Fine particulate matter and polycystic ovarian morphology.

BACKGROUND: Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM. METHODS: We conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004-2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI). RESULTS: Cumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 µg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57). CONCLUSIONS: In this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.

Efficient degradation of tetracycline by singlet oxygen-dominated peroxymonosulfate activation with magnetic nitrogen-doped porous carbon.

Nonradical reaction driven by peroxymonosulfate (PMS) based advanced oxidation processes has drawn widespread attention in water treatment due to their inherent advantages, but the degradation behavior and mechanism of organic pollutants are still unclear. In this study, the performance, intermediates, mechanism and toxicity of tetracycline (TC) degradation were thoroughly examined in the constructed magnetic nitrogen-doped porous carbon/peroxymonosulfate (Co-N/C-PMS) system. The results showed that 85.4% of TC could be removed within 15 min when Co-N/C and PMS was simultaneously added and the degradation rate was enhanced by 3.4 and 14.7 folds compared with Co-N/C or PMS alone, respectively. Moreover, the performance of Co-N/C was superior to that of most previously reported catalysts. Many lines of evidence indicated that Co-N/C-PMS system was a singlet oxygen-dominated nonradical reaction, which was less interfered by pH and water components, and displayed high adaptability to actual water bodies. Subsequently, the degradation process was elaborated on the basis of three-dimensional excitation-emission matrix spectra and liquid chromatography-mass spectrometry. At last, the toxicity of treated TC was greatly reduced by using microalgae Coelastrella sp. as ecological indicator. This study provides a promising approach based on singlet oxygen-dominated nonradical reaction for eliminating TC in water treatment.

Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy.

Parkinson's disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson's disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson's disease probands with autosomal-dominant Parkinson's disease and 1934 patients with sporadic Parkinson's disease revealed another two variants in UQCRC1 in the probands with familial Parkinson's disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson's disease.

Characterization of Antineovascularization Activity and Ocular Pharmacokinetics of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GNE-947.

The objectives of the present study were to characterize GNE-947 for its phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitory activities, in vitro anti-cell migration activity in human umbilical vein endothelial cells (HUVECs), in vivo antineovascularization activity in laser-induced rat choroidal neovascular (CNV) eyes, pharmacokinetics in rabbit plasma and eyes, and ocular distribution using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) and autoradioluminography. Its PI3K and mTOR K i were 0.0005 and 0.045 µM, respectively, and its HUVEC IC50 was 0.093 µM. GNE-947 prevented neovascularization in the rat CNV model at 50 or 100 µg per eye with repeat dosing. After a single intravenous injection at 2.5 and 500 µg/kg in rabbits, its plasma terminal half-lives (t 1/2) were 9.11 and 9.59 hours, respectively. After a single intravitreal injection of a solution at 2.5 µg per eye in rabbits, its apparent t 1/2 values were 14.4, 16.3, and 23.2 hours in the plasma, vitreous humor, and aqueous humor, respectively. After a single intravitreal injection of a suspension at 33.5, 100, 200 µg per eye in rabbits, the t 1/2 were 29, 74, and 219 days in the plasma and 46, 143, and 191 days in the eyes, respectively. MALDI-IMS and autoradioluminography images show that GNE-947 did not homogenously distribute in the vitreous humor and aggregated at the injection sites after injection of the suspension, which was responsible for the long t 1/2 of the suspension because of the slow dissolution process. This hypothesis was supported by pharmacokinetic modeling analyses. In conclusion, the PI3K/mTOR inhibitor GNE-947 prevented neovascularization in a rat CNV model, with t 1/2 up to approximately 6 months after a single intravitreal injection of the suspension in rabbit eyes. SIGNIFICANCE STATEMENT: GNE-947 is a potent phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor and exhibits anti-choroidal neovascular activity in rat eyes. The duration of GNE-947 in the rabbit eyes after intravitreal injection in a solution is short, with a half-life (t 1/2) of less than a day. However, the duration after intravitreal dose of a suspension is long, with t 1/2 up to 6 months due to low solubility and slow dissolution. These results indicate that intravitreal injection of a suspension for low-solubility drugs can be used to achieve long-term drug exposure.

The co-existence of anammox genera in an expanded granular sludge bed reactor with biomass carriers for nitrogen removal.

Anaerobic ammonium oxidation (anammox)-based nitrogen removal saves aeration energy and organic carbon costs, attributed to its anaerobic and autotrophic nature. However, due to the slow growth of anaerobic ammonium oxidation bacteria (AnAOB), drawbacks including long startup time and sensitivity to toxins still hamper the application of anammox-based processes. To cope with the slow growth of AnAOB, various bioreactor configurations have been investigated for the capability of retaining anammox biomass, among which, the expanded granular sludge bed (EGSB) reactor is a promising option. In this study, two laboratory-scale EGSB reactors were used to gain insights of microbial population and their response to amending biofilm-carriers, aiming to enhance the biomass retention of AnAOB. The respective ammonium and nitrite removal efficiencies were up to over 90%, and the overall nitrogen removal efficiency (NRE) was stable at over 70%, in the EGSB reactor amended with carriers (CEGSB). Compared to the control EGSB, CEGSB's observed performance was more stable during the 236-day operational period. The abundance of AnAOB reached 22% in the EGSB and 49% in the CEGSB. It was also observed that Ca. Brocadia (14.25%) and Asahi BRW2 (33.19%) coexisted in the CEGSB. The dynamics of major metabolisms and functional genes involved in nitrogen conversion were further observed by FAPROTAX based on the taxonomic data, providing more insights into the functions of the microbial communities.

A comprehensive comparable study of the physiological properties of four microalgal species under different light wavelength conditions.

MAIN CONCLUSION: Microalgae treated with blue light have potential for production of human nutrition supplement and biofuel due to their higher biomass productivity and favorable fatty acid composition. Chlorella vulgaris, Chlorella pyrenoidosa, Scenedesmus quadricauda and Scenedesmus obliquus are representative green microalgae which are widely reported for algal production. In this study, we provide a systematic investigation of the biomass productivity, photosynthetic pigments, chlorophyll fluorescence and fatty acid content of the four green microalgae. The strains were grown in two primary monochromatic light wavelengths [red and blue LEDs (light emitting diode)], and in white LED conditions, respectively. Among them, blue LED light was determined as the best light for growth rate, followed by red LED and white LED. The chlorophyll generation was more sensitive to the monochromatic blue light. The polyunsaturated fatty acids (PUFAs) such as α-linolenic acid (18:3), which were perfect for human nutrition supplementation, showed high concentrations in these algae strains under blue LED. Collectively, the results indicate that the blue LED is suitable for various food, feed, and algal biofuel productions due to both biomass and fatty acid productivity.

Transcriptomic Profiling and Gene Disruption Revealed that Two Genes Related to PUFAs/DHA Biosynthesis May be Essential for Cell Growth of Aurantiochytrium sp.

Aurantiochytrium sp. PKU#SW7 is a thraustochytrid strain that was found to exhibit high potential for docosahexaenoic acid (DHA, C22:6n-3) production. In this work, the transcriptome of Aurantiochytrium sp. PKU#SW7 was analyzed for the study of genes involved in basic metabolic functions and especially in the mechanisms of DHA biosynthesis. Sequence annotation and functional analysis revealed that the strain contains components of fatty acid synthesis (FAS) and polyketide synthase (PKS) pathways. Fatty acid desaturases and elongases were identified as components of FAS pathway, whilst key components of PKS pathway were also found in the cDNA library. The relative contribution of the two pathways to the synthesis of DHA was unknown, as both pathways appeared to be lacking full complement of genes for standalone synthesis of DHA. Further analysis of two putative genes encoding the very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase and dehydrase/isomerase involved in FAS and PKS pathways, respectively, revealed that under various salinity conditions, their relative expression levels changed corresponding to the variation of DHA content in Aurantiochytrium sp. Independent knock outs of these genes in Aurantiochytrium sp. resulted in poor cell growth, probably due to little or no intracellular DHA accumulation. Hence, it can be speculated that both genes are engaged in DHA biosynthesis and DHA in Aurantiochytrium sp. could be produced by jointed actions of both FAS and PKS systems.

Effects of selenite on chlorophyll fluorescence, starch content and fatty acid in the duckweed Landoltia punctata.

Developing a Se-enriched feed for animal has become a considerable effort. In this study, Landoltia punctata 7449 was grown over a 12 day period under concentrations of selenite (Na2SeO3) from 0 to 80 µmol L(-1). The growth rate, the chlorophyll fluorescence, the starch content and fatty acid were measured. Se at low concentrations of ≤20 µmol L(-1) had positive effects also on growth rate, fatty acid content and yield of the L. punctata. The appropriate Se treatment enhanced the activity of the photosynthetic system by increasing Fv, Fm, Fv/Fm and Fv/Fo and decreasing Fo. However, negative impact to the L. punctata was observed when the duckweed was exposed to high Se concentrations (≥40 µmol L(-1)). Significant increases in starch content in the duckweed were observed after Se application. The present study suggests that the changes in growth rate, the photosynthetic system, the starch content and the fatty acid were closely associated with the application of Se. An increased Se concentration (0-20 µmol L(-1)) in duckweed could positively induce photosynthesis, thereby increasing the yield of L. punctata and could be a resource for high nutritive quality Se-enrich feed.

Efficient production of triacylglycerols rich in docosahexaenoic acid (DHA) by osmo-heterotrophic marine protists.

Thraustochytrids have recently emerged as a promising source for docosahexaenoic acid (DHA) production due to their high growth rate and oil content. In this study, two thraustochytrid isolates, Aurantiochytrium sp. PKU#SW7 and Thraustochytriidae sp. PKU#Mn16 were used for DHA production. Following growth parameters were optimized to maximize DHA production: temperature, pH, salinity, and glucose concentration. Both isolates achieved the highest DHA yield at the cultivation temperature of 28 °C, pH 6, 100 % seawater, and 2 % glucose. A DHA yield of 1.395 g/l and 1.426 g/l was achieved under the optimized culture conditions. Further investigation revealed that both isolates possess simple fatty acids profiles with palmitic acid and DHA as their dominant constituents, accounting for ∼79 % of total fatty acids. To date, very few studies have focused on the DHA distribution in various lipid fractions which is an important factor for identifying strains with a potential for industrial DHA production. In the present study, the lipids profiles of each strain both revealed that the majority of DHA was distributed in neutral lipids (NLs), and the DHA distribution in NLs of PKU#SW7 was exclusively in the form of triacylglycerols (TAGs) which suggest that PKU#SW7 could be utilized as an alternative source of DHA for dietary supplements. The fermentation process established for both strains also indicating that Aurantiochytrium sp. PKU#SW7 was more suitable for cultivation in fermenter. In addition, the high percentage of saturated fatty acids produced by the two thraustochytrids indicates their potential application in biodiesel production. Overall, our findings suggest that two thraustochytrid isolates are suitable candidates for biotechnological applications.

Structural integrity affects nitrogen removal activity of granules in semi-continuous reactors.

Granules were observed after more than two years of operation in two semi-continuously fed intermittently aerated reactors treating swine wastewater with aerobic:anoxic cycles of 1:1 h and 1:4 h. Subsequently, the granules and flocs were compared with respect to physical characteristics, activity, and microbial community structure. Granules exhibited higher specific nitrification and denitrification rates than flocs. However, once granule structural integrity was disrupted, the rates decreased to levels similar to those of flocs. Membrane hybridizations using 16S rRNA-targeted probes showed that ammonia oxidizing bacteria populations in flocs and granules were dominated by Nitrosomonas and Nitrosococcus mobilis. Granules provided better conditions for Nitrospira compared to flocs. The diversities of the dominant bacterial populations in granules and flocs were not significantly different. Our findings highlight the importance of structural integrity of granules to their nitrogen removing activity.

Cupric ions inducing dynamic hormesis in duckweed systems for swine wastewater treatment: Quantification, modelling and mechanisms.

Hormesis has attracted close attention of environmental and toxicological communities over the past decades. Most studies focused on the hormesis induced by stressors in the aspect of their biotoxicity to organisms, while little research was conducted on hormesis in the aspect of biological wastewater treatment process. In this study, removal of NH4+-N and Cu2+ by S. polyrrhiza under long-term Cu2+ exposure at environmentally relevant concentrations in swine wastewater was investigated. Removal efficiencies of NH4+-N by duckweeds at 0.0, 0.1, 0.5, 1.0, 2.0 and 4.0 mg/L Cu2+ were 81.6 %, 83.7 %, 89.4 %, 74.9 %, 61.8 % and 45.1 % on day 28, however, during the initial period of cultivation (0-4 days), such hormetic effect was not observed, indicating time-dependent feature of hormesis in NH4+-N removal. The modified logistic growth model was applied to describe long-term hormesis induced by Cu2+ on NH4+-N removal and it suggested that the optimal copper exposure for ammonium removal was 0.48 mg/L. More importantly, it was found that previous exposure to low doses of Cu2+ (0-1 mg/L) could enhance NH4+-N removal performance under the second exposure. Cu2+ above 1 mg/L could switch copper bioaccumulation pattern from the Langmiur-irreversible type to reversible one, indicating risk of secondary pollution. Six components including freshly-produced humic-like substances, lignin, fulvic acid-protein complex, free amino acid-like substances, tyrosine-like substance and soluble amino acid-like substances in duckweeds were detected by parallel factor (PARAFAC) model detected. Principle component analysis (PCA) conducted on PARAFAC components suggested that enhanced synthesis of protein and growth factors intracellularly at low dose stimulation improved ammonia uptake from the environment. This study provided a novel strategy to improve treatment performance of duckweeds for copper contaminated wastewater and helped understand biochemical responses and their roles in evolutionary adaptive strategies to stresses.

Effect of composition of volatile fatty acids on yield of polyhydroxyalkanoates and mechanisms of bioconversion from activated sludge.

Polyhydroxyalkanoates (PHA) is green biodegradable natural polymer. Here PHA production from volatile fatty acids (VFAs) was investigated in sequential batch reactors inoculated with activated sludge. Single or mixed VFAs ranging from acetate to valerate were evaluated, and the dominant VFA concentration was 2 times of that of the others in the tests. Results showed that mixed substrates achieved about 1.6 times higher yield of PHA production than single substrate. The butyrate-dominated substrates maximized PHA content at 72.08% of VSS, and the valerate-dominated substrates were followed with PHA content at 61.57%. Metabolic flux analysis showed the presence of valerate in the substrates caused a more robust PHA production. There was at least 20% of 3-hydroxyvalerate in the polymer. Hydrogenophaga and Comamonas were the main PHA producers. As VFAs could be produced in anaerobic digestion of organic wastes, the methods and data here could be referred for efficient green bioconversion of PHA.

Catalytic activity and reaction mechanisms of single-atom metals anchored on nitrogen-doped carbons for peroxymonosulfate activation.

Single-atom catalysts have attracted tremendous interests in peroxymonosulfate (PMS)-based advanced oxidation processes due to their maximum atom utilization and high reactivity, however the role of nitrogen-coordinated metal (MNx) sites with different metal centers remain blurred. Herein, a series of single-atom metals anchored on nitrogen-doped carbons (denoted as M-N/C, M = Fe, Co, Cu, and Mn) using zeolitic imidazolate frameworks as precursors are constructed for PMS activation. Their catalytic activity order follows Fe > Co > undoped N/C > Cu > Mn, especially the degradation rates of the eight model pollutants for Fe-N/C and Co-N/C are 2.5-22.4 and 1.5-19.5 times higher than those for undoped N/C, respectively. Moreover, the nature of catalytic metal center can govern the degradation behaviors in the coexisting water constituents. Experimental and theoretical results reveal that singlet oxygen (1O2) is the main oxidant responsible for pollutant degradation and its evolution path over FeN4 or CoN4 sites (PMS→OH*→*O→1O2) is elucidated, between which FeN4 with lower energy barrier is more conducive to 1O2 generation. This study can not only provide guidance for the development of highly active atomic M-N/C catalysts, but also lead to a better molecular-level understanding of PMS activation mechanism over MN4 sites.

Stress of cupric ion and oxytetracycline in Chlorella vulgaris cultured in swine wastewater.

Chlorella culturing has the advantages in treatment of wastewater including swine wastewater from anaerobic digesters due to the product of biolipids and the uptake of carbon dioxide. However, there often exist high concentrations of antibiotics and heavy metals in swine wastewater which could be toxic to chlorella and harmful to the biological systems. This study examined the stress of cupric ion and oxytetracycline (OTC) at various concentrations on the nutrient removal and biomass growth in Chlorella vulgaris culturing in swine wastewater from anaerobic digesters, and its biochemical responses were also studied. Results showed that dynamic hormesis of either OTC concentration or cupric ion one on Chlorella vulgaris were confirmed separately, and the presence of OTC not only did not limit biomass growth and lipids content of Chlorella vulgaris but also could mitigate the toxicity of cupric ion on Chlorella vulgaris in combined stress of Cu2+ and OTC. Extracellular polymeric substances (EPS) of Chlorella vulgaris were used to explain the mechanisms of stress for the first time. The content of proteins and carbohydrates in EPS increased, and the fluorescence spectrum intensity of tightly-bound EPS (TB-EPS) of Chlorella vulgaris decreased with increasing concentration of stress because Cu2+ and OTC may be chelated with proteins of TB-EPS to form non-fluorescent characteristic chelates. The low concentration of Cu2+ (≤1.0 mg/L) could enhance the protein content and promote the activity of superoxide dismutase (SOD) while these parameters were decreased drastically under 2.0 mg/L of Cu2+. The activity of adenosine triphosphatase (ATPase) and glutathione (GSH) enhanced with the increase of OTC concentration under combined stress. This study helps to comprehend the impact mechanisms of stress on Chlorella vulgaris and provides a novel strategy to improve the stability of microalgae systems for wastewater treatment.

Chitosan-Fe3O4 composites enhance anaerobic digestion of liquor wastewater under acidic stress.

Acid stress in the anaerobic digestion process of liquor wastewater leads to low anaerobic treatment efficiency. Herein, chitosan-Fe3O4 was prepared, and its effects on anaerobic digestion processes under acid stress were studied. Results showed that chitosan-Fe3O4 increased the methanogenesis rate of anaerobic digestion of acidic liquor wastewater by 1.5-2.3 times and accelerated the restoration of acidified anaerobic systems. The analysis of sludge characteristics showed that chitosan-Fe3O4 promoted the secretion of proteins and humic substances in extracellular polymeric substances and increased the electron transfer activity of the system by 71.4%. Microbial community analysis indicated that chitosan-Fe3O4 enriched the abundance of Peptoclostridium, and Methanosaeta participated in direct interspecies electron transfer. Chitosan-Fe3O4 could promote the direct interspecies electron transfer pathway to maintain stable methanogenesis. These methods and results regarding the use of chitosan-Fe3O4 could be referred to for improving the efficiency of anaerobic digestion of high concentration organic wastewater under acid inhibition.

Combined effects of oxytetracycline concentration and organic loading rate on semi-continuous anaerobic digestion of swine wastewater.

High concentrations of antibiotics in swine wastewater raises concerns about the potential adverse effects of anaerobic digestion (AD). Current studies mainly focused on the effects of various antibiotic concentrations. However, these studies didn't take into account the fluctuation of swine wastewater quality and the change of reactor operating conditions in practical engineering applications. In this study, it was found that in the operating systems with COD of 3300 mg/L and hydraulic retention time (HRT) of 4.4 days, the continuous addition of oxytetracycline for 30 days had no effect on the AD performance. Nevertheless, when COD and HRT were changed to 4950 mg/L and 1.5 days respectively, oxytetracycline at 2 and 8 mg/L increased the cumulative methane yield by 27% and 38% at the cost of destroying cell membrane, respectively, while oxytetracycline at 0.3 mg/L improved the performance and stability of AD. These results could be referred for practical engineering applications.

Meta-analysis of individualized treatment rules via sign-coherency.

Medical treatments tailored to a patient's baseline characteristics hold the potential of improving patient outcomes while reducing negative side effects. Learning individualized treatment rules (ITRs) often requires aggregation of multiple datasets(sites); however, current ITR methodology does not take between-site heterogeneity into account, which can hurt model generalizability when deploying back to each site. To address this problem, we develop a method for individual-level meta-analysis of ITRs, which jointly learns site-specific ITRs while borrowing information about feature sign-coherency via a scientifically-motivated directionality principle. We also develop an adaptive procedure for model tuning, using information criteria tailored to the ITR learning problem. We study the proposed methods through numerical experiments to understand their performance under different levels of between-site heterogeneity and apply the methodology to estimate ITRs in a large multi-center database of electronic health records. This work extends several popular methodologies for estimating ITRs (A-learning, weighted learning) to the multiple-sites setting.

Effects of Sulfamethazine and Cupric Ion on Treatment of Anaerobically Digested Swine Wastewater with Growing Duckweed.

Duckweed (Spirodela polyrrhiza) has the potential to treat anaerobically digested swine wastewater (ADSW), but the effects of antibiotics and heavy metals in ADSW on the treatment performance and mechanism of Spirodela polyrrhiza are not clear. Herein, an experiment was conducted to investigate the effects of sulfamethazine (SMZ) and cupric ion on NH4+-N and total phosphorus (TP) removal from synthetic ADSW. The activity of superoxide dismutase (SOD) and the contents of photosynthetic pigments, vitamin E, and proteins in duckweed were also evaluated. Under the stress of SMZ, duckweed showed excellent removal efficiency of nutrients, and the results of SOD activity and photosynthetic pigments content indicated that duckweed had good tolerance to SMZ. Interestingly, a combined application of SMZ and cupric ion would inhibit the nutrient removal by duckweed, but significantly increased the contents of photosynthetic pigments, proteins, and vitamin E. In addition, the consequence indicated that high value-added protein and vitamin E products could be produced and harvested by cultivating duckweed in ADSW. Furthermore, possible degradation pathways of SMZ in the duckweed system were proposed based on the analysis with LC-MS/MS. This research proposed a novel view for using duckweed system to remove nutrients from ADSW and produce value-added products under the stress of SMZ and cupric ion.

Genome-centric metagenomics provides new insights into the microbial community and metabolic potential of landfill leachate microbiota.

Landfills are important sources of microorganisms associated with anaerobic digestion. However, the knowledge on microbiota along with their functional potential in this special habitat are still lacking. In this study, we recovered 1168 non-redundant metagenome-assembled genomes (MAGs) from nine landfill leachate samples collected from eight cities across China, spanning 42 phyla, 73 classes, 114 orders, 189 families, and 267 genera. Totally, 74.1% of 1168 MAGs could not be classified to any known species and 5.9% of these MAGs belonged to microbial dark matter phyla. Two putative novel classes were discovered from landfill leachate samples. The identification of thousands of novel carbohydrate-active enzymes showed similar richness level compared to the cow rumen microbiota. The methylotrophic methanogenic pathway was speculated to contribute significantly to methane production in the landfill leachate because of its co-occurrence with the acetoclastic and hydrogenotrophic methanogenic pathways. The genetic potential of dissimilatory nitrate reduction to ammonium (DNRA) was observed, implying DNRA may play a role in ammonium generation in landfill leachate. These findings implied that landfill leachate might be a valuable microbial resource repository and filled the previous understanding gaps for both methanogenesis and nitrogen cycling in landfill leachate microbiota. Our study provides a comprehensive genomic catalog and substantially provides unprecedented taxonomic and functional profiles of the landfill leachate microbiota.

A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism.

Emerging evidence suggests that cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in cancer and the development of PHGDH inhibitors in drug discovery.