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1.
Plant J ; 118(6): 2068-2084, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531629

RESUMO

Bermudagrass (Cynodon dactylon) is a globally distributed, extensively used warm-season turf and forage grass with high tolerance to salinity and drought stress in alkaline environments. However, the origin of the species and genetic mechanisms for salinity tolerance in the species are basically unknown. Accordingly, we set out to study evolution divergence events in the Cynodon genome and to identify genes for salinity tolerance. We developed a 604.0 Mb chromosome-level polyploid genome sequence for bermudagrass 'A12359' (n = 18). The C. dactylon genome comprises 2 complete sets of homoeologous chromosomes, each with approximately 30 000 genes, and most genes are conserved as syntenic pairs. Phylogenetic study showed that the initial Cynodon species diverged from Oropetium thomaeum approximately 19.7-25.4 million years ago (Mya), the A and B subgenomes of C. dactylon diverged approximately 6.3-9.1 Mya, and the bermudagrass polyploidization event occurred 1.5 Mya on the African continent. Moreover, we identified 82 candidate genes associated with seven agronomic traits using a genome-wide association study, and three single-nucleotide polymorphisms were strongly associated with three salt resistance genes: RAP2-2, CNG channels, and F14D7.1. These genes may be associated with enhanced bermudagrass salt tolerance. These bermudagrass genomic resources, when integrated, may provide fundamental insights into evolution of diploid and tetraploid genomes and enhance the efficacy of comparative genomics in studying salt tolerance in Cynodon.


Assuntos
Cynodon , Genoma de Planta , Filogenia , Tolerância ao Sal , Sequenciamento Completo do Genoma , Cynodon/genética , Tolerância ao Sal/genética , Genoma de Planta/genética , Tetraploidia , Poliploidia , Cromossomos de Plantas/genética , Genes de Plantas/genética
2.
New Phytol ; 242(3): 1238-1256, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38426393

RESUMO

Biosynthesis of flavonoid aglycones and glycosides is well established. However, key genes involved in their catabolism are poorly understood, even though the products of hydrolysis and oxidation play important roles in plant resistance to biotic stress. Here, we report on catabolism of dihydrochalcones (DHCs), the most abundant flavonoids in domesticated apple and wild Malus. Two key genes, BGLU13.1 and PPO05, were identified by activity-directed protein purification. BGLU13.1-A hydrolyzed phlorizin, (the most abundant DHC in domesticated apple) to produce phloretin which was then oxidized by PPO05. The process differed in some wild Malus, where trilobatin (a positional isomer of phlorizin) was mainly oxidized by PPO05. The effects of DHC catabolism on apple resistance to biotic stresses was investigated using transgenic plants. Either directly or indirectly, phlorizin hydrolysis affected resistance to the phytophagous pest two-spotted spider mite, while oxidation of trilobatin was involved in resistance to the biotrophic fungus Podosphaera leucotricha. DHC catabolism did not affect apple resistance to necrotrophic pathogens Valsa mali and Erwinia amylovara. These results suggest that different DHC catabolism pathways play different roles in apple resistance to biotic stresses. The role of DHC catabolism on apple resistance appeared closely related to the mode of invasion/damage used by pathogen/pest.


Assuntos
Malus , Polifenóis , Malus/metabolismo , Florizina/metabolismo , Flavonoides/metabolismo , Estresse Fisiológico/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
3.
BMC Cancer ; 24(1): 679, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831450

RESUMO

OBJECTIVE: To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS: Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS: (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS: The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).


Assuntos
Anticorpos Monoclonais Humanizados , Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Radioterapia de Intensidade Modulada , Humanos , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/tratamento farmacológico , Idoso , Quimiorradioterapia/métodos , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Resultado do Tratamento
4.
Pulm Pharmacol Ther ; 87: 102317, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154901

RESUMO

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.

5.
J Org Chem ; 89(13): 9496-9501, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965934

RESUMO

Herein, an unprecedented [4 + 2] cycloaddition of enaminone with 1,3,5-triazinane has been developed. The representative semihydrogenated aromatic heterocycle 1,2,3,4-tetrahydropyrimidines have been synthesized with a broad substrate scope, demonstrating potential antitumor activity. This approach has been smoothly conducted under additive-free and environmentally friendly conditions that are compatible with various functional groups. Furthermore, the condition optimization process reveals that the tetrahydropyrimidine product is regulated via the reaction temperature.

