Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(51): e2314264120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38100418

RESUMO

The separator with high Young's modulus can avoid the danger of large-sized dendrites, but regulating the chemical behavior of lithium (Li) at the separator/anode interface can effectively eliminate the dendrite issue. Herein, a polyimine aerogel (PIA) with accurate nitrogen (N) functional design is used as the functional separator in Li metal batteries to promote uniform Li nucleation and suppress the dendrite growth. Specifically, the imine (N1) and protonated tertiary amine (N2) sites in the molecular structure of the PIA are significantly different in electron cloud density (ECD) distribution. The N1 site with higher ECD and the N2 site with lower ECD tend to attract and repulse Li+ through electrostatic interactions, respectively. This synergy effect of the PIA separator accelerates the interfacial Li+ diffusion on the Li anode to sustain a uniform two-dimensional Li nucleation behavior. Meanwhile, the well-defined nanochannels of the PIA separator show high affinity to electrolyte and bring uniform Li+ flux for Li plating/stripping. Consequently, the dendrites are effectively suppressed by the PIA separator in routine carbonate electrolyte, and the Li metal batteries with the PIA separator exhibit high Coulombic efficiency and stable high-rate cycling. These findings demonstrate that the ingenious marriage of special chemical structure designs and hierarchical pores can enable the separator to affect the interfacial Li nucleation behavior.

2.
Chem Soc Rev ; 53(14): 7489-7530, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38894663

RESUMO

Global population growth and industrialization have exacerbated the nonrenewable energy crises and environmental issues, thereby stimulating an enormous demand for producing environmentally friendly materials. Typically, biomass-based aerogels (BAs), which are mainly composed of biomass materials, show great application prospects in various fields because of their exceptional properties such as biocompatibility, degradability, and renewability. To improve the performance of BAs to meet the usage requirements of different scenarios, a large number of innovative works in the past few decades have emphasized the importance of micro-structural design in regulating macroscopic functions. Inspired by the ubiquitous random or regularly arranged structures of materials in nature ranging from micro to meso and macro scales, constructing different microstructures often corresponds to completely different functions even with similar biomolecular compositions. This review focuses on the preparation process, design concepts, regulation methods, and the synergistic combination of chemical compositions and microstructures of BAs with different porous structures from the perspective of gel skeleton and pore structure. It not only comprehensively introduces the effect of various microstructures on the physical properties of BAs, but also analyzes their potential applications in the corresponding fields of thermal management, water treatment, atmospheric water harvesting, CO2 absorption, energy storage and conversion, electromagnetic interference (EMI) shielding, biological applications, etc. Finally, we provide our perspectives regarding the challenges and future opportunities of BAs. Overall, our goal is to provide researchers with a thorough understanding of the relationship between the microstructures and properties of BAs, supported by a comprehensive analysis of the available data.

3.
BMC Cancer ; 24(1): 276, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424484

RESUMO

BACKGROUND: Adenosine monophosphate-activated protein kinase (AMPK) is associated with the development of liver hepatocellular carcinoma (LIHC). AMPKα2, an α2 subunit of AMPK, is encoded by PRKAA2, and functions as the catalytic core of AMPK. However, the role of AMPKα2 in the LIHC tumor immune environment is unclear. METHODS: RNA-seq data were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression databases. Using the single-cell RNA-sequencing dataset for LIHC obtained from the China National Genebank Database, the communication between malignant cells and T cells in response to different PRKAA2 expression patterns was evaluated. In addition, the association between PRKAA2 expression and T-cell evolution during tumor progression was explored using Pseudotime analysis, and the role of PRKAA2 in metabolic reprogramming was explored using the R "scMetabolis" package. Functional experiments were performed in LIHC HepG2 cells. RESULTS: AMPK subunits were expressed in tissue-specific and substrate-specific patterns. PRKAA2 was highly expressed in LIHC tissues and was associated with poor patient prognosis. Tumors with high PRKAA2 expression displayed an immune cold phenotype. High PRKAA2 expression significantly promoted LIHC immune escape. This result is supported by the following evidence: 1) the inhibition of major histocompatibility complex class I (MHC-I) expression through the regulation of interferon-gamma activity in malignant cells; 2) the promotion of CD8+ T-cell exhaustion and the formation of CD4+ Treg cells in T cells; 3) altered interactions between malignant cells and T cells in the tumor immune environment; and 4) induction of metabolic reprogramming in malignant cells. CONCLUSIONS: Our study indicate that PRKAA2 may contribute to LIHC progression by promoting metabolic reprogramming and tumor immune escape through theoretical analysis, which offers a theoretical foundation for developing PRKAA2-based strategies for personalized LIHC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Quinases Ativadas por AMP , Carcinoma Hepatocelular/genética , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Neoplasias Hepáticas/genética , Exaustão das Células T , Linfócitos T Reguladores , Evasão Tumoral
4.
BMC Neurol ; 24(1): 134, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641592

