Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 226
Filtrar
1.
Eur J Med Chem ; 273: 116490, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38772136

RESUMO

Parkinson's disease profoundly compromises patients' daily lives, and the disassembly of α-synuclein aggregates, a primary pathological factor, represents a promising therapeutic approach. In this study, we conducted a systematic screening and optimization process to identify the novel scaffold B37, a 4-triazolyl-phenylamine derivative, exhibiting a potent disassembly activity of 1.1 µM against α-synuclein preformed fibrils. Notably, B37 demonstrated significant neuroprotective effects, ameliorated autophagic dysfunction induced by preformed fibrils, mitigated oxidative stress, and restored the co-localization of preformed fibrils with lysosomes. Transmission electron microscopy corroborated its in vitro disassembly function. Pharmacokinetic profiling revealed favorable parameters with a receptible blood-brain barrier permeability. B37 emerges as a promising lead compound for further optimization, aiming to develop a highly effective agent targeting the disassembly of α-synuclein aggregates to treat neurodegenerative diseases like Parkinson's disease.

2.
Small Methods ; : e2301610, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693080

RESUMO

Single impurities in insulators are now often used for quantum sensors and single photon sources, while nanoscale semiconductor doping features are being constructed for electrical contacts in quantum technology devices, implying that new methods for sensitive, non-destructive imaging of single- or few-atom structures are needed. X-ray fluorescence (XRF) can provide nanoscale imaging with chemical specificity, and features comprising as few as 100 000 atoms have been detected without any need for specialized or destructive sample preparation. Presently, the ultimate limits of sensitivity of XRF are unknown - here, gallium dopants in silicon are investigated using a high brilliance, synchrotron source collimated to a small spot. It is demonstrated that with a single-pixel integration time of 1 s, the sensitivity is sufficient to identify a single isolated feature of only 3000 Ga impurities (a mass of just 350 zg). With increased integration (25 s), 650 impurities can be detected. The results are quantified using a calibration sample consisting of precisely controlled numbers of implanted atoms in nanometer-sized structures. The results show that such features can now be mapped quantitatively when calibration samples are used, and suggest that, in the near future, planned upgrades to XRF facilities might achieve single-atom sensitivity.

3.
Commun Biol ; 7(1): 280, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38448784

RESUMO

X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.


Assuntos
Pesquisa , Tomografia Computadorizada por Raios X , Raios X , Radiografia , Imagem Óptica
4.
Orthop Surg ; 16(4): 930-942, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438157

RESUMO

OBJECTIVE: Dual-plate fixation was thought to be the gold standard for treating complicated bicondylar tibial plateau fractures, yet it was found to be hard to accommodate the posterior column in three-column fractures. Currently, column-specific fixation is becoming more and more recognized, but no comprehensive investigation has been performed to back it up. Therefore, the objective of this study was to validate the importance of posterior column fixation in the three-column tibial fractures by a finite element (FE) analysis and clinical study. METHODS: In FE analysis, three models were developed: the longitudinal triple-plate group (LTPG), the oblique triple-plate group (OTPG), and the dual-plate group (DPG). Three loading scenarios were simulated. The distribution of the displacement and the equivalent von Mises stress (VMS) in each structure was calculated. The comparative measurements including the maximum posterior column collapse (MPCC), the maximum total displacement of the model (MTD), the maximum VMS of cortical posterior column (MPC-VMS), and the maximum VMS located on each group of plates and screws (MPS-VMS). The clinical study evaluated the indicators between the groups with or without the posterior plate, including operation time, blood loss volume, full-weight bearing period, Hospital for Special Surgery Knee Scoring system (HSS), Rasmussen score, and common postoperative complications. RESULTS: In the FE analysis, the MPCC, the MPC-VMS, and the MTD were detected in much lower amounts in LTPG and OTPG than in DPG. In comparison with DPG, the LTPG and OTPG had larger MPS-VMS. In the clinical study, 35 cases were included. In the triple-plate (14) and dual-plate (21) groups, the operation took 115.6 min and 100.5 min (p < 0.05), respectively. Blood loss in both groups was 287.0 mL and 206.6 mL (p < 0.05), and the full-weight bearing period was 14.5 weeks and 16.2 weeks (p < 0.05). At the final follow-up, the HSS score was 85.0 in the triple-plate group and 77.5 in the dual-plate (p < 0.05), the Rasmussen score was 24.1 and 21.6 (p < 0.05), there were two cases with reduction loss (9.5%) in the dual-plate group and one case of superficial incision infection found in the triple-plate group. CONCLUSION: The posterior implant was beneficial in optimizing the biomechanical stability and functional outcomes in the three-column tibial plateau fractures.