6.
Eur J Nutr ; 63(7): 2437-2447, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38814365

RESUMO

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.


Assuntos
Dieta , Hipertensão , Grãos Integrais , Humanos , Hipertensão/epidemiologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , China/epidemiologia , Fatores de Risco , Adulto , Dieta/estatística & dados numéricos , Dieta/métodos , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Estudos de Coortes , Modelos de Riscos Proporcionais , Seguimentos
7.
Biotechnol Appl Biochem ; 71(5): 1129-1138, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38783542

RESUMO

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.


Assuntos
Acroleína , Aterosclerose , Inflamassomos , Isoflavonas , Fator 2 Relacionado a NF-E2 , Sirtuína 1 , Sirtuína 1/metabolismo , Isoflavonas/farmacologia , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Camundongos , Inflamassomos/metabolismo , Acroleína/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Cadeias Pesadas de Miosina/metabolismo , Masculino , Camundongos Endogâmicos C57BL
8.
BMC Public Health ; 24(1): 1193, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679720

RESUMO

BACKGROUND: Residents' adoption of preventive behaviours proved beneficial in preventing the large-scale transmission of the virus during the early stages of the COVID-19 outbreak. It is critical to investigate how social media triggers residents' preventive behaviour decisions during the COVID-19 outbreak. METHODS: This paper selected online shopping as a specific preventive behaviour for empirical investigation. An online cross-sectional survey was conducted through the Sojump website from 1 to 15 March 2020, and a total of 1,289 valid questionnaires were collected from China. This paper uses multiple regression analysis to investigate the heterogeneous impacts of different information sources on residents' online shopping willingness and online shopping behaviour and the heterogeneous impacts of different information content in social media on the transformation of residents' online shopping willingness and online shopping behaviour. RESULTS: The findings indicate that both official-media and self-media positively promote residents' online shopping willingness and behaviour, with official-media having a stronger promotional effect than self-media. Furthermore, official-media and self-media can collaboratively promote residents' online shopping willingness and online shopping behaviour. The ease-of-use and usefulness of information significantly promoted the transformation of residents' online shopping willingness. CONCLUSIONS: This study analyses the heterogeneous impacts of social media on residents' preventive behaviours from the perspectives of information source differentiation and information content differentiation, which enriches related studies and provides feasible paths for promoting residents' preventive behaviours.


Assuntos
COVID-19 , Mídias Sociais , Humanos , Mídias Sociais/estatística & dados numéricos , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/psicologia , Estudos Transversais , China/epidemiologia , Masculino , Feminino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto Jovem , Comportamentos Relacionados com a Saúde , Comportamento do Consumidor/estatística & dados numéricos
9.
Altern Ther Health Med ; 30(9): 241-249, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38290442

