RESUMO
Xylem hydraulic characteristics govern plant water transport, affecting both drought resistance and photosynthetic gas exchange. Therefore, they play critical roles in determining the adaptation of different species to environments with various water regimes. Here, we tested the hypothesis that variation in xylem traits associated with a trade-off between hydraulic efficiency and safety against drought-induced embolism contributes to niche differentiation of tree species along a sharp water availability gradient on the slope of a unique river valley located in a semi-humid area. We found that tree species showed clear niche differentiation with decreasing water availability from the bottom towards the top of the valley. Tree species occupying different positions, in terms of vertical distribution distance from the bottom of the valley, showed a strong trade-off between xylem water transport efficiency and safety, as evidenced by variations in xylem structural traits at both the tissue and pit levels. This optimized their xylem hydraulics in their respective water regimes. Thus, the trade-off between hydraulic efficiency and safety contributes to clear niche differentiation and, thereby, to the coexistence of tree species in the valley with heterogeneous water availability.
Assuntos
Árvores , ÁguaRESUMO
PURPOSE: AZD5991 is a potent and selective macrocyclic inhibitor of Mcl-1 in clinical development. Developing an intravenous solution formulation for AZD5991 proved to be challenging primarily due to the poor intrinsic solubility of AZD5991. In this article are described studies performed to select a suitable crystalline form and to assess physicochemical properties of AZD5991 to aid in the design of a solution formulation for preclinical studies. METHODS: It is preferable that the preclinical formulation has a line of sight for clinical formulation. For AZD5991, a concentration of at least 20 mg/ml was required for toxicology studies. Toward this goal, extensive pre-formulation characterization of AZD5991 including solid form analysis, pH-solubility profiling and solubility determination in cosolvents and other solubilizing media were carried out. RESULTS & DISCUSSION: Crystalline Form A, which is more stable in aqueous solution and possesses acceptable thermal stability, was selected for preclinical and clinical development of AZD5991. Extensive solubility evaluation revealed an interesting pH-solubility profile that significantly enhances solubilization at pH > 8.5 to allow solution concentrations of at least 30 mg/ml by in situ meglumine salt formation. CONCLUSION: Developing pre-clinical formulations to support in vivo studies requires a good understanding of the physicochemical properties of the drug candidates. Candidates with challenging pharmaceutic properties like the novel macrocycle molecule AZD5991, demand extensive characterization in its polymorph landscape, solubility profile and suitability evaluation of the excipients. Meglumine, a pH-adjusting and solubilizing agent, was found to be the best choice for formulating AZD5991 into an intravenous product to support preclinical studies.
Assuntos
Antineoplásicos , Meglumina , Fenômenos Químicos , Excipientes/química , Cloreto de Sódio , Solubilidade , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidoresRESUMO
Magnetic CuFe2O4 nanoparticles were successfully synthesized with a coprecipitation method at 500 °C calcination temperature, and were utilized to degrade levofloxacin (LEV) as a peroxymonosulfate (PMS) activator. The structure and composition of the nanocatalyst were characterized by a series of methods, including scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometer and thermogravimetric analysis. The effects of the PMS concentration, the catalyst dosage, the LEV initial concentration, the pH value and the inorganic anions on the LEV degradation were also explored. The results revealed that the designed CuFe2O4/PMS system had high activity and excellent stability in the complex conditions. The degradation efficiency of LEV still reached above 80% after four recycles of CuFe2O4 catalyst. The reactive species quenching experiments and electron paramagnetic resonance analysis suggested the existence of superoxide radicals, single oxygen, hydroxy radicals and sulfate radicals, and the first two were dominant radical oxygen species. Based on the mechanism analyses, the efficient degradation of LEV was probably due to the continuous generation of reactive species under the condition of Fe(III)/Fe(II) and Cu(II)/Cu(I) redox cycles. The research provided a reasonable reference for the PMS activation mechanism-based spinel-type ferrite catalysis.
