰+ MNT（24.5 mmol·L⁻¹ï¼‰. After the intervention for 24, 48 and 72 hours, firstly, the activation of podocyte proliferation was investigated. Secondly, the protein expression levels of the epithelial markers in podocytes such as nephrin and podocin, the mesenchymal markers such as desmin and collagen Ⅰ and the EMT-related mediators such as snail were detected respectively. Finally, the protein expression levels of Wnt3α and ß-catenin as the key signaling molecules in Wnt3α/ß-catenin pathway were examined severally. The results indicated that, HG could cause the low protein expression levels of nephrin and podocin and the high protein expression levels of desmin, collagen Ⅰ and snail in podocytes, and inducing podocyte EMT. On the other hand, HG could cause the high protein expression levels of Wnt3α and ß-catenin in podocytes, and activating Wnt3α/ß-catenin signaling pathway. In addition, L-TP had no effect on the activation of podocyte proliferation, the co-treatment of L-TP and HG could significantly recover the protein expression levels of nephrin and podocin, inhibit the protein expression levels of desmin, collagen I and snail in podocytes, thus, further improving podocyte EMT. And that, the co-treatment of L-TP and HG could obviously decrease the high protein expression levels of Wnt3α and ß-catenin induced by HG in podocytes, and inhibit Wnt3α/ß-catenin signaling pathway activation. On the whole, HG can induce podocyte EMT by activating Wnt3α/ß-catenin signaling pathway; L-TP can ameliorate podocyte EMT through inhibiting Wnt3α/ß-catenin signaling pathway activation, which may be one of the effects and molecular mechanisms in vitro.

[Pathomechanism and treatment of gut microbiota dysbiosis in chronic kidney disease and interventional effects of Chinese herbal medicine].

The gut microbiota dysbiosis is one of the risk factors in the progression from the advanced chronic kidney disease（CKD）to uremia, characterized by the reduction of probiotics and the increase of opportunistic pathogens including urease-related microbes, endotoxin-related microbes and toxin-related microbes, which can produce uremic toxins. According to the core point of "the gut-kidney axis" theory and "the chronic kidney disease-colonic axis" concept, the gut microbiota dysbiosis aggravates renal damage by accumulating uremic toxins and inducing the systemic micro-inflammation. The preliminary clinical trials and animal experiments show that the probiotics biologicals from Lactobacillus acidophilus or Bifidobacterium, and the prebiotics including inulin and galactooligosaccharides, as well as lubiprostone and activated carbon adsorbents can be used for improving dysfunction of CKD patients with the gut microbiota dysbiosis via reducing uremic toxins and inhibiting the systemic micro-inflammation. But not only that, it is reported that, to some extent, a number of the single Chinese herbal medicine（CHM）, the CHM prescriptions and the CHM extracts（emodin, etc.）with oral or enema administration can also regulate the gut microbiota dysbiosis, protect the intestinal epithelial barrier, reduce uremic toxins accumulation and delay CKD progression. Thereinto, Dahuang Gancao Decoction（the concentrated granule TJ-84）, a classical CHM prescription of rhubarb, can ameliorate uremic toxins accumulation in the animal models with renal failure probably through targeting the gut-kidney axis triggered from gut microbiota, but not targeting the kidney. Based on these results, the interventional studies targeting the gut microbiota-related pathological factors such as tight junction proteins, helper T cells and regulatory T cells in the intestinal tract of the advanced CKD patients will become one of the key development directions in the future.

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA （mtDNA）and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide（NMN）and FOXO4-DRI,a peptide of anti-aging. In addition,there are many new discoveries in the field of plant extracts,in which,the extracts from Chinese herbal medicine（CHM）,some single CHMs and the classical prescriptions of CHM,represented by curcumin and resveratrol,have the partial anti-aging effects by regulating the molecular mechanisms of aging both in vivo and in vitro. In brief,developing or exploring anti-aging drugs,especially the natural drugs,is one of the main development directions in the field of anti-aging research in the basis of the molecular regulative mechanisms of aging.

Dissecting yield-associated loci in super hybrid rice by resequencing recombinant inbred lines and improving parental genome sequences.

The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang-You-Pei-Jiu, the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93-11 and maternal cultivar PA64s of Liang-You-Pei-Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1, and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.