Assuntos
Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Análise de Elementos Finitos , Fixação Interna de Fraturas , Fraturas da Tíbia/cirurgia , Placas Ósseas
5.
Endokrynol Pol ; 75(1): 61-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497391

RESUMO

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients. MATERIAL AND METHODS: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways. RESULTS: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy. CONCLUSIONS: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.


Assuntos
Diabetes Gestacional , Feminino , Humanos , Gravidez , Autofagia , Proteína Beclina-1 , Diabetes Gestacional/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Nanoscale ; 16(11): 5760-5767, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38412012

RESUMO

Magnetic nanomaterials are sought to provide new functionalities for applications ranging from information processing and storage to energy generation and biomedical imaging. MXenes are a rapidly growing family of two-dimensional transition metal carbides and nitrides with versatile chemical and structural diversity, resulting in a variety of interesting electronic and optical properties. However, strategies for producing MXenes with tailored magnetic responses remain underdeveloped and challenging. Herein, we incorporate elemental Ni and Co into Ti3C2Tx MXene by mixing with dilute metal chloride solutions. We achieve a uniform distribution of Ni and Co, confirmed by X-ray fluorescence (XRF) mapping with nanometer resolution, with Ni and Co concentrations of approximately 2 and 7 at% relative to the Ti concentration. The magnetic susceptibility of these Ni- and Co-incorporated Ti3C2Tx MXenes is one to two orders of magnitude larger than pristine Ti3C2Tx, illustrating the potential for dilute metal incorporation to enhance linear magnetic responses at room temperature.

7.
Bioorg Med Chem ; 99: 117608, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271867

RESUMO

Tropomyosin receptor kinases (TRKs), the superfamily of transmembrane receptor tyrosine kinases, have recently become an attractive method for precision anticancer therapies since the approval of Larotrectinib and Entrectinib by FDA. Herein, we reported the discovery of a series of novel indazolylaminoquinazoline and indazolylaminoindazole as TRK inhibitors. The representative compound 30f exhibited good inhibitory activity against TRKWT, TRKG595R and TRKG667C with IC50 values of 0.55 nM, 25.1 nM and 5.4 nM, respectively. The compound also demonstrated potent superior to Larotrectinib antiproliferative activity against a panel of Ba/F3 cell lines transformed with both NTRK wild type and mutant fusions (IC50 = 10-200 nM). In addition, compound 30f exhibited good in vitro metabolic stability (T1/2 = 73.0 min), indicating that the quinazoline derivatives may have better metabolic stability. Finally, the binding mode of compound 30f predicted by molecular docking well explained the good enzyme inhibitory activity of indazolylaminoquinazoline compounds as TRK inhibitor. Thus, compound 30f can be used as a promising lead molecule for further structural optimization.


Assuntos
Neoplasias , Humanos , Tropomiosina , Simulação de Acoplamento Molecular , Receptores Proteína Tirosina Quinases , Inibidores de Proteínas Quinases/farmacologia
8.
Injury ; 55(3): 111256, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38049367

RESUMO

PURPOSE: The objective of this study was to measure the morphological characteristics of inferior pole fracture of the patella (IPFP) and develop a practical classification system to determine the corresponding treatment protocols for different IPFPs with specific patterns. METHODS: A retrospective radiographic review was performed on a series of 71 patients with IPFP. The preoperative CT data were collected and measured using image processing software. The number of fragments, maximum fracture fragment anteroposterior length (MFFAL), maximum fracture fragment transverse length (MFFTL), fracture fragment coronal angle (FFCA), fracture fragment sagittal angle (FFSA), maximum fracture fragment height (MFFH) and maximum transverse sectional area (MTSA) were analysed. RESULTS: The mean number of fracture fragments was 3.8. The average MFFAL was 14.9 mm, the average MFFTL was 23.5 mm, the average FFCA was 92.1°, the average FFSA was 93.0°, the average MFFH was 13.6 mm, and the average MTSA was 299.3 mm2. A new classification system was introduced to describe the varied patterns of IPFP, summarized as (I) simple IPFP; (II) comminuted IPFP; (III) simple IPFP with simple patellar body fracture; and (IV) comminuted patellar fracture involving the inferior pole. With the four-type classification system, 12 type I, 22 type II, 21 type III, and 16 type IV lesions were observed, each with specific morphological characteristics. CONCLUSION: Most IPFPs exhibited a diversiform pattern, demonstrating that coverage fixation was likely needed. The four-type classification system might offer a valuable approach to help orthopaedic surgeons make individual treatment plans.


