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1.
Anal Chem ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989993

RESUMEN

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

2.
J Chem Theory Comput ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980289

RESUMEN

Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development.

5.
BMC Ophthalmol ; 24(1): 297, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030539

RESUMEN

BACKGROUND: Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. CASE PRESENTATION: A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch's membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. CONCLUSIONS: Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.


Asunto(s)
Coriorretinitis , Angiografía con Fluoresceína , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Femenino , Adulto , Coriorretinitis/diagnóstico , Estudios de Seguimiento , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiología , Fondo de Ojo , Pueblos del Este de Asia
6.
Dalton Trans ; 53(26): 10919-10927, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38888145

RESUMEN

Electrochemical reduction of carbon dioxide (CO2) or carbon monoxide (CO) to valuable multi-carbon (C2+) products like acetate is a promising approach for a sustainable energy economy. However, it is still challenging to achieve high activity and selectivity for acetate production, especially in neutral electrolytes. Herein, a bioinspired hemin/Cu hybrid catalyst was developed to enhance the surface *CO coverage for highly efficient electroreduction of CO to acetate fuels. The hemin/Cu electrocatalyst exhibits a remarkable faradaic efficiency of 45.2% for CO-to-acetate electroreduction and a high acetate partial current density of 152.3 mA cm-2. Furthermore, the developed hybrid catalyst can operate stably at 200 mA cm-2 for 14.6 hours, producing concentrated acetate aqueous solutions (0.235 M, 2.1 wt%). The results of in situ Raman spectroscopy and theoretical calculations proved that the Fe-N4 structure of hemin could enhance the CO adsorption and enrich the local concentration of CO, thereby improving C-C coupling for acetate production. In addition, compared to the unmodified Cu catalysts, the Cu catalysts functionalized with cobalt phthalocyanine with a Co-N4 structure also exhibit improved acetate performance, proving the universality of this bioinspired molecule-enhanced strategy. This work paves a new way to designing bioinspired electrolysis systems for producing specific C2+ products from CO2 or CO electroreduction.

7.
Biomater Sci ; 12(14): 3686-3699, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38873991

RESUMEN

PROteolysis TArgeting Chimeras have received increasing attention due to their capability to induce potent degradation of various disease-related proteins. However, the effective and controlled cytosolic delivery of current small-molecule PROTACs remains a challenge, primarily due to their intrinsic shortcomings, including unfavorable solubility, poor cell permeability, and limited spatiotemporal precision. Here, we develop a near-infrared light-controlled PROTAC delivery device (abbreviated as USDPR) that allows the efficient photoactivation of PROTAC function to achieve enhanced protein degradation. The nanodevice is constructed by encapsulating the commercial BRD4-targeting PROTACs (dBET6) in the hollow cavity of mesoporous silica-coated upconversion nanoparticles, followed by coating a Rose Bengal (RB) photosensitizer conjugated poly-L-lysine (PLL-RB). This composition enables NIR light-activatable generation of cytotoxic reactive oxygen species due to the energy transfer from the UCNPs to PLL-RB, which boosts the endo/lysosomal escape and subsequent cytosolic release of dBET6. We demonstrate that USDPR is capable of effectively degrading BRD4 in a NIR light-controlled manner. This in combination with NIR light-triggered photodynamic therapy enables an enhanced antitumor effect both in vitro and in vivo. This work thus presents a versatile strategy for controlled release of PROTACs and codelivery with photosensitizers using an NIR-responsive nanodevice, providing important insight into the design of effective PROTAC-based combination therapy.