RESUMO

Background: Coronary atherosclerosis is a serious and progressive condition characterized by the accumulation of plaques, consisting of fat, cholesterol, and other substances, within the arteries that supply blood to the heart. These plaques can harden and narrow the arteries, leading to reduced blood flow to the heart muscle. Objective: The primary objective of this study is to investigate the correlation between specific cardiovascular parameters and intracoronary vascular ultrasound indexes in patients diagnosed with coronary heart disease. This investigation aims to explore the relationships between intracoronary vascular ultrasound measurements and three key cardiovascular parameters: epicardial fat pad thickness, mono-platelet polymer levels, and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. Methods: In this investigation, we applied a comprehensive method to evaluate atherosclerotic plaque characteristics in patients with diverse stages of coronary heart disease (CHD), contrasting these profiles with those of healthy individuals. Our study included 80 acute myocardial infarction (AMI) patients, 145 with unstable angina pectoris (UAP), 175 with stable angina pectoris (SAP), and 100 controls. We utilized intravascular ultrasound (IVUS), an advanced imaging technique that surpasses traditional angiography by providing detailed, high-resolution images of both the coronary artery lumen and wall, including plaque composition. This approach is pivotal for assessing plaque stability, a key factor in the risk of rupture and subsequent cardiovascular events, indicated by features like lipid-rich cores and thin fibrous caps. During IVUS, we quantified parameters such as plaque area, load, and the remodeling index, the latter offering insights into vascular adaptation to plaque buildup. Additionally, we conducted a correlation analysis between IVUS indices and three cardiovascular markers: epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels. The goal was to ascertain the predictive value of these markers in tandem with IVUS for determining the stability of coronary artery atherosclerotic plaques. This integrative approach enhances understanding of plaque formation and destabilization, potentially informing more effective CHD prevention and management strategies. Results: Our study revealed distinct variations in key parameters across patient groups with different forms of CHD and healthy controls. Notably, we observed significant differences in gender distribution, hypertension, and diabetes mellitus prevalence among these groups. In terms of IVUS indexes and cardiovascular parameters, the SAP group exhibited markedly different results compared to the AMI and UAP groups. Specifically, the SAP patients showed the lowest values for EMMA, plaque area, plaque burden, reconstruction index, and positive remodeling. Additionally, they exhibited the thickest fibrous caps. In contrast, the AMI and UAP groups presented similar outcomes in these aspects. Regarding the epicardial fat pad thickness, the positive rate of monocyte-platelet aggregates, and the levels of sdLDL-C, there were no significant differences between the AMI and UAP groups. However, these parameters were notably higher in the AMI and UAP groups compared to the SAP group. Crucially, we established a significant correlation between the thickness of the epicardial fat pad, the positive rate of monocyte-platelet aggregates, and the sdLDL-C levels with plaque loading rate and remodeling index. These correlations underscore the potential utility of these parameters as indicators of plaque stability and cardiovascular risk in patients with CHD. This highlights the complexity of atherosclerotic disease progression and underscores the importance of a multifaceted approach to assessing and managing CHD. Conclusion: Our research delineates the critical role of the remodeling index, epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels as key prognostic tools for assessing coronary plaque stability in coronary artery disease (CAD). These biomarkers collectively provide an enhanced perspective on plaque vulnerability, an essential aspect in the genesis of acute coronary events. Clinically, these findings are pivotal. They offer a refined approach to CAD management and risk evaluation, allowing for the precise identification of patients at increased risk of plaque rupture, a precursor to acute coronary syndromes. This precision facilitates the adoption of more individualized treatment strategies, focusing on aggressive interventions for high-risk patients and more conservative management for those with stable plaques.


Assuntos
Ultrassonografia de Intervenção , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ultrassonografia de Intervenção/métodos , Placa Aterosclerótica/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Doença das Coronárias/diagnóstico por imagem , LDL-Colesterol/sangue
10.
Eye Contact Lens ; 50(7): 297-304, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695745

RESUMO

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.


Assuntos
Algoritmos , Inteligência Artificial , Miopia , Procedimentos Ortoceratológicos , Prescrições , Humanos , Procedimentos Ortoceratológicos/métodos , Miopia/terapia , Miopia/fisiopatologia , Feminino , Masculino , Lentes de Contato , Criança , Ajuste de Prótese/métodos , Adolescente , Acuidade Visual/fisiologia
11.
Environ Toxicol ; 39(6): 3548-3562, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477013

RESUMO

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.


Assuntos
Bufanolídeos , Movimento Celular , MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , PTEN Fosfo-Hidrolase , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Ubiquitinação , Animais , Feminino , Humanos , Masculino , Camundongos , Bufanolídeos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Metástase Neoplásica , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Ubiquitinação/efeitos dos fármacos
12.
Nano Lett ; 23(23): 11280-11287, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38047724

RESUMO

2D van der Waals (vdW) materials offer infinite possibilities for constructing unique ferroelectrics through simple layer stacking and rotation. In this work, we stack nonferroelectric GeS2 and ferroelectric CuInP2S6 to form heterostructures by combining sliding ferroelectric polarization with displacement ferroelectric polarization to achieve multiple polarization states. First-principles calculations reveal that the polarization reversal of the CuInP2S6 component in the GeS2/CuInP2S6/GeS2 heterostructure can simultaneously drive the switching of sliding ferroelectric polarization, displaying a robust coupling of the two polarizations and leading to the overall polarization switching. Based on this, ferroelectric arrays with a density of 6.55 × 1012 cm-2 (equivalent to a storage density of 0.7 TB cm-2) were constructed in a moiré superlattice, and the polarization strength of array elements was 11.77 pC/m, higher than that of all reported 2D vdW out-of-plane ferroelectrics. High density, large polarization, and electrically switchable array elements in ferroelectric arrays provide unprecedented opportunities to design 2D high-density nonvolatile ferroelectric memories.

13.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891803

RESUMO

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.


