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[Display omitted] • Cu/γ-Al 2 O 3 and base exhibited a synergetic effect on glycerol conversion. • Dehydration and C-C cleavage were the competing reactions in glycerol conversion. • Base significantly controlled the selectivity of lactic acid/glycolic acid. • NaOH, with strong alkalinity, promoted glycerol dehydration to lactic acid. • NaHCO 3 , enhancing the proton transfer, promoted C2-C3 cleavage to glycolic acid. The numerous parallel reactions in glycerol conversion substantially challenge the effective synthesis of target chemical from oversupplied glycerol. Herein, we intensively studied the control of the complex reaction network in glycerol conversion, and realized the selective production of lactic acid or glycolic acid by integrating the use of different bases with Cu/γ-Al 2 O 3 catalyst. The results indicated that base promoted the oxidation dehydrogenation of glycerol over Cu/γ-Al 2 O 3 catalyst to glyceraldehyde intermediate. Remarkably, base significantly contributed to the control of the competitive reactions in the next glyceraldehyde transformation. DFT calculation revealed that strong base (NaOH) independently promoted the removal of H in C2 of glyceraldehyde, thereby facilitating the dehydration reaction and leading to the selective production of lactic acid. Combing with First-principles calculation, it was revealed that both NaHCO 3 and CuO species contributed to increase the electrophilicity of C2 and C3 in glyceraldehyde, thereby directing the conversion of the resultant glyceraldehyde intermediate towards the cleavage of C2-C3 to glycolal. Cu/γ-Al 2 O 3 then separately catalyzed the oxidation of glycolal selectively to glycolic acid. This work might provide a promising approach and give some clues for the valorization of glycerol in widespread applications, thus affording profitable possibilities for the sustainable biodiesel. [ABSTRACT FROM AUTHOR]

Ternary alkali-activated binder was prepared by blast furnace slag (GGBS), recycled powder (RP) and waste glass powder (WGP) using simplex centroid design method. By measuring the fluidity, setting time, drying shrinkage and mechanical property of specimen, the complementary effect of GGBS, RP and WGP was discussed. The reaction mechanism and microstructure were explored by X-ray diffraction and scanning electron microscopy. The results reveal that the addition of RP could significantly reduce the fluidity and setting time of paste, while WGP can obviously improve the rheological property and play a retarding role. The workability of paste can be effectively regulated by mixing RP and WGP together. Whether added alone or in combination, RP and WGP can effectively improve the shrinkage performance. In the ternary system, GGBS can be rapidly activated and form a skeleton structure. The fine RP particles can play a good role in filling the structure, and the pozzolanic reaction of WGP gradually occurs, which makes the microstructure more compact. The incorporation of GGBS, RP and WGP can promote the growth of hydration products, improve the density of microstructure, and form a certain complementary effect. • A ternary solid waste system was designed using simplex centroid design method. • The complementary effect of GGBS, RP and WGP was discussed. • The microstructure and reaction mechanism were analyzed. [ABSTRACT FROM AUTHOR]

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had − 11.3% (−16.4%, −5.9%), − 11.1% (−19.1%, −2.4%), and − 20.9% (−29.0%, −11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality. [Display omitted] • Semen samples were repeatedly collected from 1135 healthy men. • Seminal plasma vanadium concentrations showed fair to good reproducibility. • Poor correlation was observed between urinary and seminal plasma levels of vanadium. • Urinary and seminal plasma vanadium may be adversely related to male semen quality. [ABSTRACT FROM AUTHOR]

During development, fertilization triggers totipotency establishment, featured by zygotic genome activation/embryonic genome activation (ZGA/EGA). Mouse embryonic stem cells (mESCs) occasionally cycle through a two-cell (2C)-like status with activated expression of Dux and its targeted ZGA genes. Here, we demonstrate that deficiency of histone variant H3.3 dramatically stimulates expression of ZGA genes in mESCs. Our analysis revealed that H3.3 directly associates with Dux locus and inhibits Dux expression, therefore it is an important upstream regulator of Dux. Our finding is further supported by transcriptome change in early mouse embryos with H3.3 knockdown. We suggest that proper H3.3 level in early embryos is important to orchestrate ZGA activity for totipotency establishment. • H3.3 represses zygotic transcriptional program in mouse embryonic stem cells. • H3.3 inhibits Dux expression in mouse embryonic stem cells. • H3.3 associates with Dux locus in mouse embryonic stem cells. • H3.3 represses zygotic transcriptional program in early mouse embryos. [ABSTRACT FROM AUTHOR]

