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1.
Small ; 20(4): e2303638, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37731156

RESUMO

In the rapidly evolving field of thin-film electronics, the emergence of large-area flexible and wearable devices has been a significant milestone. Although organic semiconductor thin films, which can be manufactured through solution processing, have been identified, their utility is often undermined by their poor stability and low carrier mobility under ambient conditions. However, inorganic nanomaterials can be solution-processed and demonstrate outstanding intrinsic properties and structural stability. In particular, a series of two-dimensional (2D) nanosheet/nanoparticle materials have been shown to form stable colloids in their respective solvents. However, the integration of these 2D nanomaterials into continuous large-area thin with precise control of layer thickness and lattice orientation still remains a significant challenge. This review paper undertakes a detailed analysis of van der Waals thin films, derived from 2D materials, in the advancement of thin-film electronics and optoelectronic devices. The superior intrinsic properties and structural stability of inorganic nanomaterials are highlighted, which can be solution-processed and underscor the importance of solution-based processing, establishing it as a cornerstone strategy for scalable electronic and optoelectronic applications. A comprehensive exploration of the challenges and opportunities associated with the utilization of 2D materials for the next generation of thin-film electronics and optoelectronic devices is presented.

2.
J Magn Reson Imaging ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009385

RESUMO

BACKGROUND: Blood flow signals may be a confounder in quantifying T1 values of plaque or thrombus and how to realize black-blood T1 mapping remains a challenge task. PURPOSE: To develop a fast and three-dimensional black-blood T1 mapping technique for quantitative assessment of atherosclerosis and venous thrombosis. STUDY TYPE: Sequence development and optimization via phantoms and volunteers as well as pilot prospective. PHANTOM AND SUBJECTS: Numerical simulations, a standard phantom, 8 healthy volunteers (mean age, 22 ± 1 years; 5 males), and 19 patients (mean age, 57 ± 14 years; 13 males) with atherosclerosis or venous thrombosis. FIELD STRENGTH/SEQUENCE: 3T/inversion recovery spin-echo sequence (IR-SE), magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE), and black-blood prepared MP2RAGE (BB-MP2RAGE). ASSESSMENT: The black-blood preparation (i.e., delay alternating with nutation for tailored excitation, DANTE) was incorporated into MP2RAGE for black-blood T1 mapping. The BB-MP2RAGE was optimized numerically based on the Bloch equation, and then the phantom study was performed to verify the accuracy of T1 mapping by BB-MP2RAGE against IR-SE and MP2RAGE. Preliminary clinical validation was prospectively performed to assess the flow suppression effect and its potential application in plaque and thrombosis identification. STATISTICAL TESTS: Pearson correlation test, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. A P value <0.05 indicates a statistically significant difference. RESULTS: Phantom experiments showed comparable accuracy of T1 maps by BB-MP2RAGE with IR-SE and MP2RAGE (all r2 > 0.99); Compared to MP2RAGE, BB-MP2RAGE effectively nulled the blood flow signals, and had a significant improvement in contrast-to-noise ratio between static tissue and blood (250.5 ± 66.6 vs. 91.9 ± 35.9). BB-MP2RAGE can quantify plaque or thrombus T1 relaxation time with blood flow signal suppression. DATA CONCLUSION: Accurate T1 mapping with sufficient blood flow suppression was achieved by BB-MP2RAGE. BB-MP2RAGE has the potential to quantitatively characterize atherosclerosis and venous thrombosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

3.
BMC Pulm Med ; 23(1): 405, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884912

RESUMO

BACKGROUND: Bronchoscopic lung volume reduction (LVR) could significantly improve pulmonary function and quality of life in patients with emphysema. We aimed to assess the efficacy and safety of bronchoscopic thermal vapor ablation (BTVA) on LVR in patients with emphysema at different stage. METHODS: A systematic search of database including PubMed, Embase and Cochrane library was conducted to determine all the studies about bronchoscopic thermal vapor ablation published through Dec 1, 2022. Related searching terms were "lung volume reduction", "bronchoscopic thermal vapor ablation", "bronchial thermal vapor ablation" "BTVA" and "emphysema", "efficacy" and"safety". We used standardized mean difference (SMD) to analyze the summary estimates for BTVA therapy. RESULTS: We retrieved 30 records through database search, and 4 trials were selected for meta-analysis, including 112 patients with emphysema. Meta-analysis of the pooled effect showed that levels of forced expiratory volume in 1 s (FEV1), residual volume (RV), total lung capacity (TLC), 6-min walk distance (6MWD) and St George's Respiratory Questionnaire (SGRQ) were significantly improved in patients with emphysema following BTVA treatment between 6 months vs. baseline. Additionally, no significant changes in FEV1, RV, TLC and SGRQ occurred from 3 to 6 months of follow-up except for 6MWD. The magnitude of benefit was higher at 3 months compared to 6 months. The most common complications at 6 months were treatment-related chronic obstructive pulmonary disease (COPD) exacerbations (RR: 12.49; 95% CI: 3.06 to 50.99; p < 0.001) and pneumonia (RR: 9.49; 95% CI: 2.27 to 39.69; p < 0.001). CONCLUSIONS: Our meta-analysis provided clinically relevant information about the impact and safety of BTVA on predominantly upper lobe emphysema. Particularly, short-term significant improvement of lung function and quality of life occurred especially within the initial 3 months. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.