Assuntos
Neurônios , Proteínas de Ligação a Fosfato , Piroptose , Vírus da Raiva , Raiva , Animais , Neurônios/virologia , Neurônios/metabolismo , Neurônios/patologia , Vírus da Raiva/patogenicidade , Vírus da Raiva/fisiologia , Raiva/virologia , Raiva/patologia , Raiva/metabolismo , Camundongos , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/metabolismo , Gasderminas
14.
Environ Monit Assess ; 196(6): 576, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789652

RESUMO

Phosphorus pollution poses a significant challenge in addressing water contamination. The coagulant is one of the effective methods to remove phosphorus from wastewater. Abundant Al and Fe oxides in sludge residue make it have great potential to synthesize water treatment coagulants. However, the utilization of sludge residue for preparation of coagulant was seldom investigated. In this study, we fabricated a novel coagulant, polyaluminum ferric chloride (SM-PAC), using sludge residue as a raw material through acid leaching and polymerization processes. Characterization results confirm that the parameters of SM-PAC meet the specifications outlined in the national standard (GB/T 22627-2022). We investigated the effects of pH, dosage, initial phosphorus concentration, and contact time on the removal efficiency of SM-PAC. As anticipated, the prepared SM-PAC exhibited a significant efficacy in removing phosphorus, meeting the discharge standards set for municipal sewage. Furthermore, the adsorption kinetics analysis suggests that the predominant mode of phosphorus adsorption on SM-PAC is chemical adsorption. Furthermore, the SM-PAC was employed in the actual wastewater treatment plant and exhibited excellent efficiency in phosphorus removal. The utilization of SM-PAC can not only effectively address the issue of sludge disposal but also achieve the goal of "treating waste with waste." It is expected that the proposed method of reusing sludge residue as a resource can provide a sustainable way to synthesize a coagulant for phosphorus removal.


Assuntos
Fósforo , Reciclagem , Esgotos , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água , Fósforo/análise , Fósforo/química , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Reciclagem/métodos , Adsorção , Compostos Férricos/química , Águas Residuárias/química
15.
Angew Chem Int Ed Engl ; 63(31): e202402184, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-38750660

RESUMO

Water electrolysis is one promising and eco-friendly technique for energy storage, yet its overall efficiency is hindered by the sluggish kinetics of oxygen evolution reaction (OER). Therefore, developing strategies to boost OER catalyst performance is crucial. With the advances in characterization techniques, an extensive phenomenon of surface structure evolution into an active amorphous layer was uncovered. Surface reconstruction in a controlled fashion was then proposed as an emerging strategy to elevate water oxidation efficiency. In this work, Cr substitution induces the reconstruction of NiFexCr2-xO4 during cyclic voltammetry (CV) conditioning by Cr leaching, which leads to a superior OER performance. The best-performed NiFe0.25Cr1.75O4 shows a ~1500 % current density promotion at overpotential η=300 mV, which outperforms many advanced NiFe-based OER catalysts. It is also found that their OER activities are mainly determined by Ni : Fe ratio rather than considering the contribution of Cr. Meanwhile, the turnover frequency (TOF) values based on redox peak and total mass were obtained and analysed, and their possible limitations in the case of NiFexCr2-xO4 are discussed. Additionally, the high activity and durability were further verified in a membrane electrode assembly (MEA) cell, highlighting its potential for practical large-scale and sustainable hydrogen gas generation.

16.
Angew Chem Int Ed Engl ; 63(11): e202317957, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38270335

RESUMO

Weak adsorption of gas reactants and strong binding of intermediates present a significant challenge for most transition metal oxides, particularly in the realm of CO2 photoreduction. Herein, we demonstrate that the adsorption can be fine-tuned by phase engineering of oxide catalysts. An oxygen vacancy mediated topological phase transition in Ni-Co oxide nanowires, supported on a hierarchical graphene aerogel (GA), is observed from a spinel phase to a rock-salt phase. Such in situ phase transition empowers the Ni-Co oxide catalyst with a strong internal electric field and the attainment of abundant oxygen vacancies. Among a series of catalysts, the in situ transformed spinel/rock-salt heterojunction supported on GA stands out for an exceptional photocatalytic CO2 reduction activity and selectivity, yielding an impressive CO production rate of 12.5 mmol g-1 h-1 and high selectivity of 96.5 %. This remarkable performance is a result of the robust interfacial coupling between two topological phases that optimizes the electronic structures through directional charge transfer across interfaces. The phase transition process induces more Co2+ in octahedral site, which can effectively enhance the Co-O covalency. This synergistic effect balances the surface activation of CO2 molecules and desorption of reaction intermediates, thereby lowering the energetic barrier of the rate-limiting step.

