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1.
J Hazard Mater ; 472: 134510, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38704909

RESUMEN

Nitrogen removal is essential for restoring eutrophic lakes. Microorganisms and aquatic plants in lakes are both crucial for removing excess nitrogen. However, microplastic (MP) pollution and the invasion of exotic aquatic plants have become increasingly serious in lake ecosystems due to human activity and plant-dominant traits. This field mesocosm study explored how the diversity of invasive submerged macrophytes affects denitrification (DNF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA) in lake sediments with varying MPs. Results showed that invasive macrophytes suppressed DNF rates, but DNRA and ANA were less sensitive than DNF to the diversity of invasive species. Sediment MPs increased the biomass of invasive species more than native species, but did not affect microbial processes. The effects of MPs on nitrate dissimilatory reduction were process-specific. MPs increased DNF rates and the competitive advantage of DNF over DNRA by changing the sediment environment. The decoupling of DNF and ANA was also observed, with increased DNF rates and decreased ANA rates. The study findings suggested new insights into how the invasion of exotic submerged macrophytes affects the sediment nitrogen cycle complex environments.

2.
J Neurosci ; 44(19)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38569927

RESUMEN

GPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare G-protein-coupled receptor 37-like 1 (GPR37L1) genetic variants found among 51,289 whole-exome sequences from the DiscovEHR cohort. Rare GPR37L1 coding variants were binned according to predicted pathogenicity and analyzed by sequence kernel association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others. Since associations do not prove causality, rare GPR37L1 variants were functionally analyzed in SK-N-MC cells to evaluate potential signaling differences and pathogenicity. Notably, receptor variants exhibited varying abilities to reduce cAMP levels, activate mitogen-activated protein kinase (MAPK) signaling, and/or upregulate receptor expression in response to the agonist prosaptide (TX14(A)), as compared with the wild-type receptor. In addition to signaling changes, knock-out (KO) of GPR37L1 or expression of certain rare variants altered cellular cholesterol levels, which were also acutely regulated by administration of the agonist TX14(A) via activation of the MAPK pathway. Finally, to simulate the impact of rare nonsense variants found in the large patient cohort, a KO mouse line lacking Gpr37l1 was generated. Although KO animals did not recapitulate an acute migraine phenotype, the loss of this receptor produced sex-specific changes in anxiety-related disorders often seen in chronic migraineurs. Collectively, these observations define the existence of rare GPR37L1 variants associated with neuropsychiatric conditions in the human population and identify the signaling changes contributing to pathological processes.


Asunto(s)
Trastornos Migrañosos , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Animales , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/metabolismo , Ratones , Masculino , Femenino , Ratones Noqueados , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/metabolismo , Ratones Endogámicos C57BL , Variación Genética/genética
3.
Small ; : e2401374, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38659396

RESUMEN

The removal of uranyl ions (UO2 2+) from water is challenging due to their chemical stability, low concentrations, complex water matrix, and technical limitations in extraction and separation. Herein, a novel molybdenum disulfide/graphene oxide heterojunction (MoS2/GO-H) is developed, serving as an effective electrode for capacitive deionization (CDI). By combining the inherent advantages of electroadsorption and electrocatalysis, an innovative electroadsorption-electrocatalysis system (EES) strategy is introduced. This system utilizes interface polarization at the MoS2 and GO interface, creating an additional electric field that significantly influences carrier behavior. The MoS2/GO-H electrode, with its extraordinary adsorption capacity of 805.57 mg g-1 under optimal conditions, effectively treated uranium-laden wastewater from a mine, achieving over 90% removal efficiency despite the presence of numerous competing ions at concentrations significantly higher than UO2 2+. Employing density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations, it is found that the MoS2/GO-H total charge density at the Fermi level, enhanced by interfacial polarization, surpasses that of separate MoS2 and GO, markedly boosting conductivity and electrocatalytic effectiveness.