Assuntos
Fraturas Ósseas , Fraturas Cominutivas , Traumatismos do Joelho , Humanos , Fixação Interna de Fraturas/métodos , Patela/diagnóstico por imagem , Patela/cirurgia , Estudos Retrospectivos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Cominutivas/cirurgia , Tomografia , Computadores , Fios Ortopédicos
9.
Small ; 20(9): e2306716, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37863816

RESUMO

The interaction between catalyst and support plays an important role in electrocatalytic hydrogen evolution (HER), which may explain the improvement in performance by phase transition or structural remodeling. However, the intrinsic behavior of these catalysts (dynamic evolution of the interface under bias, structural/morphological transformation, stability) has not been clearly monitored, while the operando technology does well in capturing the dynamic changes in the reaction process in real time to determine the actual active site. In this paper, nitrogen-doped molybdenum atom-clusters on Ti3 C2 TX (MoACs /N-Ti3 C2 TX ) is used as a model catalyst to reveal the dynamic evolution of MoAcs on Ti3 C2 TX during the HER process. Operando X-ray absorption structure (XAS) theoretical calculation and in situ Raman spectroscopy showed that the Mo cluster structure evolves to a 6-coordinated monatomic Mo structure under working conditions, exposing more active sites and thus improving the catalytic performance. It shows excellent HER performance comparable to that of commercial Pt/C, including an overpotential of 60 mV at 10 mA cm-2 , a small Tafel slope (56 mV dec-1 ), and high activity and durability. This study provides a unique perspective for investigating the evolution of species, interfacial migration mechanisms, and sources of activity-enhancing compounds in the process of electroreduction.

10.
J Cell Mol Med ; 28(1): e18028, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37985436

RESUMO

Pathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)-mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)-induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague-Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II-induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II-induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II-induced Nur77 expression at the transcriptional level and promoted ubiquitination-mediated degradation of Nur77, leading to dissociation of the Nur77-LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1-AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77-LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1-AMPK pathway to protect against cardiac hypertrophy.


Assuntos
Proteínas Quinases Ativadas por AMP , Compostos Alílicos , Angiotensina II , Compostos de Bifenilo , Fenóis , Ratos , Animais , Angiotensina II/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo
11.
ESC Heart Fail ; 10(6): 3622-3636, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37798907

RESUMO

AIMS: Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. METHODS AND RESULTS: MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+ iNOS+ M1 macrophages and F4/80+ CD206+ M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose-dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis-related proteins cleaved caspase-3 and Bax but increased expression levels of Bcl-2. These effects were attributed to ITE-induced activation of AHR receptors, leading to the down-regulation of Akt and p70S6K phosphorylation. CONCLUSIONS: The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Ratos , Animais , Caspase 3 , Proteínas Quinases S6 Ribossômicas 70-kDa , Proteínas Proto-Oncogênicas c-akt , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/metabolismo , Remodelação Ventricular , Proteína X Associada a bcl-2 , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-37681834

RESUMO

Among the various thermal stress indices, apparent temperature (AT) is closely related to public health indicators, and consequently is widely used by weather agencies around the world. Therefore, in this paper we estimate the changes in AT and contributing components in Korea as a whole and in five major cities (Seoul, Gwanju, Daegu, Daejeon, and Busan) using national standard climate scenarios based on the coupled model inter-comparison project (CMIP6). In the present day, high AT occurs in major cities due to high temperature (TAS) and relative humidity (RH). Our findings reveal that even when TAS is relatively low, large AT occurs with higher humidity. Notably, in future warmer climate conditions, high AT may first appear in the five major cities and then extend to the surrounding areas. An increase in TAS and RH during the pre-hot season (March to June) may lead to earlier occurrence of thermal risks in future warmer climate conditions and more frequent occurrence of high thermal stress events. Our study can serve as a reference for future information on thermal risk changes in Korea. Considering those who have not adapted to high temperature environments, our findings imply that thermal risks will become more serious and that heat adaptation strategies will be needed during the pre-hot season under future warmer climate conditions.


Assuntos
Clima , Humanos , Umidade , Estações do Ano , Seul , Temperatura Alta
13.
Chaos ; 33(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37391880

RESUMO

With the development of information technology, more and more travel data have provided great convenience for scholars to study the travel behavior of users. Planning user travel has increasingly attracted researchers' attention due to its great theoretical significance and practical value. In this study, we not only consider the minimum fleet size required to meet the urban travel needs but also consider the travel time and distance of the fleet. Based on the above reasons, we propose a travel scheduling solution that comprehensively considers time and space costs, namely, the Spatial-Temporal Hopcroft-Karp (STHK) algorithm. The analysis results show that the STHK algorithm not only significantly reduces the off-load time and off-load distance of the fleet travel by as much as 81% and 58% and retains the heterogeneous characteristics of human travel behavior. Our study indicates that the new planning algorithm provides the size of the fleet to meet the needs of urban travel and reduces the extra travel time and distance, thereby reducing energy consumption and reducing carbon dioxide emissions. Concurrently, the travel planning results also conform to the basic characteristics of human travel and have important theoretical significance and practical application value.