Asunto(s)
Lisosomas , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Proteolisis , Humanos , Lisosomas/metabolismo , Nanopartículas/química , Nanopartículas/administración & dosificación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Animales , Proteolisis/efectos de los fármacos , Factores de Transcripción/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/química , Ratones , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Rayos Infrarrojos , Rosa Bengala/química , Rosa Bengala/farmacología , Rosa Bengala/administración & dosificación , Dióxido de Silicio/química , Polilisina/química , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Proteínas que Contienen Bromodominio
8.
Aquat Toxicol ; 273: 107006, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38909583

RESUMEN

Nanoplastics (NPs) and microcystin-LR (MC-LR) are two common and harmful pollutants in water environments, especially at aquafarm where are full of plastic products and algae. It is of great significance to study the toxic effects and mechanisms of the NPs and/or MC-LR on fish at the early stage. In this study, the embryo and larvae of a filtering-feeding fish, Aristichthys nobilis, were used as the research objects. The results showed that the survival and hatching rates of the embryo were not significantly affected by the environmental concentration exposure of these two pollutants. Scanning electron microscopy (SEM) observation displayed that NPs adhered to the surface of the embryo membrane. Transcriptomic and bioinformatic analyses revealed that the NPs exposure activated neuromuscular junction development and skeletal muscle fiber in larvae, and affected C5-Branched dibasic acid metabolism. The metabolic and biosynthetic processes of zeaxanthin, xanthophyll, tetraterpenoid, and carotenoid were suppressed after the MC-LR exposure, which was harmful to the retinol metabolism of fish. Excessive production of superoxide dismutase (SOD) was detected under the MC-LR exposure. The MC-LR and NPs coexposure triggered primary immunodeficiency and adaptive immune response, leading to the possibility of reduced fitness of A.nobilis during the development. Collectively, our results indicate that environmental concentration NPs and MC-LR coexposure could cause toxic damage and enhance sick risk in A.nobilis, providing new insights into the risk of NPs and MC-LR on filtering-feeding fish.

9.
Small Methods ; : e2400697, 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38824667

RESUMEN

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS•+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS•+, thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS•+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy.

10.
Environ Sci Technol ; 58(23): 10128-10139, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38743597

RESUMEN

Pervaporation (PV) is an effective membrane separation process for organic dehydration, recovery, and upgrading. However, it is crucial to improve membrane materials beyond the current permeability-selectivity trade-off. In this research, we introduce machine learning (ML) models to identify high-potential polymers, greatly improving the efficiency and reducing cost compared to conventional trial-and-error approach. We utilized the largest PV data set to date and incorporated polymer fingerprints and features, including membrane structure, operating conditions, and solute properties. Dimensionality reduction, missing data treatment, seed randomness, and data leakage management were employed to ensure model robustness. The optimized LightGBM models achieved RMSE of 0.447 and 0.360 for separation factor and total flux, respectively (logarithmic scale). Screening approximately 1 million hypothetical polymers with ML models resulted in identifying polymers with a predicted permeation separation index >30 and synthetic accessibility score <3.7 for acetic acid extraction. This study demonstrates the promise of ML to accelerate tailored membrane designs.


Asunto(s)
Aprendizaje Automático , Polímeros , Polímeros/química , Membranas Artificiales , Permeabilidad
11.
Environ Pollut ; 353: 124168, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38761878

RESUMEN

Multiple odour nuisance in livestock farming is a notorious problem that has a significant impact on the living environment of surrounding communities. Adsorbents based on metal-organic framework (MOF) materials show great promise for controlling odour pollution, as they offer a high specific surface area, a controllable structure and an abundance of active sites. However, the MOF formation process is prone to problems such as pore clogging or collapse and reduced porosity, which limits its further application. In this study, a series of odour adsorbents were prepared by in situ growth of NH2-UiO-66 on tea stem biochar (TSBC) using a hydrothermal method and named UiO (Zr)-TSBCx. The physical and chemical properties and composition of UiO (Zr)-TSBCx have been systematically characterized using SEM, TEM, XRD, FT-IR, N2 adsorption-desorption and XPS. The release of odours from the pig farm effluent was monitored using in-situ continuous Proton-Transfer-Reaction Mass Spectrometry (PTR-MS), and the obtained primary compositions were tested for further adsorption. In dynamic adsorption experiments focused on butyric acid, UiO (Zr)-TSBC2 showed a high adsorption capacity of 3.99 × 105 µg/g and exceptional structural stability. UiO (Zr)-TSBC2 showed variable adsorption efficiencies for different odorous gases, with the best performance for the removal of ammonia, toluene and butyric acid. It also demonstrated the ability to rapidly mitigate instantaneous high concentrations of hydrogen sulfide (H2S), methanethiol and toluene resulting from agitation. Additionally, based on the relationship between the adsorption amount and the structural characteristics of the adsorbent as well as the nature of the odours, a possible adsorption mechanism of UiO (Zr)-TSBC2 for a variety of odours released from pig farm effluent was proposed. This work demonstrates a novel approach to promote deodorization applications in livestock and poultry farming environments by the in-situ growth of NH2-UiO-66 on biochar prepared from tea stem.


Asunto(s)
Carbón Orgánico , Estructuras Metalorgánicas , Odorantes , Carbón Orgánico/química , Adsorción , Estructuras Metalorgánicas/química , Odorantes/análisis , Porosidad , Té/química , Animales , Ácidos Ftálicos
12.
Anal Chem ; 96(21): 8754-8762, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38740024

RESUMEN

Simultaneous profiling of redox-regulated markers at different cellular sublocations is of great significance for unraveling the upstream and downstream molecular mechanisms of oxidative stress in living cells. Herein, by synchronizing dual target-triggered DNA machineries in one nanoentity, we engineered a DNA walker-driven mass nanotag (MNT) assembly system (w-MNT-AS) that can be sequentially activated by oxidative stress-associated mucin 1 (MUC1) and apurinic/apyrimidinic endonuclease 1 (APE1) from plasma membrane to cytoplasm and induce recycled assembly of MNTs for multiplex detection of the two markers by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). In the working cascade, the sensing process governs the separate activation of w-MNT-AS by MUC1 and APE1 in diverse locations, while the assembly process contributes to the parallel amplification of the ion signal of the characteristic mass tags. In this manner, the differences between MCF-7, HeLa, HepG2, and L02 cells in membrane MUC1 expression and cytoplasmic APE1 activation were fully characterized. Furthermore, the oxidative stress level and dynamics caused by exogenous H2O2, doxorubicin, and simvastatin were comprehensively demonstrated by tracking the fate of the two markers across different cellular locations. The proposed w-MNT-AS coupled MS method provides an effective route to probe multiple functional molecules that lie at different locations while participating in the same cellular event, facilitating the mechanistic studies on cellular response to oxidative stress and other disease-related cellular processes.


Asunto(s)
ADN-(Sitio Apurínico o Apirimidínico) Liasa , ADN , Mucina-1 , Estrés Oxidativo , Humanos , Mucina-1/metabolismo , ADN/metabolismo , ADN/química , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Peróxido de Hidrógeno/metabolismo
13.
Anal Chem ; 96(21): 8837-8843, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38757510

RESUMEN

Breast cancer poses the significance of early diagnosis and treatment. Here, we developed an innovative photoelectrochemical (PEC) immunosensor characterized by high-level dual photocurrent signals and exceptional sensitivity. The PEC sensor, denoted as MIL&Ag2S, was constructed by incorporating Ag2S into a metal-organic framework of MIL-101(Cr). This composite not only enhanced electron-hole separation and conductivity but also yielded robust and stable dual photocurrent signals. Through the implementation of signal switching, we achieved the combined detection of cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) with outstanding stability, reproducibility, and specificity. The results revealed a linear range for CEA detection spanning 0.01-32 ng/mL, with a remarkably low detection limit of 0.0023 ng/mL. Similarly, for CA15-3 detection, the linear range extended from 0.1 to 320 U/mL, with a low detection limit of 0.014 U/mL. The proposed strategy introduces new avenues for the development of highly efficient, cost-effective, and user-friendly PEC sensors. Furthermore, it holds promising prospects for early clinical diagnosis, contributing to potential breakthroughs in medical detection and ultimately improving patient outcomes.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Antígeno Carcinoembrionario , Técnicas Electroquímicas , Estructuras Metalorgánicas , Mucina-1 , Compuestos de Plata , Estructuras Metalorgánicas/química , Humanos , Neoplasias de la Mama/diagnóstico , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Mucina-1/análisis , Mucina-1/sangre , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Compuestos de Plata/química , Inmunoensayo/métodos , Técnicas Biosensibles , Femenino , Límite de Detección , Procesos Fotoquímicos , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química
14.
Bioresour Technol ; 402: 130767, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692373