Assuntos
Técnicas de Ablação , Enfisema , Enfisema Pulmonar , Humanos , Pneumonectomia/efeitos adversos , Qualidade de Vida , Técnicas de Ablação/efeitos adversos , Volume Expiratório Forçado , Broncoscopia/efeitos adversos , Resultado do Tratamento
4.
J Environ Manage ; 332: 117395, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36738720

RESUMO

Currently, China is experiencing a phase of rapid urbanization. With the frequent occurrence of extreme rainfall events within the context of climate change, the problem of heavy rainfall and waterlogging in many cities is very prominent. In November 2020, China issued a proposal for the construction of sponge cities across the entire region to significantly enhance the rainfall flood prevention and drainage capacity of cities and effectively improve the resilience of sponge city systems for flooding management. Therefore, this paper selected the Zhu pai-chong watershed in Nanning with frequent waterlogging disasters as an example. Based on underlying surface information, We used a coupled SWMM-LISFOOD model to simulate runoff and waterlogging processes and analyze the spatial and temporal evolution characteristics of the basin under 10 designed rainstorm return periods (0.25a-50a). The results confirm the substantial spatial and temporal variabilities of the runoff coefficient in the study area; impermeability was the main factor contributing to high runoff coefficient values. The spatial distribution characteristics of inundation area was general dispersion and local linear aggregation. Furthermore, this study assessed the effect of the control rate of blue‒green‒gray facilities on the actual storms, and the value ranged from only 48.6% (0.25a)-24.05% (50a). This study quantified the two-dimensional distribution of rainfall storage volume thresholds with or without considering the discharged from the pipe network. Quantitative mapping between the elements of "rainfall-storage volume of blue‒green‒gray facilities-runoff-drainage capacity of the pipe network-waterlogging level" was conducted within the study area as an example. Finally, an overall technical process scheme for rainfall and waterlogging management was proposed. The scheme covered the hydrological‒hydraulic mechanism, storage function of sponge facilities, engineering control response, nonengineering measures and intelligent management of rainfall and waterlogging during sponge city construction, which could provide critical scientific support for effective promotion of the construction of sponge cities in China.


Assuntos
Chuva , Movimentos da Água , China , Cidades , Adaptação Psicológica
5.
Inorg Chem ; 61(9): 4092-4101, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35191302

RESUMO

High-entropy materials, with complex compositions and unique cocktail characteristics, have recently drawn significant attention. Additionally, a family of sodium super ion conductors (NASICONs)-structured phosphates in energy storage areas shows a comprehensive application for traditional alkaline ion batteries and, in particular, solid-state electrolytes. However, there is no precedent in fabricating this kind of NASICON-type high-entropy phase. Here, we report the successful fabrication of two well-crystallized high-entropy phosphates, namely, Na3(Ti0.2V0.2Mn0.2Cr0.2Zr0.2)2(PO4)3 (HE-N3M2P3) and Na(Ti0.2V0.2Mn0.2Cr0.2Zr0.2)2PO4Ox (HE-NMP). The prepared materials in which the transition metals (TMs) of Ti, V, Mn, Cr, and Zr occupy the same 12c Wykoff position can form a structure analogous to R3̅c Na3V2(PO4)3 that is carefully determined by X-ray diffraction, neutron diffraction, and transmission electron microscopy. Further, their performance for sodium ion batteries and sodium-based solid-state electrolytes was evaluated. The HE-N3M2P3 might exhibit a promising electrochemical performance for sodium storage in terms of its structure resembling that of Na3V2(PO4)3. Meanwhile, the HE-NMP shows considerable electrochemical activity with numerous broad redox ranges during extraction and insertion of Na+, related to the coexistence of several TM elements. The evaluated temperature-dependent ionic conductivity for HE-NMP solid electrolyte varies from 10-6 to 10-5 S cm-1 from room temperature to 398.15 K, offering high potential for energy storage applications as a new high-entropy system.