4.
Bioorg Med Chem Lett ; 96: 129505, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37838340

RESUMEN

RNA helicase DHX33 has been identified to be a critical factor in promoting cancer development. Genetic deletion of DHX33 significantly blocks tumorigenesis. Importantly, its helicase activity was found to be pivotal for exerting cellular functions. Herein we used a helicase-based high throughput screening (HTS) to discover DHX33 inhibitors from Chembridge chemical library containing 15,000 small molecules. We identified a hit compound containing benzimidazole ring that demonstrated activity against DHX33 with certain selectivity. Further structural optimization led to the design and synthesis of a series of analog inhibitors. Considering the potential role of DHX33 in cancer development, the compounds were evaluated based on the cytotoxicity activity in U251-MG cancer cells in vitro. Among them, compound IVa (KY386) was identified to be a selective inhibitor for DHX33 helicase with potent anti-cancer activity and moderate metabolic stability. These results support the promising role of DHX33 inhibitors for development of novel anti-cancer drugs.


Asunto(s)
Antineoplásicos , Antineoplásicos/farmacología
5.
Water Res ; 245: 120601, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37708774

RESUMEN

Changes in land-use intensity can have a far-reaching impact on river water quality and prokaryotic community composition. While research has been conducted to investigate the assembly mechanism of prokaryotic communities, the contributions of neutral theory and niche theory to prokaryotic community assembly under different land-use intensities remain unknown. In this study, a total of 251 sampling sites were set up in the Yangtze River basin to explore the assembly mechanism under different land-use intensities. Briefly, a "source" landscape can generate pollution, whereas a "sink" landscape can prevent pollution. Firstly, our result showed that higher land-use intensity might disturb the balance between the "source" and "sink" landscape patterns, resulting in water quality deterioration. Then the prokaryotic community assembly was classified into five ecological processes, namely homogeneous selection, homogenizing dispersal, undominated processes, dispersal limitation, and variable selection. The higher land-use intensity was found to strengthen the homogeneous selection, leading to the homogenization of the community at the whole basin scale. Finally, our findings demonstrated that the Yangtze River Basin's prokaryotic community displayed a distance-decay pattern when land-use intensity was low, with a greater contribution from neutral theory to its assembly. On the other hand, with a higher land-use intensity, the degradation of the aquatic environment increased the impacts of environmental filtering on the prokaryotic community, and niche theory played a stronger role in its assembly. Our findings show how land-use intensity influence the formation of prokaryotic communities, which will be an invaluable guide for managing land use and understanding the prokaryotic community assembly mechanisms in the Yangtze River Basin.

6.
bioRxiv ; 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37461723

RESUMEN

GPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare GPR37L1 genetic variants found among 51,289 whole exome sequences from the DiscovEHR cohort. Briefly, rare GPR37L1 coding variants were binned according to predicted pathogenicity, and analyzed by Sequence Kernel Association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others. Since associations do not prove causality, rare GPR37L1 variants were then functionally analyzed in SK-N-MC cells to evaluate potential signaling differences and pathogenicity. Notably, receptor variants exhibited varying abilities to reduce cAMP levels, activate MAPK signaling, and/or upregulate receptor expression in response to the agonist prosaptide (TX14(A)), as compared to the wild-type receptor. In addition to signaling changes, knockout of GPR37L1 or expression of certain rare variants altered cellular cholesterol levels, which were also acutely regulated by administration of the agonist TX14(A) via activation of the MAPK pathway. Finally, to simulate the impact of rare nonsense variants found in the large patient cohort, a knockout (KO) mouse line lacking Gpr37L1 was generated, revealing loss of this receptor produced sex-specific changes implicated in migraine-related disorders. Collectively, these observations define the existence of rare GPR37L1 variants in the human population that are associated with neuropsychiatric conditions and identify the underlying signaling changes that are implicated in the in vivo actions of this receptor in pathological processes leading to anxiety and migraine. SIGNIFICANCE STATEMENT: G-protein coupled receptors (GPCRs) represent a diverse group of membrane receptors that contribute to a wide range of diseases and serve as effective drug targets. However, a number of these receptors have no identified ligands or functions, i.e., orphan receptors. Over the past decade, advances have been made, but there is a need for identifying new strategies to reveal their roles in health and disease. Our results highlight the utility of rare variant analyses of orphan receptors for identifying human disease associations, coupled with functional analyses in relevant cellular and animal systems, to ultimately reveal their roles as novel drug targets for treatment of neurological disorders that lack wide-spread efficacy.

