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1.
PLoS Genet ; 19(2): e1010615, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36821549

RESUMEN

The worldwide sheep population comprises more than 1000 breeds. Together, these exhibit a considerable morphological diversity, which has not been extensively investigated at the molecular level. Here, we analyze whole-genome sequencing individuals of 1,098 domestic sheep from 154 breeds, and 69 wild sheep from seven Ovis species. On average, we detected 6.8%, 1.0% and 0.2% introgressed sequence in domestic sheep originating from Iranian mouflon, urial and argali, respectively, with rare introgressions from other wild species. Interestingly, several introgressed haplotypes contributed to the morphological differentiations across sheep breeds, such as a RXFP2 haplotype from Iranian mouflon conferring the spiral horn trait, a MSRB3 haplotype from argali strongly associated with ear morphology, and a VPS13B haplotype probably originating from urial and mouflon possibly associated with facial traits. Our results reveal that introgression events from wild Ovis species contributed to the high rate of morphological differentiation in sheep breeds, but also to individual variation within breeds. We propose that long divergent haplotypes are a ubiquitous source of phenotypic variation that allows adaptation to a variable environment, and that these remain intact in the receiving population probably due to reduced recombination.


Asunto(s)
Aclimatación , Oveja Doméstica , Ovinos/genética , Animales , Oveja Doméstica/genética , Haplotipos/genética , Irán , Fenotipo
2.
Int J Cancer ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733360

RESUMEN

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

3.
Opt Lett ; 49(8): 1928, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621042

RESUMEN

This publisher's note contains a correction to Opt. Lett.48, 5771 (2023)10.1364/OL.506371.

4.
Oral Dis ; 30(2): 292-306, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36704830

RESUMEN

OBJECTIVES: In order to predict the patients' prognosis with tongue squamous cell carcinoma (SCC), this study set out to develop a clinically useful and trustworthy prognostic nomogram. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to compile clinical information on patients with tongue SCC between 2010 and 2015. The likelihood of Cancer-Specific Survival (CSS) and Overall Survival (OS) for specific patients was predicted using a prognostic nomogram created with the help of the RStudio software. The nomogram's predictive ability was evaluated using the consistency index (C-index) and decision curve analysis, and the nomogram was calibrated for 1-, 2-, 3-, 5-, and 10-year CSS and OS. RESULTS: Patients numbering 6453were enrolled in this study. The primary cohort (3895) and validation cohort (2558) were each randomly assigned. Sex, age, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation were significant risk factors for OS, whereas age, TNM stage, surgery, chemotherapy, and radiotherapy were significant risk factors for CSS. Additionally, C-index and calibration curves indicated that the prognostic nomogram prediction and the actual observation in both cohorts would be very coherent. CONCLUSIONS: The predictive nomogram created in this study can offer patients with tongue SCC customized treatment and survival risk assessment.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Lengua , Humanos , Pronóstico , Nomogramas , Carcinoma de Células Escamosas/terapia , Neoplasias de la Lengua/terapia , Lengua
5.
Nucleic Acids Res ; 50(4): 2223-2239, 2022 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-35104889

RESUMEN

N 6-Threonylcarbamoyladenosine (t6A) is a universal and pivotal tRNA modification. KEOPS in eukaryotes participates in its biogenesis, whose mutations are connected with Galloway-Mowat syndrome. However, the tRNA substrate selection mechanism by KEOPS and t6A modification function in mammalian cells remain unclear. Here, we confirmed that all ANN-decoding human cytoplasmic tRNAs harbor a t6A moiety. Using t6A modification systems from various eukaryotes, we proposed the possible coevolution of position 33 of initiator tRNAMet and modification enzymes. The role of the universal CCA end in t6A biogenesis varied among species. However, all KEOPSs critically depended on C32 and two base pairs in the D-stem. Knockdown of the catalytic subunit OSGEP in HEK293T cells had no effect on the steady-state abundance of cytoplasmic tRNAs but selectively inhibited tRNAIle aminoacylation. Combined with in vitro aminoacylation assays, we revealed that t6A functions as a tRNAIle isoacceptor-specific positive determinant for human cytoplasmic isoleucyl-tRNA synthetase (IARS1). t6A deficiency had divergent effects on decoding efficiency at ANN codons and promoted +1 frameshifting. Altogether, our results shed light on the tRNA recognition mechanism, revealing both commonality and diversity in substrate recognition by eukaryotic KEOPSs, and elucidated the critical role of t6A in tRNAIle aminoacylation and codon decoding in human cells.


Asunto(s)
Eucariontes , ARN de Transferencia de Isoleucina , Adenosina/genética , Animales , Codón , Eucariontes/genética , Células HEK293 , Humanos , Mamíferos/genética , Conformación de Ácido Nucleico , ARN de Transferencia/genética , ARN de Transferencia de Metionina
6.
Nucleic Acids Res ; 50(7): 4012-4028, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35357504

RESUMEN

METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.


Asunto(s)
Metiltransferasas/metabolismo , Mitocondrias/metabolismo , ARN de Transferencia , Empalme Alternativo , Humanos , Metiltransferasas/genética , Mitocondrias/genética , ARN Mensajero , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , ARN de Transferencia de Treonina/genética
7.
Artículo en Inglés | MEDLINE | ID: mdl-38581312

RESUMEN

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

8.
Opt Express ; 31(13): 21672-21688, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37381259

RESUMEN

Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However, reliable processes capable of controlling film composition have yet to be developed. In this work, the effect of precursor partial pressure and steric hindrance on the surface activity was presented and analyzed in detail, which led to the development of a component tailoring process for ALD composition control in intralayer for the first time. Further, a homogeneous organic/inorganic hybrid film was successfully grown. The component unit of the hybrid film under the joint action of EG and O plasma could achieve arbitrary ratios by controlling the EG/O plasma surface reaction ratio via varied partial pressures. Film growth parameters (growth rate per cycle and mass gain per cycle) and physical properties (density, refractive index, residual stress, transmission, and surface morphology) could be modulated as desired. Moreover, the hybrid film with low residual stress was effectively used in the encapsulation of flexible organic light-emitting diodes (OLEDs). Such a component tailoring process is an important step forward in ALD technology, and allowing for in-situ control of thin film components at the atomic level in intralayer.

9.
Opt Lett ; 48(21): 5771-5774, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910755

RESUMEN

A bimolecular excited system is considered as a promising candidate for developing white organic light-emitting diodes (WOLEDs) with reduced phosphorescent components. However, for actualizing high-performance WOLED, little attention has been paid to electromers compared to exciplexes. Herein, we construct the bimolecular excited system to prepare fluorescent WOLEDs by combining the electromer emission with the exciplex emission, achieving a maximum power efficiency of 11.8 lm/W with a color rendering index (CRI) of over 80. Furthermore, phosphorescent dopants are doped into an exciplex host to construct hybrid WOLEDs. The fabricated complementary-color and three-color devices achieve maximum efficiencies of 55.3 cd/A (46.8 lm/W) and 34.1 cd/A (26.8 lm/W), respectively. The spectral coverages of WOLEDs are broadened by the bimolecular excited system, and CRIs are further improved at high luminance. Our strategy may bring light to the future development of highly efficient WOLEDs with economy and sustainability.

10.
J Org Chem ; 88(6): 3436-3450, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36867549

RESUMEN

Phenoxy acetophenones were usually employed as ß-O-4' lignin models for chemical conversion. Herein, an iridium-catalyzed dehydrogenative annulation between 2-aminobenzylalcohols and phenoxy acetophenones was demonstrated to prepare valuable 3-oxo quinoline derivatives, which are hard to prepare using previous methods. This operationally simple reaction tolerated a wide scope of substrates and enabled successful gram-scale preparation.

11.
Inorg Chem ; 62(4): 1539-1548, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36642893

RESUMEN

A proposed BiO(ClBr)(1-x)/2Ix-n solid solution containing abundant iodine vacancies has been constructed through a facile solvothermal treatment strategy. Fascinatingly, the iodine-vacancy BiO(ClBr)(1-x)/2Ix-n solid solution exhibits an outstanding visible-light photocatalytic degradation property for the environmentally hazardous pollutants of methyl orange, tetracycline, and phenol solutions, which is credited to the synergistic effect of iodine vacancies and the solid solution. By manipulating the molar ratios of Cl, Br, and I, the band structure of the solid solution attained is controlled, enabling the samples to maximize the harvest of visible light and to possess strong oxidation features. More importantly, the construction of iodine vacancies is bound to modulate the local surface atomic structure and promotes the efficiency of the separation of photogenerated carriers. Given these, the microstructure and physicochemical and photoelectrochemical properties of the photocatalysts are fully characterized in a series. In addition, the iodine-vacancy BiO(ClBr)(1-x)/2Ix-n solid solution has a stable crystal structure that permits favorable recyclability even after multiple cycles of degradation. This study sheds light on the significance of the simultaneous existence of vacancy and the solid solution for the enhanced performance of photocatalysts and opens up new insights for sustainable solar-chemical energy conversion.

12.
Phys Chem Chem Phys ; 25(44): 30391-30404, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37909910

RESUMEN

First-principles calculations were performed on a plutonium and americium mixed oxide (PuAmO4), aiming at revealing the effects of electron correlation, Pu/Am 5f-conduction electrons' hybridization, and relativity on its electronic properties. The many-body calculation suggests that the spin-orbit-coupling (SOC)-splitting of j = 5/2 and j = 7/2 manifolds are both in the weakly and moderately correlated states, respectively, implying that the jj coupling scheme is more appropriate for Pu/Am 5f electrons. The density of states, 5f occupation numbers, and Green's functions all suggest that both Pu and Am 5f electrons exhibit the coexistence of the localized and delocalized states. The admixture of 5fn atomic configurations, Pu/Am 5f-conduction electrons' hybridization, and dual characteristics of 5f electrons yield average occupation numbers of 5f electrons n5f = 4.78 and 5.86 for Pu and Am ions, respectively. Within the DFT+DMFT calculation, the weighted-summation-derived occupation numbers in terms of 5f4/5f5/5f6 and 5f5/5f6 configurations for Pu and Am 5f electrons, respectively, are in reasonable agreement with those of other DFT-based calculations.

13.
BMC Geriatr ; 23(1): 369, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37322416

RESUMEN

BACKGROUND: Osteosarcopenia is a syndrome with a concomitant presence of both sarcopenia and osteopenia/osteoporosis. It increases the risk of frailty, falls, fractures, hospitalization, and death. Not only does it burden the lives of older adults, but it also increases the economic burden on health systems around the world. This study aimed to review the prevalence and risk factors of osteosarcopenia to generate important references for clinical work in this area. METHODS: Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP databases were searched from inception until April 24th, 2022. The quality of studies included in the review was evaluated using the NOS and AHRQ Scale. Pooled effects of the prevalence and associated factors were calculated using random or fixed effects models. Egger's test, Begg's test, and funnel plots were used to test the publication bias. Sensitivity analysis and subgroup analysis were conducted to identify the sources of heterogeneity. Statistical analysis was performed using Stata 14.0 and Review Manager 5.4. RESULTS: A total of 31 studies involving 15,062 patients were included in this meta-analysis. The prevalence of osteosarcopenia ranged from 1.5 to 65.7%, with an overall prevalence of 21% (95% CI: 0.16-0.26). The risk factors for osteosarcopenia were female (OR 5.10, 95% CI: 2.37-10.98), older age (OR 1.12, 95% CI: 1.03-1.21), and fracture (OR 2.92, 95% CI: 1.62-5.25). CONCLUSION: The prevalence of osteosarcopenia was high. Females, advanced age, and history of fracture were independently associated with osteosarcopenia. It is necessary to adopt integrated multidisciplinary management.


Asunto(s)
Fracturas Óseas , Osteoporosis , Sarcopenia , Humanos , Femenino , Anciano , Masculino , Prevalencia , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/complicaciones , Fracturas Óseas/etiología , Factores de Riesgo , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/complicaciones
14.
Nucleic Acids Res ; 49(14): 8309-8323, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34268557

RESUMEN

tRNAs harbor the most diverse posttranscriptional modifications. The 3-methylcytidine (m3C) is widely distributed at position C32 (m3C32) of eukaryotic tRNAThr and tRNASer species. m3C32 is decorated by the single methyltransferase Trm140 in budding yeasts; however, two (Trm140 and Trm141 in fission yeasts) or three enzymes (METTL2A, METTL2B and METTL6 in mammals) are involved in its biogenesis. The rationale for the existence of multiple m3C32 methyltransferases and their substrate discrimination mechanism is hitherto unknown. Here, we revealed that both METTL2A and METTL2B are expressed in vivo. We purified human METTL2A, METTL2B, and METTL6 to high homogeneity. We successfully reconstituted m3C32 modification activity for tRNAThr by METT2A and for tRNASer(GCU) by METTL6, assisted by seryl-tRNA synthetase (SerRS) in vitro. Compared with METTL2A, METTL2B exhibited dramatically lower activity in vitro. Both G35 and t6A at position 37 (t6A37) are necessary but insufficient prerequisites for tRNAThr m3C32 formation, while the anticodon loop and the long variable arm, but not t6A37, are key determinants for tRNASer(GCU) m3C32 biogenesis, likely being recognized synergistically by METTL6 and SerRS, respectively. Finally, we proposed a mutually exclusive substrate selection model to ensure correct discrimination among multiple tRNAs by multiple m3C32 methyltransferases.


Asunto(s)
Conformación de Ácido Nucleico , ARN de Transferencia/genética , ARNt Metiltransferasas/genética , Anticodón/genética , Citidina/análogos & derivados , Citidina/genética , Humanos , ARN/genética , ARN de Transferencia/ultraestructura , Serina-ARNt Ligasa/genética , Especificidad por Sustrato
15.
Arch Pharm (Weinheim) ; 356(9): e2300175, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37421212

RESUMEN

Four new ruthenium polypyridyl complexes with prenyl groups, [Ru(bpy)2 (MHIP)](PF6 )2 (Ru(II)-1), [Ru(dtb)2 (MHIP)](PF6 )2 (Ru(II)-2), [Ru(dmb)2 (MHIP)](PF6 )2 (Ru(II)-3), and [Ru(dmob)2 (MHIP)](PF6 )2 (Ru(II)-4) (bpy = 2,2'-bipyridine, dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine, and MHIP = 2-(2,6-dimethylhepta-1,5-dien-1-yl)-1H-imidazo[4,f][1,10]phenanthroline), were synthesized and characterized. Their antibacterial activities against Staphylococcus aureus were assessed, and the minimum inhibition concentration (MIC) value of Ru(II)-2 against S. aureus was only 0.5 µg/mL, showing the best antibacterial activity among them. S. aureus could be quickly killed by Ru(II)-2 in 30 min and Ru(II)-2 displayed an obvious inhibitive effect on the formation of a biofilm, which was essential to avoid the development of drug-resistance. Meanwhile, Ru(II)-2 exhibited a stable MIC value against antibiotic-resistant bacteria. The antibacterial mechanism of Ru(II)-2 was probably related to depolarization of the cell membrane, and a change of permeability was associated with the formation of reactive oxygen species, leading to leakage of nucleic acid and bacterial death. Furthermore, Ru(II)-2 hardly showed toxicity to mammalian cells and the Galleria mellonella worm. Finally, murine infection studies also illustrated that Ru(II)-2 was highly effective against S. aureus in vivo.


Asunto(s)
Rutenio , Staphylococcus aureus , Animales , Ratones , Antibacterianos/farmacología , Rutenio/farmacología , Relación Estructura-Actividad , 2,2'-Dipiridil/farmacología , ADN , Mamíferos/metabolismo
16.
Odontology ; 111(1): 248-254, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35964264

RESUMEN

Periodontitis has a known association with pathological calcification in the cardiovascular system. Considering the close anatomic and circulatory association between dental pulp and the periodontium, this study aimed to evaluate the prevalence of pulp calcification (PC) under different periodontal conditions, as well as the associations of PC with the degree of periodontal damage, via cone beam computed tomography (CBCT) examination. In this study, 55 patients were categorized into three groups according to periodontal condition: group 1 (healthy controls), group 2 (periodontitis stage I-II), and group 3 (periodontitis stage III-IV). PC and radiographic bone loss (RBL) was assessed by CBCT in sagittal, axial, and coronal views, and statistical analyses were conducted. PC was identified in 378 of 1170 teeth (32.3%). The prevalence significantly differed among the three groups (P < 0.001). Group 2 had a 2.43-fold (P < 0.001, 95% confidence interval [CI] 1.64-3.61) higher risk of PC than group 1; and the risk of PC was 3.04-fold (P < 0.001, 95% CI 2.06-4.48) higher in group 3 than group 1. Teeth with more severe RBL exhibited a higher prevalence of PC (P < 0.001). Molar teeth had a higher risk of PC than incisors and premolars. In conclusion, the occurrence of PC is related to the periodontal state, and the prevalence of PC is higher in teeth with periodontitis; tooth type and periodontitis status are important risk factors for PC.


Asunto(s)
Periodontitis , Calcificación de Dientes , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Diente Molar , Periodontitis/complicaciones , Periodontitis/diagnóstico por imagen , Periodontitis/epidemiología , Periodoncio , Prevalencia
17.
Molecules ; 28(19)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37836658

RESUMEN

TWIK1 (K2P1.1/KCNK1) belongs to the potassium channels of the two-pore domain. Its current is very small and difficult to measure. In this work, we used a 100 mM NH4+ extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on TWIK1 was observed via a whole-cell patch clamp experiment, and it was found that magnolol had a significant inhibitory effect on TWIK1 (IC50 = 6.21 ± 0.13 µM). By molecular docking and alanine scanning mutagenesis, the IC50 of TWIK1 mutants G229A, T225A, I140A, L223A, and S224A was 20.77 ± 3.20, 21.81 ± 7.93, 10.22 ± 1.07, 9.55 ± 1.62, and 7.43 ± 3.20 µM, respectively. Thus, we conclude that the inhibition of the TWIK1 channel by magnolol is related to G229 and T225 on the P2- pore helix.


Asunto(s)
Compuestos de Bifenilo , Canales de Potasio , Humanos , Simulación del Acoplamiento Molecular , Células HEK293 , Canales de Potasio/metabolismo , Compuestos de Bifenilo/farmacología
18.
Molecules ; 28(13)2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37446837

RESUMEN

Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures. While erythromycin caused a concentration-dependent inhibition of cardiac hERG channels, it also shifted the steady-state activation and steady-state inactivation of the channel to the left and significantly accelerated the onset of inactivation at both temperatures, although temperature itself caused a profound change in the dynamics of hERG channels. Our data also suggest that the binding pattern to S6 of the channels changes at PT. In contrast, cisapride, a well-known hERG blocker whose inhibition is not affected by temperature, does not change its critical binding sites after the temperature is raised to PT. Our data suggest that erythromycin is unique and that the shift in hERG inhibition may not apply to other compounds.


Asunto(s)
Eritromicina , Canales de Potasio Éter-A-Go-Go , Eritromicina/farmacología , Temperatura , Cisaprida/metabolismo , Cisaprida/farmacología , Corazón , Canal de Potasio ERG1 , Bloqueadores de los Canales de Potasio/farmacología
19.
Entropy (Basel) ; 25(9)2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37761630

RESUMEN

This study considers a wireless network where multiple nodes transmit status updates to a base station (BS) through a shared bandwidth-limited channel. Considering the random arrival of status updates, we measure the data freshness with the age of synchronization (AoS) metric; specifically, we use the time elapsed since the latest synchronization as a metric. The objective of this study is to minimize the weighted sum of the average AoS of the entire network while meeting the minimum throughput requirement of each node. We consider both the central scheduling scenario and the distributed scheduling scenario. In the central scheduling scenario, we propose the optimal stationary randomized policy when the transmission feedback is unavailable and the max-weight policy when it is available. In the distributed scenario, we propose a distributed policy. The complexity of the three scheduling policies is significantly low. Numerical simulations show that the policies can satisfy the throughput constraint in the central controlling scenario and the AoS performance of the max-weight policy is close to the lower bound.

20.
Angew Chem Int Ed Engl ; 62(26): e202302679, 2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37106279

RESUMEN

Replacing widely used organic liquid electrolytes with solid-state electrolytes (SSEs) could effectively solve the safety issues in sodium-ion batteries. Efforts on seeking novel solid-state electrolytes have been continued for decades. However, issues about SSEs still exist, such as low ionic conductivity at ambient temperature, difficulty in manufacturing, low electrochemical stability, poor compatibility with electrodes, etc. Here, sodium carbazolide (Na-CZ) and its THF-coordinated derivatives are rationally fabricated as Na+ conductors, and two of their crystal structures are successfully solved. Among these materials, THF-coordinated complexes exhibit fast Na+ conductivities, i.e., 1.20×10-4  S cm-1 and 1.95×10-3  S cm-1 at 90 °C for Na-CZ-1THF and Na-CZ-2THF, respectively, which are among the top Na+ conductors under the same condition. Furthermore, stable Na plating/stripping is observed even over 400 h cycling, showing outstanding interfacial stability and compatibility against Na electrode. More advantages such as ease of synthesis, low-cost, and cold pressing for molding can be obtained. In situ NMR results revealed that the evaporation of THF may play an essential role in the Na+ migration, where the movement of THF creates defects/vacancies and facilitates the migration of Na+ .


Asunto(s)
Electrólitos , Sodio , Iones , Frío , Comercio
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