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1.
Nature ; 566(7745): 475-479, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30814713

RESUMEN

Topological electronic materials such as bismuth selenide, tantalum arsenide and sodium bismuthide show unconventional linear response in the bulk, as well as anomalous gapless states at their boundaries. They are of both fundamental and applied interest, with the potential for use in high-performance electronics and quantum computing. But their detection has so far been hindered by the difficulty of calculating topological invariant properties (or topological nodes), which requires both experience with materials and expertise with advanced theoretical tools. Here we introduce an effective, efficient and fully automated algorithm that diagnoses the nontrivial band topology in a large fraction of nonmagnetic materials. Our algorithm is based on recently developed exhaustive mappings between the symmetry representations of occupied bands and topological invariants. We sweep through a total of 39,519 materials available in a crystal database, and find that as many as 8,056 of them are topologically nontrivial. All results are available and searchable in a database with an interactive user interface.

2.
Nature ; 567(7749): 496-499, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30894751

RESUMEN

Chirality-the geometric property of objects that do not coincide with their mirror image-is found in nature, for example, in molecules, crystals, galaxies and life forms. In quantum field theory, the chirality of a massless particle is defined by whether the directions of its spin and motion are parallel or antiparallel. Although massless chiral fermions-Weyl fermions-were predicted 90 years ago, their existence as fundamental particles has not been experimentally confirmed. However, their analogues have been observed as quasiparticles in condensed matter systems. In addition to Weyl fermions1-4, theorists have proposed a number of unconventional (that is, beyond the standard model) chiral fermions in condensed matter systems5-8, but direct experimental evidence of their existence is still lacking. Here, by using angle-resolved photoemission spectroscopy, we reveal two types of unconventional chiral fermion-spin-1 and charge-2 fermions-at the band-crossing points near the Fermi level in CoSi. The projections of these chiral fermions on the (001) surface are connected by giant Fermi arcs traversing the entire surface Brillouin zone. These chiral fermions are enforced at the centre or corner of the bulk Brillouin zone by the crystal symmetries, making CoSi a system with only one pair of chiral nodes with large separation in momentum space and extremely long surface Fermi arcs, in sharp contrast to Weyl semimetals, which have multiple pairs of Weyl nodes with small separation. Our results confirm the existence of unconventional chiral fermions and provide a platform for exploring the physical properties associated with chiral fermions.

3.
Proc Natl Acad Sci U S A ; 119(15): e2113407119, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35380895

RESUMEN

In mammals, a larger number of neurons in V1 are devoted to cardinal (horizontal and vertical) orientations than to oblique orientations. However, electrophysiological results from the macaque monkey visual cortex are controversial. Both isotropic and anisotropic orientation distributions have been reported. It is also unclear whether different visual areas along the visual hierarchy have different orientation anisotropies. We analyzed orientation maps in a large set of intrinsic signal optical imaging data and found that both V1 and V4 exhibited significant orientation anisotropies. However, their overrepresented orientations were very different: in V1, both cardinal and radial orientations were overrepresented, while in V4, only cardinal bias was presented. These findings suggest that different cortical areas have evolved to emphasize different features that are suitable for their functional purposes, a factor that needs to be considered when efforts are made to explain the relationships between the visual environment and the cortical representation and between the cortical representation and visual perception.


Asunto(s)
Orientación , Corteza Visual , Percepción Visual , Animales , Anisotropía , Macaca , Neuronas/fisiología , Orientación/fisiología , Estimulación Luminosa , Corteza Visual/fisiología , Vías Visuales/fisiología , Percepción Visual/fisiología
4.
Br J Cancer ; 130(8): 1239-1248, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38355840

RESUMEN

BACKGROUND: Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies. METHODS: In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer. RESULTS: Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging. CONCLUSION: CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina
5.
Biochem Biophys Res Commun ; 704: 149638, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38422899

