Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.807
Filtrar
1.
J Hazard Mater ; 476: 135213, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39018602

RESUMO

Deltamethrin is a classical pyrethroid insecticide that is frequently detected in aquatic environments and organisms. Furthermore, deltamethrin has been detected in samples related to human health and is a potential risk to public health. This study aimed to investigate the mechanism of cardiotoxicity induced by deltamethrin. Zebrafish were exposed to 0.005, 0.05, or 0.5 µg/L deltamethrin for 28 days. The results showed a significant reduction in male reproduction compared to female reproduction. Additionally, the heart rate decreased by 15.75 % in F1 after parental exposure to 0.5 µg/L deltamethrin. To evaluate cardiotoxicity, deltamethrin was administered to the zebrafish embryos. By using miRNA-Seq and bioinformatics analysis, it was discovered that miR-29b functions as a toxic regulator by targeting dnmts. The overexpression of miR-29b and inhibition of dnmts resulted in cardiac abnormalities, such as pericardial edema, bradycardia, and abnormal expression of genes related to the heart. Similar changes in the levels of miR-29b and dnmts were also detected in the gonads of F0 males and F1 embryos, confirming their effects. Overall, the results suggest that deltamethrin may have adverse effects on heart development in early-stage zebrafish and on reproduction in adult zebrafish. Furthermore, epigenetic modifications may threaten the cardiac function of offspring.

2.
Eur J Oncol Nurs ; 72: 102650, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39018958

RESUMO

PURPOSE: This study aimed to develop and validate accessible artificial neural network and decision tree models to predict the risk of lower limb lymphedema after cervical cancer surgery. METHODS: We selected 759 patients who underwent cervical cancer surgery at the Hunan Cancer Hospital from January 2010 to January 2020, collecting demographic, behavioral, clinicopathological, and disease-related data. The artificial neural network and decision tree techniques were used to construct prediction models for lower limb lymphedema after cervical cancer surgery. Then, the models' predictive efficacies were evaluated to select the optimal model using several methods, such as the area under the receiver operating characteristic curve and accuracy, sensitivity, and specificity tests. RESULTS: In the training set, the artificial neural network and decision tree model accuracies for predicting lower limb lymphedema after cervical cancer surgery were 99.80% and 88.14%, and the sensitivities 99.50% and 74.01%, respectively; the specificities were 100% and 95.20%, respectively. The area under the receiver operating characteristic curve was 1.00 for the artificial neural network and 0.92 for the decision tree model. In the test set, the artificial neural network and decision tree models' accuracies were 86.70% and 82.02%, and the sensitivities 65.70% and 67.11%, respectively; the specificities were 96.00% and 89.47%, respectively. CONCLUSION: Both models had good predictive efficacy for lower limb lymphedema after cervical cancer surgery. However, the predictive performance and stability were superior in the artificial neural network model than in the decision tree model.

3.
J Phys Chem Lett ; 15(28): 7335-7341, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38986014

RESUMO

Here, a barbituric acid derivative containing pyrene rings (DPPT) was successfully synthesized, and two types of crystals were prepared by using crystal engineering methods. Orange sheet-like crystals (DPPT-O, observed in visible light), prepared in a DCM/CH3OH solution, exhibited brittleness and weak fluorescence emission, along with sunlight-induced bending and fracturing. Red needle-like crystals (DPPT-R, also observed in visible light), synthesized in a DCM/CH3CN solution, demonstrated elastic properties, strong fluorescence emission, and excellent optical waveguide performance (with an optical loss coefficient of 0.23-0.30 dB mm-1). Single-crystal data analysis revealed that the stacking arrangement of molecules critically influenced the elasticity of the crystals, while the reaction cavity size regulated the photomechanical properties of the crystals. This study achieved effective control over sunlight responsiveness and flexible optical waveguide transmission for the first time, providing innovative insights for the application of homogeneous organic polycrystalline molecular crystals in this field.

4.
J Virus Erad ; 10(2): 100382, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39015215

RESUMO

Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM. Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression. LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as "top" in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group. LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.

5.
Front Oncol ; 14: 1404799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007100

RESUMO

Background: Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Results: Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. Conclusions: This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

6.
Front Immunol ; 15: 1400177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953027

RESUMO

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.


Assuntos
Neoplasias , Receptores de IgG , Linfócitos T , Microambiente Tumoral , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Humanos , Animais , Camundongos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Imunoterapia Adotiva/métodos , Receptor ErbB-2/imunologia , Receptor ErbB-2/antagonistas & inibidores , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Feminino , Antígenos CD20/imunologia
7.
Cell Stem Cell ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38955185

RESUMO

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38981203

RESUMO

Considering comprehensive utilization of natural products, isolation and activity determination processes of bioactive compounds are essential. In this study, a combined high-speed countercurrent chromatography (HSCCC) with preparative HPLC method was developed to isolate the five antioxidant polyphenols from 75% ethanol extract of Malus pumila Mill. leaves. The HSCCC conditions were optimized by response surface methodology (RSM) considering two response indexes including retention of stationary phase and analysis time. The optimal HSCCC conditions were flow rate of 2.11 mL/min, revolution speed of 717 rpm, and temperature of 25℃, with a solvent system of ethyl acetate/methanol/water (10:1:10, v/v/v). The unseparated fractions obtained from HSCCC were subjected to preparative HPLC for further isolation. As a result, phloridzin (15.3 mg), isoquercitrin (2.1 mg), quercetin 3-O-xyloside (1.9 mg), quercetin-3-O-arabinoside (4.0 mg), and quercitrin (2.0 mg) were isolated from 200.0 mg extracts. The purities of these compounds were all above 92%. Their chemical structures were identified by mass spectrometer and nuclear magnetic resonance. The five isolated compounds were further investigated for their rat hippocampal neuroprotective effects against hydrogen peroxide-induced oxidative stress. No cytotoxicity was observed in all tested concentrations. While all five compounds except phloridzin showed significantly neurogenic activities and neuroprotective effects, especially at the concentration of 0.5 mg/L. These results demonstrate that RSM is a suitable technique for optimisation of HSCCC and the isolated polyphenols can be used as antioxidants in pharmaceutical and food products.

9.
Chemistry ; : e202401380, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987889

RESUMO

Photocatalytic ozonation is considered to be a promising approach for the treatment of refractory organic pollutants, but the design of efficient catalyst remains a challenge. Surface modification provides a potential strategy to improve the activity of photocatalytic ozonation. In this work, density functional theory (DFT) calculations were first performed to check the interaction between O3 and TiO2-OH (surface hydroxylated TiO2) or TiO2-F (surface fluorinated TiO2), and the results suggest that TiO2-OH displays better O3 adsorption and activation than does TiO2-F, which is confirmed by experimental results. The surface hydroxyl groups greatly promote the O3 activation, which is beneficial for the generation of reactive oxygen species (ROS). Importantly, TiO2-OH displays better performance towards pollutants (such as berberine hydrochloride) removal than does TiO2-F and most reported ozonation photocatalysts. The total organic carbon (TOC) removal efficiency reaches 84.4% within two hours. This work highlights the effect of surface hydroxylation on photocatalytic ozonation and provides ideas for the design of efficient photocatalytic ozonation catalysts.

10.
Bioorg Med Chem Lett ; : 129880, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996941

RESUMO

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15 Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).

11.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000099

RESUMO

Copper (Cu) is an essential nutrient for plant growth and development. This metal serves as a constituent element or enzyme cofactor that participates in many biochemical pathways and plays a key role in photosynthesis, respiration, ethylene sensing, and antioxidant systems. The physiological significance of Cu uptake and compartmentalization in plants has been underestimated, despite the importance of Cu in cellular metabolic processes. As a micronutrient, Cu has low cellular requirements in plants. However, its bioavailability may be significantly reduced in alkaline or organic matter-rich soils. Cu deficiency is a severe and widespread nutritional disorder that affects plants. In contrast, excessive levels of available Cu in soil can inhibit plant photosynthesis and induce cellular oxidative stress. This can affect plant productivity and potentially pose serious health risks to humans via bioaccumulation in the food chain. Plants have evolved mechanisms to strictly regulate Cu uptake, transport, and cellular homeostasis during long-term environmental adaptation. This review provides a comprehensive overview of the diverse functions of Cu chelators, chaperones, and transporters involved in Cu homeostasis and their regulatory mechanisms in plant responses to varying Cu availability conditions. Finally, we identified that future research needs to enhance our understanding of the mechanisms regulating Cu deficiency or stress in plants. This will pave the way for improving the Cu utilization efficiency and/or Cu tolerance of crops grown in alkaline or Cu-contaminated soils.