6.
Acta Pharmacol Sin ; 43(2): 457-469, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33850273

RESUMO

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.


Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/efeitos dos fármacos , Linfoma de Célula do Manto/tratamento farmacológico , Purinas/uso terapêutico , Quinazolinonas/uso terapêutico , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Sinergismo Farmacológico , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Camundongos , Transplante de Neoplasias
7.
Acta Pharmacol Sin ; 43(2): 470-482, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33850276

RESUMO

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is an inhibitor of GAPDH with Ki = 0.5 µM. PGG blocks GAPDH activity by a reversible and NAD+ and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD+ and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.


Assuntos
Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Taninos Hidrolisáveis/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Glucose/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Humanos , Espectrometria de Massa com Troca Hidrogênio-Deutério , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organometálicos , Reação em Cadeia da Polimerase em Tempo Real
8.
Acta Pharmacol Sin ; 43(4): 941-953, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34341511

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg-1·d-1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Carbamatos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Fígado/metabolismo , Cirrose Hepática/patologia , Metionina , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
9.
BMC Pulm Med ; 22(1): 117, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361163

RESUMO

BACKGROUND: To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs). METHODS: Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in expected consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, based on the calculation of expected diagnostic yield of R-EBUS biopsy and drop out, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed. RESULTS: In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, respectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, respectively, and the average expense was 643.44 ± 706.56 US.$ (4093.15 ± 4494.67 yuan ¥). In the controls, the positive rate of brushing and biopsy were 44%, 74%, respectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, respectively. And the average expense during diagnosis was 1009.27 ± 713.89 US.$ (6420.28 ± 4541.33 yuan ¥). There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤ 2 cm in diameter was significant. CONCLUSION: In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource.


Assuntos
Neoplasias Pulmonares , Avaliação Rápida no Local , Broncoscopia/métodos , Endossonografia/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia
10.
Chemistry ; 27(52): 13235-13241, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34268818

RESUMO

The intercalation of cations into layered-structure electrode materials has long been studied in depth for energy storage applications. In particular, Li+ -, Na+ -, and K+ -based cation transport in energy storage devices such as batteries and electrochemical capacitors is closely related to the capacitance behavior. We have exploited different sizes of cations from aqueous salt electrolytes intercalating into a layered Nb2 CTx electrode in a supercapacitor for the first time. As a result, we have demonstrated that capacitive performance was dependent on cation intercalation behavior. The interlayer spacing expansion of the electrode material can be observed in Li2 SO4 , Na2 SO4 , and K2 SO4 electrolytes with d-spacing. Additionally, our results showed that the Nb2 CTx electrode exhibited higher electrochemical performance in the presence of Li2 SO4 than in that of Na2 SO4 and K2 SO4 . This is partly because the smaller-sized Li+ transports quickly and intercalates between the layers of Nb2 CTx easily. Poor ion transport in the Na2 SO4 electrolyte limited the electrode capacitance and presented the lowest electrochemical performance, although the cation radius follows Li+ >Na+ >K+ . Our experimental studies provide direct evidence for the intercalation mechanism of Li+ , Na+ , and K+ on the 2D layered Nb2 CTx electrode, which provides a new path for exploring the relationship between intercalated cations and other MXene electrodes.

11.
Clin Sci (Lond) ; 135(7): 925-941, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33786590

RESUMO

Liver diseases present a significant public health burden worldwide. Although the mechanisms of liver diseases are complex, it is generally accepted that inflammation is commonly involved in the pathogenesis. Ongoing inflammatory responses exacerbate liver injury, or even result in fibrosis and cirrhosis. Here we report that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, exerts beneficial effects on acute and chronic liver inflammation as well as fibrosis. Animal models of lipopolysaccharide (LPS)/d-galactosamine- and acute or chronic CCl4-induced liver injury showed that roscovitine administration markedly attenuated liver injury, inflammation and histological damage in LPS/d-galactosamine- and CCl4-induced acute liver injury models, which is consistent with the results in vitro. RNA sequencing (RNA-seq) analysis showed that roscovitine treatment repressed the transcription of a broad set of pro-inflammatory genes involved in many aspects of inflammation, including cytokine production and immune cell proliferation and migration, and inhibited the TGF-ß signaling pathway and the biological process of tissue remodeling. For further validation, the beneficial effect of roscovitine against inflammation was evaluated in chronic CCl4-challenged mice. The anti-inflammation effect of roscovitine was observed in this model, accompanied with reduced liver fibrosis. The anti-fibrotic mechanism involved inhibition of profibrotic genes and blocking of hepatic stellate cell (HSC) activation. Our data show that roscovitine administration protects against liver diseases through inhibition of macrophage inflammatory actions and HSC activation at the onset of liver injury.