7.
J Hazard Mater ; 457: 131745, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37295327

RESUMEN

In order to deal with the sudden nuclear leakage event to suppress the spread of radioactive contaminants in a short period of time, it is extremely urgent needed to explore an adsorbent that could be capable of in-situ remedial actions to rapidly capture the leaked radionuclides in split second. An adsorbent was developed that MoS2 via ultrasonic to expose more surface defects afterwards functionalized by phosphoric acid resulting in more active sites being endowed on the edge S atoms of Mo-vacancy defects, while simultaneously increased the hydrophilicity and interlayer spacing. Hence, an overwhelming fast adsorption rates (adsorption equilibrium within 30 s) are presented and place the MoS2-PO4 at the top of performing sorbent materials. Moreover, the maximum capacity calculated from Langmuir model is as high as 354.61 mg·g-1, the selective adsorption capacity (SU) achieving 71.2% in the multi-ion system and with more than 91% capacity retention after 5 cycles of recycling. Finally, XPS and DFT insight into the adsorption mechanism, which can be explained as interaction of UO22+ on the surface of MoS2-PO4 by forming U-O and U-S bonds. The successful fabrication of such a material may provide a promising solution for emergency treatment of radioactive wastewater during nuclear leakage events.

8.
J Hazard Mater ; 452: 131248, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36963194

RESUMEN

Effective spatial separation and utilization of photogenerated charges are critical for photocatalysis process. Herein, novel Co3O4 @TiO2 @CdS@Au double-shelled nanocage (CTCA) with spatially separated redox centers was synthesized by loading Co3O4 and Au NP cocatalysts on the inner and outer surfaces of Z-scheme heterojunction (TiO2 @CdS). The reduction rate constant of U(VI) by CTCA reached 0.218 min-1 under simulated sunlight irradiation, which was 6.6, 3.2 and 36.3 times than that of monolayer CTCA (0.033 min-1), CTC (0.068 min-1) and CT (0.006 min-1). The full-spectrum light-assisted photothermal catalytic performance can enable CTCA to remove 98.8% of U(VI) and degrade nearly 90% of five organic pollutants simultaneously. Detailed characterizations and theory calculations revealed that the photogenerated holes and electrons in CTCA flow inward and outward. More importantly, Co3O4 acts as a "nano heater" to generate the photothermal effect for further enhancing the charge transfer and accelerating the surface reaction kinetics. Meanwhile, the photogenerated electrons and superoxide radicals play a dominant role in reducing the adsorbed U(VI) to insoluble (UO2)O2·2H2O(s). This work provides valuable input toward a novel double-shelled hollow nanocage reactor with excellent photothermal catalysis ability for efficient recovery U(VI) from uranium mine wastewater to address environmental contamination issues.

9.
J Cell Physiol ; 2023 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-36966431

RESUMEN

Amyloid precursor protein (APP) produces aggregable ß-amyloid peptides and its mutations are associated with familial Alzheimer's disease (AD), which makes it one of the most studied proteins. However, APP's role in the human brain remains unclear despite years of investigation. One problem is that most studies on APP have been carried out in cell lines or model organisms, which are physiologically different from human neurons in the brain. Recently, human-induced neurons (hiNs) derived from induced pluripotent stem cells (iPSCs) provide a practical platform for studying the human brain in vitro. Here, we generated APP-null iPSCs using CRISPR/Cas9 genome editing technology and differentiate them into matured human neurons with functional synapses using a two-step procedure. During hiN differentiation and maturation, APP-null cells exhibited less neurite growth and reduced synaptogenesis in serum-free but not serum-containing media. We have found that cholesterol (Chol) remedies those developmental defects in APP-null cells, consistent with Chol's role in neurodevelopment and synaptogenesis. The phenotypic rescue was also achieved by coculturing those cells with wild-type mouse astrocytes, suggesting that APP's developmental role is likely astrocytic. Next, we examined matured hiNs using patch-clamp recording and detected reduced synaptic transmission in APP-null cells. This change was largely due to decreased synaptic vesicle (SV) release and retrieval, which was confirmed by live-cell imaging using two SV-specific fluorescent reporters. Adding Chol shortly before stimulation mitigated the SV deficits in APP-null iNs, indicating that APP facilitates presynaptic membrane Chol turnover during the SV exo-/endocytosis cycle. Taken together, our study in hiNs supports the notion that APP contributes to neurodevelopment, synaptogenesis, and neurotransmission via maintaining brain Chol homeostasis. Given the vital role of Chol in the central nervous system, the functional connection between APP and Chol bears important implications in the pathogenesis of AD.