Assuntos
Algoritmos , Viagem , Humanos
14.
Environ Sci Nano ; 10(7): 1768-1777, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37457049

RESUMO

Coal combustion byproducts are known to be enriched in arsenic (As) and selenium (Se). This enrichment is a concern during the handling, disposal, and reuse of the ash as both elements can be harmful to wildlife and humans if mobilized into water and soils. The leaching potential and bioaccessibility of As and Se in coal fly ash depends on the chemical forms of these elements and their association with the large variety of particles that comprise coal fly ash. The overall goal of this research was to determine nanoscale and microscale solid phase mineral associations and oxidation states of As and Se in fly ash. We utilized nanoscale 2D imaging (30-50 nm spot size) with the Hard X-ray Nanoprobe (HXN) in combination with microprobe X-ray capabilities (∼5 µm resolution) to determine the As and Se elemental associations. Speciation of As and Se was also measured at the nano- to microscale with X-ray absorption spectroscopy. The enhanced resolution of HXN showed As and Se as either diffusely located around or comingled with Ca- and Fe-rich particles. The results also showed nanoparticles of Se attached to the surface of fly ash grains. Overall, a comparison of As and Se species across scales highlights the heterogeneity and complexity of chemical associations for these trace elements of concern in coal fly ash.

15.
Life Sci ; 329: 121936, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37453576

RESUMO

Retinoid X receptor (RXR), particularly RXRα, has been implicated in cardiovascular diseases. However, the functional role of RXR activation in myocardial infarction (MI) remains unclear. This study aimed to determine the effects of RXR agonists on MI and to dissect the underlying mechanisms. Sprague-Dawley (SD) rats were subjected to MI and then treated (once daily for 4 weeks) with either RXR agonist bexarotene (10 or 30 mg/kg body weight) or vehicle. Heart function was determined using echocardiography and cardiac hemodynamic measurements. Four weeks post MI, myocardial tissues were collected to evaluate cardiac remodeling. Primary cardiac fibroblasts (CFs) were treated with or without RXR ligand 9-cis-RA followed by stimulation with TGF-ß1. Immunoblot, immunofluorescence, and co-immunoprecipitation were performed to elucidate the regulatory role of RXR agonists in TGF-ß1/Smad signaling. In vivo treatment with Bexarotene moderately affects systemic inflammation and apoptosis and ameliorated left ventricular dysfunction after MI in rat model. In contrast, bexarotene significantly inhibited post-MI myocardial fibrosis. Immunoblot analysis of heart tissue homogenates from MI rats revealed that bexarotene regulated the activation of the TGF-ß1/Smad signaling pathway. In vitro, 9-cis-RA inhibited the TGF-ß1-induced proliferation and collagen production of CFs. Importantly, upon activation by 9-cis-RA, RXRα interacted with p-Smad2 in cytoplasm, inhibiting the TGF-ß1-induced nuclear translocation of p-Smad2, thereby negatively regulating TGF-ß1/Smad signaling and attenuating the fibrotic response of CFs. These findings suggest that RXR agonists ameliorate post-infarction myocardial fibrosis, maladaptive remodeling, and heart dysfunction via attenuation of fibrotic response in CFs through inhibition of the TGF-ß1/Smad pathway activation.


Assuntos
Cardiomiopatias , Infarto do Miocárdio , Ratos , Animais , Ratos Sprague-Dawley , Receptores X de Retinoides , Bexaroteno/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Remodelação Ventricular , Infarto do Miocárdio/metabolismo , Cardiomiopatias/patologia , Fibroblastos/metabolismo , Fibrose , Miocárdio/metabolismo
16.
Sci Rep ; 13(1): 7271, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142634

RESUMO

X-ray fluorescence mapping (XRF) is a highly efficient and non-invasive technique for quantifying material composition with micro and nanoscale spatial resolutions. Quantitative XRF analysis, however, confronts challenges from the long-lasting problem called self-absorption. Moreover, correcting two-dimensional XRF mapping datasets is particularly difficult because it is an ill-posed inverse problem. Here we report a semi-empirical method that can effectively correct 2D XRF mapping data. The correction error is generally less than 10% from a comprehensive evaluation of the accuracy in various configurations. The proposed method was applied to quantify the composition distribution around the grain boundaries in an electrochemically corroded stainless steel sample. Highly localized Cr enrichment was found around the crack sites, which was invisible before the absorption correction.