Assuntos
Inflamação/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Roscovitina/farmacologia , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Galactosamina/toxicidade , Humanos , Inflamação/genética , Lipopolissacarídeos/toxicidade , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Análise de Sequência de RNA
12.
BMC Musculoskelet Disord ; 22(1): 112, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499842

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment symptom in the peripheral nerves. High-frequency ultrasound (HFUS) is widely used in the diagnosis of CTS. Virtual Touch Tissue Imaging and Quantification (VTIQ), which provides more information about the hardness of organization, is used to diagnose CTS. However, the data of diagnostic value of them in various degrees of CTS are limited. Whether the combination of HFUS and VTIQ can improve the diagnostic efficiency also remains unknown. The study aimed to explore the diagnostic value of HFUS and VTIQ in various degrees of CTS and whether combination of HFUS and VTIQ could improve the diagnostic efficiency of CTS. METHODS: A collection and analysis of 133 CTS patients and 35 volunteers from January 2016 to January 2019 were performed. We compared the clinical characteristics, cross-sectional area (CSA) value and shear wave velocity SWVmean value of CTS group with volunteer group. RESULTS: The CSA value and SWVmean value of CTS cohort were significantly higher than volunteer group (10.79 ± 2.88 vs. 8.06 ± 1.39, p < 0.001, 4.36 ± 0.95 vs. 3.38 ± 1.09, p < 0.001, respectively). The area under the curve (AUC) of receiver operating characteristic (ROC) curve of CSA value and SWVmean value were 0.794 and 0.757, respectively. Hierarchical analysis of CSA value and SWVmean value showed that the AUC in the moderate and severe CTS group were higher than in mild CTS group. Furthermore, the CSA value combined with SWVmean value used to diagnose mild CTS was 0.758, which was higher than that of single CSA value or single SWVmean value. CONCLUSIONS: Both HFUS and VTIQ technology were feasible to evaluate CTS. HFUS was suitable for use in diagnosis of moderate and severe CTS. For mild CTS, combination of HFUS and VTIQ was relevant to improve the diagnostic efficiency of CTS.


Assuntos
Síndrome do Túnel Carpal , Área Sob a Curva , Síndrome do Túnel Carpal/diagnóstico por imagem , Testes Diagnósticos de Rotina , Humanos , Nervo Mediano/diagnóstico por imagem , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia
13.
J Environ Manage ; 277: 111394, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091787

RESUMO

The conservation and efficient use of water resources are directly related to the sustainable and high-quality development in China. This paper regards the pilot policy of water-saving society construction as a quasi-natural experiment, and employs a differences-in-differences approach to evaluate the effectiveness of urban water-saving policies and exploit its drive mechanism by using the panel data of 263 cities in China from 2001 to 2016. Findings show that the pilot policy of water-saving society construction can achieve better water-saving effects, which can not only promote the reduction of urban water consumption in intensity and total amount, but also improve the efficiency of water resources utilization. And this policy has brought long-term dynamic effects on the urban water resources conservation. Heterogeneous effects exist in different types of cities, that is, the water-saving performance is more significant in cities with sufficient water resources and in central China. Besides, this paper finds that the impact of this water-saving policy on urban water resource conservation is mainly through two channels such as water resources infrastructure investment and water resources pricing. These findings provide useful inspirations for local governments to take effective economic measures to manage water resources.