RESUMEN

BACKGROUND: Pheochromocytoma (PCC) is a rare neuroendocrine tumor. Angiogenesis is primary contributing factor for tumorigenesis. Cytochrome c oxidase 4I2 (COX4I2) has been confirmed to take part in the progression of cancer. Hypoxia-inducible factor 1A (HIF1A) is the main regulatory factor for the steady-state response of hypoxia, involved in metabolism and angiogenesis. In this study, we intended to explore the functions of COX4I2 in PCC and the effect mechanism between HIF1A and COX4I2. MATERIALS AND METHODS: The RNA-sequencing and immunohistochemistry tested COX4I2 expression in highly vascular PCC. Small interfering RNA (siRNA) was used to reduce the mRNA expression of COX4I2, and a small molecule inhibitor was utilized to reduce the protein expression of HIF1A. Culturing cells in 1% O2environment was performed to activate HIF1A. Western blot was applied to quantify the expression of target genes at the protein levels. The supernatant from PCC cells and fibroblasts acted as the conditioned medium. We conducted the tube formation and transwell assays in human vascular endothelial cells (HUVECs) to determine angiogenesis, the binding of COX4I2 promoter and HIF1A was evaluated by the dual luciferase reporter assay. RESULTS: COX4I2 had been rigorously shown to be overexpressed in highly vascular PCC. Knockdown of COX4I2 in PCC cells (MPC) did not significantly impact angiogenesis, while knockdown of COX4I2 in fibroblast (3T3) notably inhibited angiogenesis. RNA sequencing suggested that the expression of 11 vascular markers, such as CD34 and angiogenesis associated pathways in 3T3, decreased with knockdown of COX4I2. HIF1A had been shown to enhance the mRNA expression of COX4I2 through transcriptional regulation. Activation and inhibition of HIF1A resulted in upregulation and downregulation of COX4I2, respectively. The HIF1A inhibitor demonstrated a reduction in angiogenesis. CONCLUSION: COX4I2 is overexpressed in highly vascular PCC and contributes to angiogenesis in fibroblasts. Mechanistically, HIF1A transcriptional regulation enhances COX4I2 and its effects on angiogenesis in PCC. COX4I2 might serve as a vascular marker and represent a potential target for vascular therapy.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Feocromocitoma/genética , Células Endoteliales/metabolismo , Angiogénesis , ARN Interferente Pequeño/genética , Neoplasias de las Glándulas Suprarrenales/genética , Hipoxia/genética , ARN Mensajero/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
6.
Dement Geriatr Cogn Disord ; 53(3): 143-152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38560983

RESUMEN

INTRODUCTION: The potential influence of age at menarche (AM) on cognitive aging remains inadequate, partly because of the difficulties presented by multiple confounders. To address this issue, Mendelian randomization (MR) analysis was used to explore the causal impacts of AM on cognitive aging. METHODS: Using the publicly accessible Taiwan Biobank, we identified single nucleotide polymorphisms (SNPs) significantly associated with AM as instrumental variables to estimate the effects of instruments on cognitive function assessed with the Mini-Mental State Examination (MMSE). We employed several MR methods, including two-stage least squares, inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and constrained maximum likelihood (cML) MR methods, to ensure the stability and reliability of the results. RESULTS: MR analyses indicated no significant causal relationship between genetically determined AMs and total and subdomain MMSE scores, except the G5 subdomain (ßIVW = 0.156, 95% confidence interval [CI]: 0.005, 0.307; ßcML = 0.161, 95% CI: 0.014, 0.309). However, in a leave-one-out sensitivity analysis, we found a significant relationship between AM and cognitive aging after eliminating rs157863 and rs6758290, thus demonstrating the potential pleiotropic effects of these two SNPs. After these two SNPs were eliminated, we found a significant causal relationship between AM and overall MMSE scores (ßIVW = 0.425, 95% CI: 0.011, 0.839), though. CONCLUSION: Evidence from the present MR study did not fully support a causal relationship between AM and cognitive function decline in later life. Potential pleiotropic effects of the genes underlying these two traits are worthy of further investigation.


Asunto(s)
Envejecimiento Cognitivo , Menarquia , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Menarquia/genética , Taiwán/epidemiología , Femenino , Anciano , Factores de Edad , Pruebas de Estado Mental y Demencia , Masculino , Persona de Mediana Edad
7.
Inorg Chem ; 63(15): 7071-7079, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38561240