RESUMO

BACKGROUND: Although contrast extravasation on follow-up head computed tomography (CT) is frequently visualized after endovascular treatment, this phenomenon is rare after intravenous thrombolytic treatment in patients with acute ischemic stroke (AIS). Here, we report a case of contrast extravasation mimicking intracerebral hemorrhage (ICH) with intraventricular extension after intravenous thrombolytic treatment and computed tomography angiography (CTA). CASE PRESENTATION: A 52-year-old man presented with right-sided hemiparesis and hypoesthesia. Initial non-contrast head CT was negative for intracranial hemorrhage and acute ischemic changes. He received intravenous treatment with tenecteplase 3.8 h after the onset of stroke. CTA of the head and neck was performed at 4.3 h after stroke onset. It showed no stenosis or occlusion of the carotid and major intracranial arteries. At about 1.5 h after CTA, the right-sided hemiparesis deteriorated, accompanied by drowsiness, aphasia, and urinary incontinence. Immediate head CT showed hyperdense lesions with mild space-occupying effect in the left basal ganglia and both lateral ventricles. The hyperdense lesions were reduced in size on follow-up CT after 5 h. Two days later, CT showed that the hyperdense lesions in the lateral ventricles almost completely disappeared and only a small amount remained in the infarcted area. CONCLUSIONS: Contrast extravasation into the brain tissue and lateral ventricles, mimicking ICH with intraventricular extension, could occur after intravenous thrombolytic treatment and CTA in a patient with AIS, which might lead to misdiagnosis and wrong treatment of the patient. The rapid resolution of intracranial hyperdense lesions is key to differentiate contrast extravasation from ICH on serial non-enhanced CT.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , AVC Isquêmico/tratamento farmacológico , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/diagnóstico por imagem , Fibrinolíticos/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Extravasamento de Materiais Terapêuticos e Diagnósticos/tratamento farmacológico , Paresia
5.
Angew Chem Int Ed Engl ; 63(29): e202403391, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38717757

RESUMO

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

6.
Angew Chem Int Ed Engl ; : e202410127, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39030819

RESUMO

Polyrotaxanes (PRs) have attracted significant research attention due to their unique topological structures and high degrees of conformational freedom. Herein, we take advantage of an oligo[2]rotaxane to  construct a novel class of dynamically cross-linked rotaxane network (DCRN) mediated by metal-coordination. The oligo[2]rotaxane skeleton offers several distinct advantages: In addition to retaining the merits of traditional polymer backbones, the ordered intramolecular motion of the [2]rotaxane motifs introduced dangling chains into the network, thereby enhancing the stretchability of the DCRN. Additionally, the dissociation of host‒guest recognition and subsequent sliding motion, along with the breakage of metal-coordination interactions, represented an integrated energy dissipation pathway to enhance mechanical properties. Moreover, the resulting DCRN demonstrated responsiveness to multiple stimuli and displayed exceptional self-healing capabilities in a gel state. Upon exposure to PPh3, which induced network deconstruction by breaking the coordinated cross-linking points, the oligo[2]rotaxane could be recovered, showcasing good recyclability. These findings demonstrate the untapped potential of the oligo[2]rotaxane as a polymer skeleton to develop DCRN and open the door to extend their advanced applications in intelligent mechanically interlocked materials.

7.
Angew Chem Int Ed Engl ; : e202409705, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39072904

RESUMO

Adhesives have been widely used to splice and repair materials to meet practical needs of humanity for thousands of years. However, developing robust adhesives with balanced adhesive and cohesive properties still remains a challenging task. Herein, we report the design and preparation of a robust mechanically interlocked [an]daisy chain network (DCMIN) adhesive by orthogonal integration of mechanical bond and 2-ureido-4[1H]-pyrimidone (UPy) H-bonding in a single system. Specifically, the UPy moiety plays dual roles: cross-linking for network formation and multivalent interactions with substrate for strong interfacial bonding. Mechanically interlocked [an]daisy chain, serving as the polymeric backbone of the adhesive, is able to effectively alleviate applied stress and uphold network integrity through synergistic intramolecular motions and thus significantly improve the cohesive performance. Therefore, comparative analyses with the control made of the same quadruple H-bonding network but with non-interlocked [an]daisy chain backbones demonstrate that our DCMIN possesses superior adhesion properties over a wide temperature range. These findings not only contribute to a deep understanding of the structure-property relationships between microscopic mechanical bond motions and macroscopic adhesive properties but also provide a valuable guidance for optimizing design principles of robust adhesives.