Assuntos
Cobre , Plantas , Cobre/metabolismo , Cobre/deficiência , Plantas/metabolismo , Homeostase , Estresse Oxidativo , Estresse Fisiológico , Transporte Biológico
12.
BMC Public Health ; 24(1): 1765, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956521

RESUMO

BACKGROUND: Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. METHODS: Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. RESULTS: We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886-4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194-0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058-0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. CONCLUSIONS: The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Profilaxia Pré-Exposição , Pesquisa Qualitativa , Humanos , Masculino , Profilaxia Pré-Exposição/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Homossexualidade Masculina/psicologia , China , Adulto , Infecções por HIV/prevenção & controle , Adulto Jovem , Administração Oral , Inquéritos e Questionários , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , Adolescente
14.
Int J Clin Oncol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977538

RESUMO

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

15.
Acta Pharm Sin B ; 14(7): 3125-3139, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027250

RESUMO

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A-C (1-3), with distinctive C-C and C-O-C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

16.
Angew Chem Int Ed Engl ; : e202410596, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031951

RESUMO

Selective CO2 photoreduction to value-added multi-carbon (C2+) feedstocks, such as C2H4, holds great promise in direct solar-to-chemical conversion for a carbon-neutral future. Nevertheless, the performance is largely inhibited by the high energy barrier of C-C coupling process, thereby leading to C2+ products with low selectivity. Here we report that through facile surface immobilization of a 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) ionic liquid, plasmonic Cu nanowires could enable highly selective CO2 photoreduction to C2H4 product. At an optimal condition, the resultant plasmonic photocatalyst exhibits C2H4 production with selectivity up to 96.7% under 450 nm monochromatic light irradiation, greatly surpassing its pristine Cu counterpart. Combined in situ spectroscopies and computational calculations unravel that the addition of EMIM-BF4 ionic liquid modulates the local electronic structure of Cu, resulting in its enhanced adsorption strength of *CO intermediate and significantly reduced energy barrier of C-C coupling process. This work paves new path for Cu surface plasmons in selective artificial photosynthesis to targeted products.

17.
Epigenetics ; 19(1): 2380145, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39018487

RESUMO

Doxorubicin (DOX)-mediated cardiotoxicity can impair the clinical efficacy of chemotherapy, leading to heart failure (HF). Given the importance of circRNAs and miRNAs in HF, this paper intended to delineate the mechanism of the circular RNA 0006332 (circ -0,006,332)/microRNA (miR)-143/Toll-like receptor 2 (TLR2) axis in doxorubicin (DOX)-induced HF. The binding of miR-143 to circ -0,006,332 and TLR2 was assessed with the dual-luciferase assay, and the binding between miR-143 and circ -0,006,332 was determined with FISH, RIP, and RNA pull-down assays. miR-143 and/or circ -0,006,332 were overexpressed in rats and cardiomyocytes, followed by DOX treatment. In cardiomyocytes, miR-143 and TLR2 expression, cell viability, LDH release, ATP contents, and levels of IL-1ß, IL-18, TNF-α, and pyroptosis-related molecules were examined. In rats, cardiac function, serum levels of cardiac enzymes, apoptosis, myocardial fibrosis, and levels of IL-1ß, IL-18, TNF-α, TLR2, and pyroptosis-related molecules were detected. miR-143 diminished TLR2 expression by binding to TLR2, and circ -0,006,332 bound to miR-143 to downregulate miR-143 expression. miR-143 expression was reduced and TLR2 expression was augmented in DOX-induced cardiomyocytes. miR-143 inhibited DOX-induced cytotoxicity by suppressing pyroptosis in H9C2 cardiomyocytes. In DOX-induced rats, miR-143 reduced cardiac dysfunction, myocardial apoptosis, myocardial fibrosis, TLR2 levels, and pyroptosis. Furthermore, overexpression of circ -0,006,332 blocked these effects of miR-143 on DOX-induced cardiomyocytes and rats. Circ -0,006,332 stimulates cardiomyocyte pyroptosis by downregulating miR-143 and upregulating TLR2, thus promoting DOX-induced cardiac injury.