17.
Dalton Trans ; 52(18): 6029-6040, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37042629

RESUMO

To develop the next-generation metal agents for efficiently inhibiting tumor growth, we synthesized a series of new Zn(II) complexes (C1-C5) derived from 2-pyridinecarboxaldehyde thiosemicarbazone and investigated their structure-activity relationships. C5 bearing two methyl groups at the N-4 position of the ligand exerted the strongest inhibition effect among all the Zn(II) complexes. Importantly, C5 exerted an effective inhibitory effect on tumor growth and produced few side effects in vivo. We further confirmed the antitumor mechanisms of C5, including arresting the cell cycle at the S phase, inducing apoptosis, inducing lethal autophagy, and suppressing angiogenesis.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Tiossemicarbazonas , Humanos , Tiossemicarbazonas/farmacologia , Zinco/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
18.
Sci Transl Med ; 15(691): eabl9344, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37043558

RESUMO

Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural optimization resulted in profound antiviral activity. The lead quinazolinone, BDGR-49, potently reduced cellular VEEV and EEEV titers by >7 log at 1 µM and exhibited suitable intravenous and oral pharmacokinetic profiles in BALB/c mice to achieve excellent brain exposure. Outstanding in vivo efficacy was observed in several lethal, subcutaneous infection mouse models using an 8-day dosing regimen. Prophylactically administered BDGR-49 at 25 mg kg-1 per day fully protected against a 10× LD50 VEEV Trinidad donkey (TrD) challenge in BALB/c mice. Similarly, we observed 70% protection when 10× LD50 EEEV FL93-939-infected C57BL/6 mice were treated prophylactically with BDGR-49 at 50 mg kg-1 per day. Last, we observed 100% therapeutic efficacy when mice, challenged with 10× LD50 VEEV TrD, were dosed at 48 hours after infection with BDGR-49 at 25 mg kg-1 per day. Mouse brain viral titers at 96 hours after infection were reduced to values near the limit of detection. Collectively, these results underscore the substantial development potential of a well-tolerated, brain-penetrant lead compound that shows promise in preventing and treating encephalitic alphavirus disease.


Assuntos
Vírus da Encefalite Equina Venezuelana , Encefalomielite Equina do Leste , Humanos , Cavalos , Animais , Camundongos , Estados Unidos , Antivirais/farmacologia , Antivirais/uso terapêutico , Camundongos Endogâmicos C57BL , Encéfalo
19.
Artigo em Inglês | MEDLINE | ID: mdl-36877665

RESUMO

Osteoid osteoma (OO) is a benign osteoblastic bone tumor typically involving the diaphysis or metaphysis in long tubular bones. OO in phalanges of the great toe has been rarely reported, and it is often challenging to differentiate with subacute osteomyelitis, bone abscess, or osteoblastoma. This case report describes an uncommon case of a 13-year-old female patient with subperiosteal OO in the proximal phalanx of the great toe. The atypical location of OO should be familiarized to include appropriate differential diagnosis and to ensure accurate diagnosis by radiologic evaluations. Surgical excision remains the benchmark for the treatment of OO with its advantages on direct visualization and histologic confirmation for the diagnosis.


Assuntos
Neoplasias Ósseas , Falanges dos Dedos da Mão , Hallux , Osteoma Osteoide , Osteomielite , Neoplasias de Tecidos Moles , Feminino , Humanos , Adolescente , Osteoma Osteoide/diagnóstico por imagem , Osteoma Osteoide/cirurgia , Hallux/diagnóstico por imagem , Hallux/cirurgia , Diáfises , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia
20.
Mol Med Rep ; 27(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36453210

RESUMO

Following the publication of the above article, an interested reader drew to the authors' attention that Fig. 4A on p. 921, showing the results from cell migration assay experiments, featured a pair of duplicated data panels. After having consulted their original data, the authors have realized that Fig. 3A on the same page, showing the fluorometric images of apoptotic cells, also contained a pair of duplicated data panels. These errors in the presentation of these figures arose inadvertently as a consequence of selecting the wrong images for the 'RA NC' data panel in Fig. 3A and the NOR-FLS data panel in Fig. 5E. The revised versions of Figs. 3 and 4 are shown on the next two pages. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 11: 917­923, 2015; DOI: 10.3892/mmr.2014.2770].

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA