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1.
PLoS Pathog ; 20(4): e1012090, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38620033

RESUMEN

Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don't yet have an understanding of how genetic drift changes over time or across locations. Furthermore, noise that results from data collection can potentially confound estimates of genetic drift. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. Our method is highly scalable to increasingly large genomic datasets, which overcomes a limitation in commonly used phylogenetic methods. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium and separately infer the strength of genetic drift for pre-B.1.177, B.1.177, Alpha, and Delta. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude, which cannot be explained by literature values of superspreading. Our estimates of genetic drift suggest low and time-varying establishment probabilities for new mutations, inform the parametrization of SARS-CoV-2 evolutionary models, and motivate future studies of the potential mechanisms for increased stochasticity in this system.


Asunto(s)
COVID-19 , Flujo Genético , SARS-CoV-2 , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , COVID-19/genética , Humanos , SARS-CoV-2/genética , Inglaterra/epidemiología , Filogenia , Genoma Viral
2.
Small ; 19(26): e2207716, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36938701

RESUMEN

Metal selenides are considered as one of the most promising anode materials for Na-ion batteries owing to high specific capacity and relatively higher electronic conductivity compared with metal sulfides or oxides. However, such anodes still suffer from huge volume change upon repeated Na+ insertion/extraction processes and simultaneously undergo severe shuttle effect of polyselenides, thus leading to poor electrochemical performance. Herein, a facile chemical-blowing and selenization strategy to fabricate 3D interconnected hybrids built from metal selenides (MSe, M = Mn, Co, Cr, Fe, In, Ni, Zn) nanoparticles encapsulated in in situ formed N-doped carbon foams (NCFs) is reported. Such hybrids not only provide ultrasmall active nanobuilding blocks (≈15 nm), but also efficiently anchor them inside the conductive NCFs, thus enabling both high-efficiency utilization of active components and high structural stability. On the other hand, Cu-driven replacement reaction is utilized for efficiently inhibiting the shuttle effect of polyselenides in ether-based electrolyte. Benefiting from the combined merits of the unique MSe@NCFs and the utilization of the conversion of metal selenides to copper selenides, the as-obtained hybrids (MnSe as an example) exhibit superior rate capability (386.6 mAh g-1 up to 8 A g-1 ) and excellent cycling stability (347.7 mAh g-1 at 4.0 A g-1 after 1200 cycles).

3.
Environ Res ; 204(Pt C): 112324, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34742712

RESUMEN

Severe haze hovered over Harbin during the heating season of 2019-2020, making it one of the ten most polluted Chinese cities in January of 2020. Here we focused on the optical properties and sources of brown carbon (BrC) during the extreme atmospheric pollution periods. Enhanced formation of secondary BrC (BrCsec) was evident as relative humidity (RH) became higher, accompanied with a decrease of ozone but concurrent increases of aerosol water content and secondary inorganic aerosols. These features were generally similar to the characteristics of haze chemistry observed during winter haze events in the North China Plain, and indicated that heterogeneous reactions involving aerosol water might be at play in the formation of BrCsec, despite the low temperatures in Harbin. Although BrCsec accounted for a substantial fraction of brown carbon mass, its contribution to BrC absorption was much smaller (6 vs. 28%), pointing to a lower mass absorption efficiency (MAE) of BrCsec compared to primary BrC. In addition, emissions of biomass burning BrC (BrCBB) were inferred to increase with increasing RH, coinciding with a large drop of temperature. Since both the less absorbing BrCsec and the more absorbing BrCBB increased as RH became higher, the MAE of total BrC were largely unchanged throughout the measurement period. This study unfolded the contrast in the source apportionment results of BrC mass and absorption, and could have implications for the simulation of radiative forcing by brown carbon.


Asunto(s)
Contaminantes Atmosféricos , Carbono , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Biomasa , Carbono/análisis , Monitoreo del Ambiente , Estaciones del Año
4.
J Pak Med Assoc ; 72(2): 312-316, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35320184

RESUMEN

Breast cancer cells exhibit deregulated metabolism. They require increased glucose uptake and glycolysis-associated enzymes to produce adenosine triphosphate by aerobic glycolysis rather than oxidative phosphorylation. Glutamine metabolism and fatty acid synthesis are also enhanced to meet the rapid and sustained cell growth. Triple-negative breast cancer and human epidermal growth factor receptor-2-positive breast cancers demonstrate significant metabolic reprogramming with increased levels of glucose and glutamine metabolism. Increasing evidences also suggest that micro-ribonucleic acids play important roles in the regulation of metabolic enzymes of breast cancer cells in post-transcriptional manner. Human epidermal growth factor receptor-2 and oestrogen receptor signalling pathways could have crosstalk with micro-ribonucleic acids in metabolic regulation network. The current narrative review was planned to go through recent advances on the role of micro-ribonucleic acids on metabolic reprogramming in breast cancer cells.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Neoplasias de la Mama/genética , Femenino , Glucosa , Glucólisis , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Transducción de Señal
5.
Nat Mater ; 19(1): 56-62, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31591529

RESUMEN

The ability of energy carriers to move between atoms and molecules underlies biochemical and material function. Understanding and controlling energy flow, however, requires observing it on ultrasmall and ultrafast spatio-temporal scales, where energetic and structural roadblocks dictate the fate of energy carriers. Here, we developed a non-invasive optical scheme that leverages non-resonant interferometric scattering to track tiny changes in material polarizability created by energy carriers. We thus map evolving energy carrier distributions in four dimensions of spacetime with few-nanometre lateral precision and directly correlate them with material morphology. We visualize exciton, charge and heat transport in polyacene, silicon and perovskite semiconductors and elucidate how disorder affects energy flow in three dimensions. For example, we show that morphological boundaries in polycrystalline metal halide perovskites possess lateral- and depth-dependent resistivities, blocking lateral transport for surface but not bulk carriers. We also reveal strategies for interpreting energy transport in disordered environments that will direct the design of defect-tolerant materials for the semiconductor industry of tomorrow.

6.
Eur Radiol ; 31(3): 1569-1577, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32929642

RESUMEN

OBJECTIVES: To investigate the capacity of ultrashort echo time (UTE) T1 mapping to non-invasively assess gadolinium deposition in cortical bone after gadolinium-based contrast agent (GBCA) administration. METHODS: Twenty-eight New Zealand rabbits (male, 3.0-3.5 kg) were randomly allocated into control, macrocyclic, high-dose macrocyclic, and linear GBCA groups (n = 7 for each group), and respectively given daily doses of 0.9 ml/kg bodyweight saline, 0.3 mmol/kg bodyweight gadobutrol, 0.9 mmol/kg bodyweight gadobutrol, and 0.3 mmol/kg bodyweight gadopentetate dimeglumine for five consecutive days per week over a period of 4 weeks. After a subsequent 4 weeks of recovery, the rabbits were sacrificed and their tibiae harvested. T1 value of cortical bone was measured using a combination of UTE actual flip angle imaging and variable repetition time on a 7T animal scanner. Gadolinium concentration in cortical bone was measured using inductively coupled plasma mass spectrometry (ICP-MS). Pearson's correlation between R1 value (R1 = 1/T1) and gadolinium concentration in cortical bone was assessed. RESULTS: Bone T1 values were significantly lower in the lower-dose macrocyclic (329.2 ± 21.0 ms, p < 0.05), higher-dose macrocyclic (316.8 ± 21.7 ms, p < 0.01), and linear (296.8 ± 24.1 ms, p < 0.001) GBCA groups compared with the control group (356.3 ± 19.4 ms). Gadolinium concentrations measured by ICP-MS in the control, lower-dose macrocyclic, higher-dose macrocyclic, and linear GBCA groups were 0.04 ± 0.02 µg/g, 2.60 ± 0.48 µg/g, 4.95 ± 1.17 µg/g, and 13.62 ± 1.55 µg/g, respectively. There was a strong positive correlation between R1 values and gadolinium concentrations in cortical bone (r = 0.73, p < 0.001). CONCLUSIONS: These results suggest that UTE T1 mapping has the potential to provide a non-invasive assessment of gadolinium deposition in cortical bone following GBCA administration. KEY POINTS: • Changes in T1 value related to gadolinium deposition were found in bone after both linear and macrocyclic GBCA administrations. • R1 relaxometry correlates strongly with gadolinium concentration in cortical bone. • UTE T1 mapping provides a potential tool for non-invasively monitoring gadolinium deposition in cortical bone.


Asunto(s)
Gadolinio , Compuestos Organometálicos , Animales , Medios de Contraste , Hueso Cortical/diagnóstico por imagen , Gadolinio DTPA , Imagen por Resonancia Magnética , Masculino , Conejos
7.
J Org Chem ; 86(23): 17244-17248, 2021 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-34807586

RESUMEN

The development of a novel environmental benign and sustainable synthetic method for highly efficient construction and direct C-H functionalization of N-heterocycles remains a pivotal central research topic for organic and medicinal chemistry. Herein, a novel visible-light-enabled biomimetic aza-6π electrocyclization for efficient assembly of diverse pyridines and further tandem Minisci-type reaction were developed. A broad spectrum of polysubstituted picolinaldehydes were readily constructed with high efficacy and good functional group tolerance under metal- and oxidant-free conditions.


Asunto(s)
Luz , Piridinas , Catálisis , Metales
8.
Ecotoxicol Environ Saf ; 224: 112647, 2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34411814

RESUMEN

Anthocyanin extract has been applied in agricultural production and enhanced tolerance of plants to adverse effects of Cd stress. Rice was subjected to different concentration of Cd and blueberry anthocyanin, and the effects on rice growth, antioxidative defense, Cd distribution in rice tissues, FTIR and TEM characterization of rice leaves were examined to explain the Cd reductions in rice grains and the protective mechanisms by blueberry anthocyanin. Foliar spray of blueberry anthocyanin at tillering and booting stages was effective for reducing Cd concentration in rice grains and increasing the rice yield, anthocyanin and Cd concentration of rice leaves under 1.0 and 10.0 mg/kg Cd stress. The Cd concentration in rice grains was less than the China national standard of Cd for rice grains (0.2 mg/kg) after surface spraying by 5.0-12.5 g/L blueberry anthocyanin under 1.0 mg/kg Cd stress, while 7.5 g/L spray concentration was the best choice. Blueberry anthocyanin spraying prevents Cd from being transferred from leaves to rice grains mainly by fixation of Cd in soluble and organelle fractions at the tillering and booting stages, and reduces H2O2 and MDA accumulation in rice leaves to decrease Cd toxicity. Combined with FTIR and TEM characterization of rice leaves, the results indicated that surface spraying of 7.5 g/L blueberry anthocyanin under 1.0 mg/kg Cd stress could effectively relieve Cd oxidative damage, and form chelates with Cd ions to immobilize Cd in rice leaves. Hence, blueberry anthocyanin could be used as a foliar resistance control agent to reduce Cd accumulation in rice grains through chelate compound synthesis and decrease Cd toxicity by preventing membrane lipid peroxidation and H2O2 accumulation.

9.
J Org Chem ; 84(20): 13104-13111, 2019 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-31497964

RESUMEN

Commercially available 3,5-bis(trifluoromethyl)aniline was found to be a highly efficient monodentate transient directing group (MonoTDG) for the palladium-catalyzed direct dehydrogenative cross-coupling of benzaldehydes with arenes. A diverse set of symmetrical and unsymmetrical 9-fluorenones was readily obtained in yields of 32-72% along with excellent regioselectivities and broad functional group compatibility as well as high atom economy under mild conditions via a dual carbon-hydrogen (C-H) bond activation sequence.

10.
Plant Cell Environ ; 40(1): 165-176, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27770560

RESUMEN

Phototropism is the process by which plants grow towards light in order to maximize the capture of light for photosynthesis, which is particularly important for germinating seedlings. In Arabidopsis, hypocotyl phototropism is predominantly triggered by blue light (BL), which has a profound effect on the establishment of asymmetric auxin distribution, essential for hypocotyl phototropism. Two auxin efflux transporters ATP-binding cassette B19 (ABCB19) and PIN-formed 3 (PIN3) are known to mediate the effect of BL on auxin distribution in the hypocotyl, but the details for how BL triggers PIN3 lateralization remain poorly understood. Here, we report a critical role for clathrin in BL-triggered, PIN3-mediated asymmetric auxin distribution in hypocotyl phototropism. We show that unilateral BL induces relocalization of clathrin in the hypocotyl. Loss of clathrin light chain 2 (CLC2) and CLC3 affects endocytosis and lateral distribution of PIN3 thereby impairing BL-triggered establishment of asymmetric auxin distribution and consequently, phototropic bending. Conversely, auxin efflux inhibitors N-1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid affect BL-induced relocalization of clathrin, endocytosis and lateralization of PIN3 as well as asymmetric distribution of auxin. These results together demonstrate an important interplay between auxin and clathrin function that dynamically regulates BL-triggered hypocotyl phototropism in Arabidopsis.


Asunto(s)
Arabidopsis/fisiología , Arabidopsis/efectos de la radiación , Clatrina/metabolismo , Hipocótilo/fisiología , Ácidos Indolacéticos/metabolismo , Luz , Fototropismo/efectos de la radiación , Proteínas de Arabidopsis/metabolismo , Endocitosis/efectos de la radiación , Hipocótilo/efectos de la radiación
11.
Drug Metab Dispos ; 45(1): 109-117, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27821436

RESUMEN

In recent years, finding effective biomarkers for identifying early stage cancer and predicating prognosis is crucial for renal cell carcinoma (RCC) diagnosis and treatment. In this study, a dramatic decrease of the solute carrier family 47 member 2 (SLC47A2) mRNA in RCC comparing with the paired adjacent nontumor tissues from patients at low Tumor Node Metastasis stage was observed. Thus, patients with SLC47A2 transcriptional repression are susceptible to RCC. Little is known about the regulation mechanism of SLC47A2 We found that it was a bivalent gene that was enriched with both histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 trimethylation (H3K27me3). Loss of mixed lineage leukemia 1 binding at the gene promoter caused decreased H3K4me3 enrichment and H3K4me3/H3K27me3 ratio, and subsequently repressed the expression of SLC47A2 These two epigenetic markers modulated the expression of SLC47A2 simultaneously, suggesting the regulation pattern for bivalent genes. Histone H3 lysine 27 acetylation also contributed to the expression of SLC47A2 An E2F1-histone deacetylase 10 complex catalyzed deacetylation of H3K27, then prevented the enrichment of H3K4me3, and finally reduced SLC47A2 expression. Consequently, the combined effect of all these factors determined SLC47A2 transcriptional repression in RCC tissues.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Histonas/metabolismo , Neoplasias Renales/metabolismo , Lisina/metabolismo , Proteínas de Transporte de Catión Orgánico/genética , Transcripción Genética , Acetilación , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Epigénesis Genética , Células HEK293 , Histonas/genética , Humanos , Neoplasias Renales/genética , Metilación
12.
Eur J Oncol Nurs ; 70: 102551, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642524

RESUMEN

PURPOSE: We aimed to evaluate the effect of voice training in patients with head and neck cancer who were undergoing radiotherapy. METHOD: This study used a randomized controlled trial design. IBM SPSS 26.0 was used to randomly divide 74 patients into a control group and an experimental group. The control group followed a swallowing exercises program, and the experimental group additionally received ABCLOVE voice training. Both training programs continued throughout the entire radiotherapy cycle. We compared standardized swallowing assessment (SSA), maximum phonation time (MPT), the Voice Handicap Index-10, and incidence of complications such as difficulty opening the mouth, malnutrition, and aspiration between the two groups at T1 (0 radiotherapy sessions, before radiotherapy), T2 (15-16 radiotherapy sessions, middle of radiotherapy), and T3 (30-32 radiotherapy sessions, end of radiotherapy). RESULTS: 70 participants completed this study. Swallowing function and MPT intergroup and interaction effects were statistically significant between the two groups (P < 0.05). At the end of radiotherapy (T3), the SSA score (20.77 ± 1.96) and MPT (10.98 ± 1.75) s in the experimental group were superior to those in the control group (SSA: 22.06 ± 2.38 and MPT: 9.49±1.41 s), with statistical significance (P<0.05). Moreover, the incidence of malnutrition and aspiration in the experimental group was lower than that in the control group (P < 0.05). CONCLUSION: Voice training can improve swallowing function and MPT and reduce complications related to swallowing disorders in patients with head and neck cancer.


Asunto(s)
Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Entrenamiento de la Voz , Humanos , Masculino , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Persona de Mediana Edad , Trastornos de Deglución/etiología , Anciano , Deglución/fisiología , Adulto , Resultado del Tratamiento
13.
PLOS Glob Public Health ; 4(4): e0003039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38630670

RESUMEN

Wastewater-based epidemiology is a promising public health tool that can yield a more representative view of the population than case reporting. However, only about 80% of the U.S. population is connected to public sewers, and the characteristics of populations missed by wastewater-based epidemiology are unclear. To address this gap, we used publicly available datasets to assess sewer connectivity in the U.S. by location, demographic groups, and economic groups. Data from the U.S. Census' American Housing Survey revealed that sewer connectivity was lower than average when the head of household was American Indian and Alaskan Native, White, non-Hispanic, older, and for larger households and those with higher income, but smaller geographic scales revealed local variations from this national connectivity pattern. For example, data from the U.S. Environmental Protection Agency showed that sewer connectivity was positively correlated with income in Minnesota, Florida, and California. Data from the U.S. Census' American Community Survey and Environmental Protection Agency also revealed geographic areas with low sewer connectivity, such as Alaska, the Navajo Nation, Minnesota, Michigan, and Florida. However, with the exception of the U.S. Census data, there were inconsistencies across datasets. Using mathematical modeling to assess the impact of wastewater sampling inequities on inferences about epidemic trajectory at a local scale, we found that in some situations, even weak connections between communities may allow wastewater monitoring in one community to serve as a reliable proxy for an interacting community with no wastewater monitoring, when cases are widespread. A systematic, rigorous assessment of sewer connectivity will be important for ensuring an equitable and informed implementation of wastewater-based epidemiology as a public health monitoring system.

14.
Curr Biol ; 34(4): 855-867.e6, 2024 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-38325377

RESUMEN

Microbial communities play a critical role in ecological processes, and their diversity is key to their functioning. However, little is known about whether communities can regenerate ecological diversity following ecotype removal or extinction and how the rediversified communities would compare to the original ones. Here, we show that simple two-ecotype communities from the E. coli long-term evolution experiment (LTEE) consistently rediversified into two ecotypes following the isolation of one of the ecotypes, coexisting via negative frequency-dependent selection. Communities separated by more than 30,000 generations of evolutionary time rediversify in similar ways. The rediversified ecotype appears to share a number of growth traits with the ecotype it replaces. However, the rediversified community is also different from the original community in ways relevant to the mechanism of ecotype coexistence-for example, in stationary phase response and survival. We found substantial variation in the transcriptional states between the two original ecotypes, whereas the differences within the rediversified community were comparatively smaller, although the rediversified community showed unique patterns of differential expression. Our results suggest that evolution may leave room for alternative diversification processes even in a maximally reduced community of only two strains. We hypothesize that the presence of alternative evolutionary pathways may be even more pronounced in communities of many species where there are even more potential niches, highlighting an important role for perturbations, such as species removal, in evolving ecological communities.


Asunto(s)
Ecotipo , Escherichia coli , Escherichia coli/fisiología , Fenotipo
15.
Foods ; 13(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38790785

RESUMEN

The antioxidant properties of butterfly pea flower (BF), which is rich in natural anthocyanins, have garnered significant attention. The impact of digestion and metabolism on BF extracts and evaluate their subsequent antioxidant activities in vivo were explored in the present study. After in vitro digestion, 42.03 ± 2.74% of total anthocyanins from BF extracts remained, indicating a negative influence of the digestion process on the bioaccessibility of phenolic compounds derived from BF. Furthermore, UPLC-LTQ-Orbitrap-MS2 analysis identified a total of four prototypes and twenty-seven metabolites in rat plasma or urine samples following the intake of BF extracts. The kinetics of key metabolites including delphinidin 3-glucoside (D3G), cyanidin-3-glucoside (C3G), and 4-hydroxybenzoic acid were subsequently determined in blood, and the Cmax values were 69.034 ± 8.05 nM and 51.65 ± 3.205 nM. These key metabolites derived from BF anthocyanins, including C3G and D3G, and flavonoid quercetin exhibited main antioxidant attributes that improved the plasmic and hepatic activities of various antioxidant enzymes and the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) in a D-galactose-induced rat model. These findings provide insights into the bioaccessibility and bioavailability of bioactive constitutes derived from BF extracts, which are crucial for determining the actual efficacy of BF as well as developing functional foods based on BF.

16.
Sci Total Environ ; 940: 173647, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-38823702

RESUMEN

Soil remediation poses significant challenges due to its spatial heterogeneity, surpassing the complexities of atmospheric and water remediation. This study introduces an innovative approach to prevent soil heavy metal pollution by developing three phosphorus slow-release heavy metal soil prophylactic agents (SLPs) - Sap-11, Sap-12, and Sap-21. At a liquid-to-solid ratio of 1:20, the three types of SLPs achieve phosphorus sustained slow release amounts of 1.586 g/L, 4.259 g/L, and 1.444 g/L within 30 days, respectively. Over a cultivation period of 120 days, after amendment with the three SLPs, the surface soil demonstrates stabilization capacities for Pb of 29.56 mg/g, 46.24 mg/g, and 25.77 mg/g, respectively, representing enhancements of 283.64 %, 500.12 %, and 250.74 % compared to the control. Firstly, the direct contribution of P (up to 3.778 mg/g) released from SLPs chemically binding with Pb, and secondly, a significant proportion of the indirect contribution originating from the microbial activity and soil organic matter. In summary, SLP emerges as an effective strategy for soil heavy metal management, stabilizing heavy metals by stimulating the soil's inherent physiological and biochemical reactions. This approach provides a practical solution for the application of P-containing materials and introduces novel perspectives for soil heavy metal management strategies.


Asunto(s)
Restauración y Remediación Ambiental , Plomo , Fósforo , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Fósforo/análisis , Plomo/análisis , Suelo/química , Restauración y Remediación Ambiental/métodos , Cinética , Metales Pesados/análisis
17.
Antimicrob Agents Chemother ; 57(10): 4937-44, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23877701

RESUMEN

Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated to have strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN-ß) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients.


Asunto(s)
Antivirales/farmacología , Aptámeros de Nucleótidos/farmacología , Hepacivirus/efectos de los fármacos , Hepacivirus/metabolismo , Proteínas del Envoltorio Viral/antagonistas & inhibidores , Proteínas del Envoltorio Viral/metabolismo , Línea Celular , Humanos
18.
Chirality ; 25(6): 361-4, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23661402

RESUMEN

The stereoselective uptake of propranolol enantiomers was investigated by using the K562 and K562 adriamycin-resistant cell line (K562/ADR) as a model. An enantioselective RP-HPLC method was applied to determine the accumulation of propranolol (PPL) stereoisomers in K562 and K562/ADR cells. The concentration, time and temperature dependent studies showed that the accumulation of S-(-)-PPL was higher than R-(+)-PPL in K562 cells and uptake of R-(+)-PPL was significantly higher than that of S-(-)-PPL in K562/ADR cells. The results indicate the enantioselective accumulation of propranolol enantiomers in K562 and K562 / ADR cells.


Asunto(s)
Propranolol/química , Propranolol/metabolismo , Cromatografía Líquida de Alta Presión , Humanos , Células K562 , Estructura Molecular , Estereoisomerismo
19.
Sci Total Environ ; 891: 164390, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37236463

RESUMEN

Brown carbon (BrC) represents not only a major component of haze pollution but also a non-negligible contributor to positive radiative forcing, making it a key species for coordinating air quality and climate policies. In China, field observations on BrC remain limited given the highly variable emission sources and meteorological conditions across different regions. Here we focused on the optical properties of BrC in a distinct but rarely studied megacity in Northeast China, which is within a major agricultural region and experiences extremely cold winter. Agricultural fires were evident in April of 2021 and the fall of 2020, although open burning was strictly prohibited. Such emissions enhanced BrC's mass absorption efficiency at 365 nm (MAE365), more efficiently by the fall fires which were inferred to have relatively high combustion efficiencies (CE). After taking CE into consideration, the relationships between MAE365 and the levoglucosan to organic carbon ratio (a measure of the significance of agricultural fire influence) roughly converged for the fire episodes in different seasons, including those identified in February and March of 2019 by a previous campaign. Agricultural fires also influenced the determination of absorption Ångström exponent (AAE), by resulting in non-linearity for BrC's absorption spectra shown on ln-ln scale. Based on three indicators developed by this study, the non-linearity was inferred to be caused by similar chromophores although the fires were characterized by various CE levels in different seasons. In addition, for the samples without significant influence of open burning, coal combustion emissions were identified as the dominant influencing factor for MAE365, whereas none solid link was found between the solution-based AAE and aerosol source.

20.
bioRxiv ; 2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37205326

RESUMEN

Microbial communities play a critical role in ecological processes, and their diversity is key to their functioning. However, little is known about if communities can regenerate ecological diversity following species removal or extinction, and how the rediversified communities would compare to the original ones. Here we show that simple two-ecotype communities from the E. coli Long Term Evolution Experiment (LTEE) consistently rediversified into two ecotypes following the isolation of one of the ecotypes, coexisting via negative frequency-dependent selection. Communities separated by more than 30,000 generations of evolutionary time rediversify in similar ways. The rediversified ecotype appears to share a number of growth traits with the ecotype it replaces. However, the rediversified community is also different compared to the original community in ways relevant to the mechanism of ecotype coexistence, for example in stationary phase response and survival. We found substantial variation in the transcriptional states between the two original ecotypes, whereas the differences within the rediversified community were comparatively smaller, but with unique patterns of differential expression. Our results suggest that evolution may leave room for alternative diversification processes even in a maximally reduced community of only two strains. We hypothesize that the presence of alternative evolutionary pathways may be even more pronounced in communities of many species, highlighting an important role for perturbations, such as species removal, in evolving ecological communities.

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