9.
Micromachines (Basel) ; 15(5)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38793217

RESUMO

In this article, we demonstrate a high-energy, wide-spectrum, spatiotemporal mode-locked (STML) fiber laser. Unlike traditional single-mode fiber lasers, STML fiber lasers theoretically enable mode-locking with various combinations of transverse modes. The laser can deliver two different STML pulse sequences with different pulse widths, spectra and beam profiles, due to the different compositions of transverse modes in the output pulses. Moreover, we achieve a wide-spectrum pulsed output with a single-pulse energy of up to 116 nJ, by weakening the spectral filtering and utilizing self-cleaning. Strong spatial and spectral filtering are usually thought to be necessary for achieving STML. Our experiment verifies the necessity of spatial filtering for achieving STML, and we show that weakening unnecessary spectral filtering provides an effective way to increase the pulse energy and spectrum width of mode-locked fiber lasers.

10.
Polymers (Basel) ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732663

RESUMO

The research used polyethersulfone (PES) as a membrane material, polyvinylpyrrolidone (PVP) k30 and polyethylene glycol 400 (PEG 400) as water-soluble additives, and dimethylacetamide (DMAc) as a solvent to prepare hollow-fiber ultrafiltration membranes through a nonsolvent-induced phase separation (NIPS) process. The hydrophilic nature of PVP-k30 and PEG caused them to accumulate on the membrane surface during phase separation. The morphology, chemical composition, surface charge, and pore size of the PES membranes were evaluated by SEM, FTIR, zeta potential, and dextran filtration experiments. The paper also investigated how different spinning solution compositions affected membrane morphology and performance. The separation efficiency of membranes with four different morphologies was tested in single-protein and double-protein mixed solutions. The protein separation effectiveness of the membrane was studied through molecular weight cutoff, zeta potential, and static protein adsorption tests. In addition, the operating pressure and pH value were adjusted to improve ultrafiltration process conditions. The PES membrane with an intact sponge-like structure showed the highest separation factor of 11, making it a prime candidate membrane for the separation of bovine serum albumin (BSA) and lysozyme (LYS). The membrane had a minimal static protein adsorption capacity of 48 mg/cm2 and had excellent anti-fouling properties. When pH = 4, the BSA retention rate was 93% and the LYS retention rate was 23%. Furthermore, it exhibited excellent stability over a pH range of 1-13, confirming its suitability for protein separation applications.

11.
J Orthop Surg Res ; 19(1): 31, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178210

RESUMO

BACKGROUND: Osteoarthritis is a prevalent degenerative joint condition typically found in individuals who are aged 50 years or older. In this study, the focus is on PIWI-interacting RNA (piRNA), which belongs to a category of small non-coding RNAs. These piRNAs play a role in the regulation of gene expression and the preservation of genomic stability. The main objective of this research is to examine the expression of a specific piRNA called hsa_piR_019949 in individuals with osteoarthritis, to understand its impact on chondrocyte metabolism within this condition. METHODS: We analyzed piRNA expression in osteoarthritis cartilage using the GEO database. To understand the impact of inflammatory factors on piRNA expression in chondrocytes, we conducted RT-qPCR experiments. We also investigated the effect of piRNA hsa_piR_019949 on chondrocyte proliferation using CCK-8 and clone formation assays. Furthermore, we assessed the influence of piRNA hsa_piR_019949 on chondrocyte apoptosis by conducting flow cytometry analysis. Additionally, we examined the differences in cartilage matrix composition through safranine O staining and explored the downstream regulatory mechanisms of piRNA using transcriptome sequencing. Lentiviral transfection of NEAT1 and NLRP3 was performed to regulate the metabolism of chondrocytes. RESULTS: Using RNA sequencing technology, we compared the gene expression profiles of 5 patients with osteoarthritis to 3 normal controls. We found a gene called hsa_piR_019949 that showed differential expression between the two groups. Specifically, hsa_piR_019949 was downregulated in chondrocytes when stimulated by IL-1ß, an inflammatory molecule. In further investigations, we discovered that overexpression of hsa_piR_019949 in vitro led to increased proliferation and synthesis of the extracellular matrix in chondrocytes, which are cells responsible for cartilage formation. Conversely, suppressing hsa_piR_019949 expression resulted in increased apoptosis (cell death) and degradation of the extracellular matrix in chondrocytes. Additionally, we found that the NOD-like receptor signaling pathway is linked to the low expression of hsa_piR_019949 in a specific chondrocyte cell line called C28/I2. Furthermore, we observed that hsa_piR_019949 can inhibit the expression of a long non-coding RNA called NEAT1 in chondrocytes. We hypothesize that NEAT1 may serve as a downstream target gene regulated by hsa_piR_019949, potentially influencing chondrocyte metabolism and function in the context of osteoarthritis. CONCLUSIONS: PiRNA hsa_piR_019949 has shown potential in promoting the proliferation of chondrocytes and facilitating the synthesis of extracellular matrix in individuals with osteoarthritis. This is achieved by inhibiting the expression of a long non-coding RNA called NEAT1. The implication is that by using hsa_piR_019949 mimics, which are synthetic versions of the piRNA, as a therapeutic approach, it may be possible to effectively treat osteoarthritis.


Assuntos
Osteoartrite , RNA Longo não Codificante , Humanos , Condrócitos/metabolismo , RNA de Interação com Piwi , RNA Longo não Codificante/metabolismo , Cartilagem/metabolismo , Apoptose/genética , Osteoartrite/genética , Osteoartrite/metabolismo
12.
BMJ Open ; 14(4): e079370, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670618

RESUMO

INTRODUCTION: Myocardial injury is a relatively common complication of traumatic brain injury (TBI). However, the incidence and clinical impact of myocardial injury characterised by elevated cardiac troponin (cTn) levels after TBI are still poorly known. The objective of our study is to assess the global incidence of myocardial injury characterised by elevated cTn in adult patients with TBI and its association with in-hospital mortality. METHODS AND ANALYSIS: The protocol of our systematic review and meta-analysis is performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. We will search the Medline, Embase, Cochrane Library, Scopus and Web of Science databases from inception to 1 January 2024, for observational studies in any language that reported the incidence of elevated cTn and/or in-hospital mortality associated with elevated cTn among adult patients with TBI. Two reviewers will independently assess study eligibility, extract the data and assess the risk of bias. ORs and 95% CIs will be used with a random-effects or fixed-effects model according to the estimated heterogeneity among studies assessed by the I2 index. We will perform a quantitative synthesis for the incidence of elevated cTn and in-hospital mortality data. If sufficient data are available, we will perform subgroup analysis and meta-regression to address the heterogeneity. In addition, we will perform a narrative analysis if quantitative synthesis is not appropriate. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. We intend to publish our findings in a high-quality, peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023454686.


Assuntos
Lesões Encefálicas Traumáticas , Mortalidade Hospitalar , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Humanos , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Incidência , Troponina/sangue , Troponina/metabolismo , Projetos de Pesquisa , Adulto
13.
Fundam Res ; 4(2): 300-306, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38933516

RESUMO

Mechanically interlocked polymers (MIPs) are promising candidates for the construction of elastomeric materials with desirable mechanical performance on account of their abilities to undergo inherent rotational and translational mechanical movements at the molecular level. However, the investigations on their mechanical properties are lagging far behind their structural fabrication, especially for linear polyrotaxanes in bulk. Herein, we report stretchable poly[2]rotaxane elastomers (PREs) which integrate numerous mechanical bonds in the polymeric backbone to boost macroscopic mechanical properties. Specifically, we have synthesized a hydroxy-functionalized [2]rotaxane that subsequently participates in the condensation polymerization with diisocyanate to form PREs. Benefitting from the peculiar structural and dynamic characteristics of the poly[2]rotaxane, the representative PRE exhibits favorable mechanical performance in terms of stretchability (∼1200%), Young's modulus (24.6 MPa), and toughness (49.5 MJ/m3). Moreover, we present our poly[2]rotaxanes as model systems to understand the relationship between mechanical bonds and macroscopic mechanical properties. It is concluded that the mechanical properties of our PREs are mainly determined by the unique topological architectures which possess a consecutive energy dissipation pathway including the dissociation of host-guest interaction and consequential sliding motion of the wheel along the axle in the [2]rotaxane motif.

