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1.
J Hazard Mater ; 480: 136068, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39378596

RESUMEN

Microplastics (MPs) potentially alter physicochemical and transformation of heavy metals (HMs) in soils, which may depend on the specific characteristics of soil types. However, the dynamical and long-term mechanisms remain to be elucidated. A five-year incubation experiment was conducted to evaluate the influence of MPs on the chemical speciation of Pb, Ni, Cu, Cr, Cd, and As in the meadow, tidal, cinnamon, saline-alkali, and brown soils. From the first year to the fifth year, the clay value of the meadow, tidal, cinnamon, and saline-alkali soils was increased by 31.35 %, 9.63 %, 30.12 %, and 33.12 %, respectively; the pH values of the cinnamon and saline-alkali soils were increased by 15.02 % and 15.86 %, respectively. Besides, speciation distribution results suggested that the application of MPs reduced the liable available (LB) form (F2-dissolved and F3-ion exchangeable) of HMs and increased the potentially available (PB) form (F5-minerals and F6-organic-bound fraction) of HMs in all soils. Compared with other forms, F2 HMs fraction was the most responsive to MPs. Furthermore, the average bioconcentration factor (BCF) of Cr and Pb decreased by 73.75 % and 70.41 % in soils, respectively. Interestingly, soil type showed more impact on the form of HMs, which was associated with the different physicochemical parameters of soils, while application time displayed more impact on the bioavailability of HMs. Moreover, our results suggested that soils with higher clay content and pH values (such as cinnamon and saline-alkali soils) may mitigate the bioavailability of HMs more effectively in the presence of MPs, while soils with lower clay content may be more vulnerable to HMs contamination over time. This work highlights the importance of long-term monitoring of the impact of MPs on HMs dynamics for effective mitigation of soil contamination risks. Our study provides valuable guidance for soil remediation strategies and environmental quality management across different soil types.

2.
Small ; : e2405817, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377313

RESUMEN

2D MXene nanomaterials have excellent potential for application in novel electrochemical energy storage technologies such as supercapacitors and batteries, but the existing pure MXene is difficult to meet the practical needs. Although the electrochemical properties of modified MXene have been improved, the unclear ion storage mechanism still hinders the development of MXene-based electrode materials. Herein, the study develops flexible self-supported nitrogen-doped Ti3C2 (Py-Ti3C2) films by the highly mobile, high nitrogen content, oxygen-free pyridine-assisted solvothermal method, and then deeply investigates the energy storage mechanism of hybrid supercapacitors in four aqueous electrolytes (H2SO4, Li2SO4, Na2SO4, and MgSO4). The experimental results suggest that the Py-Ti3C2 film electrode exhibits a pseudocapacitance-dominated energy storage mechanism. Particularly, the specific capacity of the Py-Ti3C2 in 1 M H2SO4 (506 F g-1 at 0.1 A g-1) is 4-5 times higher than other electrolytes (≈110 F g-1), which could be attributed to the substantially higher ionic diffusion coefficient of H+ than those of Li+, Na+, Mg2+ with small ionic size, high ionic conductivity, and fast pseudocapacitance response. Theoretical analysis further confirms that Py-Ti3C2 has strengthened conductivity and electrical double-layer capacitance performance. Meanwhile, it has lower free energy for protonation and deprotonation of functional groups, which gives excellent pseudocapacitance performance.

3.
ACS Nano ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39380455

RESUMEN

Nanofertilizers comprising engineered nanoparticles (ENPs) have great potential in sustainable agriculture due to their strong capabilities of improving crop yields. As an effective fertilization strategy, foliar spraying could lead to broken and splashed ENP droplets, resulting in inaccurate leaf targeting and potential environmental contamination. Herein, we propose embedding Fe-based ENPs into a supramolecular hydrogel to effectively enhance the deposition amount on leaves and thus the bioavailability. The proper rheological properties of the hydrogel droplets and their robust interaction with soybean leaf simultaneously reduce the droplet rebound and fragmentation, especially under elevated impact speeds, resulting in up to 168.9% more droplet deposition compared to the ENP suspension. Computational fluid dynamics simulation analysis suggests that the contact angle is a key sensitive factor influencing the dynamic deposition behavior of the hydrogel droplet. A 15% reduction in the contact angle results in a 14% reduction of the highest bouncing height. The incorporation of ENPs enhances the viscous dissipation rate by 7.4% in comparison with pure hydrogel droplets. The hydrogel embedding also causes a 1.5-fold increase in ENP uptake compared to that of the ENP suspension. The hydrogel embedding delivers a reduction of 80% in the ENP application amount, compared to ENP suspensions, while achieving a 28% increase in the fresh weight of soybean seedlings. This work provides an effective method to enhance the deposition of ENPs during foliar application.

