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1.
Sci Total Environ ; 934: 173202, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38754517

RESUMEN

Net ecosystem exchange (NEE) of carbon dioxide (CO2) in disturbed tidal wetlands remain less investigated, albeit the importance of these 'blue carbon' ecosystems in mitigating climate change has been increasingly recognized. The invasion of smooth cordgrass into China's unvegetated tidal wetlands promotes the carbon sink, however little is known about the changes in NEE when the cordgrass is intensively removed. Here, two-year continuous eddy covariance measurements from Nov. 2021 to Oct. 2023 were used to examine how intensive cordgrass removal affects NEE in a cordgrass-dominated saltmarsh-mangrove ecotone of Southeast China. The results showed (a) this wetland acted as a monthly CO2 sink throughout the pre-removal year with nearly 90 % of the annual sink (-719.7 g C m-2 yr-1) in the cordgrass growing season from Apr. to Oct.; (b) the cordgrass removal turned this high-sink wetland into a weak CO2 source at an annual scale (39.0 g C m-2 yr-1), while the change of the sink was diurnally and seasonally unequal with daytime and growing season, respectively, accounting for the majority of the reduction; (c) tidal inundation exerted inhibitive effects on the response of daytime and nighttime NEE to photosynthetically active radiation and air temperature, respectively, with the changes in all-day NEE more driven by photosynthesis than ecosystem respiration. As one of the first assessments on the impacts of cordgrass removal on NEE, this study confirms the reduction in annual CO2 sink is predominantly attributed to the cordgrass removal instead of the climatic difference. This study highlights the importance of the interactive effects among phenological, meteorological, and tidal factors in regulating the seasonality of NEE and its changes along with cordgrass removal. Future longer flux measurements with extended years are needed to complement the present assessment of the cordgrass removal-induced impacts on NEE from a long-term perspective.

2.
Sensors (Basel) ; 24(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38676175

RESUMEN

The identification of multi-source signals with time-frequency aliasing is a complex problem in wideband signal reception. The traditional method of first separation and identification especially fails due to the significant separation error under underdetermined conditions when the degree of time-frequency aliasing is high. The single-mode recognition method does not need to be separated first. However, the single-mode features contain less signal information, making it challenging to identify time-frequency aliasing signals accurately. To solve the above problems, this article proposes a time-frequency aliasing signal recognition method based on multi-mode fusion (TRMM). This method uses the U-Net network to extract pixel-by-pixel features of the time-frequency and wave-frequency images and then performs weighted fusion. The multimodal feature scores are used as the classification basis to realize the recognition of the time-frequency aliasing signals. When the SNR is 0 dB, the recognition rate of the four-signal aliasing model can reach more than 97.3%.

3.
Nat Commun ; 15(1): 2098, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459034

RESUMEN

Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock's origin using a digital twin. We estimate internal friction angle within 21.5°-42.0° and associated cohesion of 520-3154 Pa in the Chang'E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°-16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang'E-4 site, implying a more complicated geological history in the vicinity.

4.
J Vet Pharmacol Ther ; 47(2): 134-142, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37853794

RESUMEN

Enrofloxacin (ENR) is widely used in aquaculture practice, but little is known about its pharmacokinetic, withdrawal period and dietary risk in fish via bath administration. The purpose of this study was to provide data support for the use of ENR bath therapy in the northern snakehead (Channa argus). The pilot study was carried out to evaluate the therapy concentrations of ENR in northern snakehead with immersion concentrations ranged from 5 to 40 mg/L for 6 h. Based on results of the pilot study, an ENR immersion concentration of 20 mg/L was used for the formal experiment. At this dose, the peak concentrations of ENR in plasma, muscle plus skin, liver and kidney were 4.85, 4.55, 3.87 and 7.42 µg/mL (or g), respectively. According to the AUC0-∞ values, the distribution of ENR in northern snakehead followed the order of kidney > plasma > liver > muscle + skin. The elimination of ENR in northern snakehead was very slow, the half-lives (T1/2λz ) were up to 90.31, 85.5, 104.56 and 120.9 h in plasma, muscle plus skin, liver and kidney, respectively. Ciprofloxacin (CIP) was not detected in any samples in the pilot study and was only occasionally detected in muscle plus skin and liver samples in formal experiment. Based on the calculated PK/PD index AUC/MIC and Cmax /MIC, the current bath treatment regimen will have a good therapeutic effect on infections caused by bacteria with MIC below 0.6 µg/mL. The dietary risk assessment suggested that there was a dietary risk (Hazard Quotients > 10%) until day 6 after bath treatment. It is mandatory for ENR to maintain a withdrawal period of at least 450°C-day in northern snakehead after bath treatment ceased.


Asunto(s)
Peces , Animales , Enrofloxacina/farmacocinética , Proyectos Piloto , Área Bajo la Curva
6.
Acta Virol ; 67(1): 51-58, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950885

RESUMEN

The hepatitis B virus (HBV) infection remains highly prevalent globally. The present study aimed to explore the possible therapeutic effect of notoginsenoside R1, which has attracted considerable attention due to its diverse pharmacological effects, on HBV infection. The HBV-containing hepatocellular carcinoma cell lines, HepG2 and MHCC97H, were used in this study. We first treated the two cell lines with different concentrations of notoginsenoside R1 and subsequently measured the relative levels of HBV DNA, HBV surface antigen, HBV core antigen, and sirtuin 1 (SIRT1) using reverse transcription-quantitative polymerase chain reaction and western blotting. Finally, an HBV hemodynamic replication model was created to test the effect of notoginsenoside R1 on HBV replication. Notoginsenoside R1 inhibited the replication of HBV. This inhibitory effect was mediated through the downregulation of SIRT1 activity. Additionally, the inhibition of SIRT1 activity by silencing its expression or treatment with the SIRT1 inhibitor, selisistat, suppressed HBV replication. Furthermore, our animal experiments demonstrated that notoginsenoside R1 was effective at suppressing HBV replication in vivo. Thus, notoginsenoside R1 suppresses HBV replication by downregulating SIRT1 activity in vitro and in vivo. Keywords: notoginsenoside R1; hepatitis B virus; SIRT1.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Animales , Virus de la Hepatitis B/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Replicación Viral , Hepatitis B/tratamiento farmacológico , Hepatitis B/genética , ADN Viral
7.
Antiviral Res ; 209: 105485, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36509208

RESUMEN

The HBV core protein plays an integral role in multiple steps of the HBV lifecycle. Consequently, HBV core inhibitors interrupt multiple steps of the replication cycle, including blocking pgRNA encapsidation and prematurely disassembling existing nucleocapsids, thereby preventing them from transporting relaxed circular (rcDNA) to the nucleus for conversion to covalently closed circular DNA (cccDNA). ABI-H2158 is an HBV core inhibitor that advanced into Phase 2 clinical trials for the treatment of chronic hepatitis B virus infection (cHBV) but was discontinued due to hepatotoxicity. Here, the potency, selectivity, and mechanisms of action of ABI-H2158 were evaluated using a variety of cell-based assays. Antiviral activity was measured by quantifying intracellular or secreted HBV DNA, RNA, and antigens. ABI-H2158 inhibited HBV replication by blocking pgRNA encapsidation in induced HepAD38 cells (EC50 = 22 nM) and had similar potency in HBV-infected HepG2-NTCP cells (EC50 = 27 nM) and primary human hepatocytes (PHH) (EC50 = 41 nM). ABI-H2158 is a pan-genotypic HBV inhibitor, with EC50s ranging from 7.1 to 22 nM across HBV genotypes A-E. ABI-H2158 also potently blocked the formation of cccDNA in de novo HBV infections with EC50s of ∼200 nM in HepG2-NTCP and PHH assays. These results indicate ABI-H2158 has dual mechanisms of action, inhibiting both early and late steps of the HBV replication cycle.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Hepatitis B Crónica/tratamiento farmacológico , Replicación Viral/genética , Células Hep G2 , Hepatocitos , ADN Circular/metabolismo , ADN Viral/genética , ADN Viral/metabolismo
8.
J Environ Manage ; 325(Pt A): 116498, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36265234

RESUMEN

The co-combustion of coal and biomass in O2/CO2 conditions is a promising technology for CO2 capture and waste disposal. Little attention has been paid to the interaction between different biomass in co-combustion process, which is of great significance to the study of the co-combustion mechanism. The co-combustion behavior of coal and multiple biomass under isothermal conditions was characterized by thermogravimetric method, and the interaction between different biomass was investigated from the perspective of thermogravimetric and proximate analysis. It found that biomass blending could remarkably improve the combustion performance of coal. Compared to the theoretical prediction, the interaction between coal and biomass showed remarkably promoting effects when the coal was blended with different biomass. While the interaction between different biomass was weak. Moreover, the influence of proximate analysis on combustion characteristic parameters was studied by establishing the linear relationship between combustion characteristic parameters and proximate analysis. The effects of proximate analysis on characteristic time/S were divided into five categories, and it were mainly controlled by the interaction both between coal with biomass and between different biomass.


Asunto(s)
Dióxido de Carbono , Carbón Mineral , Biomasa , Termogravimetría
9.
Zool Stud ; 61: e17, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330025

RESUMEN

Male red nuptial coloration is a primary mating signal for three-spined sticklebacks (Gasterosteus aculeatus), and the retinae of both sexes are especially sensitive to red during the breeding season. Red sensitivity is an important aspect of female mate choice in this species, but only when they are ready to spawn and not over the entire breeding period. Here, we aimed to determine if the red sensitivity of female sticklebacks change over their repeat spawning cycle. To this end, we assessed retinal opsin mRNA levels and behavioral red sensitivity in females over this cycle. Both methods indicated that females were more sensitive to red during spawning than in the inter-spawning intervals. Relative expression levels of red color opsin genes (lws) and optical motor sensitivity were high during spawning, decreased after the spawning period, and then increased again 72-96 h later when they were ready to spawn again. Thus, female sticklebacks altered their color sensitivity according to need, but the underlying mechanism remains unclear.

10.
Ecotoxicol Environ Saf ; 241: 113751, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35691199

RESUMEN

Pyrethroids pesticides (PPs) are the widely adopted synthetic pesticides for agriculture and fishery. The frequent use of these pesticides leads to the accumulation of residues in the freshwater environments in China, subsequently affecting aquatic organisms and ecosystems. However, there are few reports on the toxicological and risk assessment of aquaculture aquatic products. In this study, the uptake, depuration kinetics and potential risk to human health and ecology of fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were assessed using tilapia. The results indicated that four PPs were readily accumulated by tilapia. The bioconcentration factors (BCF) of the PPs in plasma and muscle were between 71.3 and 2112.1 L/kg and 23.9-295.3 L/kg, respectively. The half-lives (t1/2) of muscle and plasma were 2.90-9.20 d and 2.57-8.15 d. The risks of PPs residues in the muscle of tilapia and exposed water were evaluated by hazard quotient (HQ) and risk quotient (RQ). Although PPs residues in tilapia had a low dietary risk to human health, the residues in the exposed water had a high ecological risk to fish, daphnia, and green algae. Therefore, assessing the PPs content in freshwater aquaculture and monitoring their dosages and frequencies are highly necessitated to avoid their adverse effect on the aquaculture environment.


Asunto(s)
Plaguicidas , Piretrinas , Tilapia , Contaminantes Químicos del Agua , Animales , Ecosistema , Humanos , Piretrinas/toxicidad , Medición de Riesgo , Toxicocinética , Agua , Contaminantes Químicos del Agua/farmacocinética , Contaminantes Químicos del Agua/toxicidad
11.
Front Vet Sci ; 9: 872828, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35498735

RESUMEN

The pharmacokinetics, tissue distribution, and elimination of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated to the crucian carp (Carassius auratus gibelio) after single (20 mg/kg b. w.) and multiple oral administration (20 mg/kg b.w. one time daily for 5 days) at 28°C. The concentrations of ENR and CIP in the plasma and tested tissues (muscle/skin, liver, and kidney) were detected simultaneously by high-performance liquid chromatography (HPLC), and the pharmacokinetic data were analyzed with a non-compartmental model using WinNonLin 6.1 PK software (Pharsight Corporation, Mountain View, CA, USA). The pharmacokinetic characteristics of ENR in crucian carp exhibited slow absorption, wide tissue distribution, and long elimination half-life. In the single-dose group, the peak concentrations (Cmax) of ENR in the plasma, muscle/skin, liver, and kidney were 8.93 µg/mL, 13.9 µg/g, 31.2 µg/g, and 27.3 µg/g, respectively, observed at 3 h, 6 h, 1 h, and 3 h after dosing. The elimination half-lives (T1/2λz ) of ENR in plasma, muscle/skin, liver, and kidney were calculated to be 67.4, 82.8, 94.4, and 114 h, respectively. In the multiple-dose group, the Cmax of ENR in the plasma, muscle/skin, liver, and kidney were 18.4 µg/mL, 26.8 µg/g, 82.8 µg/g, and 74.5 µg/g, respectively, achieved at 3 h, 6 h, 1 h, and 1 h after the last dose. The T1/2λz of ENR in the plasma, muscle/skin, liver, and kidney were calculated to be 76.4 h, 91.5 h, 114 h, and 148 h, respectively. During the multiple-dose administration, significant accumulations of ENR and CIP were observed in the plasma and tissues of crucian carp, possibly due to their long elimination half-lives. In both dose groups, the AUC0-∞ for both ENR and CIP followed the order of liver > kidney > muscle/skin > plasma. The finding suggested that the liver may play an important role in the metabolism of ENR. According to the calculated PK/PD indices of Cmax/minimum inhibitory concentrations (MIC) and AUC24h/MIC, the multiple-dose regimen would be highly effective against pathogenic bacteria with a MIC value of ≤ 1.84 µg/ml. Depletion studies indicated that a withdrawal period of at least 29 or 32 days was necessary to guarantee food security after single or multiple oral gavage administration at 28°C.

12.
ACS Omega ; 7(17): 14944-14951, 2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35557660

RESUMEN

Hydrogen, as a noncarbon energy source, plays a significant role in future clean energy vectors. However, concerns about the safe storage and transportation of hydrogen gas limit its wide application. Featured with high H2 volumetric density, nontoxicity, and nonflammability, formic acid (FA) is regarded as one of the most encouraging chemical hydrogen carriers. The search for heterogeneous catalysts with decent catalytic activity and stability for FA decomposition is one of the hottest research topics in this area. In this paper, three weakly basic resins with different functional groups, including D201 with -N+(CH3)3, D301 with -N(CH3)2, and D311 with -NH2, were investigated as alternative catalyst supports for Pd catalysts. The prepared basic resin-supported Pd catalysts were evaluated for the FA dehydrogenation reaction under atmospheric pressure and temperatures ranging from 30 to 70 °C. The results showed that the catalytic activity of the three different resin-supported Pd catalysts follows the order of Pd/D201 > Pd/D301 > Pd/D311. Particularly, a high turnover frequency value of 547.6 h-1 was achieved when employing Pd/D201 as the FA dehydrogenation reaction catalyst at 50 °C. The apparent activation energies for the three different Pd/resin catalysts were calculated, of which the Pd/D210 catalyst demonstrates the lowest activation energy of 42.9 kJ mol-1. The reasons for the superior catalytic behavior, together with the reaction mechanism, were then investigated and illustrated.

13.
Molecules ; 27(9)2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35566056

RESUMEN

A titanate nanotube catalyst for ozonation was synthesized with a simple one-step NaOH hydrothermal treatment without energy-consuming calcination. The synthesized titania catalysts were characterized by X-ray diffraction (XRD), Raman, porosimetry analysis, high-resolution transmission electron microscopy (HR-TEM), Fourier transformed infrared (FTIR), and electron paramagnetic resonance (EPR) analysis. The catalyst treated with a higher concentration of NaOH was found to be more catalytically active for phenol removal due to its higher titanate content that would facilitate more OH groups on its surface. Furthermore, the main active oxidizing species of the catalytic ozonation process were recognized as singlet oxygen and superoxide radical, while the hydroxyl radical may only play a minor role. This work provides further support for the correlation between the properties of titania and catalytic performance, which is significant for understanding the mechanism of catalytic ozonation with titania-based materials.


Asunto(s)
Ozono , Contaminantes Químicos del Agua , Catálisis , Radical Hidroxilo , Ozono/análisis , Fenol/análisis , Hidróxido de Sodio , Contaminantes Químicos del Agua/análisis
15.
Small Methods ; 5(12): e2100834, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34928041

RESUMEN

Electrocatalytic oxygen evolution reaction (OER), an important electrode reaction in electrocatalytic and photoelectrochemical cells for a carbon-free energy cycle, has attracted considerable attention in the last few years. Metal oxides have been considered as good candidates for electrocatalytic OER because they can be easily synthesized and are relatively stable during the OER process. However, inevitable structural variations still occur to them due to the complex reaction steps and harsh working conditions of OER, thus impending the further insight into the catalytic mechanism and rational design of highly efficient electrocatalysts. The aim of this review is to disclose the current research progress toward the structural variations of metal oxide-based OER electrocatalysts. The origin of structural variations of metal oxides is discussed. Based on some typical oxides performing OER activity, the external and internal factors that influence the structural stability are summarized and then some general approaches to regulate the structural variation process are provided. Some operando methods are also concluded to monitor the structural variation processes and to identify the final active structure. Additionally, the unresolved problems and challenges are presented in an attempt to get further insight into the mechanism of structural variations and establish a rational structure-catalysis relationship.

16.
J Diabetes Res ; 2021: 4542367, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34869777

RESUMEN

The objective of the study is to analyze the association between early pregnancy body mass index (BMI), gestational weight gain (GWG), and maternal and neonatal outcomes. The retrospective cohort study was conducted at Quanzhou First Hospital Affiliated to Fujian Medical University from January 2018 to May 2021, with 552 women enrolled. Women were divided into the underweight group, normal weight group, overweight group, and obese group according to early pregnancy BMI. Univariate and multivariate logistic regression analyses were performed. The absolute risk of adverse maternal and neonatal outcomes in the early pregnancy BMI group was calculated to further analyze the association between GWG and adverse maternal and neonatal outcomes. Of the 552 women, 390 (70.65%) women had adverse maternal and neonatal outcomes. The result revealed that overweight was associated with increased risk of adverse maternal and neonatal outcomes (odds ratio (OR): 1.643, 95% confidence interval (CI): 1.006-2.684), maternal complications (OR: 1.937, 95% CI: 1.188-3.159), and large for gestational age (LGA) (OR: 1.905, 95% CI: 1.061-3.422). In the obese group, the risk of adverse maternal and neonatal outcomes (OR: 5.760, 95% CI: 1.997-16.786), maternal complications (OR: 3.112, 95% CI: 1.645-5.887), gestational diabetes mellitus (GDM) (OR: 2.943, 95% CI: 1.509-5.741), cesarean section (OR: 1.899, 95% CI: 1.002-3.599), and preterm delivery (OR: 4.752, 95% CI: 1.395-16.185) increased. Besides, there was an association between insufficient GWG and decreased risk of LGA (OR: 0.392, 95% CI: 0.187-0.826) and higher risk of preterm delivery (OR: 2.818, 95% CI: 1.171-6.784). This study demonstrates that BMI and GWG are related to maternal and neonatal outcomes. It is necessary to regularly monitor the weight of pregnant women during pregnancy. And regional guidelines for GWG also need to be explored.


Asunto(s)
Índice de Masa Corporal , Ganancia de Peso Gestacional/fisiología , Resultado del Embarazo/epidemiología , Adulto , China/epidemiología , Estudios de Cohortes , Femenino , Ganancia de Peso Gestacional/etnología , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos
17.
Oncol Rep ; 44(4): 1343-1354, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32945477

RESUMEN

Increasing research has demonstrated that lncRNAs participate in the development of multiple cancer types. However, the role of TTN­AS1 in endometrial cancer (EC) remains unknown. The present study aimed to explore the function of titin­antisense RNA1 (TTN­AS1) in EC progression and the underlying mechanisms. qRT­PCR was performed to assess the TTN­AS1 expression patterns in EC tissues and cell lines. Loss of function experiments were carried out to estimate the effects of TTN­AS1 on EC cell proliferation, migration and invasion. To reveal the underlying mechanisms, informatics tools were used to predict the targets. Rescue experiments were performed to investigate the TTN­AS1­regulated miR­376a­3p/pumilio homolog 2 (PUM2) axis involved. The results of the present study revealed that TTN­AS1 was highly expressed in both EC tissues and cell lines, and TTN­AS1 knockdown inhibited EC cell proliferation, migration and invasion. With respect to the mechanisms, miR­376a­3p was revealed to be targeted by TTN­AS1, and reversed the effects on EC development induced by TTN­AS1. In addition, PUM2 was positively regulated by TTN­AS1, and miR­376a­3p mediated the regulation between them. Furtherly, in vivo experiments confirmed the results. Collectively, TTN­AS1 enhanced EC cell proliferation and metastasis by targeting the miR­376a­3p/PUM2 axis, which may shed light on EC diagnosis and treatment.


Asunto(s)
Conectina/genética , Neoplasias Endometriales/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos
18.
Chem Commun (Camb) ; 56(80): 12001-12004, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-32901627

RESUMEN

A novel CFCl2CF2Cl(R113)/H2 gas treatment process was proposed and successfully applied for the redispersion of a sintered alloy PdCu/AC catalyst. The redispersion process was initiated by the formation of an oxidative PdCuClx intermediate, which can easily migrate to a nearby catalyst surface and then be reduced to smaller PdCu NPs.

19.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-32868329

RESUMEN

ABI-H0731, a first-generation hepatitis B virus (HBV) core protein inhibitor, has demonstrated effective antiviral activity in chronic hepatitis B (CHB) patients in a phase 1b clinical trial and is currently being further evaluated in phase 2 clinical trials. Here, we report the preclinical profile of ABI-H0731. In in vitro cell culture systems (HepG2-derived cell lines HepAD38 and HepG2-NTCP and primary human hepatocytes [PHHs]), ABI-H0731 exhibited selective inhibition of HBV DNA replication (50% effective concentration [EC50] from 173 nM to 307 nM). Most importantly, ABI-H0731 suppressed covalently closed circular DNA (cccDNA) formation in two de novo infection models with EC50s from 1.84 µM to 7.3 µM. Mechanism-of-action studies indicated that ABI-H0731 is a direct-acting antiviral that targets HBV core protein, preventing HBV pregenomic RNA (pgRNA) encapsidation and subsequent DNA replication. The combination of ABI-H0731 with entecavir appears to decrease viral DNA faster and deeper than nucleoside/nucleotide analogue (NrtI) therapy alone. In addition, ABI-H0731 disrupts incoming nucleocapsids, causing the premature release of relaxed circular DNA (rcDNA) before delivery to the nucleus, and thus prevents new cccDNA formation. ABI-H0731 exhibits pangenotypic activity and is additive to moderately synergistic when combined with an NrtI. In addition to its potency and novel mechanism of action, ABI-H0731 possesses drug-like properties and a preclinical pharmacokinetic profile supportive of once-daily dosing in patients with CHB. Taken together, these data support the ongoing clinical development of ABI-H0731 as a treatment for HBV.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Hepatitis C Crónica , Antivirales/farmacología , Antivirales/uso terapéutico , ADN Circular/genética , ADN Viral/genética , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Proteínas del Núcleo Viral/genética , Replicación Viral
20.
ACS Omega ; 5(30): 19194-19201, 2020 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-32775922

RESUMEN

Potassium hydroxide-impregnated char sorbents (KOH/char) prepared via an ultrasonic-assisted method were used for SO2 removal from flue gas. The desulfurization experiment was analyzed using a fixed-bed reactor under 40-150 °C temperature range, using simulated flue gas. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) were used to analyze both the chemical and physical characteristics of the sorbents. The analyzed results exposed that the complete elimination of SO2 from flue gas was achieved when using the char/KOH sorbent with a mass ratio of char to KOH of 11:1. It was noted that temperature had a substantial influence on the desulfurization performance with sulfur capacity maximized at 100 °C. Experimental results also revealed that a small amount of O2 present in the solvent could improve the SO2 removal efficiency of the sorbent. The analyzed XRD patterns showed that K2SO4 was the main desulfurization product, which was consistent with the SEM/EDS analysis. The experimental results were well-described with the Lagergren first-order adsorption kinetics model with the activation energy (E a) of the SO2 adsorption by KOH/char sorbent of 20.25 kJ/mol.

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