17.
Angew Chem Int Ed Engl ; : e202415797, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438270

RESUMO

Oxygen evolution and reduction reactions (OER and ORR) play crucial roles in energy conversion processes such as water splitting and air batteries, where spin dynamics inherently influence their efficiency. However, the specific contribution of spin has yet to be fully understood. In this study, we intentionally introduce a spin channel through the transformation of trigonal antiferromagnetic SrCoO2.5 into cubic ferromagnetic SrCoO3, aiming to deepen our understanding of spin dynamics in catalytic reactions. Based on the results from spherical-aberration-corrected microscope, synchrotron absorption spectra, magnetic characterizations, and density functional theory calculations, it is revealed that surface electron transfer is predominantly governed by local geometric structures, while the presence of the spin channel significantly enhances the bulk transport of spin-polarized electrons, particularly under high current densities where surface electron transfer is no longer the limiting factor. The overpotential for OER is reduced by at least 70 mV at 150 mA cm-2 due to the enhanced conductivity from spin-polarized electrons facilitated by spin channels, with an expectation of even more significant reductions at higher current densities. This work provides a clearer picture of the role of spin in oxygen-involved electrocatalysis, providing critical insights for the design of more efficient catalytic systems in practical applications.

18.
Rep Prog Phys ; 86(9)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37343543

RESUMO

Recently, the remarkable advances in thermally activated delayed fluorescence (TADF) materials have attracted much attention due to their 100% exciton utilization efficiency in organic light-emitting diodes (OLEDs). Although the commercialization of TADF materials is at an early stage, they exhibit enormous potential for next-generation OLEDs due to the comparable electroluminescence performance to metal of their phosphorescent complex counterparts, but without the presence of precious metal elements. This review summarizes the different types of TADF small molecules with various photophysical properties and the state-of-the-art molecular design strategies. Furthermore, the device engineering is discussed, and emerging optoelectronic applications, such as organic light-emitting electrochemical cells, organic lasing, and organic scintillators, are introduced. It is anticipated that this review can clarify the design of efficient TADF emitters and point out the direction of future development.

19.
Ophthalmology ; 130(5): 542-550, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36642334

RESUMO

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Miopia , Humanos , Criança , Adolescente , Miopia/terapia , Refração Ocular , Óculos , Progressão da Doença , Face
20.
Invest New Drugs ; 41(3): 438-452, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37097369

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide. Combination of drugs targeting independent signaling pathways would effectively block the proliferation of cancer cells with lower concentrations and stronger synergy effects. Dasatinib, a multi-targeted protein tyrosine kinase inhibitor targeting BCR-ABL and kinases of SRC family, has been successfully applied in the treatment of chronic myeloid leukemia (CML). BMS-754807, an inhibitor targeting the insulin-like growth factor 1 receptor (IGF-IR) and insulin receptor (IR) family kinases, has been in phase I development for the treatment of a variety of human cancers. Herein, we demonstrated that dasatinib in combination with BMS-754807 inhibited lung cancer cell growth, while induced autophagy as well as cell cycle arrest at the G1 phase. Dasatinib in combination with BMS-754807 suppressed the expression of cell cycle marker proteins, Rb, p-Rb, CDK4, CDK6 and Cyclin D1, and the PI3K/Akt/mTOR signaling pathway. Dasatinib in combination with BMS-754807 induced autophagy in lung cancer cells, evidenced by the upregulation of LC3B II and beclin-1, the downregulation of LC3B I and SQSTM1/p62, and the autophagic flux observed with a confocal fluorescence microscopy. Furthermore, dasatinib (18 mg/kg) in combination with BMS-754807 (18 mg/kg) inhibited the growth of tumors in NCI-H3255 xenografts without changing the bodyweight. Overall, our results suggest that dasatinib in combination with BMS-754807 inhibits the lung cancer cell proliferation in vitro and tumor growth in vitro, which indicates promising evidence for the application of the drug combination in lung cancer therapy.


Assuntos
Neoplasias Pulmonares , Fosfatidilinositol 3-Quinases , Humanos , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Tiazóis/farmacologia , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proliferação de Células , Pontos de Checagem do Ciclo Celular , Fase G1 , Autofagia , Apoptose , Linhagem Celular Tumoral
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