Okadaic acid (OA) is one of the most prevalent marine phycotoxin with complex toxicity, which can lead to toxic symptoms such as diarrhea, vomiting, nausea, abdominal pain, and gastrointestinal discomfort. Studies have shown that the main affected tissue of OA is digestive tract. However, its toxic mechanism is not yet fully understood. In this study, we investigated the changes that occurred in the epithelial microenvironment following OA exposure, including the epithelial barrier and gut bacteria. We found that impaired epithelial cell junctions, mucus layer destruction, cytoskeletal remodeling, and increased bacterial invasion occurred in colon of rats after OA exposure. At the same time, the gut bacteria decreased in the abundance of beneficial bacteria and increased in the abundance of pathogenic bacteria, and there was a significant negative correlation between the abundance of pathogenic bacteria represented by Escherichia/Shigella and animal body weight. Metagenomic analysis inferred that Escherichia coli and Shigella spp. in Escherichia/Shigella may be involved in the process of cytoskeletal remodeling and mucosal layer damage caused by OA. Although more evidence is needed, our results suggest that opportunistic pathogens may be involved in the complex toxicity of OA during OA-induced epithelial barrier damage. [Display omitted] • OA exposure interfered the colonic epithelial microenvironment. • OA exposure disrupted the epithelial barrier and gut bacterial composition. • Disrupted colonic epithelial barrier is accompanied by increased bacterial invasion. • Invaded pathogens may complicate the oral toxicity of OA in rats. [ABSTRACT FROM AUTHOR]

Highlights • Propose a novel ordinal metric learning methodology (i.e. OSPL) from the viewpoint of representation learning. • Present an alternating optimization algorithm to solve the OSPL model with complexity analysis. • Experimentally evaluate the effectiveness and superiority of the proposed method. Graphical abstract Abstract Ordinal metric learning (OML) is an important research branch of metric learning and has attracted increasing attention due to its wide applications where there typically exists a global order (i.e. , ordinal) relationship among the data classes, such as human age estimation and head pose recognition, etc. Although several works have been proposed to perform OML, they suffer from two critical drawbacks: 1) only the local ordinal relationships among classes rather than the global one are considered, and 2) the very time-consuming semi-definite programming is commonly involved. To avoid these shortcomings, in this paper we propose a novel OML approach, named ordinal space projection learning (OSPL) by representing one class with its neighbor classes whose representation weights are proportional to their class distance (i.e. , absolute label difference), in which the neighboring ordinal class similarities are taken into account in their reconstruction. Then, we present an alternating optimization algorithm to solve the proposed method to learn an ordinal distance space. Finally, extensive experiments on ordinal estimation tasks demonstrate effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

The need for recovery of phosphorus (P) from wastewater has accelerated the retrofitting of existing bio-nutrient removal (BNR) processes into bio-nutrient removal-phosphorus recovery processes (BNR-PR). A periodical carbon source supplement is needed to facilitate the P-recovery. But the impact of this amendment on the cold resistances of the reactor and the functional microorganisms (for nitrogen and phosphorus (P) removal/recovery) are still unknown. This study presents the performances of a biofilm BNR process with a carbon source regulated the P recovery (BBNR-CPR) process operating at different temperatures. When the temperature was decreased from 25 ± 1 °C to 6 ± 1 °C, the system total nitrogen and total phosphorus removals and the corresponding kinetic coefficients decreased moderately. The indicative genes of the phosphorus-accumulating organisms (e.g., Thauera spp. and Candidatus Accumulibacter spp.) increased significantly. An increase of Nitrosomonas spp. genes aligned to polyhydroxyalkanoates (PHAs), glycine, and extracellular polymeric substance synthesis were observed, which was probably related to cold resistance. The results provide a new vision for understanding the advantages of P recovery-targeted carbon source supplementation for constructing a new type of cold-resistant BBNR-CPR processes. [Display omitted] • Nitrosomonas genes for PHAs, glycine, EPS synthase increased with decreased temperature. • Thauera spp. as putative PAOs were selected under low temperature conditions. • The highest transcription level of chaperone was observed followed by PHA synthesis. [ABSTRACT FROM AUTHOR]

Most of today's popular deep architectures are hand-engineered to be generalists. However, this design procedure usually leads to massive redundant, useless, or even harmful features for specific tasks. Unnecessarily high complexities render deep nets impractical for many real-world applications, especially those without powerful GPU support. In this paper, we attempt to derive task-dependent compact models from a deep discriminant analysis perspective. We propose an iterative and proactive approach for classification tasks which alternates between (1) a pushing step, with an objective to simultaneously maximize class separation, penalize co-variances, and push deep discriminants into alignment with a compact set of neurons, and (2) a pruning step, which discards less useful or even interfering neurons. Deconvolution is adopted to reverse 'unimportant' filters' effects and recover useful contributing sources. A simple network growing strategy based on the basic Inception module is proposed for challenging tasks requiring larger capacity than what the base net can offer. Experiments on the MNIST, CIFAR10, and ImageNet datasets demonstrate our approach's efficacy. On ImageNet, by pushing and pruning our grown Inception-88 model, we achieve more accurate models than Inception nets generated during growing, residual nets, and popular compact nets at similar sizes. We also show that our grown Inception nets (without hard-coded dimension alignment) clearly outperform residual nets of similar complexities. • Proactive pruning can be more effective than after-the-fact pruning. • Maximizing, unraveling, and pushing discriminants into neurons prepare for pruning. • Growing the pruning base can boost accuracy and offer more sub-architecture choices. • Inception architectures can beat residual ones at similar complexities on ImageNet. [ABSTRACT FROM AUTHOR]

Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn. • We collected 5617 semen samples from 1159 healthy men. • Seminal plasma Se concentrations were inversely associated with sperm mtDNAcn. • Seminal plasma Se was positively related to sperm concentration and total count. • The association of Se with semen quality was partly mediated by sperm mtDNAcn. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) are a powerful tool for pathogenetic studies of complex diseases. The rich genetic information of GWAS data is mostly not fully utilized. In this study, we developed a sliding window-based genotype dependence testing tool SWGDT. SWGDT can be applied to GWAS data for genome-wide susceptibility gene scan utilizing known causal gene information. To evaluate the performance of SWGDT, a real GWAS dataset of Kashin-Beck disease (KBD) was analyzed. Immunohistochemistry was also performed to validate the relevance of identified gene with KBD. SWGDT analysis of KBD GWAS data identified a novel candidate gene TACR1 for KBD. Immunohistochemistry observed that the expression level of TACR1 protein in KBD articular cartilage was significantly higher than that in healthy articular cartilage. The real GWAS data analysis results illustrate the performance of SWGDT for genome-wide susceptibility gene scan. SWGDT can help to identify novel disease genes that may be missed by GWAS. [ABSTRACT FROM AUTHOR]

With deep learning's success, a limited number of popular deep nets have been widely adopted for various vision tasks. However, this usually results in unnecessarily high complexities and possibly many features of low task utility. In this paper, we address this problem by introducing a task-dependent deep pruning framework based on Fisher's Linear Discriminant Analysis (LDA). The approach can be applied to convolutional, fully-connected, and module-based deep network structures, in all cases leveraging the high decorrelation of neuron motifs found in the pre-decision space and cross-layer deconv dependency. Moreover, we examine our approach's potential in network architecture search for specific tasks and analyze the influence of our pruning on model robustness to noises and adversarial attacks. Experimental results on datasets of generic objects (ImageNet, CIFAR100) as well as domain specific tasks (Adience, and LFWA) illustrate our framework's superior performance over state-of-the-art pruning approaches and fixed compact nets (e.g. SqueezeNet, MobileNet). The proposed method successfully maintains comparable accuracies even after discarding most parameters (98%–99% for VGG16, up to 82% for the already compact InceptionNet) and with significant FLOP reductions (83% for VGG16, up to 64% for InceptionNet). Through pruning, we can also derive smaller, but more accurate and more robust models suitable for the task. • Overparameterization of deep networks can hurt speed, accuracy, and robustness. • Our pruning utility captures final class separation and its cross-layer dependency. • We prune by performing discriminative dimension reduction in the deep feature space. • The method selects the numbers and types of filters on different abstraction levels. • The method can help boost model robustness against adversarial attacks and noises. [ABSTRACT FROM AUTHOR]

Ultrasmall-sized, positively charged gold nanoclusters have been synthesized by a facile, one-step strategy, which exhibit significant antibacterial activity towards a wide spectrum of pathogenic bacteria. Positively charged gold nanoclusters (AuNCs) hold great promises as novel nanoagents in many biomedical applications, but their controllable synthesis in a simple and efficient manner remains a challenge. In the present work, by using a commercial cationic ligand, (11-mercaptoundecyl) - N,N , N -trimethylammonium bromide (MUTAB), we demonstrated that water-soluble, positively charged AuNCs can be facilely synthesized in a one-step reaction. These MUTAB-AuNCs possess near-infrared luminescence, ultra-small size, good stability and biocompatibility as well as abundant positive charges in a wide pH range. Importantly, these positively charged MUTAB-AuNCs exhibit efficient antibacterial activity against both Gram-negative bacteria and Gram-positive bacteria without inducing drug-resistance, including multidrug-resistant (MDR) bacteria and clinical bacteria. The unique antibacterial mechanism of these positively charged AuNCs was also systematically investigated by different techniques, including surface plasmon resonance, scanning electron microscopy, fluorescence imaging, DNA leakage and reactive oxygen species (ROS) assays. [ABSTRACT FROM AUTHOR]

This paper proposes a multiband imaging method for optical fiber intrusion signals to realize the multi-dimensional analysis and the characteristic spectrum extraction. Firstly, the time-frequency analysis technique is performed on the initial collected intrusion signals to obtain the time-frequency distribution at each spatial intrusion position, on which energy band-wise integration is carried out along the frequency direction to generate spatial-temporal two-dimensional images in each frequency band. Then, these images are further stacked up as layers resulting in a spatial-temporal-frequency three-dimensional (3-D) cubic data. Based on this data, we extract the characteristic spectrums as the features of the intrusion signals. The real data experiments verify the effectiveness of this method. [ABSTRACT FROM AUTHOR]

Abstract: We present, analytically, self-similar rogue wave solutions (rational solutions) of the inhomogeneous nonlinear Schrödinger equation (NLSE) via a similarity transformation connected with the standard NLSE. Then we discuss the propagation behaviors of controllable rogue waves under dispersion and nonlinearity management. In an exponentially dispersion-decreasing fiber, the postponement, annihilation and sustainment of self-similar rogue waves are modulated by the exponential parameter . Finally, we investigate the nonlinear tunneling effect for self-similar rogue waves. Results show that rogue waves can tunnel through the nonlinear barrier or well with increasing, unchanged or decreasing amplitudes via the modulation of the ratio of the amplitudes of rogue waves to the barrier or well height. [Copyright &y& Elsevier]

Abstract: Planarians exhibit an extraordinary ability to regenerate lost body parts which is attributed to an abundance of pluripotent somatic stem cells called neoblasts. In this article, we report a transcriptome sequence of a Planaria subspecies Dugesia japonica derived by high-throughput sequencing. In addition, we researched transcriptome changes during different periods of regeneration by using a tag-based digital gene expression (DGE) system. Consequently, 11,913,548 transcriptome sequencing reads were obtained. Finally, these reads were eventually assembled into 37,218 unique unigenes. These assembled unigenes were annotated with various methods. Transcriptome changes during planarian regeneration were investigated by using a tag-based DGE system. We obtained a sequencing depth of more than 3.5million tags per sample and identified a large number of differentially expressed genes at various stages of regeneration. The results provide a fairly comprehensive molecular biology background to the research on planarian development, particularly with regard to its regeneration progress. [Copyright &y& Elsevier]

Abstract: A biosensor for rapid detection of bacterial count based on adenosine 5′-triphosphate (ATP) bioluminescence has been developed. The biosensor is composed of a key sensitive element and a photomultiplier tube used as a detector element. The disposable sensitive element consists of a sampler, a cartridge where intracellular ATP is chemically extracted from bacteria, and a microtube where the extracted ATP reacts with the luciferin–luciferase reagent to produce bioluminescence. The bioluminescence signal is transformed into relevant electrical signal by the detector and further measured with a homemade luminometer. Parameters affecting the amount of the extracted ATP, including the types of ATP extractants, the concentrations of ATP extractant, and the relevant neutralizing reagent, were optimized. Under the optimal experimental conditions, the biosensor showed a linear response to standard bacteria in a concentration range from 103 to 108 colony-forming units (CFU) per milliliter with a correlation coefficient of 0.925 (n =22) within 5min. Moreover, the bacterial count of real food samples obtained by the biosensor correlated well with those by the conventional plate count method. The proposed biosensor, with characteristics of low cost, easy operation, and fast response, provides potential application to rapid evaluation of bacterial contamination in the food industry, environment monitoring, and other fields. [Copyright &y& Elsevier]

Abstract: Despite the obvious importance of limbal stem cells in corneal homeostasis and tumorigenesis, little is known about their specific biological characteristics. The purpose of this study was to characterize limbal slow-cycling cells based on the expression of ABCG2 and major histocompatibility complex (MHC) class II and the cell size. Wistar rats were daily injected with 5-bromo-2-deoxyuridine (BrdU) at a dose of 5mg/100g for 2 weeks. After 4-week BrdU-free period, corneal tissues were excised, and immunofluorescence staining for ABCG2, BrdU, and MHC class II was performed by confocal microscopy. In another series, corneal tissues of normal rat were double immunostained for ABCG2, keratin 14, keratin 3, CD11c, and MHC class II. In addition, limbal, peripheral and central corneal epithelial sheets were isolated by Dispase II digestion and dissociated into single cell by trypsin digestion and cytospin preparations were double immunostained for ABCG2 and MHC class II. The cell size and nucleus-to-cytoplasm (N/C) ratio of limbal ABCG2+ cells were analyzed and compared with those of cells from other zones. BrdU label-retaining cells (LRCs) with expression of ABCG2 were found in the limbal epithelial basal layer, but not in other parts of the cornea. Approximately 20% of these cells were MHC class II positive. All MHC class II+ cells in the corneal epithelium were positive for CD11c, a marker for dendritic cells (DCs). Double labeling with ABCG2 and keratin 14 showed that nearly four-fifth of limbal ABCG2+ cells were positive for keratin 14 but negative for keratin 3, exhibiting an undifferentiated epithelial cell lineage. Cytospin sample analysis revealed the presence of a distinct population of smaller ABCG2+ cells with expression of MHC class II with a larger N/C ratio in the limbal epithelium. A new population of small slow-cycling cells with large N/C ratio has been found to express ABCG2 in the limbal epithelial basal layer. Some of these cells normally express MHC class II antigen. These findings may have important implications for our understanding of the characteristics of limbal slow-cycling cells. [Copyright &y& Elsevier]

Abstract: Localization of CaMKIIα in lipid rafts was demonstrated in both cultured neurons and mammalian cells transfected with plasmid with an insert of CaMKIIα cDNA by using sucrose gradient centrifugation and the sensitivity to a cholesterol-extractor, methyl-β-cyclodextrin. CaMKIIα was targeted to lipid rafts possibly through protein–protein interactions via at least three domains (a.a. 261–309, 371–420, and 421–478). The multimeric structure of the full-length molecule also appeared to contribute to efficient lipid raft-targeting. Acylation of CaMKIIα did not appear to be a mechanism for the targeting. [Copyright &y& Elsevier]

Previous work have shown several key brain nuclei involved in acute psychological stress and glucose homeostasis. Acute stress influences glucose metabolism via released stress hormones by activating the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Little is known about the brain nuclei which response to peripheral glucose alteration are either abundant with glucosesensing neurons or the activations are secondary to stress. Here we profile and compare the brain nuclei that response to stress and glucose homeostasis in mouse models of acute restraint stress, glucose and 2-DG injections respectively. Our present work provide a comprehensive depiction on key brain nuclei involved in CNS control of stress and glucose homeostasis, which gives clue for functional identification of brain nuclei that regulate glucose homeostasis under stress. • Restraint stress and ER stress activate differential brain areas. • Low and high level energy states have differential responded brain areas. • Stress responding brain areas overlap with energy responding brain areas. [ABSTRACT FROM AUTHOR]

Blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) are the leading candidate biomarkers for disinfection byproduct (DBP) exposure. However, no studies have assessed the exposure profiles, temporal variability, and potential predictors of these biomarkers during pregnancy. Here we collected blood (n = 4304) and urine samples (n = 4165) from 1760 Chinese pregnant women during early, mid-, and late pregnancy, which were separately analyzed for 4 THMs and 2 HAAs. We calculated the intraclass correlation coefficients (ICCs) to assess the variability of these biomarkers and estimated their correlations with sociodemographic, water-use behavioral, dietary and sample collection factors using mixed models. The median concentrations of TCM, BDCM, Br-THMs [sum of BDCM, dibromochloromethane (DBCM), bromoform (TBM)], total THMs (TTHMs, sum of TCM and Br-THMs), DCAA and TCAA in the water distribution system were 4.2 μg/L, 1.7 μg/L, 2.9 μg/L, 7.1 μg/L, 3.4 μg/L and 8.2 μg/L, respectively. Chloroform (TCM), bromodichloromethane (BDCM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected in > 75% of the biospecimens. Repeated measurements of blood TCM, BDCM, Br-THMs and TTHMs and urinary DCAA and TCAA uniformly exhibited high variability (ICCs = 0.01–0.13); the use of a single measurement to classify gestational average exposure resulted in a high degree of exposure misclassification. The sampling season was a strong predictor of all analyzed DBPs. Additionally, we detected a positive association of blood TCM and BDCM with household income, urinary DCAA with age, and urinary TCAA with tap water usage, education level and amount of tap water consumed. Inverse associations were found between blood BDCM and vegetable consumption, and between blood Br-THM and TTHM and time interval since the last bathing/showering. Afternoon samples had lower DCAA concentrations than did early morning samples. Our results indicate that blood THM and urinary HAA concentrations vary greatly over the course of pregnancy and are affected by sampling season, time of day of blood/urine collection, sociodemographic factors, recent water-use activities and dietary intake. • Blood (n = 4304) and urine samples (n = 4165) were collected from 1760 pregnant women. • TCM, BDCM, DCAA and TCAA were detected in > 75% of the samples. • Repeated measurements of blood THMs and urinary HAAs all exhibited high variability. • Single specimen may not accurately estimate average DBP exposure during pregnancy. • Sampling season, sociodemographic, behavioral and dietary affect DBP variability. [ABSTRACT FROM AUTHOR]

Abstract Marsdenia tenacissima exhibits biological activity with heat-clearing and detoxifying properties, relieving coughs and asthma and exerting anticancer and anti-HIV effects. Tenacissioside H (TH) is a Chinese medicine monomer extracted from the dried stem of Marsdenia tenacissima. We investigated the in vivo anti-inflammatory activity of TH using three different zebrafish inflammation models: local inflammation induced by tail cutting, acute inflammation induced by CuSO 4, and systemic inflammation induced by lipopolysaccharide (LPS). Real time-polymerase chain reaction (RT-PCR) was used to elucidate the mechanism of TH action against LPS-induced inflammatory responses. Our results showed TH significantly reduced the number of macrophages in the injured zebrafish tail, inhibited CuSO 4 -induced migration of macrophages toward the neural mound, and decreased the distribution of macrophages in tail fin compared to LPS-treated group. Furthermore, TH inhibits LPS-induced inflammation responses in zebrafish by modulating the nuclear factor κB (nf-κb) and p38 pathways to regulate inflammatory cytokines, such as tumor necrosis factor-α (tnf-α), cyclooxygenase (cox-2), interleukin-1b (il-1b), interleukin-8 (il-8), interleukin-10 (il-10), nitric oxide synthase (nos2b) and prostaglandin E synthase (ptges). In conclusion, TH possesses anti-inflammation activity via the regulation of the nf-κb and p38 pathways. This finding provides a reference for the clinical application of Xiaoaiping (the trade name of Marsdenia tenacissima extract). Graphical abstract Image 1 Highlights • TH significantly inhibits inflammatory responses in zebrafish in three different inflammatory models. • TH could down-regulate inflammatory cytokines against LPS-induced inflammatory responses, such as tnf-α and nos2b. • TH inhibits LPS-induced inflammation responses in zebrafish by modulating the nuclear factor κB and p38 pathways. [ABSTRACT FROM AUTHOR]

In recent years, the interest in cider produced from pear has considerably increased as a way to add value to fruits unsuitable for direct consumption or to valorize pear varieties grown in restricted regions. In the current study, with the China National Geographic Indication Products Guangan honey pear as raw material, four commercial Saccharomyces cerevisiae strains, namely RW, SY, DV10 and Drop Acid Yeast (DAY), were used to produce pear cider, comparing their taste characteristics and metabolomic profiles changes through the combination of GC-MS, 1H-NMR and E-tongue. The results showed that there was a clear classification from the data obtained according to different yeast strains fermented Guangan honey pear cider, represented by a high discrimination index. Several pathways were altered during fermentation due to the distinct yeast strains, namely arginine and proline metabolism, glycine and serine metabolism, urea cycle, alanine metabolism, citric acid cycle, amino sugar metabolism, carnitine synthesis and warburg effect. This study could help improve the quality of Guangan honey pear cider by selecting different Saccharomyces cerevisiae yeasts and, in turn, it could shed lights on the large-scale production of pear cider. • The metabolomic profiles of pear cider were evaluated. • E-tongue can effectively distinguish different yeast strains fermented pear cider. • The combination of GC-MS and NMR provided a comprehensive metabolomic fingerprint. • Amino acids metabolism pathway was highlighted due to the distinct yeast strains. • This work could provide a theoretical basis for pear cider large-scale production. [ABSTRACT FROM AUTHOR]