4.
Nat Commun ; 15(1): 8534, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358376

RESUMEN

Grain boundaries in noble metal catalysts have been identified as critical sites for enhancing catalytic activity in electrochemical reactions such as the oxygen reduction reaction. However, conventional methods to modify grain boundary density often alter particle size, shape, and morphology, obscuring the specific role of grain boundaries in catalytic performance. This study addresses these challenges by employing gold nanoparticle assemblies to control grain boundary density through the manipulation of nanoparticle collision frequency during synthesis. We demonstrate a direct correlation between increased grain boundary density and enhanced two-electron oxygen reduction reaction activity, achieving a significant improvement in both specific and mass activity. Additionally, the gold nanoparticle assemblies with high grain boundary density exhibit remarkable electrochemical stability, attributed to boron segregation at the grain boundaries, which prevents structural degradation. This work provides a promising strategy for optimizing the activity, selectivity, and stability of noble metal catalysts through precise grain boundary engineering.

5.
Sci Rep ; 14(1): 22937, 2024 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358407

RESUMEN

Although sodium-glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48-72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0-20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.


Asunto(s)
Lesión Renal Aguda , Medios de Contraste , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Lesión Renal Aguda/inducido químicamente , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Medios de Contraste/efectos adversos , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Angiografía Coronaria/efectos adversos , Creatinina/sangre , Incidencia , Factores de Riesgo
6.
ACS Nano ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363419

RESUMEN

The low permeability and heterogeneous distribution of drugs (including nanomedicines) have limited their deep penetration into solid tumors. Herein we report the design of gold nanoparticles with virus-like spikes (AuNVs) to mimic viral shapes and facilitate tumor penetration. Mechanistic studies revealed that AuNVs mainly entered cells through macropinocytosis, then transported to the Golgi/endoplasmic reticulum system via Rab11-regulated pathway, and finally exocytosed through recycling endosomes, leading to high cellular uptake, effective transcytosis, and deep tumor penetration compared to gold nanospheres (AuNPs) and gold nanostars (AuNSs). The high tumor accumulation and deep tumor penetration of mitoxantrone (MTO) facilitated by AuNVs endowed effective chemophotothermal therapy when exposed to a near-infrared II laser, significantly reducing tumor sizes in a mouse model of colorectal cancer. This study reveals a potent mechanism of viral-like structures in tissue penetration and highlights their potential as effective drug delivery carriers.

7.
Innovation (Camb) ; 5(5): 100691, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39285902

RESUMEN

This paper explores the evolution of geoscientific inquiry, tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence (AI) and data collection techniques. Traditional models, which are grounded in physical and numerical frameworks, provide robust explanations by explicitly reconstructing underlying physical processes. However, their limitations in comprehensively capturing Earth's complexities and uncertainties pose challenges in optimization and real-world applicability. In contrast, contemporary data-driven models, particularly those utilizing machine learning (ML) and deep learning (DL), leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge. ML techniques have shown promise in addressing Earth science-related questions. Nevertheless, challenges such as data scarcity, computational demands, data privacy concerns, and the "black-box" nature of AI models hinder their seamless integration into geoscience. The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm. These models, which incorporate domain knowledge to guide AI methodologies, demonstrate enhanced efficiency and performance with reduced training data requirements. This review provides a comprehensive overview of geoscientific research paradigms, emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience. It examines major methodologies, showcases advances in large-scale models, and discusses the challenges and prospects that will shape the future landscape of AI in geoscience. The paper outlines a dynamic field ripe with possibilities, poised to unlock new understandings of Earth's complexities and further advance geoscience exploration.

8.
Expert Opin Ther Pat ; : 1-12, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39267345

RESUMEN

INTRODUCTION: ClpP is a highly conserved serine protease that plays a crucial role in maintaining protein homeostasis in both bacterial cells and human mitochondria. Several studies have demonstrated the potential of ClpP as a drug target, with ClpP modulators, including both inhibitors and activators, showing promise in treating a range of conditions such as drug-resistant bacteria, malignant cancers, and fatty liver disease. AREA COVERED: This review provides an overview of patents related to ClpP modulators filed over the last five years, detailing their claims and therapeutic applications. The sources of patent information included databases of the European Patent Office, the China Patent Office and the U.S.A. patent Office, while relevant research articles were accessed through PubMed. EXPERT OPINION: The number of patents concerning ClpP modulators is on the rise, reflecting advancements in related research. By summarizing and outlining relevant patents, we aim to stimulate further interest among researchers, ultimately leading to the development of effective drugs based on ClpP modulators. The broad spectrum of diseases associated with ClpP dysfunction underscores the potential for ClpP modulators to address a wide range of therapeutic needs.

9.
Environ Sci Technol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39262330

RESUMEN

Sulfidation of nanoscale zerovalent iron (nZVI) can enhance particle performance. However, the underlying mechanisms of nZVI sulfidation are poorly known. We studied the effects of Fe2+ on 24-h dynamics of nZVI sulfidation by HS- using a dosed S to Fe molar ratio of 0.2. This shows that in the absence of Fe2+, HS- rapidly adsorbed onto nZVI particles and reacted with surface iron oxide to form mackinawite and greigite (<0.5 h). As nZVI corrosion progressed, amorphous FeSx in solution deposited on nZVI, forming S-nZVI (0.5-24 h). However, in the initial presence of Fe2+, the rapid reaction between HS- and Fe2+ produced amorphous FeSx, which deposited on the nZVI and corroded the surface iron oxide layer (<0.25 h). This was followed by redeposition of colloidal iron (hydr)oxide on the particle surface (0.25-8 h) and deposition of residual FeSx (8-24 h) on S-nZVI. S loading on S-nZVI was 1 order of magnitude higher when Fe2+ was present. Surface characterization of the sulfidated particles by TEM-SAED, XPS, and XAFS verified the solution dynamics and demonstrated that S2- and S22-/Sn2- were the principal reduced S species on S-nZVI. This study provides a methodology to tune sulfur loading and S speciation on S-nZVI to suit remediation needs.

10.
Small ; : e2406229, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263781

RESUMEN

Highly vertically thermally conductive silicon rubber (SiR) composites are widely used as thermal interface materials (TIMs) for chip cooling. Herein, inspired by water transport and transpiration of Moso bamboo-forests extensively existing in south China, and guided by filler self-assembly simulation, bamboo-forest-like heat conduction networks, with bamboo-stems-like vertically aligned polydopamine-coated carbon fibers (VA-PCFs), and bamboo-leaves-like horizontally layered Al2O3(HL-Al2O3), are rationally designed and constructed. VA-PCF/HL-Al2O3/SiR composites demonstrated enhanced heat conduction properties, and their through-plane thermal conductivity and thermal diffusivity reached 6.47 W (mK)-1 and 3.98 mm2 s-1 at 12 vol% PCF and 4 vol% Al2O3 loadings, which are 32% and 38% higher than those of VA-PCF (12 vol%) /SiR composites, respectively. The heat conduction enhancement mechanisms of VA-PCF/HL-Al2O3 networks on their SiR composites are revealed by multiscale simulation: HL-Al2O3 bridges the separate VA-PCF heat flow channels, and transfers more heat to the matrix, thereby increasing the vertical heat flux in composites. Along with high volume resistivity, low compression modulus, and coefficient of thermal expansion, VA-PCF/HL-Al2O3/SiR composites demonstrate great application potential as TIMs, which is proven using multiphysics simulation. This work not only makes a meaningful attempt at simulation-driven biomimetic material structure design but also provides inspiration for the preparation of TIMs.

11.
Org Lett ; 26(36): 7757-7762, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39267494

RESUMEN

A Cs2CO3-promoted [4 + 2] cycloaddition of 1,6-enynes under mild reaction conditions has been developed. This protocol provides a facile approach to a series of tetrahydro-1H-benzo[f]isoindole isomerized products promoted by Cs2CO3 with moderate to high yields. By simply switching the reaction solvent and controlling the reaction time, two isomerization products could be obtained, both with good selectivity.

12.
Molecules ; 29(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39274920

RESUMEN

OBJECTIVE: The aim of this study was to optimize the formulation of a C60-modified self-microemulsifying drug delivery system loaded with triptolide (C60-SMEDDS/TP) and evaluate the cytoprotective effect of the C60-SMEDDS/TP on normal human cells. RESULTS: The C60-SMEDDS/TP exhibited rapid emulsification, an optimal particle size distribution of 50 ± 0.19 nm (PDI 0.211 ± 0.049), and a near-neutral zeta potential of -1.60 mV. The release kinetics of TP from the C60-SMEDDS/TP exhibited a sustained release profile and followed pseudo-first-order release kinetics. Cellular proliferation and apoptosis analysis indicated that the C60-SMEDDS/TP (with a mass ratio of TP: DSPE-PEG-C60 = 1:10) exhibited lower toxicity towards L02 and GES-1 cells. This was demonstrated by a higher IC50 (40.88 nM on L02 cells and 17.22 nM on GES-1 cells) compared to free TP (21.3 nM and 11.1 nM), and a lower apoptosis rate (20.8% on L02 cells and 26.3% on GES-1 cells, respectively) compared to free TP (50.5% and 47.0%) at a concentration of 50 nM. In comparison to the free TP group, L02 cells and GES-1 cells exposed to the C60-SMEDDS/TP exhibited a significant decrease in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM). On the other hand, the C60-SMEDDS/TP demonstrated a similar inhibitory effect on BEL-7402 cells (IC50 = 28.9 nM) and HepG2 cells (IC50 = 107.6 nM), comparable to that of the free TP (27.2 nM and 90.4 nM). The C60-SMEDDS/TP group also exhibited a similar intracellular level of ROS and mitochondrial membrane potential compared to the SMEDDS/TP and free TP groups. METHOD: Fullerenol-Grafted Distearoyl Phosphatidylethanolamine-Polyethylene Glycol (DSPE-PEG-C60) was synthesized and applied in the self-microemulsifying drug delivery system. The C60-SMEDDS/TP was formulated using Cremophor EL, medium-chain triglycerides (MCT), PEG-400, and DSPE-PEG-C60, and loaded with triptolide (TP). The toxicity and bioactivity of the C60-SMEDDS/TP were assessed using normal human liver cell lines (L02 cells), normal human gastric mucosal epithelial cell lines (GES-1 cells), and liver cancer cell lines (BEL-7402 cells and HepG2 cells). The production of reactive oxygen species (ROS) after the C60-SMEDDS/TP treatment was assessed using 2',7'-dichlorofluorescein diacetate (DCFDA) staining. The alterations in mitochondrial membrane potential (ΔψM) were assessed by measuring JC-1 fluorescence. CONCLUSIONS: The cytoprotection provided by the C60-SMEDDS/TP favored normal cells (L02 and GES-1) over tumor cells (BEL-7402 and HepG2 cells) in vitro. This suggests a promising approach for the safe and effective treatment of TP.


Asunto(s)
Apoptosis , Diterpenos , Sistemas de Liberación de Medicamentos , Emulsiones , Compuestos Epoxi , Fulerenos , Fenantrenos , Humanos , Diterpenos/farmacología , Diterpenos/química , Fenantrenos/química , Fenantrenos/farmacología , Compuestos Epoxi/química , Compuestos Epoxi/farmacología , Fulerenos/química , Fulerenos/farmacología , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Citoprotección/efectos de los fármacos , Tamaño de la Partícula , Proliferación Celular/efectos de los fármacos
14.
Nanoscale ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39308319

RESUMEN

Direct visualization of the states originating from electron-electron interactions is of great importance for engineering the surface and interfacial properties of graphene-based quantum materials. For instance, the rotational symmetry breaking or nematic phase inferred from spectroscopic imaging has confirmed the existence of correlated states in a wide range of moiré materials. Here, we study the atomic-scale spatial distributions and symmetry of wave functions in gate-tunable twisted double bilayer graphene by employing scanning tunneling microscopy/spectroscopy and continuum model calculations. A series of spectroscopic imaging analyses are used to identify dominant symmetry breaking of the emergent states. Interestingly, in non-integer hole fillings, a completely new localized electronic state with rotational symmetry breaking is observed on the left side of the valence flat band. The degree of anisotropy is found to increase from the conduction flat band through the valence flat band to the new state. Our results provide an essential microscopic insight into the flat band and its adjacent state for a full understanding of their electric field response in twisted graphene systems.

15.
Int J Biol Macromol ; : 135879, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39322154

RESUMEN

The extensive use of tetracycline (TC) for disease control and the residuals in wastewater has resulted in the spread and accumulation of antibiotic resistance genes, posing a severe threat to the human health and environmental safety. To solve this problem, a series of double-network hydrogel beads based on sodium alginate and polyvinyl alcohol were constructed with the introduction of various surfactants to modulate the morphology. The results showed that the introduction of surfactants can modulate the surface morphology and internal structure, which can also regulate the adsorption ability of the hydrogel beads. The SDS-B beads with SDS as surfactant exhibited highest adsorption efficiency for removal of TC with a maximum adsorption capacity up to 121.6 mg/g, which possessed a resistance to various cations and humic acid. The adsorption mechanism revealed that the superior adsorption performance of the hydrogel beads was primarily attributed to hydrogen bonding, electrostatic attraction, and π-π EDA interactions. Adsorption kinetics demonstrated that the pseudo-second-order model fitted the adsorption process well and adsorption isotherm showed the adsorption of TC occurred through both chemical and physical interactions. Moreover, the adsorption efficiency remained approximately 87.5 % after three adsorption-desorption cycles, which may have potential application and practical value in TC adsorption.

16.
Small ; : e2404810, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39252642

RESUMEN

High-performance sensors capable of detecting multidirectional strains are indispensable to understand the complex motions involved in flexible electronics. Conventional isotropic strain sensors can only measure uniaxial deformations or single stimuli, hindering their practical application fields. The answer to such challenge resides in the construction of engineered anisotropic sensing structures. Herein, a hierarchically aligned carbon nanofiber (CNF)/polydimethylsiloxane nanocomposite strain sensor is developed by one-step 3D printing. The precisely controlled printing path and shear flow bring about highly aligned nanocomposite filaments at macroscale and orientated CNF network within each filament at microscale. The periodically orientated nanocomposite filaments along with the inner aligned CNF network successfully control the strain distribution and the appearance of microcracks, giving rise to anisotropic structural response to external deformations. The synergetic effect of the multiscale structural design leads to distinguishable gauge factors of 164 and 0.5 for applied loadings along and transverse to the alignment direction, leading to an exceptional selectivity of 3.77. The real-world applications of the hierarchically aligned sensors in multiaxial movement detector and posture-correction device are further demonstrated. The above findings propose new ideas for manufacturing nanocomposites with engineered anisotropic structure and properties, verifying promising applications in emerging wearable electronics and soft robotics.

17.
Biomolecules ; 14(9)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39334873

RESUMEN

Arabinoside and derived nucleoside analogs, a family of nucleoside analogs, exhibit diverse typically biological activities and are widely used as antibacterial, antiviral, anti-inflammatory, antitumor, and other drugs in clinical and preclinical trials. Although with a long and rich history in the field of medicinal chemistry, the biosynthesis of arabinoside has only been sporadically designed and studied, and it remains a challenge. Here, we constructed an in vitro multi-enzymatic cascade for the biosynthesis of arabinosides. This artificial biosystem was systematically optimized, involving an exquisite pathway design, NADP+ regeneration, meticulous enzyme selection, optimization of the key enzyme dosage, and the concentration of inorganic phosphate. Under the optimized conditions, we achieved 0.37 mM of vidarabine from 5 mM of sucrose and 2 mM of adenine, representing 18.7% of the theoretical yield. Furthermore, this biosystem also has the capability to produce other arabinosides, such as spongouridine, arabinofuranosylguanine, hypoxanthine arabinofuranoside, fludarabine, and 2-methoxyadenine arabinofuranoside, from sucrose, and corresponding nucleobase by introducing different nucleoside phosphorylases. Overall, our biosynthesis approach provides a pathway for the biosynthesis of arabinose-derived nucleoside analogs, offering potential applications in the pharmaceutical industry.


Asunto(s)
Sacarosa , Sacarosa/metabolismo , Sacarosa/química , Vidarabina/análogos & derivados , Vidarabina/química , Vidarabina/metabolismo , Pentosiltransferasa/metabolismo , Pentosiltransferasa/genética , NADP/metabolismo
18.
Bioorg Chem ; 153: 107788, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39265524

RESUMEN

Breast cancer stands as the cancer with the highest incidence and mortality rates among women globally, in which triple-negative breast cancer has been ranked as the most difficult one. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been exhibited notable inhibitory effect on both hormone-dependent breast cancer cells and triple-negative breast cancer cells, but showing very low in vivo effeacy. In order to obtain more effective antitumor derivatives than BZA, we have employed a structurally diverse design and synthesis of 57 novel 2-phenylindole amides for detecting their cytotoxities against triple-negative mammary cancer cell line, CMT-7364. Among them, 21 compounds demonstrated significant inhibitory activity against CMT-7364 cells (IC50 < 20 µM). Notably, compound 49 stood out, displaying both similar tumor cell inhibition (20 % reduce in IC50 value) and higher selectivity (4.6 times higher in SI value), compared to Bazedoxifene. Additionally, compound 49 exhibited desirable antitumor effects in a CMT-7364 cell-derived mouse in vivo model, achieving the best inhibition rate of 43.1 % and establishing strong molecular bonding with GP130. Our findings are also supported by comprehensive SAR and 3D-QSAR analyses. Furthermore, the best potent compound 49 was determined to block the cell cycle of canine breast cancer cells in the G0G1 phase in a time-dependent manner, by inducing apoptosis and autophagy. In conclusion, this work presents a valuable lead compound as a potential GP130 inhibitor against triple-negative breast cancer cell lines, laying the foundation for further antitumor drug development.

19.
ACS Nano ; 18(39): 26631-26642, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39297401

RESUMEN

Understanding the trophic transfer and ecological cascade effects of nanofertilizers and nanopesticides in terrestrial food chains is crucial for assessing their nanotoxicity and environmental risks. Herein, the trophic transfer of La2O3 (nLa2O3) and CuO (nCuO) nanoparticles from tomato leaves to Helicoverpa armigera (Lepidoptera: Noctuidae) caterpillars and their subsequent effects on caterpillar growth and intestinal health were investigated. We found that 50 mg/L foliar nLa2O3 and nCuO were transferred from tomato leaves to H. armigera, with particulate trophic transfer factors of 1.47 and 0.99, respectively. While nCuO exposure reduced larval weight gain more (34.7%) than nLa2O3 (11.3%), owing to higher oxidative stress (e.g., MDA and H2O2) and more serious intestinal pathological damage (i.e., crumpled columnar cell and disintegrated goblet cell) by nCuO. Moreover, nCuO exposure led to a more compact antagonism between the phyllosphere and gut microbiomes compared to nLa2O3. Specifically, nCuO exposure resulted in a greater increase in pathogenic bacteria (e.g., Mycobacterium, Bacillus, and Ralstonia) and a more significant decrease in probiotics (e.g., Streptomyces and Arthrobacter) than nLa2O3, ultimately destroying larval intestinal immunity. Altogether, our findings systematically revealed the cascade effect of metal oxide nanomaterials on higher trophic consumers through alteration in the phyllosphere and insect gut microbiome interaction, thus providing insights into nanotoxicity and environmental risk assessment of nanomaterials applied in agroecosystems.


Asunto(s)
Cadena Alimentaria , Microbioma Gastrointestinal , Nanopartículas del Metal , Estrés Oxidativo , Solanum lycopersicum , Animales , Solanum lycopersicum/microbiología , Solanum lycopersicum/efectos de los fármacos , Solanum lycopersicum/metabolismo , Estrés Oxidativo/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Nanopartículas del Metal/química , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/microbiología , Óxidos/química , Óxidos/farmacología , Hojas de la Planta/metabolismo , Cobre/farmacología , Cobre/química , Helicoverpa armigera
20.
Environ Sci Technol ; 58(39): 17355-17363, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39301696

RESUMEN

Solubility largely determines the impacts of aerosol Fe on marine ecosystems and human health. Currently, modeling studies have large uncertainties in aerosol Fe solubility due to inadequate understanding of the sources of dissolved Fe. This work investigated seasonal variations of Fe solubility in coarse and fine aerosols in Qingdao, a coastal city in the Northwest Pacific, and utilized a receptor model for source apportionment of total and dissolved aerosol Fe. Desert dust was found to be the main source of total Fe, contributing 65 and 81% annually to total Fe in coarse and fine particles, respectively; in contrast, dissolved aerosol Fe originated primarily from combustion, industrial, and secondary sources. The annual average contributions to dissolved Fe in coarse and fine particles were 68 and 47% for the secondary source and 32 and 33% for the combustion source, respectively. Aerosol Fe solubility was found to be highest in summer and lowest in spring, showing seasonal patterns similar to those of aerosol acidity. Increase in Fe solubility in atmospheric particles, when compared to desert dust, was mainly caused by secondary processing and combustion emission, and the effect of secondary processes was dictated by aerosol acidity and liquid water content.


Asunto(s)
Aerosoles , Polvo , Hierro , Solubilidad , Hierro/química , Estaciones del Año , Contaminantes Atmosféricos/análisis , Tamaño de la Partícula , Material Particulado , Monitoreo del Ambiente
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