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1.
Environ Sci Ecotechnol ; 21: 100422, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38746775

ABSTRACT

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

2.
Curr Neuropharmacol ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38752632

ABSTRACT

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that greatly affects the health and life quality of the elderly population. Existing drugs mainly alleviate symptoms but fail to halt disease progression, underscoring the urgent need for the development of novel drugs. Based on the neuroprotective effects of flavonoid quercetin in AD, this study was designed to identify potential AD-related targets for quercetin and perform in silico prediction of promising analogs for the treatment of AD. Database mining suggested death-associated protein kinase 1 (DAPK1) as the most promising AD-related target for quercetin among seven protein candidates. To achieve better biological effects for the treatment of AD, we devised a series of quercetin analogs as ligands for DAPK1, and molecular docking analyses, absorption, distribution, metabolism, and excretion (ADME) predictions, as well as molecular dynamics (MD) simulations, were performed. The energy for drug-protein interaction was predicted and ranked. As a result, quercetin-A1a and quercetin-A1a1 out of 19 quercetin analogs exhibited the lowest interaction energy for binding to DAPK1 than quercetin, and they had similar dynamics performance with quercetin. In addition, quercetin-A1a and quercetin-A1a1 were predicted to have better water solubility. Thus, quercetin-A1a and quercetin-A1a1 could be promising agents for the treatment of AD. Our findings paved the way for further experimental studies and the development of novel drugs.

3.
Environ Sci Technol ; 58(9): 4193-4203, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38393778

ABSTRACT

Sulfur disproportionation (S0DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S0DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m3/d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m3/d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m3/d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S0DP functional community from S0DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S0DP reaction to +2.56 kJ, thermodynamically suppressing the S0DP occurrence. Therefore, a multisubunit design along with S0DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S0DP in various practical sulfur-packed bioreactors.


Subject(s)
Carbonates , Ecosystem , Ferric Compounds , Nitrates , Nitrates/metabolism , Autotrophic Processes , Temperature , Sulfur/metabolism , Bioreactors , Denitrification , Nitrogen
4.
Bioresour Technol ; 393: 130081, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37993067

ABSTRACT

The sulfur fluidizing bioreactor (S0FB) has significant superiorities in treating nitrate-rich wastewater. However, substantial self-acidification has been observed in engineering applications, resulting in frequent start-up failures. In this study, self-acidification was reproduced in a lab-scale S0FB. It was demonstrated that self-acidification was mainly induced by sulfur disproportionation process, accounting for 93.4 % of proton generation. Supplying sufficient alkalinity to both the influent (3000 mg/L) and the bulk (2000 mg/L) of S0FB was essential for achieving a successful start-up. Furthermore, the S0FB reached 10.3 kg-N/m3/d of nitrogen removal rate and 0.13 kg-PO43-/m3/d of phosphate removal rate, respectively, surpassing those of the documented sulfur packing bioreactors by 7-129 times and 26-65 times. This study offers a feasible and practical method to avoid self-acidification during restart of S0FB and highlights the considerable potential of S0FB in the treatment of nitrate-rich wastewater.


Subject(s)
Nitrates , Wastewater , Autotrophic Processes , Denitrification , Sulfur , Bioreactors , Hydrogen-Ion Concentration , Nitrogen
5.
Environ Sci Technol ; 57(43): 16522-16531, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37844031

ABSTRACT

Reactive fillers consisting of reduced sulfur and iron species (SFe-ReFs) have received increasing attention in tertiary wastewater treatment for nitrate and phosphate coremoval. However, the existing SFe-ReFs suffer from either low performance (e.g., pyrrhotite and pyrite) or unsatisfactory use in terms of combustible risk and residual nonreactive impurities (e.g., sulfur mixing with natural iron ores). Here, we developed a new type of sulfur-siderite composite ReF (SSCReF) with a structure of natural siderite powders eventually embedded into sulfur. SSCReFs exhibited many excellent properties, including higher mechanical strengths and hardness and especially much poorer ignitability compared to pure sulfur. By using SSCReF to construct packed-bed reactors, the highest denitrification and dephosphorization rates reached 829.70 gN/m3/d (25 wt % siderite) and 36.70 gP/m3/d (75 wt % siderite), respectively. Dephosphorization was demonstrated to be dependent on sulfur-driven denitrification, in which the acid produced from the later process promoted Fe(II) dissolution, which then directly combined with phosphate to form vivianite or further converted into phosphate adsorbents (ferrihydrite, a green rust-like compound). Water flush was an effective way to finally wash out these surface deposited Fe-P compounds, as well as those nonreactive impurities (Si and Al-bearing compounds) detached from SSCReF. Such a highly efficient and safe SSCReF holds considerable application potential in secondary effluent polishing.