Assuntos
Compostos Férricos , Nanopartículas , Catálise , Cobre , Levofloxacino , Fenômenos Magnéticos , PeróxidosRESUMO
BACKGROUND: LINC00689 acts one critical regulatory role in several tumors. However, the functional, regulatory mechanism and expression of LINC00689 remains unknown in gastric cancer. METHODS: LINC00689 and miR-338-3p levels were determined using a quantitative reverse transcriptase-polymerase chain reaction analysis and an enzyme-linked immunoassay and a cell-counting kit-8 assay were utilized to detect interleukin (IL)-8, IL-6 and IL-1ß expression and cell proliferation, respectively. RESULTS: We found that LINC00689 and HOXA3 are overexpressed and miR-338-3p is decreased in gastric cancer cells. Compared to control specimens, LINC00689 is overexpressed in gastric cancer specimens and the level of LINC00689 was up-regulated in 32 cases (32/40; 80.0%) compared to control samples. LINC00689 increased cell growth, epithelial-mesenchymal transition (EMT) development and secretion of inflammatory factors in gastric cancer. Compared to control specimens, miR-338-3p expression was decreased in gastric cancer specimens and a Pearson's correlation assay revealed that miR-338-3p was negatively correlated with LINC00689 expression in gastric cancer specimens. HOXA3 was identified as one target gene of miR-338-3p and Ectopic expression of LINC00689 suppressed miR-338-3p and enhanced HOXA3 expression in HGC-27 cells. LINC00689 enhanced cell growth, EMT development and secretion of inflammatory factors by promoting HOXA3. CONCLUSIONS: LINC00689 may present a potential future target for gastric cancer treatment.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Proteínas de Homeodomínio/genética , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. RESULTS: Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. CONCLUSION: Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients.
Assuntos
Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal/genética , Microbiota/genética , RNA Ribossômico 16S/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Bactérias/genética , Biomarcadores Tumorais/genética , Carcinogênese , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Citocromo P-450 CYP3A/genética , Expressão Gênica , Humanos , Proteínas de Neoplasias/genética , Proteobactérias/genética , Análise de SobrevidaRESUMO
The gut microbiota plays an important role in pheromone production, pesticide degradation, vitamin synthesis, and pathogen prevention in the host animal. Therefore, similar to gut morphology and digestive enzyme activity, the gut microbiota may also get altered under plant defensive compound-induced stress. To test this hypothesis, Dendrolimus superans larvae were fed either aconitine- or nicotine-treated fresh leaves of Larix gmelinii, and Lymantria dispar larvae were fed either aconitine- or nicotine-treated fresh leaves of Salix matsudana. Subsequently, the larvae were sampled 72hr after diet administration and DNA extracted from larval enteric canals were employed for gut microbial 16S ribosomal RNA gene sequencing (338 F and 806 R primers). The sequence analysis revealed that dietary nicotine and aconitine influenced the dominant bacteria in the larval gut and determined their abundance. Moreover, the effect of either aconitine or nicotine on D. superans and L. dispar larvae had a greater dependence on insect species than on secondary plant metabolites. These findings further our understanding of the interaction between herbivores and host plants and the coevolution of plants and insects.
Assuntos
Aconitina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Mariposas/microbiologia , Nicotina/farmacologia , Animais , Bactérias/classificação , Bactérias/genética , Larix , Larva/efeitos dos fármacos , Larva/microbiologia , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Folhas de Planta , RNA Ribossômico 16S , SalixRESUMO
The frequently observed forest decline in water-limited regions may be associated with impaired tree hydraulics, but the precise physiological mechanisms remain poorly understood. We compared hydraulic architecture of Mongolian pine (Pinus sylvestris var. mongolica) trees of different size classes from a plantation and a natural forest site to test whether greater hydraulic limitation with increasing size plays an important role in tree decline observed in the more water-limited plantation site. We found that trees from plantations overall showed significantly lower stem hydraulic efficiency. More importantly, plantation-grown trees showed significant declines in stem hydraulic conductivity and hydraulic safety margins as well as syndromes of stronger drought stress with increasing size, whereas no such trends were observed at the natural forest site. Most notably, the leaf to sapwood area ratio (LA/SA) showed a strong linear decline with increasing tree size at the plantation site. Although compensatory adjustments in LA/SA may mitigate the effect of increased water stress in larger trees, they may result in greater risk of carbon imbalance, eventually limiting tree growth at the plantation site. Our results provide a potential mechanistic explanation for the widespread decline of Mongolian pine trees in plantations of Northern China.
Assuntos
Agricultura Florestal , Pinus sylvestris/crescimento & desenvolvimento , Envelhecimento/fisiologia , China , Pinus sylvestris/fisiologia , Transpiração Vegetal , Água/metabolismoRESUMO
BMS-707035 is an HIV-1 integrase strand transfer inhibitor (INSTI) discovered by systematic optimization of N-methylpyrimidinone carboxamides guided by structure-activity relationships (SARs) and the single crystal X-ray structure of compound 10. It was rationalized that the unexpectedly advantageous profiles of N-methylpyrimidinone carboxamides with a saturated C2-substitutent may be due, in part, to the geometric relationship between the C2-substituent and the pyrimidinone core. The single crystal X-ray structure of 10 provided support for this reasoning and guided the design of a spirocyclic series 12 which led to discovery of the morpholino-fused pyrimidinone series 13. Several carboxamides derived from this bicyclic scaffold displayed improved antiviral activity and pharmacokinetic profiles when compared with corresponding spirocyclic analogs. Based on the excellent antiviral activity, preclinical profiles and acceptable in vitro and in vivo toxicity profiles, 13a (BMS-707035) was selected for advancement into phase I clinical trials.
Assuntos
Fármacos Anti-HIV/farmacologia , Descoberta de Drogas , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , HIV/efeitos dos fármacos , Pirimidinas/farmacologia , Pirimidinonas/farmacologia , Tiazinas/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Relação Dose-Resposta a Droga , Inibidores de Integrase de HIV/síntese química , Inibidores de Integrase de HIV/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinonas/síntese química , Pirimidinonas/química , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/químicaRESUMO
This letter describes the further chemical optimization of the 5-amino-thieno[2,3-c]pyridazine series (VU0467154/VU0467485) of M4 positive allosteric modulators (PAMs), developed via iterative parallel synthesis, culminating in the discovery of the non-human primate (NHP) in vivo tool compound, VU0476406 (8p). VU0476406 is an important in vivo tool compound to enable translation of pharmacodynamics from rodent to NHP, and while data related to a Parkinson's disease model has been reported with 8p, this is the first disclosure of the optimization and discovery of VU0476406, as well as detailed pharmacology and DMPK properties.
Assuntos
Descoberta de Drogas , Piridazinas/farmacologia , Tiofenos/farmacologia , Pesquisa Translacional Biomédica , Regulação Alostérica , Animais , Cristalografia por Raios X , Ligação de Hidrogênio , Piridazinas/química , Ratos , Relação Estrutura-Atividade , Tiofenos/químicaRESUMO
Cyclopentylamine 4 was identified as a potent dual NK1R antagonist-SERT inhibitor. This compound demonstrated significant oral activity in the gerbil forced swimming test, suggesting that dual NK1R antagonists-SERT inhibitors may be useful in treating depression disorders.
Assuntos
Ciclopentanos/química , Antagonistas dos Receptores de Neurocinina-1/química , Receptores da Neurocinina-1/química , Inibidores Seletivos de Recaptação de Serotonina/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/química , Administração Oral , Animais , Cristalografia por Raios X , Ciclopentanos/síntese química , Ciclopentanos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Gerbillinae , Humanos , Conformação Molecular , Atividade Motora/efeitos dos fármacos , Antagonistas dos Receptores de Neurocinina-1/metabolismo , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Ligação Proteica , Receptores da Neurocinina-1/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/síntese química , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
We established the systematic concept framework of shelterbelt construction, with "shelterbelts" as the core concern in the construction of integrated ecosystems including mountain, river, forest, farmland, lake, grassland and sandy-land in semi-arid wind-sand areas. In the construction of shelterbelts, it is necessary to adhere to the principles of scientific coordination and systematic management, considering the carrying capacity of water resources, the demand for dust control, the greening and beautification effects, as well as the principle of improving economic benefits. In practice, the construction methods should base on the types and temporal-spatial distribution of shelterbelts, following the shelterbelts construction theory and technology to form different structure and service functions, achieving the functional goals of shelterbelts. By focusing on the key elements including people, forests, grass, fields, water, and sand, we put forward the timeliness, practicality, and scientificity of shelterbelt construction, proposing construction methods for farmland shelterbelts, pastureland shelterbelts, windbreak and sand-fixing forests and protective forest around village (city), which might provide production technical support for the high-quality construction of green ecological barrier in northern China.
Assuntos
Ecossistema , Vento , Humanos , Fazendas , Pradaria , Rios , Lagos , Florestas , Conservação dos Recursos Naturais , ChinaRESUMO
Metronidazole (MNZ), a commonly used antibiotic, poses risks to water bodies and human health due to its potential carcinogenic, mutagenic, and genotoxic effects. In this study, mesoporous cobalt-manganese layered double hydroxides (CoxMny-LDH) with abundant oxygen vacancies (Ov) were successfully synthesized using the co-precipitation method and used to activate calcium sulfite (CaSO3) with slight soluble in water for MNZ degradation. The characterization results revealed that Co2Mn-LDH had higher specific areas and exhibited good crystallinity. Co2Mn-LDH/CaSO3 exhibited the best catalytic performance under optimal conditions, achieving a remarkable MNZ degradation efficiency of up to 98.1 % in only 8 min. Quenching experiments and electron paramagnetic resonance (EPR) tests showed that SO4â¢- and 1O2 played pivotal roles in the MNZ degradation process by activated CaSO3, while the redox cycles of Co2+/Co3+ and Mn3+/Mn4+ on the catalyst surface accelerated electron transfer, promoting radical generation. Three MNZ degradation routes were put forward based on the density functional theory (DFT) and liquid chromatography-mass spectrometer (LC-MS) analysis. Meanwhile, the toxicity analysis result demonstrated that the toxicity of intermediates post-catalytic reaction was decreased. Furthermore, the Co2Mn-LDH/CaSO3 system displayed excellent stability, reusability, and anti-interference capability, and achieved a comparably high removal efficiency across various organic pollutant water bodies. This study provides valuable insights into the development and optimization of effective heterogeneous catalysts for treating antibiotic-contaminated wastewater.
Assuntos
Cobalto , Hidróxidos , Manganês , Metronidazol , Cobalto/química , Metronidazol/química , Hidróxidos/química , Manganês/química , Porosidade , Propriedades de Superfície , Sulfitos/química , Catálise , Tamanho da Partícula , Teoria da Densidade Funcional , Poluentes Químicos da Água/químicaRESUMO
Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date.
Assuntos
RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Vírus Sinciciais Respiratórios/enzimologia , Proteínas Virais/antagonistas & inibidores , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Azepinas/síntese química , Azepinas/química , Azepinas/farmacologia , Linhagem Celular , RNA Polimerases Dirigidas por DNA/metabolismo , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Humanos , Relação Estrutura-Atividade , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
In this study, cobalt copper-layered double hydroxides (CoCu-LDHs) were prepared by coprecipitation as catalysts to activate CaSO3 for metronidazole (MNZ) degradation. This is the first report on layered double hydroxides activating sulfite for the degradation of organic pollutants. Meanwhile, to address the issue of self-quenching reactions readily occurring in conventional sulfite advanced oxidation systems and resulting in low oxidant efficiency, CaSO3 with slightly soluble in water was used instead of commonly used Na2SO3, to improve the limitations of traditional systems. The results showed that in the CoCu-LDHs/CaSO3 system, the degradation rate of MNZ reached 98.7% within 5 min, representing a 23.0% increase compared to the CoCu-LDHs/Na2SO3 system. Owing to the excellent catalytic performance exhibited by CoCu-LDHs, characterizations including XRD, FTIR, SEM, TEM, BET and XPS were carried out to investigate this further. The results confirmed the successful synthesis of CoCu-LDH, and the activation mechanism study revealed that Co and Cu were considered to the main elements in activating CaSO3, demonstrating good synergistic effects. In addition, the oxygen vacancies on the catalyst surface also played a positive role in generating radicals and promoting electron transfer. Subsequently, the effects of Co/Cu ratio, catalyst dosage, oxidant concentration, pollutant concentration, pH and coexisting substances on MNZ degradation were investigated. Additionally, based on the LC-MS analysis of degradation products and toxicity tests, MNZ was transformed into different intermediates with low toxicity through four pathways, eventually mineralizing into inorganic small molecules. After six cycles, the MNZ degradation rate still reached 82.1%, exhibiting excellent stability and recyclability. In general, this study provides new ideas for activating sulfite, while providing theoretical support for subsequent research on sulfite advanced oxidation system.
Assuntos
Cálcio , Poluentes Ambientais , Cobre , Metronidazol/toxicidade , Sulfitos , Hidróxidos , OxidantesRESUMO
Both environment and human beings were menaced by the widespread application of radioactive uranium, high-performance and effective elimination of uranium from wastewater is of important meaning for development of environmental sustainability in the future. In this study, the water-stable MOF material and the highly crystalline COF were compounded by a mild hydrothermal strategy, which achieved efficient removal of U(VI) through the synergistic effect. The composites showed the characteristics of both COFs and MOFs, which will possess higher stability, larger surface area and faster adsorption efficiency that cannot be carried out by a single component. Batch experiments and characterizations (SEM, TEM, XRD, FT-IR, BET, XPS, etc.) indicated that UiO-66-NH2@LZU1 had more stable and multi-layer pore structure and rich active functional groups. The Langmuir model and the pseudo-second-order kinetics fitting was more suitable for the U(VI) elimination process. The greatest uranium adsorbing capacity of UiO-66-NH2@LZU1 (180.4 mg g-1) was observed to exceed the UiO-66-NH2 (108.8 mg g-1) and COF-LZU1 (65.8 mg g-1), which reached the excellent hybrid effects. Furthermore, FT-IR and XPS analyses confirmed that the most nitrogen-containing group from COF-LZU1 and oxygen-containing group of UiO-66-NH2 could be combined with U(VI). In addition, electrostatic interaction was also a mechanism during the removal process. This work displayed that UiO-66-NH2@LZU1 was a prospective hybrid material for radioactive waste remediation. The compound method and application mentioned in this work had provided a theoretical basis for designing and developing multi-functional composite adsorbents, which contributed to the development of new materials for radioactive wastewater treatment technologies.
Assuntos
Urânio , Humanos , Estudos Prospectivos , Espectroscopia de Infravermelho com Transformada de Fourier , AdsorçãoRESUMO
ZIF-8, a sort of zeolitic imidazolate frameworks (ZIFs), had showed superior adsorptive property of typical radionuclide U(VI), but it reminded uncertain how the performance of ZIF-8 would be affected by adding humic acid (HA). HA could significantly change the surface charge of ZIFs and the transport of U(VI) in natural settings, which affected the eradication of U(VI) in aquatic ecology. Thus the impact of HA for the U(VI) removal by ZIF-8 as well as its mechanism had been analyzed by batch experiments and spectral analyses. It was demonstrated that the addition of HA increased the maximum removal capacity towards U(VI) from 781.2 mg g-1 to 1398.5 mg g-1. Moreover, removal property in acidic solution was improved, and the influence of background ions on ZIF-8 was reduced. The detailed mechanism was further explored by microscopic spectral analysis. The zeta potential showed that HA enhanced the electronegativity of ZIF-8 thus enhancing the electrostatic interaction with positive ions. Moreover, FT-IR and XPS further indicated that HA enhanced the removal capacity by affecting the surface complexation phenomena and strong chemical interactions between U(VI) and ZIF-8. Also, investigations indicated that the incorporation of HA improved the removal efficiency for U(VI), which had far-reaching significance for the application of ZIF-8 in practical environment.
Assuntos
Substâncias Húmicas , Zeolitas , Substâncias Húmicas/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Íons , Adsorção , Zeolitas/químicaRESUMO
The recent discovery of complete ammonia oxidation (comammox) bacteria has fundamentally upended the traditional two-step nitrification conception, but their functional importance in wastewater treatment plants (WWTPs) is still poorly understood. This study investigated distributions of comammox Nitrospira, ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in activated sludge samples collected from 25 full-scale WWTPs. Using quantitative PCR (qPCR) and 16S rRNA gene amplicon sequencing, our results revealed that comammox Nitrospira ubiquitously occurred in all of 25 WWTPs and even outnumbered AOB and AOA with an average abundance of 1â¼183 orders of magnitude higher in 19 WWTPs. Moreover, DNA-based stable isotope probing (DNA-SIP) assays validated that comammox Nitrospira actively participated in ammonia oxidation in the three microcosms seeding with activated sludge from three typical WWTPs, in which the ratios of comammox amoA to AOB amoA were at the range of 1â¼10, 10â¼100 and >100, respectively. Phylogenetic analysis in heavy fractions further indicated that Nitrospira nitrosa (N. nitrosa) was the dominant and active species. We quantified the contribution of ammonia oxidizers based on the currently available kinetic parameters of the representative species and found that comammox made major contributions to ammonia oxidation than other nitrifiers (5 â¼ 106 times that of AOB). The findings not only demonstrate the ubiquitous occurrence of comammox, but also highlight their functional dominance in ammonia oxidation in WWTPs.
Assuntos
Esgotos , Purificação da Água , Amônia , Filogenia , RNA Ribossômico 16S/genética , Oxirredução , Bactérias/genética , Archaea/genética , Nitrificação , DNARESUMO
Herein, we report the optimization of a meta-substituted series of selective estrogen receptor degrader (SERD) antagonists for the treatment of ER+ breast cancer. Structure-based design together with the use of modeling and NMR to favor the bioactive conformation led to a highly potent series of basic SERDs with promising physicochemical properties. Issues with hERG activity resulted in a strategy of zwitterion formation and ultimately in the identification of 38. This compound was shown to be a highly potent SERD capable of effectively degrading ERα in both MCF-7 and CAMA-1 cell lines. The low lipophilicity and zwitterionic nature led to a SERD with a clean secondary pharmacology profile and no hERG activity. Favorable physicochemical properties resulted in good oral bioavailability in preclinical species and potent in vivo activity in a mouse xenograft model.
Assuntos
Neoplasias da Mama , Receptores de Estrogênio , Camundongos , Humanos , Animais , Feminino , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Antagonistas de Estrogênios/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Linhagem CelularRESUMO
Tetracycline (TC) is a typical ecotoxic antibiotic, which easily causes bacterial resistance. Therefore, it is necessary to remove TC from the water environment. In recent years, advanced oxidation processes (AOPs) rely on the use of highly reactive oxidizing sulfate radical which is turning into an increasingly popular as a tool of the removal of TC. In this study, cobalt-doped pomelo peel carbon composite (Co-PPCC) was prepared by the impregnation coprecipitation method to activate peroxymonosulfate (PMS) to remove TC. SEM, BET, XRD, FTIR, XPS, TGA, and other analytical techniques indicated that a carbon composite catalyst with excellent performance has been successfully prepared. TC was removed by the synergistic effect of adsorption and catalytic degradation processes. The adsorption capacity was limited (only approximately 20% within 60 min) and tending to saturation, which indicated that the removal of TC in the Co-PPCC/PMS system was mainly due to oxidative degradation. The influence of the Co-PPCC and PMS dosage, initial TC concentration, initial pH values, and coexisting anions on the removal efficiency of TC was investigated. When the Co-PPCC catalyst dosage was 1 g/L, PMS concentration was 2 g/L, and pH value was 11, the removal efficiency of TC with a concentration of 50 mg/L reached 99% within 60 min. Free radical quenching experiment and electron paramagnetic resonance (EPR) analysis indicated that the free radical and non-radical degradation processes exist in the Co-PPCC/PMS/TC system. The main degradation products and the possible transformation pathways of TC were explored by LC-MS. In addition, after four cycles of Co-PPCC tests, the removal efficiency of TC can reach 64%. This study provides a new method to reuse abandoned pomelo peels and synthesize an economical and environmentally friendly catalyst for activating peroxymonosulfate to remove TC antibiotics in water.
Assuntos
Carbono , Cobalto , Antibacterianos , Catálise , Oxirredução , Estresse Oxidativo , Peróxidos , TetraciclinaRESUMO
In recent years, white rot fungi (WRFs) have received tremendous attention as a biotechnological tool for environmental pollution control. In order to systematically and comprehensively describe the progress, trends, and hotspots of WRF biotechnology in the field of environmental pollution control, the 3967 related publications from 2003 to 2020 were collected from Web of Science Core Collection database, and the bibliometric characteristics including publication output, country, institution, journal, author, citation frequency, h-index, and research focus were evaluated by using Excel 2007, CiteSpace V, and VOSviewer. The results indicated that the number of research publications increased rapidly before 2009, but after that, the number of publications fluctuated in a certain range. China and USA were the most productive countries and the most active country in international cooperation. In this field, most authors tend to cooperate within a small group. The journal and subject category with the largest number of publications are "International Biodeterioration & Biodegradation" and "Biotechnology Applied Microbiology", respectively. The analysis of high-frequency keywords revealed that "laccase", "biodegradation", "decolorization", and "Phanerochaete chrysosporium" were the most cited terms among all publications. The pretreatment of biomass waste, decolorization of dye wastewater, and bioremediation of polluted environment are the key research directions of WRF biotechnology. Finally, the frontier topics and active authors in this research field were identified using burst detection. We believe that this bibliometric study provides a comprehensive and systematic overview and promoted the future cooperative research and knowledge exchange in this field of WRF biotechnology for environmental applications.