Manipulation of monoterpene synthases to maximize flux towards targeted products from GPP (geranyl diphosphate) is the main challenge for heterologous monoterpene overproduction, in addition to cell toxicity from compounds themselves. In our study, by manipulation of the key enzymes geraniol synthase (GES) and farnesyl diphosphate synthase (Erg20), geraniol (a valuable acyclic monoterpene alcohol) overproduction was achieved in Saccharomyces cerevisiae with truncated 3-hydroxy-3-methylglutaryl-coenzyme reductase (tHMGR) and isopentenyl diphosphate isomerase (IDI1) overexpressed. The expressions of all above engineered genes were under the control of Gal promoter for alleviating product toxicity. Geraniol production varied from trace amount to 43.19 mg/L (CrGES, GES from Catharanthus roseus ) by screening of nine GESs from diverse species. Further through protein structure analysis and site-directed mutation in CrGES, it was firstly demonstrated that among the high-conserved amino acid residues located in active pocket, Y436 and D501 with strong affinity to diphosphate function group, were critical for the dephosphorylation (the core step for geraniol formation). Moreover, the truncation position of the transit peptide from the N-terminus of CrGES was found to influence protein expression and activity significantly, obtaining a titer of 191.61 mg/L geraniol in strain with CrGES truncated at S43 (t3CrGES). Furthermore, directed by surface electrostatics distribution of t3CrGES and Erg20 WW (Erg20 F96W-N127W ), co-expression of the reverse fusion of Erg20 ww /t3CrGES and another copy of Erg20 WW promoted the geraniol titer to 523.96 mg/L at shakes flask level, due to enhancing GPP accessibility led by protein interaction of t3CrGES-Erg20 WW and the free Erg20 WW . Eventually, a highest reported titer of 1.68 g/L geraniol in eukaryote cells was achieved in 2.0 L fed-batch fermentation under carbon restriction strategy. Our research opens large opportunities for other microbial production of monoterpenes. It also sets a good reference for desired compounds overproduction in microorganisms in terms of manipulation of key enzymes by protein engineering and metabolic engineering. [ABSTRACT FROM AUTHOR]

Land use change and excessive nitrogen (N) loading threaten the health of receiving water bodies worldwide. However, the role of hydrological connectivity in linking watershed land use, N biogeochemistry and river water quality remain unclear. In this study, we investigated 15 subwatersheds in the Jiulong River watershed (southeastern China) during a dry baseflow period in 2018, combined with 3‒year (2017–2019) nutrient monitoring in 5 subwatersheds to explore river N dynamics (dissolved nutrients, dissolved gases and functional genes) and their controlling factors at three hydrological connectivity scales, i.e., watershed, hydrologically sensitive areas (HSAs) and riparian zone. The results show that land use at HSAs (less than 20% of watershed area) and watershed scales contributed similarly to river N variation, indicating that HSAs are hotspots for transporting land N into river channels. In particular, the agricultural land was the main factor affecting river nitrate and nitrous oxide (N 2 O) concentrations, while the built–up land significantly affected river ammonium and nitrite. At the riparian zone scale, soils and sediments substantially influenced river N retention processes (i.e., nitrification and denitrification). Management and protection measures targeting HSAs and riparian zones are expected to efficiently reduce river N loading and improve water quality. [Display omitted] • Land use at HSAs and watershed scales contributes similarly to river N. • HSAs are hotspots for transporting land N into river channels. • Soil erosion and sediment denitrification significantly affect river N retention. • Management targeting HSAs and riparian zones could efficiently improve water quality. [ABSTRACT FROM AUTHOR]