14.
Biomater Res ; 28: 0043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011520

RESUMO

Acute liver failure (ALF) is a complex syndrome that impairs the liver's function to detoxify bilirubin, ammonia, and other toxic metabolites. Bioartificial liver (BAL) aims to help ALF patients to pass through the urgent period by temporarily undertaking the liver's detoxification functions and promoting the recovery of the injured liver. We genetically modified the hepatocellular cell line HepG2 by stably overexpressing genes encoding UGT1A1, OATP1B1, OTC, ARG1, and CPS1. The resulting SynHeps-II cell line, encapsulated by Cytopore microcarriers, dramatically reduced the serum levels of bilirubin and ammonia, as demonstrated both in vitro using patient plasma and in vivo using ALF animal models. More importantly, we have also completed the 3-dimensional (3D) culturing of cells to meet the demands for industrialized rapid and mass production, and subsequently assembled the plasma-cell contacting BAL (PCC-BAL) system to fulfill the requirements of preclinical experiments. Extracorporeal blood purification of ALF rabbits with SynHeps-II-embedded PCC-BAL saved more than 80% of the animals from rapid death. Mechanistically, SynHeps-II therapy ameliorated liver and brain inflammation caused by high levels of bilirubin and ammonia and promoted liver regeneration by modulating the nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Also, SynHeps-II treatment reduced cerebral infiltration of neutrophils, reduced reactive oxygen species (ROS) levels, and mitigated hepatic encephalopathy. Taken together, SynHeps-II cell-based BAL was promising for the treatment of ALF patients and warrants clinical trials.

15.
ACS Appl Mater Interfaces ; 16(21): 27794-27803, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38748448

RESUMO

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

16.
Cancer Lett ; 597: 217023, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38852701

RESUMO

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.


Assuntos
Benzamidas , Janus Quinase 2 , Pirimidinas , Receptor ErbB-2 , Receptor trkA , Neoplasias de Mama Triplo Negativas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Benzamidas/farmacologia , Animais , Feminino , Pirimidinas/farmacologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Linhagem Celular Tumoral , Receptor trkA/metabolismo , Receptor trkA/antagonistas & inibidores , Receptor trkA/genética , Camundongos , Proliferação de Células/efeitos dos fármacos , Indazóis/farmacologia , Pirazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Camundongos Nus , Sinergismo Farmacológico , Hidrocarbonetos Aromáticos com Pontes
17.
Acta Neuropathol Commun ; 12(1): 7, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212848

RESUMO

Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power field, which can mitigate subjective random errors in mitosis detection originating from individual detection errors. By depth-first search algorithm (1) , we analyzed 19 meningioma slides and discovered that the proposed algorithm upgraded two borderline cases verified at consensus conferences. This improvement is attributed to the algorithm's ability to quantify the mitotic count more comprehensively compared to other conventional methods of counting mitoses. In implementing a collaborative sphere (2) , we evaluated the correctness of mitosis detection from grouped pathologists and/or pathology residents, where each member of the group annotated a set of 48 high-power field images for mitotic figures independently. We report that groups with sizes of three can achieve an average precision of 0.897 and sensitivity of 0.699 in mitosis detection, which is higher than an average pathologist in this study (precision: 0.750, sensitivity: 0.667). The proposed computational strategy can be integrated with artificial intelligence workflow, which envisions the future of achieving a rapid and robust mitosis assessment by interactive assisting algorithms that can ultimately benefit patient management.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/patologia , Índice Mitótico/métodos , Inteligência Artificial , Mitose , Neoplasias Meníngeas/patologia
18.
Nanomaterials (Basel) ; 13(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38133031

RESUMO

Perovskites have been recognized as a class of promising materials for optoelectronic devices. We intentionally include excessive Cs+ cations in precursors in the synthesis of perovskite CsPbBr3 nanocrystals and investigate how the Cs+ cations influence the lattice strain in these perovskite nanocrystals. Upon light illumination, the lattice strain due to the addition of alkali metal Cs+ cations can be compensated by light-induced lattice expansion. When the Cs+ cation in precursors is about 10% excessive, the electron-phonon coupling strength can be reduced by about 70%, and the carrier cooling can be slowed down about 3.5 times in lead halide perovskite CsPbBr3 nanocrystals. This work reveals a new understanding of the role of Cs+ cations, which take the A-site in ABX3 perovskite and provide a new way to improve the performance of perovskites and their practical devices further.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa