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1.
ACS Pharmacol Transl Sci ; 7(7): 2196-2203, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39022367

RESUMEN

Histone deacetylase 6 (HDAC6) enzyme plays a crucial role in a variety of cellular processes related to cancer, and inhibition of HDAC6 is emerging as an effective strategy for cancer treatment. Although several hydroxamate-based HDAC6 inhibitors showed promising anticancer activities, the intrinsic defects such as poor selectivity, stability, and pharmacokinetics limited their application. In this study, a potent selenocyanide-bearing HDAC6 inhibitor, 5-phenylcarbamoylpentyl selenocyanide (SelSA), was evaluated for its antihepatocellular carcinoma (HCC) activity and further explored for its antitumor mechanisms. In vitro studies demonstrated that SelSA exhibited excellent antiproliferative activity against three HCC cells HepG2 (2.3 ± 0.29 µM), Huh7 (0.83 ± 0.48 µM), and LM3 (2.6 ± 0.24 µM). Further studies indicated that SelSA could downregulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, inhibit the growth, invasion, and migration of Huh7 cells, and promote their apoptosis. Moreover, SelSA significantly suppressed tumor growth in Huh7 xenograft mouse models. Our findings suggest that SelSA could be a potential therapeutic agent for HCC.

2.
J Phys Chem Lett ; 14(26): 6009-6017, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37350652

RESUMEN

Understanding the synergistic effect of Cu-based alloys on the adsorption behavior and selectivity of the CO2 reduction reaction is a crucial step toward directional catalyst design. To this end, density functional theory calculations are employed to investigate Cu-based alloys with diverse doping elements and contents. The results show that the scaling relation still holds in the alloy system, and the strategies to improve the selectivity are put forward based on the adsorption strength of *C and *OCHO intermediates. Further, a model combining the adsorption theory and machine learning algorithm is proposed to capture the relationship between the adsorption energy and the geometric environment. It explains that the difference in d-band centers between the doped metals and Cu affects the variation trend of the adsorption strength and reveals that the intermetallic synergistic effect can be quantified by the bonding distance and d orbital radius on both the adsorbate and metal side.

3.
J Environ Manage ; 319: 115718, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35868183

RESUMEN

Effective and efficient disposal of radioactive pollution has been crucial for responding to unexpected nuclear accidents and guaranteeing the sustainable development of nuclear energy. In this study, a kind of porous zirconium phosphate was synthesized with a sol-gel process followed by a post-synthesis modification to remove the radioactive Sr2+ from wastewater. The prepared materials were characterized by different technologies including FT-IR, SEM-EDS, XRD and XPS, and then the adsorption performance was evaluated in batch and column modes. Experimental results suggested that the porous zirconium phosphate adsorbent was successfully prepared with Na+ dispersed in the channels for exchange. It inherited the excellent properties of zirconium dioxide aerogel and exhibited mesoporous structure and large specific surface area. Compared with traditional zirconium phosphate, the adsorption kinetics and the adsorption capacity were improved simultaneously. Especially, it showed excellent selectivity towards Sr2+ among different cations, and even could remove the low-level Sr2+ from natural seawater efficiently, which powerfully demonstrated that the prepared material could be applied in the treatment of practical wastewater. Spectra studies uncovered that the adsorption activities were dominated by the ion exchange mechanism between external Sr2+ and interlaminar Na+ or H+. In conclusion, this paper not only reports a novel synthesis strategy for the acquisition of porous zirconium phosphate, but also presents a promising adsorbent for the Sr2+ removal.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Adsorción , Concentración de Iones de Hidrógeno , Cinética , Fosfatos/química , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Estroncio , Contaminantes Químicos del Agua/química , Circonio/química
4.
J Phys Chem Lett ; 13(20): 4434-4440, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35549269

RESUMEN

Electrochemical CO2 reduction technology plays an important role in reducing CO2 into valuable chemical fuels. Therein, Cu-based catalysts show superior performance for producing high-value C2+ products. Here, we illustrate the ascendency of high-index facets of Cu catalysts in producing C2+ products and find that two kinds of sites favor C-C coupling on the surface. One is prone to adsorb the C-C coupling structure by spanning stepped coppers with different coordination numbers. The other is to embed the structure along two columns of Cu with similar characteristics through O and C adsorbed simultaneously. Within all research surfaces, the coupling energy barrier is lowest on the Cu(911) facet, which is consistent with the experiment. The less charged sites promote the stabilization of the CO-CO structure as determined by charge analysis. Furthermore, our results suggest that the high selectivity for C2+ products on a Cu surface could significantly come from the contribution of the high-index facet.

5.
IEEE Trans Biomed Circuits Syst ; 15(4): 802-819, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34388094

RESUMEN

This work presents an 8-channel closed-loop neuromodulation chipset with 2-level seizure classification. The power-consuming fine classifier is only enabled when the coarse classifier in the frontend chip judges the patient's status as "suspected seizure". This scheme can reduce the overall power consumption extensively since seizure usually occurs with very low possibility. In the capacitive-coupled instrument amplifier (CCIA) of the front-end IC, a feedback based common-mode (CM) cancellation circuit is proposed to suppress large-scale CM interferences and the stimulation artifacts are suppressed by a mixed-signal loop with fast response. An auto-zero based pre- charge path is adopted to boost the input impedance, while the electrode DC offset is canceled by a DC servo loop with very-large and accurate time constant. The 2.32-mm2 front-end chip and 3.51-mm2 DSP chip implemented in 0.18 µm CMOS are applied in a deep-brain stimulation (DBS) neuromodulator. Measurement results show that the CCIA can suppress 1.5-Vpp CM interference, and achieve an accurate high-pass corner frequency as low as 0.1 Hz and an input impedance greater than 2.2 GΩ. The overall classifier achieves 97.8% sensitivity and consumes only 1.16-µW average power for the CHB-MIT database test. The chipset has been verified by in vivo measurement, showing that the stimulation artifact can be suppressed by 35 dB within 0.5 ms.


Asunto(s)
Artefactos , Procesamiento de Señales Asistido por Computador , Amplificadores Electrónicos , Electrodos , Diseño de Equipo , Humanos , Convulsiones/diagnóstico
6.
Environ Pollut ; 289: 117710, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34243057

RESUMEN

Puberty is a critical period for growth and development. This period is sensitive to external stimuli, which ultimately affects the development of nerves and the formation of social behaviour. 17ß-Trenbolone (17ß-TBOH) is an endocrine disrupting chemicals (EDCs), which had been widely reported in aquatic vertebrates. But there is little known about the effects of 17ß-TBOH on mammals, especially on adolescent neurodevelopment. In this study, we found that 17ß-TBOH acute 1 h exposure can cause the activation of the dopamine circuit in pubertal male balb/c mice. At present, there is little known about the effects of puberty exposure of endocrine disruptors on these neurons/nerve pathways. Through a series of behavioural tests, exposure to 80 µgkg-1 d-1 of 17ß-TBOH during adolescence increased the anxiety-like behaviour of mice and reduced the control of wheel-running behaviour and the response of social interaction behaviour. The results of TH immunofluorescence staining showed that exposure to 17ß-TBOH reduced dopamine axon growth in the medial prefrontal cortex (mPFC). In addition, the results of real-time PCR showed that exposure to 17ß-TBOH not only down-regulated the expression of dopamine axon development genes, but also affected the balance of excitatory/inhibitory signals in mPFC. In this research, we reveal the effects of 17ß-TBOH exposure during adolescence on mammalian behaviour and neurodevelopment, and provide a reference for studying the origin of adolescent diseases.


Asunto(s)
Disruptores Endocrinos , Acetato de Trembolona , Animales , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales , Masculino , Ratones , Conducta Social , Interacción Social
7.
Chemosphere ; 245: 125679, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31869672

RESUMEN

17ß-Trenbolone (17ß-TBOH) is an endocrine disruptor that has been widely reported in aquatic organisms. However, little is known about the effect of 17ß-TBOH on mammals, particularly on the development of adolescents. Through a series of behavioural experiments, exposure to at 80 µg kg -1 d -1 and 800 µg kg -1 d -1 17ß-TBOH during puberty (from PND 28 to 56, male mice) increased anxiety-like behaviours. Exposure to the low dose of 80 µg kg -1 d -1 resulted in a clear social avoidance behaviour in mice. The two doses affected testicular development and endogenous androgen synthesis in male mice. In addition, 17ß-TBOH exposure altered the differentiation of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex (mPFC). These results reveal the effects of 17ß-TBOH on the behaviours, gonadal and neurodevelopment of adolescent mammals. In addition, the inhibition of the secretion of endogenous hormones and decrease in the formation of the myelin sheath in mPFC may be associated with the 17ß-TBOH-induced behavioural changes in mice.


Asunto(s)
Hormonas Esteroides Gonadales/biosíntesis , Conducta Social , Acetato de Trembolona/farmacología , Animales , Ansiedad/inducido químicamente , Reacción de Prevención/efectos de los fármacos , Disruptores Endocrinos/farmacología , Masculino , Ratones , Vaina de Mielina/efectos de los fármacos , Oligodendroglía/efectos de los fármacos
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