RESUMEN

Spatial confinement of organic pollutants and reactive oxygen species (e.g., SO4•- and •OH) with ultrashort lifetime inside the scale of chemical theoretical diffusion could provide a greatly promising strategy to overcome the limitation of mass transfer in the heterogeneous Fenton-like oxidation process. Herein, we first reported spatial confinement of cobalt nanoparticles in N-doped carbon nanorods (Co-NCNRs), by encapsulating Co nanoparticles into N-doped carbon nanorods, in activating CaSO3 for antibiotic degradation. Compared to Na2SO3 and NaHSO3, CaSO3 could slowly and persistently discharge SO32- due to its low solubility, thus avoiding the depletion of the generated SO3•- and •OH under the high concentration of sulfite ions. Fully physical characterizations confirmed that the 3D hydrogel was mostly transformed into the nanorod structure of Co-NCNRs at 550 °C. Co atoms were successfully nanoconfined into N-doped carbon nanorods, which contributes to mass transfer and prevents the agglomeration of Co nanoparticles, thus enhancing its catalytic activity and stability in activating CaSO3 for water decontamination. The catalytic performance, kinetic research, influences of inorganic anions, pH, and degradation mechanism of chlortetracycline degradation catalyzed by the Co-NCNRs/CaSO3 system have been studied in detail. This work not only proposed a facile method for synthesis of nanoconfined catalyst but also provided an excellent Co-NCNRs/CaSO3 system for wastewater treatment.

8.
Org Biomol Chem ; 22(9): 1794-1799, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38348741

RESUMEN

A novel and efficient method for the synthesis of aryl phosphonates from aryl halides and trialkylphosphites via EDA complex-based photochemistry has been developed. It is demonstrated that aryl radicals, generated from the photoexcitation of the EDA complex formed by aryl halide and potassium thioacetate, could be intercepted with trialkylphosphite to produce the corresponding aryl phosphonates in moderate to good yields. It should be noted that the reaction is performed at room temperature in the absence of any transition metal catalyst, oxidant and photocatalyst, exhibiting high efficiency, high selectivity, and operational simplicity.

9.
Ren Fail ; 46(1): 2310081, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38321925

RESUMEN

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.


Asunto(s)
Lesión Renal Aguda , Sepsis , Humanos , Nomogramas , Estudios Retrospectivos , China
10.
J Environ Manage ; 360: 121163, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38749130

RESUMEN

In this study, the effects of micro-positive pressure formed by covering with a semipermeable membrane in the heating phase of dairy manure composting on greenhouse gas emissions and the mechanism of reducing methane emissions by the archaeal community were investigated. A large-scale experiment was conducted with semipermeable membrane-covered composting (SMC), forced aeration composting (FAC), and traditional static composting (TSC) groups. The results showed that the oxygen concentration and methanogen abundance were key factors in regulating methane emissions. In the heating phase of SMC, the micro-positive pressure could enhance the O2 utilization rate and heating rate, resulting in Methanobrevibacter and Methanobacterium greatly decreasing, and the abundance of mcrA decreased by 90.03%, while that of pmoA did not increase. Compared with FAC and TSC, the cumulative methane emissions in SMC decreased by 51.75% and 96.04%, respectively. Therefore, the micro-positive pressure could effectively reduce greenhouse gas emissions by inhibiting the growth of methanogens.


Asunto(s)
Archaea , Compostaje , Gases de Efecto Invernadero , Estiércol , Metano , Compostaje/métodos , Gases de Efecto Invernadero/análisis , Metano/metabolismo , Archaea/metabolismo , Animales , Industria Lechera
11.
Neuroimage ; 271: 120019, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36914108

RESUMEN

Studies of resting-state functional connectivity (rsFC) have provided rich insights into the structures and functions of the human brain. However, most rsFC studies have focused on large-scale brain connectivity. To explore rsFC at a finer scale, we used intrinsic signal optical imaging to image the ongoing activity of the anesthetized macaque visual cortex. Differential signals from functional domains were used to quantify network-specific fluctuations. In 30-60 min resting-state imaging, a series of coherent activation patterns were observed in all three visual areas we examined (V1, V2, and V4). These patterns matched the known functional maps (ocular dominance, orientation, color) obtained in visual stimulation conditions. These functional connectivity (FC) networks fluctuated independently over time and exhibited similar temporal characteristics. Coherent fluctuations, however, were observed from orientation FC networks in different areas and even across two hemispheres. Thus, FC in the macaque visual cortex was fully mapped both on a fine scale and over a long range. Hemodynamic signals can be used to explore mesoscale rsFC in a submillimeter resolution.


Asunto(s)
Conectoma , Macaca fascicularis , Descanso , Corteza Visual , Macaca fascicularis/fisiología , Corteza Visual/irrigación sanguínea , Corteza Visual/fisiología , Corteza Visual/ultraestructura , Masculino , Animales , Descanso/fisiología , Estimulación Luminosa , Imagen Óptica , Hemodinámica
12.
Phys Rev Lett ; 131(3): 036402, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37540867

RESUMEN

In this Letter, we introduce the concept of dynamical degeneracy splitting to describe the anisotropic decay behaviors in non-Hermitian systems. We demonstrate that systems with dynamical degeneracy splitting exhibit two distinctive features: (i) the system shows frequency-resolved non-Hermitian skin effect; (ii) Green's function exhibits anomalous behavior at given frequency, leading to uneven broadening in spectral function and anomalous scattering. As an application, we propose directional invisibility based on wave packet dynamics to investigate the geometry-dependent skin effect in higher dimensions. Our work elucidates a faithful correspondence between non-Hermitian skin effect and Green's function, offering a guiding principle for exploration of novel physical phenomena emerging from this effect.

13.
Langmuir ; 39(46): 16457-16471, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37946515

RESUMEN

Monolayers self-assembled by triphenyleneethynylene (TPE) compounds bearing two terminal alkynyl chains were polymerized by Glaser-Hay (G-H) alkyne coupling at the acetonitrile-HOPG interface. The alkynyl chains extend into the solution due to the monolayer's dense-packed morphology. Reacting substructures that have no morphology-determining roles is a potential strategy for preserving monolayer morphology throughout polymerization. Monolayer G-H reaction kinetics and polymerized monolayer durability were characterized by using mass spectrometry and fluorescence. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and time-of-flight (TOF) MS were used to identify TPE-oligomers in the monolayer and to track the monolayer populations of TPE-monomer, -dimer, and -trimer as a function of G-H reaction duration. Comparison of the observed kinetics to a Monte Carlo simulation provided evidence of step-growth polymerization. The durability of polymerized monolayers depended strongly on the length of the alkynyl chains linked by G-H reaction. Polymerized T6y monolayers (O(CH2)3C≡CH alkynyl chains) desorbed minimally during 16-h immersion in 90 °C o-dichlorobenzene (oDCB), whereas polymerized T8y (O(CH2)5C≡CH alkynyl chains) and polymerized T11y (O(CH2)8C≡CH alkynyl chains), desorbed 33 and 60%, respectively, of their TPE units after 4 h in 90 °C oDCB. All the polymerized monolayers are much more durable than unpolymerized monolayers, which desorb quantitatively from HOPG when rinsed with 25 µL of oDCB. Polymerized T6y monolayer is a highly durable anchor that may be adapted to build multilayer structures "permanently" attached to the HOPG surface. The alkynyl chain length dependence may be useful for tuning polymerized TPE monolayer durability for specific applications.

14.
Int J Legal Med ; 137(5): 1327-1335, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37264192

RESUMEN

In forensic investigations, age estimation is vital for determining whether a suspect is under or over the legally defined adult age. With breakthroughs in RNA sequencing technology, small noncoding RNAs have provided new ways to solve problems related to the age estimation of trace or aged samples, owing to their small molecular weight and better stability. In our previous study, we had applied miRNAs for the age estimation of bloodstains; however, further improvement of the existing model is needed. PIWI-interacting RNAs (PiRNAs), which are 24-32 nt noncoding small RNA molecules involved in the PIWI-piRNA pathway, play an important role in the aging process. In this study, we explored the possibility of simultaneously analyzing piRNAs and miRNAs for better age estimation purpose. Through massively parallel sequencing, five age-related piRNAs were identified in blood samples that had been stored for eight years. Further real-time PCR analysis revealed that two piRNAs (piR-000753 and piR-020548) showed relatively higher efficiency in age estimation. Additionally, two age-related miRNAs (miR-324-3p and miR-330-5p) were used to build the estimation model. Among all algorithms tested, gradient boosting showed the lowest mean absolute error (MAE) and root mean square error (RMSE) values (3.171 and 4.403 years, respectively) for the validation dataset (n = 110). The errors of the model were less than 5 years and 10 years for 81.82% and 96.36% of the samples, respectively. The results suggest that the combined use of piRNA and miRNA markers may increase the accuracy of age estimation, and our new model has great potential for application in forensic casework.


Asunto(s)
Manchas de Sangre , MicroARNs , ARN Pequeño no Traducido , Humanos , Adulto , Anciano , Niño , MicroARNs/genética , ARN de Interacción con Piwi , ARN Interferente Pequeño/genética
15.
Bioorg Chem ; 141: 106908, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37827016

RESUMEN

Lysosome-targeting chimeras (LYTACs) have emerged as a promising technique to extend the scope of targeted protein degradation to extracellular proteins, e.g., secreted proteins and membrane-anchored proteins. However, up to now, only a small number of lysosomal targeting receptors (LTRs), such as cation-independent mannose 6-phosphate receptor (CI-M6PR) and asialoglycoprotein receptor (ASGPR), were reported to build LYTACs for degradation of extracellular proteins. Therefore, it is important to explore more functionalized ligands for the relevant LTRs to expand the LYTAC framework. Herein, we demonstrate a new LTR ligand-glucagon like peptide 1 (GLP-1) based targeted degradation platform, termed GLP-1 receptor-targeting chimeras (GLP-1-LYTAC). GLP-1-LYTACs are formed by conjugating GLP-1 with targeted binder (such as antibody) through Click Chemistry, showing efficiently lysosomal degradation of both extracellular proteins (GFP and Neutravidin) as well as cell membrane proteins (EGFR and PD-L1). We believe that this novel GLP-1-LYTAC will open up a new dimension for targeted protein breakdown.


Asunto(s)
Péptido 1 Similar al Glucagón , Proteolisis
16.
Sensors (Basel) ; 23(5)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36904913

RESUMEN

A wireless channel digital twin is a useful tool to evaluate the performance of a communication system at the physical or link level by generating the physical channel controllably. In this paper, a stochastic general fading channel model is proposed, which considered most of the channel fading types for various communication scenarios. By using the sum-of-frequency-modulation (SoFM) method, the phase discontinuity of the generated channel fading was well addressed. On this basis, a general and flexible generation architecture for channel fading was developed on a field programmable gate array (FPGA) platform. In this architecture, improved CORDIC-based hardware circuits for the trigonometric function, exponential function, and natural logarithm were designed and implemented, which improved the real-time performance of the system and the utilization rate of the hardware resources compared with the traditional LUT and CORDIC method. For a 16-bit fixed-point data bit width single-channel emulation, the hardware resource consumption was significantly reduced from 36.56% to 15.62% for the overall system by utilizing the compact time-division (TD) structure. Moreover, the classical CORDIC method brought an extra latency of 16 system clock cycles, while the latency caused by the improved CORDIC method was decreased by 62.5%. Finally, a generation scheme of a correlated Gaussian sequence was developed to introduce a controllable arbitrary space-time correlation for the channel generator with multiple channels. The output results of the developed generator were consistent with the theoretical results, which verified the correctness of both the generation method and hardware implementation. The proposed channel fading generator can be applied for the emulation of large-scale multiple-input, multiple-output (MIMO) channels under various dynamic communication scenarios.

17.
Heart Lung Circ ; 32(7): 852-869, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37230806

RESUMEN

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide and the primary underlying risk factor for heart failure. Despite decades of research and clinical trials, there are no drugs currently available to prevent organ damage from acute ischaemic injuries of the heart. In order to address the increasing global burden of heart failure, drug, gene, and cell-based regeneration technologies are advancing into clinical testing. In this review we highlight the burden of disease associated with AMI and the therapeutic landscape based on market analyses. New studies revealing the role of acid-sensitive cardiac ion channels and other proton-gated ion channels in cardiac ischaemia are providing renewed interest in pre- and post-conditioning agents with novel mechanisms of action that may also have implications for gene- and cell-based therapeutics. Furthermore, we present guidelines that couple new cell technologies and data resources with traditional animal modelling pipelines to help de-risk drug candidates aimed at treating AMI. We propose that improved preclinical pipelines and increased investment in drug target identification for AMI is critical to stem the increasing global health burden of heart failure.


Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Animales , Daño por Reperfusión Miocárdica/prevención & control , Infarto del Miocardio/tratamiento farmacológico , Corazón , Insuficiencia Cardíaca/prevención & control
18.
Molecules ; 28(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37446692

RESUMEN

Heavy metal pollution caused by industrial wastewater such as mining and metallurgical wastewater is a major global concern. Therefore, this study used modified lignite as a low-cost adsorbent for heavy metal ions. Pingzhuang lignite was dissolved and modified using Fusarium lignite B3 to prepare a biotransformed-lignite adsorbent (BLA). The O, H, and N contents of the BLA increased after transformation, and the specific surface area increased from 1.81 to 5.66 m2·g-1. Various adsorption properties were investigated using an aqueous solution of Cu(Ⅱ). The kinetic and isothermal data were well-fitted by pseudo-second-order and Langmuir models, respectively. The Langmuir model showed that the theoretical Cu(II) adsorption capacity was 71.47 mg·g-1. Moreover, large particles and a neutral pH were favorable for the adsorption of heavy metal ions. The adsorption capacities of raw lignite and BLA were compared for various ions. Microbial transformation greatly improved the adsorption capacity, and the BLA had good adsorption and passivation effects with Cu(II), Mn(II), Cd(II), and Hg(II). Investigation of the structural properties showed that the porosity and specific surface area increased after biotransformation, and there were more active groups such as -COOH, Ar-OH, and R-OH, which were involved in the adsorption performance.


Asunto(s)
Mercurio , Metales Pesados , Contaminantes Químicos del Agua , Carbón Mineral , Aguas Residuales , Metales Pesados/análisis , Agua , Iones , Adsorción , Cinética , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno
19.
BMC Cancer ; 22(1): 373, 2022 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-35395756

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) modulate gene expression in various malignancies. However, their roles in the occurrence of bladder cancer (BC) and their underlying mechanisms of action are currently unclear. METHODS: We measured levels of the circRNA phenylalanyl-tRNA synthetase subunit alpha (circFARSA) and target microRNAs (miRNAs/miRs) in BC tissues and cell lines using quantitative polymerase chain reactions. The functions of circFARSA in tumor formation were examined in mice with BC xenografts in vivo and in BC cells via determination of their proliferation, activity, apoptosis, metastasis, and invasion in vitro using cell counting kit-8 assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, western blotting, Transwell assays, and cell wound healing assays. Interactions between miR-330 and circFARSA were predicted and confirmed by bioinformatic processing and dual-luciferase reporter gene assays, respectively. Expression profiles of miR-330 targets in BC cells were assessed via western blotting. RESULTS: circFARSA expression was markedly upregulated in BC tissues and cell lines compared with that in normal bladder samples. Silencing circFARSA expression decreased BC cell proliferation, invasion, and migration but induced their apoptosis in vitro. Downregulating circFARSA expression slowed tumor growth in vivo and directly sponged miR-330 and inhibited its function in BC cells in vitro. Inhibiting miR-330 expression abolished the regulatory effects of circFARSA silencing on the tumor phenotypes of BC cells. CONCLUSIONS: circFARSA expression is upregulated and exerts oncogenic functions in BC by sponging miR-330.


Asunto(s)
MicroARNs , ARN Circular , Neoplasias de la Vejiga Urinaria , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , MicroARNs/genética , Fenotipo , ARN Circular/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología
20.
BMC Cancer ; 22(1): 741, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35799161

RESUMEN

BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces neutropenia events and is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small-cell lung cancer (NSCLC) patients following postoperative chemotherapy are not clear. METHODS: A retrospective cohort study was performed on NSCLC patients who underwent complete surgical resection and postoperative systemic chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed with other confounding factors using Cox regression analyses. RESULTS: We identified 307 NSCLC patients who received postoperative systemic chemotherapy (n = 246 in the rhG-CSF group, n = 61 in the No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than in patients without rhG-CSF treatment (48.3% vs. 27.9%, p < 0.05). Univariate regression analysis revealed that rhG-CSF and pathological stage were independent risk factors for metastasis-free survival (MFS) (p < 0.05). RhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31-4.15) than nonusers of rhG-CSF. The association between rhG-CSF and the risk of DOM was significant only in patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86-6.02) and not in patients without myelosuppression (HR: 0.71, 95% CI: 0.17-2.94, Interaction p-value< 0.01). The risk increased with higher dose density of rhG-CSF compared to rhG-CSF versus no users (p for trend< 0.001). CONCLUSION: These analyses indicate that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Factor Estimulante de Colonias de Granulocitos , Neoplasias Pulmonares , Metástasis de la Neoplasia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Proteínas Recombinantes/efectos adversos , Estudios Retrospectivos
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