Motif-based community detection in heterogeneous multilayer networks.

Multilayer networks composed of intralayer edges and interlayer edges are an important type of complex networks. Considering the heterogeneity of nodes and edges, it is necessary to design more reasonable and diverse community detection methods for multilayer networks. Existing research on community detection in multilayer networks mainly focuses on multiplexing networks (where the nodes are homogeneous and the edges are heterogeneous), but few studies have focused on heterogeneous multilayer networks where both nodes and edges represent different semantics. In this paper, we studied community detection on heterogeneous multilayer networks and proposed a motif-based detection algorithm. First, the communities and motifs of multilayer networks are defined, especially the interlayer motifs. Then, the modularity of multilayer networks based on these motifs is designed, and the community structure of the multilayer network is detected by maximizing the modularity of multilayer networks. Finally, we verify the effectiveness of the detection algorithm on synthetic networks. In the experiments on synthetic networks, comparing with the classical community detection algorithms (without considering interlayer heterogeneity), the motif-based modularity community detection algorithm can obtain better results under different evaluation indexes, and we found that there exists a certain relationship between motifs and communities. In addition, the proposed algorithm is applied in the empirical network, which shows its practicability in the real world. This study provides a solution for the investigation of heterogeneous information in multilayer networks.

[Impact of Climate Warming on Paddy Soil Organic Carbon Change in the Sichuan Basin of China].

Climate warming can increase soil temperature and lead to soil carbon release, but it can also increase soil organic carbon by increasing primary productivity. Cropland soils are considered to have a huge potential to sequester carbon; however, direct observations for the responses of cropland soil organic carbon to climate warming over broad geographic scales are rarely documented. Paddy soil is one of the important cultivated soils in China. Based on the data of 2217 sampling points obtained during the second national soil survey and the data of 2382 sampling points collected during 2017-2019, this study analyzed the change characteristics of soil organic carbon content of paddy surface soil in Sichuan Basin of China and explored the relationships between the soil organic carbon change of paddy soil and temperature, precipitation, cropland use type, fertilization intensity, and grain yield. The results showed that the content of soil organic carbon of paddy soil changed from 13.33 g·kg-1to 15.96 g·kg-1, with an increase of 2.63 g·kg-1, suggesting that soils in the Sichuan Basin have acted as a carbon sink over past 40 years. The soil organic carbon increment of paddy soil varied with different geomorphic regions and different secondary basins. The increase in SOC content in paddy soil was positively correlated with annual average temperature; negatively correlated with annual average precipitation; and initially increased and then decreased with annual average fertilizer application, annual average increase rate of fertilizer application, annual average grain yield, and annual average grain yield growth rate. The relationship between the increase in SOC content and the annual average temperature growth rate was different under different farmland utilizations, and the increase in the annual average temperature growth rate had significant effects with the increase in SOC content only on paddy-dryland rotation. These results indicate that the paddy soil organic carbon change in Sichuan Basin was co-affected by various factors, but climate warming was an important factor leading to the paddy soil organic carbon change, and its influence was controlled by the water conditions determined by farmland use.

Divergent responses of cropland soil organic carbon to warming across the Sichuan Basin of China.

Cropland soils are considered to have the potential to sequester carbon (C). Warming can increase soil organic C (SOC) by enhancing primary production, but it can also cause carbon release from soils. However, the role of warming in governing cropland SOC dynamics over broad geographic scales remains poorly understood. Using over 4000 soil samples collected in the 1980s and 2010s across the Sichuan Basin of China, this study assessed the warming-induced cropland SOC change and the correlations with precipitation, cropland type and soil type. Results showed mean SOC content increased from 11.10 to 13.85 g C kg-1. Larger SOC increments were observed under drier conditions (precipitation < 1050 mm, dryland and paddy-dryland rotation cropland), which were 1.67-2.23 times higher than under wetter conditions (precipitation > 1050 mm and paddy fields). Despite the significant associations of SOC increment with crop productivity, precipitation, fertilization, cropland type and soil type, warming also acted as one of major contributors to cropland SOC change. The SOC increment changed parabolically with the rise in temperature increase rate under relatively drier conditions, while temperature increase had no impact on cropland SOC increment under wetter conditions. Meanwhile, the patterns of the parabolical relationship varied with soil types in drylands, where the threshold of temperature increase rate, the point at which the SOC increment switched from increasing to decreasing with warming, was lower for clayey soils (Ali-Perudic Argosols) than for sandy soils (Purpli-Udic Cambosols). These results illustrate divergent responses of cropland SOC to warming under different environments, which were contingent on water conditions and soil types. Our findings emphasize the importance of formulating appropriate field water management for sustainable C sequestration and the necessity of incorporating environment-specific mechanisms in Earth system models for better understanding of the soil C-climate feedback in complex environments.

Microstructure and properties evolution of Mg-2Y-0.6Nd-0.6Zr alloy rolled at room and liquid nitrogen temperature.

The microstructure evolution, texture, mechanical behavior and twin deformation of the ECAPed Mg-2Y-0.6Nd-0.6Zr alloy at room and liquid nitrogen temperature were investigated by rolling samples. The ECAP processed material appeared the texture of 45° to the extrusion direction and its yield strength reached 93.6 MPa. The results showed that cryorolling encourages twinning in Mg-2Y-0.6Nd-0.6Zr alloy, enhancing the tensile strength and texture. Activation of {10-12} twinning during rolling was found to be more pronounced in the cryorolled samples than in the cold rolled samples owing to a lower temperature. As a result, the cryorolled samples had more twins than and cold rolled ones, the proportion of twin areas of room temperature rolling and ultra-low temperature rolling were: 2.45% and 4.23%.

Depth-dependent soil organic carbon dynamics of croplands across the Chengdu Plain of China from the 1980s to the 2010s.

Agricultural soils have tremendous potential to sequester soil organic carbon (SOC) and mitigate global climate change. However, agricultural land use has a profound impact on SOC dynamics, and few studies have explored how agricultural land use combined with soil conditions affect SOC changes throughout the soil profile. Based on a paired soil resampling campaign in the 1980s and 2010s, this study investigated the SOC changes of the soil profile caused by agricultural land use and the correlations with parent material and topography across the Chengdu Plain of China. The results showed that the SOC content increased by 3.78 g C/kg in the topsoil (0-20 cm), but decreased in the 20-40 cm and 40-60 cm soil layers by 0.90 and 1.26 g C/kg respectively. SOC increases in topsoil were observed for all types of agricultural land. Afforestation on former agricultural land also caused SOC decreases in the 20-60 cm soil layers, while SOC decreases only occurred in the 40-60 cm soil layer for agricultural land using a traditional crop rotation (i.e. traditional rice-wheat/rapeseed rotation) and with rice-vegetable rotations converted from the traditional rotations. For each agricultural land use, SOC decreases in deep soils only occurred in high relief areas and in soils formed from Q4 (Quaternary Holocene) grey-brown alluvium and Q4 grey alluvium that had a relatively low soil bulk density and clay content. The results indicated that SOC change caused by agricultural land use was depth dependent and that the effects of agricultural land use on soil profile SOC dynamics varied with soil characteristics and topography. Subsoil SOC decreases were more likely to occur in high relief areas and in soils with low soil bulk density and low clay content.

Soil acidification of the soil profile across Chengdu Plain of China from the 1980s to 2010s.

Soil acidification is a major environmental issue associated with intensive agricultural land use. Rapid urbanization has inevitably caused great changes in agricultural land use around urban areas. However, the effects of agricultural land-use change and soil parent material on the pH dynamics of the whole soil profile remain poorly understood. Based on a paired soil resampling campaign in the 1980s and 2010s, this study evaluated the effects of agricultural land-use change and parent materials on the pH dynamics of the soil profile across the Chengdu Plain of China. The results showed that soil pH significantly decreased by 1.20, 0.72, 0.66 and 0.68 units at the 0-20, 20-40, 40-60 and 60-100 cm soil depths, respectively. Conversions of traditional rice-wheat/rapeseed rotations to rice-vegetable rotations and afforested land significantly increased the magnitude of pH decline at the 0-60 cm soil depth. Soils formed from Q4 grey-brown alluvium and Q4 grey alluvium, which had a lower soil bulk density (BD) and higher sand content, showed a much higher magnitude of pH decline than soils formed from Q3 (Quaternary Pleistocene) old alluvium, and significant acidification of deep soils only occurred in soils formed from Q4 (Quaternary Holocene) grey-brown alluvium and Q4 grey alluvium. These results suggested that agricultural land-use change aggravated acidification in the soil profile and the soil acidification degrees were parent material-dependent; in particular, significant acidification of deep soils was more inclined to occur in soils with lower soil BD and higher sand content due to their effects on the downward movement of acids and the penetration resistance of plant roots. More attention should be given to minimizing or preventing acidification of both topsoil and deep soils aggravated by agricultural land-use change across urban agricultural areas.

Characterization and Genome Analysis of a Nicotine and Nicotinic Acid-Degrading Strain Pseudomonas putida JQ581 Isolated from Marine.

The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium-strain JQ581-was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously.

Synthesis and Evaluation of the Metabolites of AMG 221, a Clinical Candidate for the Treatment of Type 2 Diabetes.

All eight of the major active metabolites of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221, compound 1), an inhibitor of 11ß-hydroxysteroid dehydrogenase type 1 that has entered the clinic for the treatment of type 2 diabetes, were synthetically prepared and confirmed by comparison with samples generated in liver microsomes. After further profiling, we determined that metabolite 2 was equipotent to 1 on human 11ß-HSD1 and had lower in vivo clearance and higher bioavailability in rat and mouse. Compound 2 was advanced into a pharmacodynamic model in mouse where it inhibited adipose 11ß-HSD1 activity.

Aryl sulfonamides containing tetralin allylic amines as potent and selective bradykinin B1 receptor antagonists.

The bradykinin B1 receptor has been shown to mediate pain response and is rapidly induced upon injury. Blocking this receptor may provide a promising treatment for inflammation and pain. We previously reported tetralin benzyl amines as potent B1 antagonists. Here we describe the synthesis and SAR of B1 receptor antagonists with homobenzylic amines. The SAR of different linkers led to the discovery of tetralin allylic amines as potent and selective B1 receptor antagonists (hB1 IC(50)=1.3 nM for compound 16). Some of these compounds showed modest oral bioavailability in rats.

2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice.

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has attracted considerable attention during the past few years as a potential target for the treatment of diseases associated with metabolic syndrome. In our ongoing work on 11beta-HSD1 inhibitors, a series of new 2-amino-1,3-thiazol-4(5 H)-ones were explored. By inserting various cycloalkylamines at the 2-position and alkyl groups or spirocycloalkyl groups at the 5-position of the thiazolone, several potent 11beta-HSD1 inhibitors were identified. An X-ray cocrystal structure of human 11beta-HSD1 with compound 6d (Ki=28 nM) revealed a large lipophilic pocket accessible by substitution off the 2-position of the thiazolone. To increase potency, analogues were prepared with larger lipophilic groups at this position. One of these compounds, the 3-noradamantyl analogue 8b, was a potent inhibitor of human 11beta-HSD1 (Ki=3 nM) and also inhibited 11beta-HSD1 activity in lean C57Bl/6 mice when evaluated in an ex vivo adipose and liver cortisone to cortisol conversion assay.

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors.

A series of 2-anilinothiazolones were prepared as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The most potent compounds contained a 2-chloro or 2-fluoro group on the aniline ring with an isopropyl substituent on the 5-position of the thiazolone ring (compounds 2 and 3, respectively). The binding mode was determined through the X-ray co-crystal structure of the enzyme with compound 3. This compound was also approximately 70-fold selective over 11beta-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11beta-HSD1 cell assay when tested in the presence of 3% human serum albumin.

Potent nonpeptide antagonists of the bradykinin B1 receptor: structure-activity relationship studies with novel diaminochroman carboxamides.

The bradykinin B1 receptor is induced following tissue injury and/or inflammation. Antagonists of this receptor have been studied as promising candidates for treatment of chronic pain. We have identified aryl sulfonamides containing a chiral chroman diamine moiety that are potent antagonists of the human B1 receptor. Our previously communicated lead, compound 2, served as a proof-of-concept molecule, but suffered from poor pharmacokinetic properties. With guidance from metabolic profiling, we performed structure-activity relationship studies and have identified potent analogs of 2. Variation of the sulfonamide moiety revealed a preference for 3- and 3,4-disubstituted aryl sulfonamides, while bulky secondary and tertiary amines were preferred at the benzylic amine position for potency at the B1 receptor. Modifying the beta-amino acid core of the molecule lead to the discovery of highly potent compounds with improved in vitro pharmacokinetic properties. The most potent analog at the human receptor, compound 38, was also active in a rabbit B1 receptor cellular assay. Furthermore, compound 38 displayed in vivo activity in two rabbit models, a pharmacodynamic model with a blood pressure readout and an efficacy model of inflammatory pain.

Oxa-enediynes: probing the electronic and stereoelectronic contributions to the Bergman cycloaromatization.

Efficient routes to three classes of 10-membered oxa-enediynes are presented. The electronic and stereoelectronic contributions to half-lives are supported by density functional theory calculations. One member of this class cyclizes to give an isochroman which binds to and degrades the aryl hydrocarbon receptor (AhR).