Whole-genome resequencing of major populations revealed domestication-related genes in yaks.

BACKGROUND: The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. MATERIAL AND METHOD: Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. RESULTS: By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). CONCLUSIONS: We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.

Transcriptomics and metabolomics of blood, urine and ovarian follicular fluid of yak at induced estrus stage.

To gain a deeper understanding of the metabolic differences within and outside the body, as well as changes in transcription levels following estrus in yaks, we conducted transcriptome and metabolome analyses on female yaks in both estrus and non-estrus states. The metabolome analysis identified 114, 13, and 91 distinct metabolites in urine, blood, and follicular fluid, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted an enrichment of pathways related to amino acid and lipid metabolism across all three body fluids. Our transcriptome analysis revealed 122 differentially expressed genes within microRNA (miRNA) and 640 within long non-coding RNA (lncRNA). Functional enrichment analysis of lncRNA and miRNA indicated their involvement in cell signaling, disease resistance, and immunity pathways. We constructed a regulatory network composed of 10 lncRNAs, 4 miRNAs, and 30 mRNAs, based on the targeted regulation relationships of the differentially expressed genes. In conclusion, the accumulation of metabolites such as amino acids, steroids, and organic acids, along with the expression changes of key genes like miR-129 during yak estrus, provide initial insights into the estrus mechanism in yaks.

Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Allorhizobium sonneratiae sp. nov., an endophytic bacterium isolated from the root of Sonneratia apetala.

A novel endophytic bacterium, designated strain BGMRC 0089T, was isolated from a surface-sterilized root of Sonneratia apetala. Cells were observed to be Gram-negative, rod-shaped and motile with polar flagella. Strain BGMRC 0089T was found to grow optimally at 28-30 °C, pH 7.0-8.0 and in the presence of 1 % (w/v) NaCl. Strain BGMRC 0089T contained ubiquinone Q-10 and the predominant fatty acid was summed feature 8. The polar lipid profile of strain BGMRC 0089T was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine. Based on the results of 16S rRNA gene analysis, this isolate has the closest phylogenetic relationships with Rhizobium lemnae L6-16T (96.5 %) and Allorhizobium oryziradicis N19T (96.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of the isolate with the type strains of the genera Rhizobium and Allorhizobium were below 84.6, 73.9 and 22.1  %, respectively. Analysis the 4.55 Mb draft genome of strain BGMRC 0089T revealed several plant-associated genes, which may play important roles for the plant in the adaptation to the mangrove habitat. Based on its distinct phylogenetic, phenotypic and chemotaxonomic characteristics, strain BGMRC 0089T is proposed to represent a novel Allorhizobium species, for which the name Allorhizobium sonneratiae sp. nov. is proposed (type strain BGMRC 0089T=DSM 100171T=MCCC 1K04805T).

Parvularcula maris sp. nov., an algicidal bacterium isolated from seawater.

A taxonomic study was carried out on strain BGMRC 0090T, which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090T belonged to the genus Parvularcula, with highest sequence similarity to Parvularcula lutaonensis CC-MMS-1T (98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090T and five strains of the genus Parvularcula with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090T was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090T contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C18 : 1ω7c/ω6c) and C16 : 0. Based on the polyphasic evidence presented in this paper, strain BGMRC 0090T is concluded to represent a novel species of the genus Parvularcula, for which the name Parvularcula maris sp. nov. is proposed. The type strain is BGMRC 0090T (= KCTC 92591T=MCCC 1K08100T).

Muscle myosins form folded monomers, dimers, and tetramers during filament polymerization in vitro.

Muscle contraction depends on the cyclical interaction of myosin and actin filaments. Therefore, it is important to understand the mechanisms of polymerization and depolymerization of muscle myosins. Muscle myosin 2 monomers exist in two states: one with a folded tail that interacts with the heads (10S) and one with an unfolded tail (6S). It has been thought that only unfolded monomers assemble into bipolar and side-polar (smooth muscle myosin) filaments. We now show by electron microscopy that, after 4 s of polymerization in vitro in both the presence (smooth muscle myosin) and absence of ATP, skeletal, cardiac, and smooth muscle myosins form tail-folded monomers without tail-head interaction, tail-folded antiparallel dimers, tail-folded antiparallel tetramers, unfolded bipolar tetramers, and small filaments. After 4 h, the myosins form thick bipolar and, for smooth muscle myosin, side-polar filaments. Nonphosphorylated smooth muscle myosin polymerizes in the presence of ATP but with a higher critical concentration than in the absence of ATP and forms only bipolar filaments with bare zones. Partial depolymerization in vitro of nonphosphorylated smooth muscle myosin filaments by the addition of MgATP is the reverse of polymerization.

Transcriptomic analysis of yak longissimus dorsi muscle identifies genes associated with tenderness.

Meat tenderness is an important sensory index when consumers choose meat products, which determines the value of meat products and consumers' buying intentions. Yak meat is rich in nutrition and unique in flavor, which is favored by consumers. However, its meat has the deficiencies of low tenderness and poor taste, which has a negative impact on the value of its meat products and customer satisfaction. To identify the genes affecting the yak meat tenderness, we used RNA-seq to analyze the longissimus dorsi muscle of yaks with different tenderness, screened a total of 1120 differentially expressed genes (DEGs). Meanwhile, 23 pathways were significantly enriched. By further analysis, we identified eight genes related to yak meat tenderness (WNT5A, ARID5B, SERPINE1 KLHL40, RUNX1, MAFF, RFX7 and ARID5A). Notably, SERPINE1 was involved in the significant enrichment pathways of 'complement and coagulation cascade pathway', 'HIF-1 signaling pathway' and 'AGE-RAGE signaling pathway in diabetic complications' which can regulate meat tenderness. This implies that SERPINE1 may play an important regulatory role among them. The DEGs associated with yak meat quality screened in this work will be helpful to identify potential biomarkers related to meat tenderness.

Rhamnazin Enhanced Anti-Tumor Efficacy of Anti-PD-1 Therapy for Lung Cancer in Mice through Inhibition of PD-L1 Expression.

Emerging studies suggest the significance of broadening the benefit of anti-programmed cell death 1 (PD-1) therapy for lung cancer. The anti-angiogenic agents have been reported to alter the tumor microenvironment and contributes to efficiency of anti-PD-1 therapy. This study aims to investigate whether the anti-angiogenic agent rhamnazin enhances the efficacy of anti-PD-1 therapy in lung cancer. In Lewis lung carcinoma (LLC) xenografts, the combination of rhamnazin and anti-PD-1 treatment suppressed tumor growth, elevated the infiltration of CD4+ T and CD8+ T cells in tumors and up-regulated interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and granzyme B. Furthermore, the combination reduced programmed cell death ligand 1 (PD-L1) expression in tumors more significant than anti-PD-1 treated group. In LLC cell experiments, rhamnazin inhibited vascular endothelial growth factor A (VEGFA)-stimulated vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation and PD-L1 expression, whereas VEGFR2 overexpression reversed these trends. T cell proliferation and cytotoxic factor production were evaluated after co-culturing with non-small cell lung cancer (NSCLC) H1975 cells. Rhamnazin promotes T cell proliferation and up-regulated IFN-γ, TNF-α and granzyme B in the co-culture system, while VEGFR2 overexpression abrogated these changes. These data suggest that rhamnazin enhances anti-tumor effect of anti-PD-1 therapy for lung cancer in mice via inhibition of PD-L1 expression.

Epigenomics Analysis of the Suppression Role of SIRT1 via H3K9 Deacetylation in Preadipocyte Differentiation.

Sirtuin 1 (SIRT1) overexpression significantly inhibits lipid deposition during yak intramuscular preadipocyte (YIMA) differentiation; however, the regulatory mechanism remains unknown. We elucidated the role of SIRT1 in YIMA differentiation using lentivirus-mediated downregulation technology and conducted mRNA-seq and ChIP-seq assays using H3K9ac antibodies after SIRT1 overexpression in order to reveal SIRT1 targets during YIMA adipogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed in order to identify the functional annotation of common genes. In addition, a potential target of SIRT1 was selected to verify its effects on the differentiation and proliferation of YIMAs. SIRT1 interfered with lipid deposition and promoted YIMA differentiation. In total, 143,518 specific peaks were identified after SIRT1 overexpression, where genes associated with downregulation peaks were enriched in transcription, gene expression, lipid-related processes, and classical lipid-related pathways. The H3K9ac signal in the whole genome promoter region (2 kb upstream and downstream of the transcription start site (TSS)) was weakened, and the peaks were distributed across all gene functional regions. Genes that lost signals in their TSS region or gene body region were enriched in both biological processes and pathways associated with lipogenesis. The ChIP-seq results revealed 714 common differential genes in mRNA-seq, which were enriched in "MAPK signaling", "lipid and atherosclerosis", "mTOR signaling", and "FoxO signaling" pathways. A total of 445 genes were downregulated in both their H3K9ac signals and mRNA expression, and one of their most significantly enriched pathways was FoxO signaling. Nine genes (FBP2, FPGT, HSD17B11, KCNJ15, MAP3K20, SLC5A3, TRIM23, ZCCHC10, and ZMYM1) lost the H3K9ac signal in their TSS regions and had low mRNA expression, and three genes (KCNJ15, TGM3, and TRIM54) had low expression but lost their H3K9ac signal in the gene body region. The interference of TRIM23 significantly inhibited fat deposition during preadipocyte differentiation and promoted cell proliferation by increasing S-phase cell numbers. The present study provides new insights into the molecular mechanism of intramuscular fat content deposition and the epigenetic role of SIRT1 in adipocyte differentiation.

Danshao Shugan Granule therapy for non-alcoholic fatty liver disease.

BACKGROUND: Danshao Shugan Granules (DSSG), a traditional Chinese medicine (TCM), is given to protect the liver. The objective is to evaluate the mechanisms of the effects of DSSG on non-alcoholic fatty liver disease (NAFLD). METHODS: 260 patients with NAFLD were randomly allocated to positive control drugs rosiglitazone (n = 30) and Silibinin (n = 50) as well as DSSG (n = 130) and combined DSSG/Silibinin (n = 50) groups, from which 90 patients in the DSSG group were further subdivided into 3 groups (n = 30, each) depending on the severity of symptoms. In total 33 Sprague-Dawley rats were assigned to normal (n = 10) or 45% high-fat diet (n = 23) groups, from which 9 rats served as negative controls, 10 as model controls and 10 were treated with DSSG. RESULTS: DSSG medications had significantly highest effects on B-ultrasonography finding improvements, and reductions of total cholesterol, triglyceride, aspartate transaminase and γ-glutamyl transpeptidase in NAFLD patients. Silibinin application only led to significantly highest alanine transaminase reductions and rosiglitazone medication to significantly highest fasting plasma glucose reductions. In a murine in vivo NAFLD model glucose (GLU), total cholesterol (TC) triacylglycerol (TG) as well as glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and gamma-glutamyl transferase (GGT) serum concentrations were all significantly reduced (P < 0.001) and the expression of nuclear factor-κB (NF­κB) was significantly decreased in DSSG treated compared to untreated NAFLD animals (P < 0.001). In addition, the DSSG treated rats exhibited increased superoxide dismutase activity and reduced malondialdehyde values. CONCLUSIONS: DSSG was effective for treating NAFLD patients, which could be attributed to increased activity of superoxide dismutase, a decrease of malondialdehyde as well as reduced NF­κB activity in a NAFLD rat model.

CircHOMER1 aggravates oxidative stress, inflammation and extracellular matrix deposition in high glucose-induced human mesangial cells.

BACKGROUND: Circular RNAs (circRNAs) play an important regulatory role in human diseases, including diabetic nephropathy (DN). The purpose of this study was to investigate the role and mechanism of circHOMER1 action in DN. METHODS: Human mesangial cells (HMCs) were tested with high glucose (HG) to mimic DN cell models. Quantitative real-time PCR was performed to determine circHOMER1, microRNA (miR)-137 and SRY-box transcription factor 6 (SOX6) expression. SOD activity and MDA level were detected to evaluate cell oxidative stress. ELISA assay was used to analyse the levels of inflammation factors. The protein levels of extracellular matrix (ECM) deposition-related markers and SOX6 were assessed by western blot analysis. The interaction between miR-137 and circHOMER1 or SOX6 was analysed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: CircHOMER1 was highly expressed in HG-induced HMCs and DN patients. Downregulation of circHOMER1 suppressed oxidative stress, inflammation and ECM deposition in HMCs induced by HG. In terms of mechanism, circHOMER1 could sponge miR-137 to regulate SOX6. Function assays showed that miR-137 inhibitor or SOX6 overexpression revoked the negative regulation of circHOMER1 knockdown on HG-induced HMCs injury. In addition, miR-137 expression was negatively correlated with circHOMER1 and SOX6 expression in DN patients. CONCLUSION: CircHOMER1 promoted HG-induced HMCs oxidative stress, inflammation and ECM accumulation via the miR-137/SOX6 axis, suggesting that circHOMER1 might be a target for DN treatment.

Pollution characteristics and vertical cutoff wall optimization at an industrial contaminated site in China.

Vertical cutoff walls have been widely used in the remediation of contaminated sites. However, determining the best method for evaluating the long-term barrier performance of vertical cutoff walls presents a major difficulty in actual projects. Here, a case study is presented for a typical electroplating, medical, and chemical industrial park in China. Based on the analysis of groundwater pollution characteristics at the site, pollutants included metals (Ni, Al), ammonia nitrogen, and 1,2-dichloroethane. Finite element model simulations of Ni transport at the site showed that a vertical cutoff wall with a thickness of 60 cm and a hydraulic conductivity of 1.0 × 10-8 cm/s could significantly attenuate pollutant transport in the horizontal direction. Compared with other methods such as reducing the hydraulic conductivity or increasing the adsorption retardation factor of the vertical cutoff wall, increasing the thickness was more effective in controlling pollutant transport at the study site. Doubling the thickness would cause the Ni leakage concentration to decrease by more than 98% and the breakthrough time to increase by more than 47 years. It is recommended that the thickness of cutoff walls be maximized to optimize their effects on pollutant transport.

Adipose-Secreted Exosomes and Their Pathophysiologic Effects on Skeletal Muscle.

Due to its prominent secretory activity, adipose tissue (AT) is now considered a major player in the crosstalk between organs, especially with skeletal muscle. In which, exosomes are effective carriers for the intercellular material transfer of a wide range of molecules that can influence a series of physiological and pathological processes in recipient cells. Considering their underlying roles, the regulatory mechanisms of adipose-secreted exosomes and their cellular crosstalk with skeletal muscle have received great attention in the field. In this review, we describe what is currently known of adipose-secreted exosomes, as well as their applications in skeletal muscle pathophysiology.

Effect of gas pressure on municipal solid waste landfill slope stability.

Slope failure in municipal solid waste (MSW) landfills is a common environmental disaster that poses serious ecological and health risks. Landfill slope stability (SS) is sensitive to leachate levels and gas pressure (GP) caused by the degradation of organic material, but the extent of these combined effects remains poorly understood. In this study, a simplified landfill GP calculation method is presented and a circular slide method that considers the combined effects of leachate and GP is established. The results show that the landfill GP is mainly affected by the gas production rate, gas conductivity of the solid waste (SW), and landfill depth. The safety factor of landfill SS is also significantly lower when GP is considered. The distribution of GP is affected by the depth of the failure circle and SW. Landfill slope instability can be explained by localized damage caused by GP breakthrough of the filled SW. This study probably provides important guidance for the design, operation, and management of MSW landfills.

The genetics of venous thromboembolism: a systematic review of thrombophilia families.

Genetic risk factors are important for the occurrence and prognosis of venous thromboembolism (VTE). The studies of thrombophilia families are important for dissecting the genetic background of the thrombotic disease. We conducted the systematic review of all published family-based studies on VTE genetics across all racial groups through PubMed and Embase prior to 13th April 2020. This systematic review of 287 families (including 225 Caucasian families, 52 East Asian families, and families of other ethnicities) revealed a total of 21 different genes; the five most reported mutated genes were F5 (88/287, 30.7%), SERPINC1 (67/287, 23.3%), PROC (65/287, 22.6%), F2 (40/287, 13.9%) and PROS1 (48/287, 16.7%). For Caucasian families, F5 mutations were most frequently reported at 37.8% (85/225), while PROS1 mutations were most frequently reported, at 40.4% (21/52), for East Asian families (Chinese, Japanese and Korean). Factor V Leiden was reported more frequently in Caucasians than in East Asians. Missense mutations were reported frequently in the SERPINC1, PROC and PROS1 genes. In conclusion, our study found the most likely mutated genes associated with VTE among different ethnic groups and provided indications for VTE genetic testing and research in the future.

Polymerization pathway of mammalian nonmuscle myosin 2s.

The three mammalian nonmuscle myosin 2 (NM2) monomers, like all class 2 myosin monomers, are hexamers of two identical heavy (long) chains and two pairs of light (short) chains bound to the heavy chains. The heavy chains have an N-terminal globular motor domain (head) with actin-activated ATPase activity, a lever arm (neck) to which the two light chains bind, and a coiled-coil helical tail. Monomers polymerize into bipolar filaments, with globular heads at each end separated by a bare zone, by antiparallel association of their coiled-coil tails. NM2 filaments are highly dynamic in situ, frequently disassembling and reassembling at different locations within the cell where they are essential for multiple biological functions. Therefore, it is important to understand the mechanisms of filament polymerization and depolymerization. Monomers can exist in two states: folded and unfolded. It has been thought that unfolded monomers form antiparallel dimers that assemble into bipolar filaments. We now show that polymerization in vitro proceeds from folded monomers to folded antiparallel dimers to folded antiparallel tetramers that unfold forming antiparallel bipolar tetramers. Folded dimers and tetramers then associate with the unfolded tetramer and unfold, forming a mature bipolar filament consisting of multiple unfolded tetramers with an entwined bare zone. We also demonstrate that depolymerization is essentially the reverse of the polymerization process. These results will advance our understanding of NM2 filament dynamics in situ.

Comparing desorption properties of pollutants on bentonite particles and in compacted bentonite.

Desorption is one of the main factors causing groundwater and soil pollution. Therefore, the study of clay desorption characteristics is important for the prediction of groundwater and soil pollution. In previous studies, batch tests and column tests were used to study the desorption characteristics of pollutants on clay. However, the desorption parameters obtained via the two test methods were often quite different. To investigate differences in the desorption characteristics of different pollutants on clay particles and in compacted clay, batch and column desorption tests were conducted using cadmium chloride, fulvic acid, and sodium phosphate as the adsorbates and bentonite as the adsorbent. It was found that the unit particle surface area desorption distribution coefficients of pollutants on bentonite particles were approximately equal to the unit pore surface area distribution coefficients of pollutants in compacted bentonite. This indicates that the desorbed amount per unit of surface area is basically consistent, regardless of whether they are sorbed on particles or in compacted bentonite. A simple formula for determining the desorption retardation factor of pollutants in compacted bentonite is presented. The results of this study provide a reference for the prediction and evaluation of groundwater and soil pollution.

The safety and tolerability of alkaloids from Alstonia scholaris leaves in healthy Chinese volunteers: a single-centre, randomized, double-blind, placebo-controlled phase I clinical trial.

CONTEXT: Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. OBJECTIVE: To observe the clinical safety and tolerability of CALAS. MATERIALS AND METHODS: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. RESULTS: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). DISCUSSION AND CONCLUSIONS: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Effect of elevated temperature on solid waste shear strength and landfill slope stability.

Slope instability occurs in landfills owing to increased internal temperatures. However, strength characteristic tests for solid waste (SW) and landfill slope stability (SS) calculations that consider temperature variations are scarce in the literature. In this study, we conducted triaxial tests on SW under a range of temperature conditions and proposed the circular slide method (CSM) for calculating SS in consideration of temperature effects. SW cohesion decreased linearly with increasing temperature, whereas the internal friction angle remained essentially unchanged. Our results showed that higher temperatures reduced the SW shear strength, changing the most dangerous sliding arc away from the slope toe. The landfill slope safety factor decreased by more than 20% with an increase of the maximum temperature from 20°C to 50°C. Reduction of the leachate level (LL) led to a decrease in the landfill high-temperature zone and the safety factor increased according to LL and temperature distribution. If cooling pipes are used to control the SW temperature, we recommend arranging the cooling pipes on the landfill liner. The proposed CSM can be used to analyse landfill SS.

Effect of competitive adsorption on the transport of multiple pollutants through a compacted clay liner.

Leachate transport through municipal solid waste (MSW) landfill liners can be slowed considerably by adsorption. MSW landfill leachate contains a large variety of pollutants at very different concentrations, and there will be competitive adsorption as these pollutants are transported through the landfill's compacted clay liner (CCL). In this study, we used batch adsorption tests and geotechnical centrifuge modelling to examine how the adsorption of pollutants commonly found in leachate changed under competitive adsorption conditions and how competitive adsorption affected the CCL breakthrough of multiple pollutants. The results showed that the adsorption of the target pollutant on clay decreased by approximately 30% when competing pollutants were added. The speed at which the pollutants were transported through a 2-m-thick CCL increased, and the breakthrough times reduced by up to 24.8%, when the competing pollutants were mixed. Competitive adsorption significantly promoted the CCL breakthrough of pollutants at low concentrations, but it had limited effect on pollutants at high concentrations.