Subject(s)
Denitrification , Nitrates , Bioreactors , Sulfur , Iron , Phosphates , Nitrogen , Autotrophic Processes
6.
Environ Res ; 238(Pt 2): 117213, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37776937

ABSTRACT

Sulfur-packed beds (SPBs) have been increasingly incorporated into constructed wetland systems to overcome limitations in achieving satisfactory nitrate removal efficiency. However, the underlying impact of hydraulic regimes on SPB performance remains understudied. This study investigated the performance of a pilot-scale SPB, encompassing sulfur autotrophic denitrification (SAD) and sulfur disproportionation (SDP) processes, under various horizontal flow (HF) and vertical flow (VF) regimes. The HF regime exhibited superior SAD efficiency, achieving 3.1-4.4 mg-N/L of nitrate removal compared to 0.9-2.8 mg-N/L under VF regimes. However, greater sulfide production of 3.8-5.6 mg/L was observed, in contrast to only 1.5-2.3 mg/L under VF regimes when SDP occurred. Employing current computational fluid dynamics simulations could predict general regimes but lacked precision in detailing sulfur layer dynamics. In contrast, determining the spatial distribution of SAD substrates and SDP products offered a viable solution, revealing stagnate, short-circuit, and back flows. Moreover, the feasibility of an aeration approach to reduce sulfide emissions below 0.5 mg/L in case of accidental SDP occurrence was confirmed. This study offers a method for assessing detailed hydraulic regimes within SPBs. Additionally, it provides guidance on optimizing the packing of sulfur-based materials when implementing SPBs in constructed wetland systems and presents a strategy for mitigating excessive sulfide emissions.


Subject(s)
Denitrification , Nitrates , Sulfur , Wetlands , Sulfides , Bioreactors , Nitrogen
7.
Molecules ; 28(17)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37687230

ABSTRACT

A versatile mono-Schiff compound consisting of o-aminobenzene-hydroxyjulolidine (ABJ-MS) has been easily synthesized using a one-step reaction. ABJ-MS displays four diverse fluorescence responses to the addition of Zn2+/Al3+/Fe3+/Ag+, with the maximum fluorescence emission at 530 nm undergoing a hypsochromic shift to 502/490/440/430 nm, synchronously with the discriminating fluorescence enhancement being 10.6/22.8/2.6/7.1-fold, respectively. However, the addition of Cu2+ into ABJ-MS leads to an opposite behavior, namely, fluorescence quenching. Meanwhile, ABJ-MS also displays distinct absorption changes after adding these five metal ions due to different binding affinities between them and ABJ-MS, which gives ABJ-MS quite a versatile detecting nature for Cu2+/Zn2+/Al3+/Fe3+/Ag+. Moreover, ABJ-MS can mimic a series of versatile AND/OR/INH-consisting logic circuits on the basis of the Cu2+/Zn2+/Al3+/Fe3+/Ag+-mediated diverse optical responses. These will endow the smart ABJ-MS molecule and potential applications in the multi-analysis chemosensory and molecular logic material fields.

8.
Water Res ; 243: 120356, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37516076

ABSTRACT

Elemental sulfur packed-bed (S0PB) bioreactors for autotrophic denitrification have gained more attention in wastewater treatment due to their organic carbon-free operation, low operating cost, and minimal carbon emissions. However, the rapid development of microbial S0-disproportionation (MS0D) in S0PB reactor during deep denitrification poses a significant drawback to this new technology. MS0D, the process in which sulfur is used as both an electron donor and acceptor by bacteria, plays a crucial role in the microbial-driven sulfur cycle but remains poorly understood in wastewater treatment setups. In this study, we induced MS0D in a pilot-scale S0PB reactor capable of denitrifying over 1000 m3/d nitrate-containing wastewater. Initially, the S0PB reactor stably removed 6.6 mg-NO3--N/L nitrate at an empty bed contact time (EBCT) of 20 mins, which was designated the S0-denitrification stage. To induce MS0D, we reduced the influent nitrate concentrations to allow deep nitrate removal, resulted in the production of large quantities of sulfate and sulfide (SO42-:S2- 3.2 w/w). Meanwhile, other sulfur-heterologous electron acceptors (SHEAs), e.g., nitrite and DO, were also kept at trace levels. The negative correlations between the SHEAs concentrations and the sulfide productions indicated that the absence of SHEAs was a primary inducing factor to MS0D. The microbial community drastically diverged in response to the depletion of SHEAs during the switch from S0-denitrification to S0-disproportionation. An evident enrichment of sulfur-disproportionating bacteria (SDBs) was found at the S0-disproportionation stage, accompanied by the decline of sulfur-oxidizing bacteria (SOBs). In the end, we discovered that shortening the EBCT and increasing the reflux ratio could inhibit sulfide production by reducing it from 43.9 mg/L to 3.2 mg/L or 25.5 mg/L. In conclusion, our study highlights the importance of considering MS0D when designing and optimizing S0PB reactors for sustainable autotrophic sulfur denitrification in real-life applications.


Subject(s)
Denitrification , Nitrates , Autotrophic Processes , Sulfur , Bioreactors/microbiology , Bacteria , Sulfides , Nitrogen
9.
Environ Res ; 231(Pt 1): 116061, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37149027

ABSTRACT

Dosing sulfide into the sulfur-packed-bed (S0PB) has great potential to enhance the denitrification efficiency by providing compensatory electron donors, however, the response of sulfur-metabolizing biofilm to various sulfide dosages has never been investigated. In this study, the S0PB reactor was carried out with increasing sulfide dosages by 3.6 kg/m3/d, presenting a decreasing effluent nitrate from 14.2 to 2.7 mg N/L with accelerated denitrification efficiency (k: 0.04 to 0.27). However, 6.5 mg N/L of nitrite accumulated when the sulfide dosage exceeded 0.9 kg/m3/d (optimum value). The increasing electron export contribution of sulfide a maximum of 85.5% illustrated its competition with the in-situ sulfur. Meanwhile, over-dosing sulfide caused serious biofilm expulsion with significant decreases in the total biomass, live cell population, and ATP by 90.2%, 86.7%, and 54.8%, respectively. This study verified the capacity of dosing sulfide to improve the denitrification efficiency in S0PB but alerted the negative effect of exceeded dosing.


Subject(s)
Bioreactors , Denitrification , Sulfides , Sulfur , Biofilms
10.
Bioresour Technol ; 367: 128238, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36334869

ABSTRACT

The effect of particle morphology on denitrification performance in element sulfur-based denitrification (ESDeN) packed-bed process is a gap. In this study, three different types of commercial sulfur particles were selected to build the ESDeN reactors. The results showed the reactors filled with rougher sulfur particles took shorter time to reach stable denitrification performance in the start-up stage. The reactors filled with cap-shape sulfur particles received the maximum nitrate removal rate of 849.49 ± 79.29 g N m-3 d-1 at empty bed contact time of 0.50 h, which was 2.34 times higher than that with ball-shape sulfur particles in the steady stage. The superior denitrification performance in the cap-shape particles set linked to its larger effective volumetric surface area (ωe, 1.67 times larger) and to the longer actual hydraulic retention time (AHRT, 1.80 times longer). This study extends the knowledge of the dependency of sulfur particle properties on denitrification performance in ESDeN packed-bed reactor.


Subject(s)
Bioreactors , Denitrification , Sulfur , Nitrates , Autotrophic Processes , Nitrogen
11.
Environ Res ; 215(Pt 2): 114348, 2022 12.
Article in English | MEDLINE | ID: mdl-36155154

ABSTRACT

Nitrate pollution is an important cause of eutrophication and ecological disruption. Recently, element sulfur-based denitrification (ESDeN) has attracted increasing attention because of its non-carbon source dependence, low sludge yield, and cost-effectiveness. Although the denitrification performance of sulfur autotrophic denitrifying bacteria at different temperatures has been widely studied, there are still many unknown factors about the adaptability and the shaping of microbial community. In this study, we comprehensively understood the shaping of ESDeN microbial communities under different temperature conditions. Results revealed that microbial communities cultivated at temperatures ranging from 10 °C to 35 °C could be classified as high-temperature (35 °C), middle-temperature (30, 25 and 20 °C), and low-temperature (15 and 10 °C) communities. Dissolved oxygen in water was an important factor that, in combination with temperature, shaped microbial community structure. According to network analysis, the composition of keystone taxa was different for the three groups of communities. Some bacteria that did not have sulfur compound oxidation function were identified as the "keystone species". The abundances of carbon, nitrogen, and sulfur metabolism of the three microbial communities were significantly changed, which was reflected in that the high-temperature and middle-temperature communities were dominated by dark oxidation of sulfur compounds and dark sulfide oxidation, while the low-temperature community was dominated by chemoheterotrophy and aerobic chemoheterotrophy. The fact that the number of microorganisms with dark oxidation of sulfur compounds capacity was quite higher than that of microorganisms with dark sulfur oxidation capacity suggested that the sulfur bioavailability at different temperatures, especially low temperature, was the main challenge for the development of efficient ESDeN process. This study provided a biological basis for developing a high-efficiency ESDeN process to cope with temperature changes in different seasons or regions.


Subject(s)
Denitrification , Microbiota , Bacteria , Bioreactors/microbiology , Nitrates/chemistry , Nitrogen/metabolism , Oxygen/metabolism , Sewage/microbiology , Sulfides , Sulfur/chemistry , Sulfur/metabolism , Sulfur Compounds/metabolism , Temperature , Water
12.
Int J Biol Sci ; 18(14): 5260-5275, 2022.
Article in English | MEDLINE | ID: mdl-36147457

ABSTRACT

Warburg effect of aerobic glycolysis in hepatic M1 macrophages is a major cause for metabolic dysfunction and inflammatory stress in non-alcoholic fatty liver disease (NAFLD). Plant-derived triterpene celastrol markedly inhibited macrophage M1 polarization and adipocyte hypertrophy in obesity. The present study was designed to identify the celastrol-bound proteins which reprogrammed metabolic and inflammatory pathways in M1 macrophages. Pyruvate kinase M2 (PKM2) was determined to be a major celastrol-bound protein. Peptide mapping revealed that celastrol bound to the residue Cys31 while covalent conjugation altered the spatial conformation and inhibited the enzyme activity of PKM2. Mechanistic studies showed that celastrol reduced the expression of glycolytic enzymes (e.g., GLUT1, HK2, LDHA, PKM2) and related signaling proteins (e.g., Akt, HIF-1α, mTOR), shifted aerobic glycolysis to mitochondrial oxidative phosphorylation and skewed macrophage polarization from inflammatory M1 type to anti-inflammatory M2 type. Animal experiments indicated that celastrol promoted weight loss, reduced serum cholesterol level, lipid accumulation and hepatic fibrosis in the mouse model of NAFLD. Collectively, the present study demonstrated that celastrol might alleviate lipid accumulation, inflammation and fibrosis in the liver via covalent modification of PKM2.


Subject(s)
Non-alcoholic Fatty Liver Disease , Triterpenes , Animals , Anti-Inflammatory Agents/therapeutic use , Cholesterol/metabolism , Glucose Transporter Type 1/metabolism , Lipids , Macrophages/metabolism , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Pentacyclic Triterpenes , Proto-Oncogene Proteins c-akt/metabolism , Pyruvate Kinase/metabolism , TOR Serine-Threonine Kinases/metabolism , Triterpenes/pharmacology
13.
Stem Cell Res ; 63: 102859, 2022 08.
Article in English | MEDLINE | ID: mdl-35870248

ABSTRACT

Ras-related GTP-binding protein A (RagA), encoded by RRAGA gene, initially senses the availability of cellular amino acids (e.g., leucine) and controls the translocation of mTORC1 to the lysosomal membrane. RagA overexpression appears to be associated with the onset of depression. To discover the biological roles of RagA, we employed the CRISPR/Cas9 system to generate a RRAGA gene knockout stem cell line from human induced pluripotent stem cell (iPSC) iPSN0003. Such RRAGA knockout iPSC cell line may help the development of new therapeutics for depression.


Subject(s)
Cell Line , Induced Pluripotent Stem Cells , Monomeric GTP-Binding Proteins , CRISPR-Cas Systems , Humans , Induced Pluripotent Stem Cells/metabolism , Mechanistic Target of Rapamycin Complex 1/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Monomeric GTP-Binding Proteins/deficiency , Monomeric GTP-Binding Proteins/genetics , Monomeric GTP-Binding Proteins/metabolism
14.
Environ Res ; 210: 113009, 2022 07.
Article in English | MEDLINE | ID: mdl-35218715

ABSTRACT

This study was carried out to determine the inhibition of low temperature on the performance of S0-based autotrophic denitrification (S0-SAD) biofilter, and proposed to enhance the nitrate removal efficiency with thiosulfate as external electron donor. With the decline of temperature from 30 °C to 10 °C at 0.25 h of empty bed contact time (EBCT), the nitrate removal rate presented a logarithmical drop, and the effluent nitrate dramatically increased from 9.19 mg L-1 to 15.13 mg L-1. EBCT was prolonged until 0.33 h for 20 °C, 0.66 h for 15 °C and 1.5 h for 10 °C, respectively, to maintain the effluent nitrate below 10 mg L-1. Such excessive variation of EBCT for different temperature is undoubtedly incredible for practical engineering. Thiosulfate, as the external electron donor, was adopted to compensate the efficiency loss during temperature decrease, which significantly prompted nitrate removal rate to 0.59, 0.53 and 0.31 kg N m-3 d-1 at 20 °C, 15 °C and 10 °C conditions, respectively, even at a short EBCT of 0.25 h. It not only acted as compensatory electron donor for nitrate removal, but also promoted the contribution of elemental sulfur via accelerating the DO consumption and extended larger effective volume of S0-layer for denitrification. Meanwhile, the significant enrichment of Sulfurimonas and Ferritrophicum provided biological evidences to the enhancement process. However, the incomplete consumption of thiosulfate was observed especially at EBCT of 0.25 h and 10 °C, and the thiosulfate runoff needs to be concerned in case of contaminating the effluent. Herein, approximately extending EBCT to 0.66 h and decreasing thiosulfate dosage were conducted simultaneously, thereby achieving 100% thiosulfate utilization efficiency and expected nitrate removal. This study provided a fundamental guidance to design and operate S0-SAD biofilter in response to seasonal temperature variation for practical engineering.


Subject(s)
Denitrification , Thiosulfates , Bioreactors , Electrons , Nitrates , Nitrogen , Temperature
15.
Environ Res ; 204(Pt A): 112016, 2022 03.
Article in English | MEDLINE | ID: mdl-34509485

ABSTRACT

This study was carried out to determine the effect of influent nitrate loading on nitrite accumulation during elemental-sulfur based denitrification process, and proposed to enhance the nitrogen removal efficiency by mitigating nitrite accumulation with thiosulfate as external electron donor. Along with increasing the nitrate influent loading (from 0.09 kg N/m3/d to 1.73 kg N/m3/d) by shortening the empty bed contact time (EBCT) (from 5 h to 0.25 h), the nitrate removal loading increased from 0.08 to 0.83 kg N/m3/d. Meanwhile, the raise of the nitrate influent loading obviously aggravated the nitrite accumulation. Herein, nitrite began to accumulate since the nitrate influent loading was over 0.86 kg N/m3/d, and a maximum nitrite accumulation of 2.39 mg/L was observed under the 0.25 h of EBCT and 15 mg/L of nitrate influent concentration condition. Thiosulfate was used as the external electron donor to accelerate the nitrite reduction rate in order to mitigate the nitrite accumulation. As a result, the nitrite accumulation significantly decreased from 2.39 mg/L to 0.17 mg/L with the thiosulfate dosage of 13.36 mg/L. However, the nitrite accumulation bounced with the on-going increase of the thiosulfate dosage, indicating that the nitrate reduction rate and nitrite reduction rate were accelerated alternatively. After dosing thiosulfate, the relative abundances of sulfurimonas and ferritrophicum grew up significantly.


Subject(s)
Nitrites , Thiosulfates , Bioreactors , Denitrification , Electrons , Nitrates , Nitrogen
16.
Front Psychiatry ; 13: 1054726, 2022.
Article in English | MEDLINE | ID: mdl-36620687

ABSTRACT

Depression is clinically defined as a mood disorder with persistent feeling of sadness, despair, fatigue, and loss of interest. The pathophysiology of depression is tightly regulated by the biosynthesis, transport and signaling of neurotransmitters [e.g., serotonin, norepinephrine, dopamine, or γ-aminobutyric acid (GABA)] in the central nervous system. The existing antidepressant drugs mainly target the dysfunctions of various neurotransmitters, while the efficacy of antidepressant therapeutics is undermined by different adverse side-effects. The present review aimed to dissect the molecular mechanisms underlying the antidepressant activities of herbal medicines toward the development of effective and safe antidepressant drugs. Our strategy involved comprehensive review and network pharmacology analysis for the active compounds and associated target proteins. As results, 45 different antidepressant herbal medicines were identified from various in vivo and in vitro studies. The antidepressant mechanisms might involve multiple signaling pathways that regulate neurotransmitters, neurogenesis, anti-inflammation, antioxidation, endocrine, and microbiota. Importantly, herbal medicines could modulate broader spectrum of the cellular pathways and processes to attenuate depression and avoid the side-effects of synthetic antidepressant drugs. The present review not only recognized the antidepressant potential of herbal medicines but also provided molecular insights for the development of novel antidepressant drugs.

17.
AAPS PharmSciTech ; 22(3): 132, 2021 Apr 13.
Article in English | MEDLINE | ID: mdl-33851275

ABSTRACT

The main objective of this study was to develop an in vivo predictive dissolution (IVPD) model for topiroxostat immediate-release (IR) formulation by the combination of mechanistic absorption model (MAM) deconvolution method with time shifting factor (TSF) adjustment. The in vitro dissolution profiles in different biorelevant dissolution media containing different concentrations of sodium lauryl sulfate (SLS) were obtained from dissolution testing with the paddle method of the US Pharmacopeia, while the human pharmacokinetic profile was taken from the published experimental results. The GastroPlus™ software was used to observe the linear relationship between in vitro drug dissolution and in vivo absorption. The pharmacokinetic profile of topiroxostat IR tablet was first deconvoluted through the MAM method to obtain the fraction absorbed in vivo. Next, Levy plot was constructed to estimate the TSF, and the time scale for both processes of dissolution and absorption was then adjusted to be superimposable. The IVPD modelling was subsequently established with data between in vitro dissolution profiles and fraction absorbed in vivo. Finally, the dissolution profiles of topiroxostat IR tablet were translated into a pharmacokinetic curve in terms of convolution method. The comparison between translated and observed pharmacokinetic data will validate the performance of the developed IVPD model. This new linear IVPD model with high predictive power for the tablet can predict the in vivo pharmacokinetic differences through in vitro dissolution data, and it can be utilized as a risk-control tool for the formulation development of the topiroxostat IR tablet and the quality control of product batches.


Subject(s)
Computer Simulation , Models, Biological , Nitriles/chemistry , Nitriles/pharmacokinetics , Pyridines/chemistry , Pyridines/pharmacokinetics , Adult , Drug Liberation/physiology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Female , Forecasting , Humans , Linear Models , Male , Middle Aged , Tablets , Young Adult
18.
Environ Res ; 197: 111029, 2021 06.
Article in English | MEDLINE | ID: mdl-33744267

ABSTRACT

Sulfur autotrophic denitrification (SAD) process, as an alternative to heterotrophic denitrification (HD) filter, receives growing interest in polishing the effluent from secondary sewage treatment. Although individual studies have indicated several advantages of SAD over HD, rare study has compared these two systems under identical condition and by using real secondary effluent. In this study, two small pilot scale filters (SAD and HD) were designed with identical configuration and operated parallelly by feeding the real secondary effluent from a WWTP. The results showed SAD filter can be started up without the addition of soluble electron donor, although the time (14 days) was about 3 times longer than that of HD filter. The nitrate removal rate of SAD filter at HRT of 1.4 h was measured as 0.268 ± 0.047 kg N/(m3∙d). Similar value was observed in HD filter with supplementing 90 mg/L COD. The COD concentration of effluent always kept lower than that of influent in SAD filter but not in HD filter. In addition, SAD filter could maintain a stable denitrification performance without backwash for 15 days, while decline of nitrate removal rate was observed in HD filter just 2 days after stopping the backwash. This different behavior was further confirmed as the SAD filter had a better hydraulic flow pattern. Analysis according to high-throughput 16S rRNA gene-based Illumina MiSeq sequencing clearly showed the microbial community evolution and differentiation among the samples of seed sludge, SAD and HD filters. Finally, the economic assessment was carried out, showing the operation cost of SAD filter was over 50% lower than that of HD filter.


Subject(s)
Denitrification , Hydrodynamics , Bioreactors , Nitrates , Nitrogen , RNA, Ribosomal, 16S/genetics , Sulfur
19.
Environ Res ; 183: 109248, 2020 04.
Article in English | MEDLINE | ID: mdl-32085997

ABSTRACT

The C/N ratio in wastewater differs in place and time and affects the nitrogen removal performance of wastewater treatment. However, studies have focused only on the direct relationship between C/N and nitrogen removal efficiency but disregarded the significant role of soluble microbial products (SMPs) as an intermediate electron station. In this work, the contribution of SMPs to TN removal for treating wastewater with different C/N in a sequencing batch reactor (SBR) was investigated to extend relevance from C/N-TN removal to C/N-SMP-TN removal. TN removal efficiency was improved by increasing the influent C/N. The relative contribution of SMPs increased from 15% (C/N = 2) to 54% (C/N = 8), including 25.5% via utilization-associated product (UAP)-dependent denitrification and 28.5% via biomass-associated product (BAP)-dependent denitrification. The direct contribution of influent organic substrates dramatically decreased from 85.1% to 46%. In addition, providing an anoxic phase effectively enhanced BAP-dependent denitrification and achieved an increment of the SMP absolute contribution from 20.3% to 43% at C/N = 8 with 6.7 mg/L of TN additionally removed. This work clarified the significant contribution of SMPs to the nitrogen removal process, particularly in treating wastewater with high C/N. It also presented a new strategy for improving nitrogen removal performance via SMP reclamation.


Subject(s)
Denitrification , Nitrogen , Waste Disposal, Fluid , Bioreactors , Electrons , Wastewater
20.
PLoS One ; 14(9): e0221803, 2019.
Article in English | MEDLINE | ID: mdl-31525220

ABSTRACT

How might nonverbal synchrony naturally evolve in a social virtual reality environment? And how can avatar embodiment affect how participants coordinate nonverbally with each other? In the following pre-registered between-subjects experiment, we tracked the movements of pairs of users during a collaborative or competitive task in immersive virtual reality. Each conversational partner controlled either a customized avatar body or an abstract cube that responded to their movements. We compared the movements of the actual user pairs between the two conditions, and to an artificial "pseudosynchrony" dataset composed of the movements of randomly combined participant pairs who did not actually interact. We found stronger positive and negative correlations between real pairs compared to pseudosynchronous pairs, providing evidence for naturally occurring nonverbal synchrony between pairs in virtual reality. We discuss this in the context of the relationships between avatar appearance, task success, social closeness and social presence.


Subject(s)
Nonverbal Communication/psychology , Virtual Reality , Adult , Female , Humans , Male , Movement , Perception , Social Behavior
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