[Open, multicenter, phase â £ clinical trial of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome].

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.

Climate warming impacts chewing Spodoptera litura negatively but sucking Corythucha marmorata positively on native Solidago canadensis.

Insect-plant interactions are among importantly ecological processes, and rapid environmental changes such as temperature and resource fluctuations can disrupt long-standing insect-plant interactions. While individual impacts of climate warming, atmospheric nitrogen (N) deposition, and plant provenance on insect-plant interactions are well studied, their joint effects on insect-plant interactions are less explored in ecologically realistic settings. To this end, we performed five experiments with native and invasive Solidago canadensis populations from home and introduced ranges and two insect herbivores (leaf-chewing Spodoptera litura and sap-sucking Corythucha marmorata) in the context of climate warming and N deposition. We determined leaf defensive traits, feeding preference, and insect growth and development, and quantified the possible associations among climate change, host-plant traits, and insect performance with structural equation modeling. First, native S. canadensis populations experienced higher damage by S. litura but lower damage by C. marmorata than invasive S. canadensis populations in the ambient environment. Second, warming decreased the leaf consumption, growth, and survival of S. litura on native S. canadensis populations, but did not affect these traits on invasive S. canadensis populations; warming increased the number of C. marmorata on native S. canadensis populations via direct facilitation, but decreased that on invasive S. canadensis populations via indirect suppression. Third, N addition enhanced the survival of S. litura on native S. canadensis populations, and its feeding preference and leaf consumption on invasive S. canadensis populations. Finally, warming plus N addition exhibited non-additive effects on insect-plant interactions. Based on these results, we tentatively conclude that climate warming could have contrasting effects on insect-plant interactions depending on host-plant provenance and that the effects of atmospheric N deposition on insects might be relatively weak compared to climate warming. Future studies should focus on the molecular mechanisms underlying these different patterns.

Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing.

BACKGROUND: Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. RESULTS: A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. CONCLUSIONS: Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.

[Applications and approved projectsof general program, young scientist fund and fund for less developedregion of national natural science funds in discipline of Chinese materia medica, NSFC in 2012].

The applications accepted and approved by general program, young scientist fund and fund for less developed region of national natural science funds in the discipline of Chinese materia medica, NSFC in 2012 have been introduced. The research contents of the funded projects in the popular research areas have been summarized and the problems in the applications have been analyzed to give a reference to the scientists in the field of Chinese materia medica.

A shift from inorganic to organic nitrogen-dominance shapes soil microbiome composition and co-occurrence networks.

Soil microbiomes are characterized by their composition and networks, which are linked to soil nitrogen (N) availability. In nature, inorganic N dominates at one end and organic N dominates at the other end along soil N gradients; however, little is known about how this shift influences soil microbiome composition and co-occurrence networks, as well as their controls. To this end, we conducted an experiment with the host plant Solidago canadensis, which was subject to three N regimes: inorganic N-dominated, co-dominated by inorganic and organic N (CIO), and organic N-dominated. Organic N dominance exhibited stronger effects on the composition and co-occurrence networks of soil microbiomes than inorganic N dominance. The predominant control was plant traits for bacterial and fungal richness, and soil pH for keystone species. Relative to the CIO regime, inorganic N dominance did not affect fungal richness and increased keystone species; organic N dominance decreased fungal richness and keystone species. Pathogenic fungi and arbuscular mycorrhizal fungi were suppressed by organic N dominance but not by inorganic N dominance. These findings suggest that the shift from soil inorganic N-dominance to soil organic N-dominance could strongly shape soil microbiome composition and co-occurrence networks by altering species diversity and topological properties.

Astragalus Total Saponins Ameliorate Peritoneal Fibrosis by Promoting Mitochondrial Synthesis and Inhibiting Apoptosis.

Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an in vitro model of PF. Furthermore, siRNA of PGC-1[Formula: see text] was used to inhibit the expression of PGC-1[Formula: see text] to further investigate the mechanism of the protective effect of ATS on PF. In both in vivo and in vitro models, ATS treatment showed a protective effect against PF, with ATS reducing the thickness of peritoneal tissues in PF rats, increasing the viability of PMCs, increasing the mitochondrial membrane potential and reducing apoptosis ratio. ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.

A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1.

Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation.