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1.
Artículo en Inglés | MEDLINE | ID: mdl-39364552

RESUMEN

As a novel approach to pursue high-performance multifunctional materials, the structural design of cutting-edge two-dimensional (2D) materials has ignited substantial interests. Borophene, an emerging member in the realm of 2D materials, exhibits crucial attributes, including high theoretical carrier density, electrical conductivity, magnetism, and high aspect ratio, rendering it highly promising for diverse applications. Yet, the exploration of porous structural configurations of borophene remains untapped. Addressing this gap, our study focuses on the fabrication of a multifunctional borophene hybrid foam (CMB-foam). This hybridization leverages the exceptional multifunctionality of MXene alongside borophene within a three-dimensional porous framework, facilitating reflection and absorption of electromagnetic waves, thereby demonstrating remarkable electromagnetic interference (EMI) shielding capabilities. Moreover, this structural configuration exposes an enlarged surface area, thus shortening the transport pathway for electrolyte ions, leading to an excellent energy storage performance. Additionally, CMB-foam performs well in thermal management and thermal insulation. These findings underscore the potential of borophene-based materials in multifunctional applications and offer valuable insights into further performance explorations in this domain.

2.
Dalton Trans ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39355983

RESUMEN

Human calcitonin (hCT) is an endogenous polypeptide commonly employed in treating bone resorption-related illnesses, but its clinical application is limited due to its high aggregation tendency. Metalloporphyrins are effective in suppressing amyloid fibrillation, positioning them as potential drug candidates for amyloidogenic disorders like Alzheimer's and type 2 diabetes. In this work, we investigated the effects of Fe(III) meso-tetra(4-sulfonatophenyl)porphine chloride (FeTPPS), a highly efficient ONOO- decomposition catalyst, on hCT aggregation. Our findings reveal that FeTPPS effectively precludes hCT fibrillation by stabilizing the monomers and delaying the structural transition from α-helix bundles to ß-sheet-rich aggregates. The macrocyclic ring of FeTPPS plays a significant role in disrupting hCT self-associations. Among various porphyrin analogs, those with an iron center and negatively charged peripheral substituents exhibit a stronger inhibitory effect on hCT aggregation. Spectroscopic analyses and computational simulations indicate that FeTPPS binds to hCT's core aggregation region via complexation with His20 in a 1 : 1 molar ratio. Hydrophobic interaction, hydrogen bonding, and π-π stacking with the residues involving Tyr12, Phe19, and Ala26 also contribute to the interactions. Collectively, our study provides a promising approach for developing novel hCT drug formulations and offers theoretical guidance for designing metalloporphyrin-based inhibitors for various amyloidosis conditions.

3.
J Colloid Interface Sci ; 678(Pt C): 300-308, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39298982

RESUMEN

Although Platinum (Pt)-based alloys have garnered significant interest within the realm of direct methanol fuel cells (DMFCs), there still exists a notable dearth in the exploration of the catalytic behavior of the liquid fuels on well-defined active sites and unavoidable Pt poisoning because of the adsorbed CO species (COads). Here, we propose an electronegativity-induced electronic redistribution strategy to optimize the adsorption of crucial intermediates for the methanol oxidation reaction (MOR) by introducing the Co element to form the PtCo alloys. The optimal PtCo hollow nanospheres (HNSs) exhibit excellent high-quality activity of 3.27 A mgPt-1, which is 11.6 times and 13.1 times higher than that of Pt/C and pure Pt, respectively. The in-situ Fourier transform infrared reflection spectroscopy validates that electron redistribution could weak CO adsorption, and subsequently decrease the CO poisoning adjacent the Pt active sites. Theoretical simulations result show that the introduction of Co optimize surface electronic structure and reduce the d-band center of Pt, thus optimized the adsorption behavior of COads. This study not only employs a straightforward method for the preparation of Pt-based alloys but also delineates a pathway toward designing advanced active sites for MOR via electronegativity-induced electronic redistribution.

4.
Phys Chem Chem Phys ; 26(37): 24564-24576, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39268710

RESUMEN

Transforming growth factor ß type 1 receptor (TGFßR1), a crucial serine-threonine kinase, is central to the TGFß/Smad signaling pathway, governing cellular processes like growth, differentiation, apoptosis, and immune response. This pathway is closely linked to the epithelial-mesenchymal transition (EMT) process, which plays an important role in the metastasis of hepatocellular carcinoma (HCC). To date, only limited inhibitors targeting TGFßR1 have entered clinical trials, yet they encounter challenges, notably high toxicity, in clinical applications. Herein, an efficient virtual screening pipeline was developed. Eighty compounds were screened from a pool of over 17 million molecules based on docking scores and binding free energy. Four compounds were manually selected with the assistance of enhanced sampling method BPMD (binding pose metadynamics). The binding stability of these four compounds complexed with TGFßR1 was subsequently studied through long-timescale conventional molecular dynamics simulations. The three most promising compounds were subjected to in vitro bioactivity assays. Cpd272 demonstrated moderate inhibitory activity against TGFßR1, with an IC50 value of 1.57 ± 0.33 µM. Moreover, it exhibited cytotoxic effects on human hepatocellular carcinoma cell line Bel-7402. By shedding light on the binding mode of the receptor-ligand complexes, Cpd272 was identified as a hit compound featuring a novel urea-based scaffold capable of effectively inhibiting TGFßR1.


Asunto(s)
Simulación de Dinámica Molecular , Receptor Tipo I de Factor de Crecimiento Transformador beta , Urea , Humanos , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/química , Urea/química , Urea/farmacología , Urea/análogos & derivados , Simulación del Acoplamiento Molecular , Descubrimiento de Drogas , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Línea Celular Tumoral , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología
5.
Environ Int ; 191: 108995, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39241331

RESUMEN

Traditional methods for identifying endocrine-disrupting chemicals (EDCs) that activate androgen receptors (AR) are costly, time-consuming, and low-throughput. This study developed a knowledge-based deep neural network model (AR-DNN) to predict AR-mediated adverse outcomes on female zebrafish fertility. This model started with chemical fingerprints as the input layer and was implemented through a five-layer virtual AR-induced adverse outcome pathway (AOP). Results indicated that the AR-DNN effectively and accurately screens new reproductive toxicants (AUC = 0.94, accuracy = 0.85), providing potential toxicity pathways. Furthermore, 1477 and 2448 chemicals that could lead to infertility were identified in the plastic additives list (PLASTICMAP, n = 7112) and the Inventory of Existing Chemical Substances in China (IECSC, n = 17741), respectively. Colourants containing steroid-like structures are the major active plastic additives that might lower female zebrafish fertility through AR binding, DNA binding, and transcriptional activation. While active IECSC chemicals primarily have the same fragments, such as benzonitrile, nitrobenzene, and quinolone. The predicted toxicity pathways were consistent with existing fish evidence, demonstrating the model's applicability. This knowledge-based approach offers a promising computational toxicology strategy for predicting and characterising the endocrine-disrupting effects and toxic mechanisms of organic chemicals, potentially leading to more efficient and cost-effective screening of EDCs.


Asunto(s)
Disruptores Endocrinos , Aprendizaje Automático , Receptores Androgénicos , Pez Cebra , Animales , Receptores Androgénicos/metabolismo , Disruptores Endocrinos/toxicidad , Femenino , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad
6.
Angew Chem Int Ed Engl ; : e202416832, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315906

RESUMEN

Electrosynthesis of urea from co-reduction of carbon dioxide and nitrate is a promising alternative to the industrial process. However, the overwhelming existence of proton and nitrate as well as the insufficient supply of CO2 at the reaction interface usually result in complex product distributions from individual nitrate reduction or hydrogen evolution, instead of C-N coupling. In this work, we systematically optimize this microenvironment through orderly coating of bilayer polymer to specifically tackle the above challenges. Polymer of intrinsic microporosity is chosen as the upper polymer to achieve physical sieving, realizing low water diffusivity for suppressing hydrogen evolution and high gas permeability for smooth mass transfer of CO2 at the same time. Polyaniline with abundant basic amino groups is capable of triggering chemical interaction with acidic CO2 molecules, so that is used as the underlying polymer to serve as CO2 concentrator and facilitate the carbon source supply for C-N coupling. Within this tailored microenvironment, a maximum urea generation yield rate of 1671.6 µg h-1 mg-1 and a high Faradaic efficiency of 75.3% are delivered once coupled with efficient electrocatalyst with neighboring active sites, which is among the most efficient system of urea electrosynthesis.

7.
J Phys Chem Lett ; 15(35): 8990-8996, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39186307

RESUMEN

Ammonia (NH3) electrosynthesis from nitrogen (N2) provides a promising strategy for carbon neutrality, circumventing the energy-intensive and carbon-emitting Haber-Bosch process. However, the current system still presents unsatisfactory performance, and the bottleneck lies in the rational synthesis of catalytic centers with efficient N2 chemisorption ability. Herein, a heteroatom ensemble effect is deliberately triggered over RuFe alloy with spatial proximity of metal sites to promote electrocatalytic nitrogen reduction. The heteronuclear RuFe ensemble with increased surface polarization and modulated electronic structure offers the feasibility to optimize the adsorption configuration of electroactive substances and facilitate chemical bond scission. The promotion of N2 chemisorption and the following hydrogenation are demonstrated by the in situ Fourier transform infrared spectroscopy characterizations. The catalyst thus permits significantly enhanced conversion of N2 to NH3 in a 0.1 M HCl environment, with a maximum ammonia yield rate of 75.45 µg h-1 mg-1 and a high Faradaic efficiency of 35.49%.

8.
J Phys Chem Lett ; 15(33): 8427-8433, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39116387

RESUMEN

Infrared solar cells (IRSCs), capable of converting low-energy infrared photons to electron-hole pairs, are promising infrared optoelectronic devices because of their extended utilization region of the solar to short-wavelength infrared region. For PbS QDs IRSCs, charge extraction loss, easily generated at the interfaces, has been one of the dominate obstacles impeding the improvement of device efficiencies due to too many trap states and mismatched energy levels between the photoactive layer and electron transport layer (ETL). Herein, an advanced ZnO ETL was developed to improve the extraction of photogenerated charges from the PbS QD photoactive layer to ETLs. The advanced ETL film exhibited effectively suppressed trap states and better-matched energy levels compared with the QD layer. As a consequence, high-performance PbS QD IRSCs with the highest infrared power conversion efficiencies of 1.26% under 1100 nm filtered solar illumination are achieved, suggesting an effective and facile route for enhancing the charge extraction in infrared photovoltaics.

9.
Dig Dis Sci ; 69(9): 3442-3449, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39009916

RESUMEN

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Indometacina , Pancreatitis , Stents , Humanos , Indometacina/uso terapéutico , Indometacina/administración & dosificación , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/prevención & control , Pancreatitis/etiología , Pancreatitis/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Stents/efectos adversos , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Administración Rectal , Estudios Retrospectivos , Tiempo de Internación/estadística & datos numéricos , Factores de Riesgo , Estudios de Cohortes , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología
10.
Front Vet Sci ; 11: 1389738, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974336

RESUMEN

The experiment aimed to evaluate the effects of different ratios of Clostridium autoethanogenum protein (CAP) used in the diets on the growth performance, muscle quality, serum indexes, and mTOR pathway of white feather broilers. Four hundred and eighty 1-day-old Arbor Acres (AA) broilers, comprising equal numbers of males and females, were randomly assigned to one of four treatments, and each treatment consisted of 12 replicates of 10 birds. Four diets were formulated based on isoenergetic and isonitrogenous principles. The control group (CAP 0) did not receive any CAP, while the experimental groups received 2% (CAP 2), 3% (CAP 3), and 4% (CAP 4) of CAP for six weeks. Compared with the CAP0, (1) The feed conversion ratio (FCR) was lower (p < 0.05), and the leg muscle yield was higher (p < 0.05) in the CAP3 and CAP4; (2) The serum levels of TP, ALB, T-AOC, and SOD were improved in the CAP3 (p < 0.05); (3) The expression of Lipin-1 gene was down-regulated and AMPKɑ2, Akt, and 4E-BP1 genes were up-regulated in the experiment group (p < 0.05); (4) The inclusion of 3% CAP in the diet increased the levels of 4E-BP1, S6K1, Akt, and AMPKɑ2 phosphorylation by modulating the mTOR signaling pathway (p < 0.05). In conclusion, broiler diets containing 3% CAP can activate the mTOR signaling pathway to promote muscle synthesis and improve growth performance.

11.
BMC Med Educ ; 24(1): 738, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982322

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the effectiveness and efficiency of implementing a data-driven blended online-offline (DDBOO) teaching approach in the medicinal chemistry course. METHODS: A total of 118 third-year students majoring in pharmacy were enrolled from September 2021 to January 2022. The participants were randomly assigned to either the DDBOO teaching group or the traditional lecture-based learning (LBL) group for medicinal chemistry. Pre- and post-class quizzes were administered, along with an anonymous questionnaire distributed to both groups to assess students' perceptions and experiences. RESULTS: There was no significant difference in the pre-class quiz scores between the DDBOO and LBL groups (T=-0.637, P = 0.822). However, after class, the mean quiz score of the DDBOO group was significantly higher than that of the LBL group (T = 3.742, P < 0.001). Furthermore, the scores for learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, innovation ability, and satisfaction, as measured by the questionnaire, were significantly higher in the DDBOO group than in the traditional group (all P < 0.05). CONCLUSION: The DDBOO teaching method effectively enhances students' academic performance and satisfaction. Further research and promotion of this approach are warranted.


Asunto(s)
Química Farmacéutica , Educación en Farmacia , Evaluación Educacional , Estudiantes de Farmacia , Femenino , Humanos , Masculino , Adulto Joven , Química Farmacéutica/educación , Instrucción por Computador/métodos , Curriculum , Educación a Distancia , Educación en Farmacia/métodos , Encuestas y Cuestionarios
12.
Helicobacter ; 29(4): e13109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38951739

RESUMEN

BACKGROUND: Integrin-linked kinase (ILK) is crucial in solid tumors by regulating the Hippo-Yes-associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori-induced gastric cancer. MATERIALS AND METHODS: GES-1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20-like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and nitric oxide (NO) levels in mice gastric tissues were detected by real-time PCR, H&E, and ELISA assays. RESULTS: In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES-1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST-T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week-aged mice. OST-T315 also reduced the release of TNF-α, IL-6, IL-1ß, and NO, as well as the progression of gastric cancer caused by H. pylori and N-Nitroso-N-methylurea (NMU) treatment. CONCLUSION: Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori-induced gastric cancer.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Proteínas Serina-Treonina Quinasas , Neoplasias Gástricas , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Animales , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Ratones , Humanos , Modelos Animales de Enfermedad , Línea Celular , Masculino
13.
J Phys Chem A ; 128(31): 6337-6350, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39047261

RESUMEN

Photoinduced excited-state energy transfer (EET) processes play an important role in solar energy conversions. Owing to their excellent photoharvesting and exciton-transport properties, phenylene ethynylene (PE) dendrimers display great potential for improving the efficiency of solar cells. In this work, we investigated the intramolecular EET dynamics in a dendrimer composed of two linear PE units (2-ring and 3-ring) using a fully quantum description based on the tensor network method. We first constructed a diabatic model Hamiltonian based on the electronic structure calculations. Using this diabatic vibronic coupling model, we tried to obtain the main features of the EET dynamics in terms of the several diabatic models with different numbers of vibrational modes (from 4 modes to 129 modes) and to explore the corresponding vibronic coupling interactions. The results show that the EET in this PE dendrimer is ultrafast. Four modes of A' symmetry play dominant roles in the dynamics; the remaining 86 modes of A' symmetry can dampen the electronic coherence; and the modes of A″ symmetry do not exhibit significant influence on the EET process. Overall, the first-order intrastate vibronic coupling terms show the dominant role in the EET dynamics, while the second-order intrastate vibronic coupling terms cause damping of the electronic coherence and slow down the overall EET process. This work provides a microscopic understanding of the EET dynamics in PE dendrimers.

14.
Inorg Chem ; 63(26): 12146-12155, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946339

RESUMEN

The electrochemical conversion of nitrate pollutants into value-added ammonia (NH3) is an appealing alternative synthetic route for sustainable NH3 production. However, the development of the electrocatalytic nitrate-to-ammonia reduction reaction (NO3RR) has been hampered by unruly reactants and products at the interface and the accompanied sluggish kinetic rate. In this work, a built-in positive valence space is successfully constructed over FeCu nanocrystals to rationally regulate interfacial component concentrations and positively shift the chemical equilibrium. With positive valence Cu optimizing the active surface, the space between the stern and shear layers becomes positive, which is able to continuously attract the negatively charged NO3- reactant and repulse the positively charged NH4+ product even under high current density, thus significantly boosting the NO3RR kinetics. The system with a built-in positive valence space affords an ampere-level NO3RR performance with the highest NH3 yield rate of 150.27 mg h-1 mg-1 at -1.3 V versus RHE with an outstanding NH3 current density of 189.53 mA cm-2, as well as a superior Faradaic efficiency (FE) of 97.26% at -1.2 V versus RHE. The strategy proposed here underscores the importance of interfacial concentration regulation and can find wider applicability in other electrochemical syntheses suffering from sluggish kinetics.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38822760

RESUMEN

OBJECTIVE: Recognition of auditory brainstem response (ABR) waveforms may be challenging, particularly for older individuals or those with hearing loss. This study aimed to investigate deep learning frameworks to improve the automatic recognition of ABR waveforms in participants with varying ages and hearing levels. STUDY DESIGN: The research used a descriptive study design to collect and analyze pure tone audiometry and ABR data from 100 participants. SETTING: The research was conducted at a tertiary academic medical center, specifically at the Clinical Audiology Center of Tsinghua Chang Gung Hospital (Beijing, China). METHODS: Data from 100 participants were collected and categorized into four groups based on age and hearing level. Features from both time-domain and frequency-domain ABR signals were extracted and combined with demographic factors, such as age, sex, pure-tone thresholds, stimulus intensity, and original signal sequences to generate feature vectors. An enhanced Wide&Deep model was utilized, incorporating the Light-multi-layer perceptron (MLP) model to train the recognition of ABR waveforms. The recognition accuracy (ACC) of each model was calculated for the overall data set and each group. RESULTS: The ACC rates of the Light-MLP model were 97.8%, 97.2%, 93.8%, and 92.0% for Groups 1 to 4, respectively, with a weighted average ACC rate of 95.4%. For the Wide&Deep model, the ACC rates were 93.4%, 90.8%, 92.0%, and 88.3% for Groups 1 to 4, respectively, with a weighted average ACC rate of 91.0%. CONCLUSION: Both the Light-MLP model and the Wide&Deep model demonstrated excellent ACC in automatic recognition of ABR waveforms across participants with diverse ages and hearing levels. While the Wide&Deep model's performance was slightly poorer than that of the Light-MLP model, particularly due to the limited sample size, it is anticipated that with an expanded data set, the performance of Wide&Deep model may be further improved.

16.
Cell Mol Life Sci ; 81(1): 256, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866991

RESUMEN

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.


Asunto(s)
Adenosina , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Metiltransferasas , MicroARNs , Miocitos del Músculo Liso , Arteria Pulmonar , Factor 4 Similar a Kruppel/metabolismo , Animales , MicroARNs/genética , MicroARNs/metabolismo , Arteria Pulmonar/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Miocitos del Músculo Liso/metabolismo , Ratones , Adenosina/análogos & derivados , Adenosina/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Ratas , Fenotipo , Masculino , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Músculo Liso Vascular/metabolismo , Ratones Endogámicos C57BL , Remodelación Vascular/genética , Ratas Sprague-Dawley , Humanos
17.
Sci Adv ; 10(21): eadn8490, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38781339

RESUMEN

Glacier and permafrost shrinkage and land-use intensification threaten mountain wildlife and affect nature conservation strategies. Here, we present paleometagenomic records of terrestrial and aquatic taxa from the southeastern Tibetan Plateau covering the last 18,000 years to help understand the complex alpine ecosystem dynamics. We infer that steppe-meadow became woodland at 14 ka (cal BP) controlled by cryosphere loss, further driving a herbivore change from wild yak to deer. These findings weaken the hypothesis of top-down control by large herbivores in the terrestrial ecosystem. We find a turnover in the aquatic communities at 14 ka, transitioning from glacier-related (blue-green) algae to abundant nonglacier-preferring picocyanobacteria, macrophytes, fish, and otters. There is no evidence for substantial effects of livestock herding in either ecosystem. Using network analysis, we assess the stress-gradient hypothesis and reveal that root hemiparasitic and cushion plants are keystone taxa. With ongoing cryosphere loss, the protection of their habitats is likely to be of conservation benefit on the Tibetan Plateau.


Asunto(s)
Ecosistema , Sedimentos Geológicos , Metagenómica , Tibet , Animales , Metagenómica/métodos , Sedimentos Geológicos/microbiología , Cubierta de Hielo/microbiología , Herbivoria , Hielos Perennes/microbiología
18.
ACS Appl Mater Interfaces ; 16(19): 24572-24579, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38690767

RESUMEN

Infrared (IR) solar cells, capable of converting low-energy IR photons to electron-hole pairs, are promising optoelectronic devices by broadening the utilization range of the solar spectrum to the short-wavelength IR region. The emerging PbS colloidal quantum dot (QD) IR solar cells attract much attention due to their tunable band gaps in the IR region, potential multiple exciton generation, and facile solution processing. In PbS QD solar cells, ZnO is commonly utilized as an electron transport layer (ETL) to establish a depleted heterostructure with a QD photoactive layer. However, band gap shrinkage of large PbS QDs makes it necessary to tailor the behaviors of the ZnO ETL for efficient carrier extraction in the devices. Herein, the characteristics of ZnO ETL are efficiently and flexibly tailored to match the QD layer by handily adjusting the postannealing process of ZnO ETL. With a suitable temperature, the well-matched energy level alignment and suppressed trap states are simultaneously achieved in the ZnO ETL, effectively reducing the nonradiative recombination and accelerating the electron injection from the QD layer to ETL. As a consequence, a high-performance PbS QD photovoltaic device with power conversion efficiencies (PCEs) of 10.09% and 1.37% is obtained under AM 1.5 and 1100 nm filtered solar illumination, demonstrating a simple and effective approach for achieving high-performance IR photoelectric devices.

19.
J Colloid Interface Sci ; 669: 126-136, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38713952

RESUMEN

The shuttle effect and sluggish redox kinetics of polysulfides have hindered the development of lithium-sulfur batteries (LSBs) as premier energy storage devices. To address these issues, a high-entropy metal phosphide (NiCoMnFeCrP) was synthesized using the sol-gel method. NiCoMnFeCrP, with its rich metal species, exhibits strong synergistic effects and provides numerous catalytic active sites for the conversion of polysulfides. These active sites, possessing significant polarity, can bond with polysulfides. In situ ultraviolet-visible were conducted to monitor the dynamic changes in species and concentrations of polysulfides, validating the ability of NiCoMnFeCrP to facilitate the conversion of polysulfides. The batteries with the NiCoMnFeCrP catalyst as functional separators exhibited minimal capacity decay rates of 0.04 % and 0.23 % after 100 cycles at 0 °C and 60 °C, respectively. This indicates that the NiCoMnFeCrP catalyst possesses good thermal stability. Meanwhile, its area capacity can reach 4.78 mAh cm-2 at a high sulfur load of 4.54 mg cm-2. In conclusion, NiCoMnFeCrP achieves the objective of mitigating the shuttle effect and accelerating the kinetics of the redox reaction, thereby facilitating the commercialization of LSBs.

20.
J Phys Chem Lett ; 15(20): 5495-5500, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38748898

RESUMEN

Single-atom catalysts (SACs) have been widely studied in a variety of electrocatalysis. However, its application in the electrocatalytic nitrogen reduction reaction (NRR) field still suffers from unsatisfactory performance, due to the sluggish mass transfer and significant kinetic barriers. Herein, a novel rare-earth-lanthanum-evoked optimization strategy is proposed to boost ambient NRR over SACs. The incorporation of La with a large atomic radius tends to break the atomic long-range order and trigger the amorphization of SACs, endowing a greater density of dangling bonds that could modify affinity for reactants and adsorbates. Moreover, with unique 5d16s2 valence-electron configurations, its presence could further enrich the electron density and enhance the intrinsic activity of single-metal center via the valence orbital coupling. As expected, the La-modified catalyst presents excellent activity toward the electrochemical NRR, delivering a maximum ammonia yield rate of 33.91 µg h-1 mg-1 and a remarkable Faradaic efficiency of 53.82%.

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