RESUMEN

The study assessed the effect of salinity and lead (Pb(II)) on the anammox sludge for nitrogen removal from saline wastewater. Results showed decreased nitrogen removal and specific anammox activity (SAA) with elevated salinity and Pb(II). SAA reduced from 541.3 ± 4.3 mg N g-1 VSS d-1 at 0.5 mg/L Pb(II) to 436.0 ± 0.2 mg N g-1 VSS d-1 at 30 g/L NaCl, further to 303.6 ± 7.1 mg N g-1 VSS d-1 under 30 g/L NaCl + 0.5 mg/L Pb(II). Notably, the combined inhibition at salinity (15-20 g/L NaCl) and Pb(II) (0.3-0.4 mg/L) exhibited synergistic effect, while higher salinity and Pb(II) aligned with independent inhibition models. Combined inhibition decreased protein/polysaccharides ratio, indicating more severe negative effect on anammox aggregation capacity. Metagenomics confirmed decreased Candidatus Kuenenia, and enhanced denitrification under elevated salinity and Pb(II) conditions. This study offers insights into anammox operation for treating saline wastewater with heavy metals.


Asunto(s)
Plomo , Nitrógeno , Salinidad , Aguas Residuales , Aguas Residuales/química , Plomo/metabolismo , Nitrógeno/metabolismo , Purificación del Agua/métodos , Oxidación-Reducción , Aguas del Alcantarillado/microbiología , Anaerobiosis/efectos de los fármacos , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Reactores Biológicos , Microbiota/efectos de los fármacos , Desnitrificación/efectos de los fármacos
15.
ACS Nano ; 18(22): 14546-14557, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38776420

RESUMEN

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

16.
Front Med (Lausanne) ; 11: 1363484, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756948

RESUMEN

Objective: This study aimed to evaluate the cost-effectiveness of two Chinese patent medicines, including Kang Ai injection and Shenqi Fuzheng injection with each combined with platinum-based chemotherapy as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) in China. Methods: From Chinese healthcare system perspective, a three state Markov model with a cycle of 3 weeks and a 10-year horizon was constructed to derive the incremental cost-effectiveness ratio (ICER). Since only individual patient data of progression-free survival (PFS) of Kang Ai injection group can be obtained, we extrapolated median overall survival (mOS) of Kang Ai injection group and median progression-free survival (mPFS) and mOS of Shenqi Fuzheng injection group based on published literature and methods. Then survival curves were estimated by the method of declining exponential approximation of life expectancy (DEALE), which is based on the assumption that survival follows a declining exponential function. We performed one-way sensitivity analysis and probabilistic sensitivity analysis to test the robustness. Additionally, a scenario analysis was adopted to investigate the impact of using best-fitting distribution for PFS curve of Kang Ai injection group on the economic conclusion. Results: The base-case result indicated that Kang Ai injection group provided 0.217 incremental quality-adjusted life years (QALYs) at an incremental cost of $103.38 compared with Shenqi Fuzheng injection group. The ICER was $476.41/QALY, which was much lower than the willingness to pay threshold of one time the GDP per capita of China in 2022 ($12,070/QALY). Deterministic sensitivity analysis result showed that ICER was most sensitive to the changes in odds ratio (OR) value. The probabilistic sensitivity analysis confirmed the robustness of base-case analysis results. The scenario analysis result showed that by using Log-Normal distribution to fit the PFS curve of Kang Ai injection group and shortening the time horizon to 5 years, the ICER was $4,081.83/QALY, which was still much lower than the willingness to pay threshold. Conclusion: Kang Ai injection combined with platinum-based chemotherapy appeared to be more cost-effective for the treatment of advanced NSCLC than Shenqi Fuzheng injection combined with platinum-based chemotherapy.

17.
Chem Biodivers ; 21(6): e202400086, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38619074

RESUMEN

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.


Asunto(s)
Antineoplásicos , Artemisininas , Neoplasias de la Mama , Proliferación Celular , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas , Humanos , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/metabolismo , Artemisininas/farmacología , Artemisininas/química , Artemisininas/síntesis química , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proliferación Celular/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Relación Estructura-Actividad , Línea Celular Tumoral , Estructura Molecular , Femenino , Relación Dosis-Respuesta a Droga , Simulación del Acoplamiento Molecular
18.
J Environ Manage ; 358: 120870, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38640757

RESUMEN

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study. Approximately 88.31% of 100 mg/L Cr(VI) was continuously removed within 72 h, while it could resist up to 300 mg/L Cr(VI). Metal ions Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance to 14.41% and 3.41% under the optimal conditions, respectively. Cr(VI) removal performances by subcellular extracts showed that nearly 45.28% of 100 mg/L extracellular Cr(VI) was efficaciously reduced to Cr(III), while only 14.27%, 6.40%, and 2.73% of the cell-free extract, resting cells, and cell debris were reduced, respectively. This suggested that extracellular bioreduction was the primary Cr(VI) detoxification strategy despite a small part of Cr(VI) reduction took place intracellularly. In particular, the reduction products of the intracellular and extracellular compounds significantly differed, with organo-Cr(III) complex outside the cell and crystalline Cr(III) precipitate inside. Such observation was also evidenced by the intracellular black precipitate observed in the TEM image. XRD, XPS, and EPR analysis showed different Cr(III) compositions of intracellular and extracellular products. This study deepens our insights into the different fates of microorganisms that reduce Cr(VI) intracellularly and extracellularly.


Asunto(s)
Bacillus , Biodegradación Ambiental , Cromo , Bacillus/metabolismo , Cromo/metabolismo , Oxidación-Reducción
19.
Sci Total Environ ; 928: 172422, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38614329

RESUMEN

The oily wastewater and heavy metal ions have been increasingly discharged into water environment, posting a serious threat to ecosystems and human health. However, it remains challenging to use single separation technology to effectively remove oil and heavy metal ions in oil-water mixtures simultaneously. Herein, novel hydrophobic/hydrophilic composites (HHC) were successfully prepared by using A4 paper-derived hydrophilic cellulose as the modified matrix, modifying the polydopamine layer and in-situ growth nanoscale zero-valent iron as active adsorption materials, combined with oleic acid-modified hydrophobic magnetic hollow carbon microspheres, which were used to efficiently and rapidly adsorb heavy metals and oil in oil-water mixtures. Under the optimal adsorption conditions, the adsorption amounts of As(III), As(V), Pb(II) and Cu(II) were 289.6 mg/g, 341.9 mg/g, 241.2 mg/g and 277.5 mg/g, respectively, and the mass transfer rate of HHC to the target ions is fast. The HHC have efficient separation performance for layered oil-water mixtures and emulsified oil-water mixtures, with separation efficiency of 97 % and 92 %. At the same time, due to the abundant adsorption sites, the HHC also exhibit splendid regeneration performance for the four ions after multiple adsorption utilization. Our work designed a approach to achieving promising oil and heavy metal adsorbents with higher adsorption capacity and better regenerative properties.

20.
JACS Au ; 4(3): 1155-1165, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38559721

RESUMEN

Mechanical signals in animal tissues are complex and rapidly changed, and how the force transduction emerges from the single-cell adhesion bonds remains unclear. DNA-based molecular tension sensors (MTS), albeit successful in cellular force probing, were restricted by their detection range and temporal resolution. Here, we introduced a plasmonic tension nanosensor (PTNS) to make straight progress toward these shortcomings. Contrary to the fluorescence-based MTS that only has specific force response thresholds, PTNS enabled the continuous and reversible force measurement from 1.1 to 48 pN with millisecond temporal resolution. We used the PTNS to visualize the high dynamic range single-molecule force transitions at cell-matrix adhesions during adhesion formation and migration. Time-resolved force traces revealed that the lifetime and duration of stepwise force transitions of molecular clutches are strongly modulated by the traction force through filamentous actin. The force probing technique is sensitive, fast, and robust and constitutes a potential tool for single-molecule and single-cell biophysics.

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