Assuntos
Conservação dos Recursos Hídricos , Água , China , Cidades , Conservação dos Recursos Naturais , Recursos Hídricos
14.
Bioorg Med Chem Lett ; 30(22): 127598, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33011288

RESUMO

SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase, is reported to catalyze the methylation of lysine residues on histone and non-histone proteins. As a potential target for cancer therapy, there are several SMYD2 inhibitors are reported, LLY-507 as a cell-active inhibitor exhibits submicromolar potency against SMYD2 in several cancer cell lines. To know which structural fragment of LLY-507 is suitable for chemical modification, three sites are chosen for structure-activity relationship studies (SARs). Among our focused library, compounds 43 and 44 with amide link on site C showed reasonably improved potency indicating that modification on this fragment is more flexible and introduction of electrophilic warheads in this position might provide lysine-targeting covalent inhibitors for SMYD2.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Inibidores Enzimáticos/farmacologia , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Pirrolidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Estrutura Molecular , Pirrolidinas/síntese química , Pirrolidinas/química , Relação Estrutura-Atividade
15.
Acta Pharmacol Sin ; 41(2): 286-292, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31253937

RESUMO

The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC50 value of 744.3 nM. This compound bound to CBP BrD with a KD value of 4.01 µM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC50 value of 19.2 µM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein.


Assuntos
Antineoplásicos/farmacologia , Proteína de Ligação a CREB/antagonistas & inibidores , Ensaios de Triagem em Larga Escala , Leucemia/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Descoberta de Drogas/métodos , Transferência Ressonante de Energia de Fluorescência , Humanos , Concentração Inibidora 50 , Leucemia/patologia , Modelos Moleculares , Domínios Proteicos , Bibliotecas de Moléculas Pequenas
16.
Paediatr Anaesth ; 30(12): 1322-1330, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32978991

RESUMO

BACKGROUND: α2 adrenoceptor agonists have been proposed as adjuncts to prolong analgesia in pediatric caudal block. The aim of this meta-analysis was to compare the analgesic efficacy of caudal vs intravenous α2 adrenoceptor agonists during pediatric caudal block. METHODS: A systematic search, data extraction, bias risk assessment, and pooled data analysis were performed following the PRISMA guidelines. All randomized controlled trials comparing caudal with intravenous α2 adrenoceptor agonists in pediatric caudal block were included. Relative risk and weighted mean differences (the corresponding 95% confidence intervals) were calculated for dichotomous and continuous data, respectively. Trial sequential analyses were performed to evaluate the credibility of the meta-analysis. RESULTS: A total of 244 patients in five trials were identified. Compared with the intravenous group (9.56 ± 4.23 hours), the time to the first rescue analgesia was prolonged in the caudal α2 adrenoceptor agonists group (12.72 ± 5.99 hours) by a weighted mean difference of 2.98 hours [95% confidence interval: 0.59-5.36 hours; P = .01]. The number of children requiring rescue analgesia in the caudal group (64, 66.67%) was lower than that in the intravenous group (80, 81.63%) [relative risk = 0.82; 95% confidence interval: 0.69-0.97; P = .02]. These findings were also verified by trial sequential analysis. There were no significant differences in the side effects. CONCLUSION: Caudal α2 adrenoceptor agonists as adjuncts to local anesthetic during pediatric caudal block are more effective than intravenous injection. However, the results were affected by small sample size and significant heterogeneity.


Assuntos
Analgesia , Dor Pós-Operatória , Administração Intravenosa , Anestésicos Locais/uso terapêutico , Criança , Humanos , Dor Pós-Operatória/tratamento farmacológico , Receptores Adrenérgicos/uso terapêutico
17.
Clin Proteomics ; 14: 2, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28077936

RESUMO

BACKGROUND: Autism is a severe childhood neurological disorder with poorly understood etiology and pathology. Currently, there is no authentic laboratory test to confirm the diagnosis of autism. Oxidative damage may play a central role in the pathogenesis of autism. Present study is an effort to search for possible biomarkers of autism and further clarify the molecular changes associated with oxidative stress that occurs in the plasma of autistic children. METHODS: We performed redox proteomics analysis to compare carbonylated proteins in the plasma of autistic subjects and healthy controls. Immunoprecipitation and Western blot analysis were used to validate carbonylated proteins identified by the redox proteomics. RESULTS: Protein carbonylation levels in two proteins, complement component C8 alpha chain and Ig kappa chain C were found to be significantly increased in autistic patients compared with controls. These two proteins were successfully validated via immunoprecipitation and Western blot analysis. CONCLUSIONS: The results further highlight the role of oxidative stress in the pathogenesis of autism and provide some information for the diagnosis and/or monitoring of autism.

18.
J Sep Sci ; 40(21): 4191-4202, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28869337

RESUMO

Psoraleae Fructus is one of the most popular traditional Chinese medicines. Coumarins, flavonoids, and meroterpenes are the main contributors to the biological activity of Psoraleae Fructus. In this study, a new method for the quality control of Psoraleae Fructus was developed, through the quantitative analysis of multicomponents by single marker with diode array detector. Thirteen components, including psoralenoside, isopsoralenoside, psoralen, isopsoralen, psoralidin, neobavaisoflavone, bavachin, corylin, isobavachalcone, corylifol A, bavachinin, bavachalcone, and bakuchiol were rapidly separated and identified within 12 min by the newly developed method. The feasibility and reliability of this method were corroborated. The method was also compared to the external standard method and detection by corona charged aerosol detector. The results of percent difference (%) and cos (θ) have shown that there were no significant differences observed between the quantitative analysis of multicomponents by single marker and external standard method analyses; psoralen and isopsoralen were undetectable with the corona charged aerosol detector due to their but the sensitivity for all the compounds except bakuchiol detected by corona charged aerosol detector are higher than those obtained by diode array detector. In addition, the newly method developed was applied to the quality evaluation of Chinese patent medicines containing Psoraleae Fructus.


Assuntos
Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/análise , Psoralea/química , Cromatografia Líquida de Alta Pressão , Frutas/química , Reprodutibilidade dos Testes
19.
Phytochem Anal ; 28(3): 137-143, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27880856

RESUMO

INTRODUCTION: The increasing popularity of traditional Chinese medicines (TCMs) necessitates rapid and reliable methods for controlling their quality. Direct analysis in real-time mass spectrometry (DART-MS) represents a novel approach to analysing TCMs. OBJECTIVE: To develop a quick and reliable method of identifying TCMs with coumarins as primary characteristics. METHODOLOGY: DART-MS coupled with ion trap mass spectrometry was employed to rapidly identify TCMs with coumarins as primary characteristics and to explore the ionisation mechanisms of simple coumarins, furocoumarins and pyranocoumarins in detail. With minimal sample pretreatment, mass spectra of Fraxini Cortex, Angelicae Pubescentis Radix, Peucedani Radix and Psoraleae Fructus samples were obtained within seconds. The operating parameters of the DART ion source (e.g. grid electrode voltage and ionisation gas temperature) were carefully investigated to obtain high-quality mass spectra. The mass spectra of samples and DART-MS/MS spectra of marker compounds were used to identify sample materials. RESULTS: Successful authentication was achieved by analysing the same materials of different origins. Some simple coumarins, furocoumarins and pyranocoumarins can be directly detected by DART-MS as marker compounds. CONCLUSION: Our results demonstrated that DART-MS can provide a rapid and reliable method for the identification of TCMs containing different configurations of coumarins; the method may also be applicable to other plants. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Cumarínicos/análise , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas/métodos , Aesculus , Cumarínicos/química , Medicamentos de Ervas Chinesas/química , Furocumarinas/análise , Espectrometria de Massas/instrumentação , Medicina Tradicional Chinesa , Controle de Qualidade , Espectrometria de Massas em Tandem/métodos
20.
Molecules ; 22(2)2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28157159

RESUMO

In this study, magnetic graphene oxide (MGO) nanomaterials were synthesized based on covalent binding of amino Fe3O4 nanoparticles onto the graphene oxide (GO), and the prepared MGO was successfully applied as support for the immobilization of laccase. The MGO-laccase was characterized by transmission electron microscopy (TEM) and a vibrating sample magnetometer (VSM). Compared with free laccase, the MGO-laccase exhibited better pH and thermal stabilities. The optimum pH and temperature were confirmed as pH 3.0 and 35 °C. Moreover, the MGO-laccase exhibited sufficient magnetic response and satisfied reusability after being retained by magnetic separation. The MGO-laccase maintained 59.8% activity after ten uses. MGO-laccase were finally utilized in the decolorization of dye solutions and the decolorization rate of crystal violet (CV), malachite green (MG), and brilliant green (BG) reached 94.7% of CV, 95.6% of MG, and 91.4% of BG respectively. The experimental results indicated the MGO-laccase nanomaterials had a good catalysis ability to decolorize dyes in aqueous solution. Compared with the free enzyme, the employment of MGO as enzyme immobilization support could efficiently enhance the availability and facilitate the application of laccase.


Assuntos
Corantes/química , Enzimas Imobilizadas , Grafite/química , Lacase/química , Nanopartículas de Magnetita/química , Óxidos/química , Adsorção , Catálise , Ativação Enzimática , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/ultraestrutura , Temperatura
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