10.
Huan Jing Ke Xue ; 43(8): 3998-4007, 2022 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-35971698

RESUMEN

To explore the periphytic algae community structure in the Yangtze River basin, samples were collected from 130 sampling sites, including the source to the estuary along the mainstream of the Yangtze River, eight primary tributaries, and the tributary of the Three Gorges area. The periphytic algae densities of different areas in the mainstream of the Yangtze River ranked from high to low were the upstream area, source area, middle and lower area, and the Jinsha River. The high periphytic algae density in the upstream area was associated with the shift in nutrition level, and the high periphytic algae density in the source area was associated with human activity. The spatial pattern of the periphytic algae community in the whole main stream from west to east presented the alternating dominance of Bacillariophyta and Cyanophyta; the Bacillariophyta (Navicula) had a competitive advantage in the main stream, and the distribution of the periphytic algae community was driven by total nitrogen, total phosphorus, and pH. For the tributary of the Yangtze River, the periphytic algae density in the Three Gorges tributary area was far higher than those in the eight primary tributaries; the periphytic algae community was dominated by Cyanophyta (Lyngbya), which had a competitive advantage in the tributaries of the Yangtze River. The distribution of the periphytic community was driven by dissolved oxygen and pH. According to the diversity analysis and assessment, the periphytic algae community in the source area showed lower species richness and higher evenness, thus leading to a high α-diversity and good assessment result (mesosaprobic zone). The middle and lower reaches of the Yangtze River also showed the same assessment result, the mesosaprobic zone. However, the community evenness of the middle and lower reaches was significantly lower than that of the source area, thus making the middle and lower reaches of the Yangtze River have a significantly lower α-diversity than that of the source area. All areas of the Yangtze River showed good water quality assessment; however, different areas had different WQI index numbers, and the assessment results of the WQI index were inconsistent with the results of the aquatic assessment. Therefore, a comprehensive assessment of aquatic ecosystem health should use both aquatic assessments and water quality assessments.


Asunto(s)
Cianobacterias , Diatomeas , China , Ecosistema , Monitoreo del Ambiente/métodos , Humanos , Fósforo/análisis , Ríos/química , Calidad del Agua
11.
Huan Jing Ke Xue ; 43(3): 1414-1423, 2022 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-35258205

RESUMEN

To explore the bacterioplankton community structure in the Yangtze River basin, water samples were collected from 177 sampling sites, including the source to the estuary along the mainstream of the Yangtze River, eight primary tributaries, and several lakes and reservoirs. The 16S rRNA genes were used to explore the bacterioplankton communities based on single molecule real-time sequencing, with the aim to study the diversity and community characteristics in a border sampling area and higher species annotation accuracy. Based on α-diversity analysis, the river area had higher species richness than that of the lake/reservoir area, resulting in these two areas having different bacterioplankton community diversities. Based on the ß diversity analysis, the bacterioplankton showed different community compositions between the river and lake/reservoir areas; temperature was the key environmental factor for the river area, and pH was the key environmental factor for the lake/reservoir area. In order to study the influence of different bacterioplankton communities, this study further investigated the species, function, and community differences between the river and lake/reservoir areas. The results were as follows:for the river area, the eutrophication level gradually increased from west to east along the mainstream of the Yangtze River, resulting in a gradually increased relative abundance of specific species. The lake/reservoir area had a higher risk of cyanobacteria bloom, and the opportunistic pathogen had a high relative abundance in the Danjiangkou Reservoir, indicating a higher ecological risk. For species composition, the river and lake/reservoir areas shared most OTUs (84%); however, some uncultured bacteria showed a high relative abundance in the Yangtze River, meaning the bacterioplankton of the Yangtze River basin still requires further study. In general, the river and lake/reservoir shared most species; however, the different bacterioplankton diversity, community composition, and enriched species made the river and lake/reservoir have different key environmental factors, and they also showed differences in ecological functions.


Asunto(s)
Cianobacterias , Lagos , Organismos Acuáticos , China , Ecosistema , Lagos/microbiología , ARN Ribosómico 16S/genética , Ríos/microbiología
12.
ACS Med Chem Lett ; 12(9): 1389-1395, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34531947

RESUMEN

An unbiased phenotypic neuronal assay was developed to measure the synaptotoxic effects of soluble Aß oligomers. A collection of CNS druglike small molecules prepared by conditioned extraction was screened. Compounds that prevented and reversed synaptotoxic effects of Aß oligomers in neurons were discovered to bind to the sigma-2 receptor complex. Select development compounds displaced receptor-bound Aß oligomers, rescued synapses, and restored cognitive function in transgenic hAPP Swe/Ldn mice. Our first-in-class orally administered small molecule investigational drug 7 (CT1812) has been advanced to Phase II clinical studies for Alzheimer's disease.

13.
Environ Pollut ; 285: 117471, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34082372

RESUMEN

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), an alternative to brominated flame retardants, might pose an exposure risk to humans and wild animals during fetal development. Our recent study suggested that short-term TDCIPP exposure during early development caused sex-dependent behavioral alteration in adults. In the present study, multigenerational neurodevelopmental toxicity upon early-life exposure of parental zebrafish was evaluated, and the possible underlying mechanisms were further explored. Specifically, after embryonic exposure (0-10 days post-fertilization, dpf) to TDCIPP (0, 0.01, 0.10, and 1.00 µM), zebrafish larvae were cultured in clean water until the sexually matured to produce progeny (F1). The results confirmed neurodevelopmental toxicity in F1 larvae characterized by changes of developmental endpoints, reduced thigmotaxis, as well as altered transcription of genes including myelin basic protein a (mbpa), growth associated protein (gap43) and synapsin IIa (syn2a). Sex-specific changes in thyroid hormones (THs) indicated the relationship of abnormal THs levels with previously reported neurotoxicity in adult females after early-life exposure to TDCIPP. Similar changing profiles of TH levels (increased T3 and decreased T4) in adult females and F1 eggs, but not in F1 larvae, suggested that the TH disruptions were primarily inherited from the maternal fish. Further results demonstrated hypermethylation of global DNA and key genes related to TH transport including transthyretin (ttr) and solute carrier family 16 member 2 (slc16a2), which might affect the transport of THs to target tissues, thus at least partially contributing to the neurodevelopmental toxicity in F1 larvae. Overall, our results confirmed that early-life TDCIPP exposure of parental fish could affect the early neurodevelopment of F1 offspring. The underlying mechanism could involve altered TH levels inherited from maternal zebrafish and epigenetic modifications in F1 larvae.


Asunto(s)
Retardadores de Llama , Simportadores , Contaminantes Químicos del Agua , Animales , Epigénesis Genética , Femenino , Retardadores de Llama/toxicidad , Humanos , Larva/metabolismo , Masculino , Transportadores de Ácidos Monocarboxílicos , Compuestos Organofosforados , Fosfatos/metabolismo , Hormonas Tiroideas , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/metabolismo
14.
J Hazard Mater ; 401: 123295, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-32659574

RESUMEN

Due to poor mass transfer performance and high energy consumption of the traditional electrochemical flow-by mode, this study developed a high-efficiency electrochemical oxidation system in flow-through mode based on three-dimensional macroporous enhanced TiO2 nanotube array/SnO2-Sb (MP-Ti-ENTA/SnO2-Sb) anode. The effects of initial pH, current density and flow rate on the COD degradation of reverse osmosis concentrates (ROCs) from reclaimed wastewater plant were investigated. Besides, the energy efficiency, biodegradability and acute biotoxicity were studied during electrochemical flow-through process. Compared with the flow-by mode, the flow-through mode based on the MP-Ti-ENTA/SnO2-Sb anode had a COD removal rate of 0.38 mg min-1 (current density: 5 mA cm-2) and an electrical efficiency per order (EE/O) of 5.3 kW h m-3. The three-dimensional fluorescence spectrum showed that the fulvic acids, humic acids and soluble microbial metabolites of ROCs could be effectively removed by the flow-through anode. In addition, the luminescence inhibition rate of the effluent was 22.4 %, indicating that the acute biotoxicity was reduced by more than 40 %. The electrochemical flow-through process of ROCs treatment required relatively low energy consumption without extra chemical agent addition, showing a broader application prospect.


Asunto(s)
Titanio , Contaminantes Químicos del Agua , Conservación de los Recursos Energéticos , Técnicas Electroquímicas , Electrodos , Ósmosis , Oxidación-Reducción , Fenómenos Físicos , Titanio/toxicidad , Contaminantes Químicos del Agua/toxicidad
15.
Chemosphere ; 273: 128569, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33139053

RESUMEN

The efficient removal of uranium from aqueous solution remains of great challenge in securing water environment safety. In this paper, we reported a high temperature electrochemical method for the preparation of EuVO4 with different morphologies from rare earth oxides and vanadate, which solved the problems of rare earth and vanadium recovery. The effects of pH, ionic strength, contact time, initial concentration and reaction temperature on the adsorption of U(VI) by prepared adsorbent were studied by static batch experiments. When the concentration of U(VI) standard is 100 mg g-1, the maximum adsorption capacity of EuVO4 is 276.16 mg g-1. The adsorption mechanism was elucidated with zeta potential and XPS: 1) negatively charged EuVO4 attracted UO22+ by electrostatic attraction; 2) exposed Eu, V, and O atoms complexed with U(VI) through coordination; 3) the hybrid of Eu was complex, which accommodated different electrons to interact. In the multi-ion system with Al3+, Zn2+, Cu2+, Ni2+, Cr2+ and Mn2+, EuVO4 also showed good selective adsorption properties for U(VI). Five adsorption and desorption cycle experiments demonstrated that EuVO4 possessed good renewable performance.


Asunto(s)
Uranio , Contaminantes Químicos del Agua , Adsorción , Concentración de Iones de Hidrógeno , Cinética , Óxidos , Uranio/análisis , Contaminantes Químicos del Agua/análisis
16.
Nat Commun ; 11(1): 5597, 2020 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-33154358

RESUMEN

Seasonal influenza epidemics lead to 3-5 million severe infections and 290,000-650,000 annual global deaths. With deaths from the 1918 influenza pandemic estimated at >50,000,000 and future pandemics anticipated, the need for a potent influenza treatment is critical. In this study, we design and synthesize a bifunctional small molecule by conjugating the neuraminidase inhibitor, zanamivir, with the highly immunogenic hapten, dinitrophenyl (DNP), which specifically targets the surface of free virus and viral-infected cells. We show that this leads to simultaneous inhibition of virus release, and immune-mediated elimination of both free virus and virus-infected cells. Intranasal or intraperitoneal administration of a single dose of drug to mice infected with 100x MLD50 virus is shown to eradicate advanced infections from representative strains of both influenza A and B viruses. Since treatments of severe infections remain effective up to three days post lethal inoculation, our approach may successfully treat infections refractory to current therapies.


Asunto(s)
Antivirales/administración & dosificación , Antivirales/farmacología , Inmunoterapia/métodos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , 2,4-Dinitrofenol/administración & dosificación , 2,4-Dinitrofenol/química , 2,4-Dinitrofenol/inmunología , Administración Intranasal , Animales , Anticuerpos/administración & dosificación , Anticuerpos/inmunología , Antivirales/química , Línea Celular , Citotoxicidad Inmunológica/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/enzimología , Virus de la Influenza A/fisiología , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/enzimología , Virus de la Influenza B/fisiología , Infusiones Parenterales , Ratones , Ratones Endogámicos BALB C , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/metabolismo , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Unión Proteica , Resultado del Tratamiento , Liberación del Virus/efectos de los fármacos , Zanamivir/administración & dosificación , Zanamivir/química , Zanamivir/farmacología
17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1954-1957, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33018385

RESUMEN

Water quality has a direct impact on industry, agriculture, and public health. Algae species are common indicators of water quality. It is because algal communities are sensitive to changes in their habitats, giving valuable knowledge on variations in water quality. However, water quality analysis requires professional inspection of algal detection and classification under microscopes, which is very time-consuming and tedious. In this paper, we propose a novel multi-target deep learning framework for algal detection and classification. Extensive experiments were carried out on a large-scale colored microscopic algal dataset. Experimental results demonstrate that the proposed method leads to the promising performance on algal detection, class identification and genus identification.


Asunto(s)
Aprendizaje Profundo , Plantas , Agricultura , Microscopía , Calidad del Agua
18.
Environ Int ; 140: 105813, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32480113

RESUMEN

This paper reports on the development of macroporous flow-through anodes. The anodes comprised an enhanced TiO2 nanotube array (ENTA) that was grown on three macroporous titanium substrates (MP-Ti) with nominal pore sizes of 10, 20, and 50 µm. The ENTA was then covered with SnO2-Sb2O3. We refer to this anode as the MP-Ti-ENTA/SnO2-Sb2O3 anode. The morphology, pore structure, and electrochemical properties of the anode were characterized. Compared with the traditional NTA layer, we found that the MP-Ti-ENTA/SnO2-Sb2O3 anode has a service lifetime that was 1.56 times larger than that of MP-Ti-NTA/SnO2-Sb2O3. We used 2-methyl-4-isothiazolin-3-one (MIT), a common biocide, as the target pollutant. We evaluated the impact of the operating parameters on energy efficiency and the oxidation rate of MIT. Furthermore, the apparent rate constants were 0.38, 1.63, and 1.24 min-1 for the 10, 20, and 50 µm nominal pore sizes of the MP-Ti substrates, respectively, demonstrating the different coating-loading mechanisms for the porous substrate. We found that hydroxyl radicals were the dominant species in the MIT oxidation in the HO radical scavenging experiments. The radical and nonradical oxidation contributions to the MIT degradation for different current densities were quantitatively determined as 72.1%-74.8% and 25.2%-27.9%, respectively. Finally, we summarized the oxidation performance for MIT destruction for (1) the published literature on various advanced oxidation technologies, (2) the published literature on various anodes, and (3) our flow-by and -through anodes. Accordingly, we found that our flow-through anode has a much lower electrical efficiency per order value (0.58 kWh m-3) than the flow-by anodes (6.85 kWh m-3).


Asunto(s)
Nanotubos , Contaminantes Químicos del Agua , Electrodos , Oxidación-Reducción , Titanio
19.
Water Sci Technol ; 77(9-10): 2509-2516, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29893740

RESUMEN

The effects of Mn(II) on Fenton system to treat papermaking wastewater and the mechanism of Mn(II) enhanced Fenton reaction were investigated in this study. The chemical oxygen demand (COD) removal efficiency was enhanced in the presence of Mn(II), which increased by 19% compared with that of the Fenton system alone. The pseudo-first order reaction kinetic rate constant of Mn(II)/Fenton system was 2.11 times higher than that of Fenton system. 67%-81% COD were removed with the increasing Mn(II) concentration from 0 to 0.8 g/L. COD removal efficiency was also enhanced in a wider pH range (3-7), which indicated the operation parameters of Fenton technology could be broadened to a milder condition. The study of the mechanism showed that Mn(II) participated in the oxidation and coagulation stages in Fenton system. In the oxidation stage, Mn(II) promotes the production of HO2•/ O2•-, then HO2•/ O2•- reacts with Fe(III) to accelerate the formation of Fe(II), and finally accelerates the production of HO•. Meantime MnMnO3 and Fe(OH)3 forms in the coagulation stage, facilitating the removal of suspended substances and a large amount of COD, which enhances the overall COD removal of papermaking wastewater. This study provided a detailed mechanism to improve practical applications of Fenton technology.


Asunto(s)
Manganeso/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Análisis de la Demanda Biológica de Oxígeno , Peróxido de Hidrógeno/química , Residuos Industriales , Hierro/química , Cinética , Oxidación-Reducción , Papel
20.
PLoS One ; 12(7): e0180190, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28727837

RESUMEN

Inflammatory bowel disease (IBD) is associated with a loss of intestinal barrier function and dysregulated immune responses. It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs. In this study, we investigated the effects of SCFAs in comparison to highly specific GPR43 agonists on human intestinal epithelial and immune cells. Our results confirm that SCFAs are enhancers of barrier function in intestinal epithelial cells. Additionally, SCFAs also displayed potent immunoregulatory properties based upon the ability to inhibit LPS-induced cytokine production in PBMC, and human T cell proliferation and cytokine production. Unexpectedly, and in contrast to the current belief, specific GPR43 agonists failed to exhibit similar barrier enhancing and anti-inflammatory properties. These findings demonstrate that SCFA possess broad protective functions in IBD and agonizing GPR43 alone is unlikely to be beneficial in patients.


Asunto(s)
Células Epiteliales/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Receptores de Superficie Celular/agonistas , Animales , Células CACO-2 , Línea Celular , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Ácidos Grasos Volátiles , Humanos , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Ratones
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