In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0–9, 10–14, 15–69, or >69 days) to explore potential windows of susceptibility. After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15–69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction. [Display omitted] • Blood THMs and sperm mtDNAcn and TL were determined among 958 healthy men. • Blood TBM, Br-THMs, and TTHM were inversely associated with sperm mtDNAcn. • Blood TCM, Br-THMs, Cl-THMs, and TTHMs were inversely associated with sperm TL. • Part of these associations differed across the duration of spermatogenesis. [ABSTRACT FROM AUTHOR]

Objectives: We seek to investigate the joint effects of age and body mass index (BMI) on the incident hypertension subtypes among Chinese adults during 1989-2011.Methods: We investigated the Incidence rates (IRs, per 100person-years) of hypertension subtypes, adjusted relative risks (RRs) and population attributable risk percent (PAR%) of BMI for hypertension, and clarified the age-specific effect of BMI on incident hypertension utilizing a dynamic cohort study from the China Health and Nutrition Survey (CHNS) 1989-2011.Results: Normotensive participants (n=53,028) at baseline were included, with mean age was 41.7 (95% CI, 41.6-41.7)years old. During a total of 118,694person years (average was 6.38years) of follow-up, a total of 5208 incident cases of hypertension were documented. The IRs of hypertension were 4.4 (95% CI, 4.3-4.5), which increased gradually by age and BMI (Ptrend<0.001). Compared with those with BMI<22kg/m(2), the RR of hypertension was 3.13 (95% CI, 2.84-3.45) in the group with BMI≥28kg/m(2). The PAR% (BMI>22 vs. BMI<22) for hypertension in Chinese population was 32% (95% CI, 29-34%). Similar trends were observed in all age and BMI groups for both isolated systolic hypertension and systolic-diastolic hypertension, which were mainly affected by age. In contrast, the peak IR of isolated diastolic hypertension was observed in participants aged 30-49years with higher BMIs.Conclusions: The PAR% (IR of BP≥140/90 or treatment for BMI>22 vs. IR for BMI<22) of elevated body weight for hypertension was 32% in Chinese population. [ABSTRACT FROM AUTHOR]

Abstract: Neural stem cells (NSCs) are of great value for clinical application and scientific research. The development of efficient cryopreservation protocols could significantly facilitate the storage and transportation for clinic applications. The objective of the present study is to improve the survival rate and viability of NSCs. Neural stem cells with three states of single-cell suspension, NSC spheres with diameters of 30–50μm and 80–100μm, were cryopreserved by slow-freezing method with the cryoprotective agent (CPA) of dimethyl sulfoxide (Me2SO), respectively. Then the post-thawing NSCs were tested for the survival rate and the differentiation ability. As a result, NSC spheres with diameter of 80–100μm and Me2SO concentration of 8% achieve the survival rate of 82.9%, and the NSCs still sustain the multi-differentiation potentiality. These results indicated that both the subtle interaction among NSCs and sphere diameters may affect the survival rate together. [Copyright &y& Elsevier]

Abstract: The objective of this work was to select and test systematically possible cryoprotective agents (CPAs) and to obtain a suitable formula for vitrification of corneal endothelial cells (CECs). Fresh bovine CECs were isolated and tested with an optimized vitrification protocol with multi-step CPA loading and removal. Three types of CPAs components, i.e. the penetrating CPAs, sugars and macromolecular compounds, were experimentally evaluated using the viability assayed by trypan blue. Dimethyl sulfoxide, ethylene glycol (EG), 1,2-propanediol, 2,3-butanediol, acetamide and ethylene glycol monomethyl ether were chosen as the penetrating CPA components. Sugars including xylose, fructose, mannose, glucose, maltose, sucrose and trehalose were tested. Ficoll (MW 7kDa), dextran (MW 7kDa), chondroitin sulfate (CS, MW 18–30kDa), bovine serum albumin (MW 68kDa) and polyethylene glycol (MW 6kDa, 10kDa and 20kDa) were chosen as the macromolecular compounds. CECs were also preserved by slow freezing as a control. The results showed that EG was the most suitable penetrating CPA component and glucose the most suitable sugar, and CS the most suitable macromolecule. The optimized concentrations for each component in the vitrification solution were 52% (w/w) EG, 8% (w/w) glucose and 3% (w/w) CS. The CEC survival rate of 89.4±2.1% (mean±SD) was obtained using this formula and established vitrification protocol which was comparable to that by slow freezing. [Copyright &y& Elsevier]