Assuntos
Doxorrubicina , MicroRNAs , Miócitos Cardíacos , Piroptose , RNA Circular , Receptor 2 Toll-Like , Animais , Doxorrubicina/efeitos adversos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Piroptose/efeitos dos fármacos , RNA Circular/genética , RNA Circular/metabolismo , Ratos , Masculino , Ratos Sprague-Dawley , Cardiotoxicidade/metabolismo , Cardiotoxicidade/genética , Cardiotoxicidade/etiologia , Transdução de Sinais/efeitos dos fármacos
18.
Quant Imaging Med Surg ; 14(7): 5131-5143, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022294

RESUMO

Background: Accurate and reproducible assessment of left ventricular (LV) volumes is important in managing various cardiac conditions. However, patients are required to hold their breath multiple times during data acquisition, which may result in discomfort and restrict cardiac motion, potentially compromising the accuracy of the detected results. Accelerated imaging techniques can help reduce the number of breath holds needed, potentially improving patient comfort and the reliability of the LV assessment. This study aimed to prospectively evaluate the feasibility and accuracy of LV assessment with a model-based low-rank plus sparse network (L+S-Net) for accelerated magnetic resonance (MR) cine imaging. Methods: Fourty-one patients with different cardiac conditions were recruited in this study. Both accelerated MR cine imaging with L+S-Net and traditional electrocardiogram (ECG)-gated segmented cine were performed for each patient. Subjective image quality (IQ) score and quantitative LV volume function parameters were measured and compared between L+S-Net and traditional standards. The IQ score and LV volume measurements of cardiovascular magnetic resonance (CMR) images reconstructed by L+S-Net and standard cine were compared by paired t-test. The acquisition time of the two methods was also calculated. Results: In a quantitative analysis, L+S-Net and standard cine yielded similar measurements for all parameters of LV function (ejection fraction: 35±22 for standard vs. 33±23 for L+S-Net), although L+S-Net had slightly lower IQ scores than standard cine CMR (4.2±0.5 for L+S-Net vs. 4.8±0.4 for standard cine; P<0.001). The mean acquisition time of L+S-Net and standard cine was 0.83±0.08 vs. 6.35±0.78 s per slice (P<0.001). Conclusions: Assessment of LV function with L+S-Net at 3.0 T yields comparable results to the reference standard, albeit with a reduced acquisition time. This feature enhances the clinical applicability of the L+S-Net approach, helping alleviate patient discomfort and motion artifacts that may arise due to prolonged acquisition time.

19.
Opt Express ; 32(10): 18007-18016, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858967

RESUMO

Based on current laboratory laser parameters and the low density target that is induced by the inevitable prepulse, we propose what we believe to be a new scheme to enhance the proton energy by employing a laser pulse with two different peak intensities. Initially, the lower-intensity peak of the laser pulse P1, irradiates the low-density plasma target induced by the prepulse to form a significantly denser plasma target. Such a compressed high-density target is critical for supporting the subsequent main pulse P2 with higher peak intensity to drive proton acceleration. As an example, particle-in-cell (PIC) simulations reveal that when using a circularly polarized (CP) flat-top P1 with a peak intensity of approximately 1.71 × 10 19 W/cm2, full-width at half-maximum(FWHM) duration of 325 fs and a CP P2 with a peak intensity of 1.54 × 10 22 W/cm2, FWHM duration of 26.5 fs, and focal spot radius of 4 µm successively acting on a target with an initial density of 8nc, protons with cut-off energy of 940 MeV can be obtained from the cascaded acceleration scheme. Compared with the case without P1, the cutoff energy increased by 340 MeV. Owing to the intervention of P1, this scheme overcomes the limitation of laser contrast and is more feasible to be implemented experimentally.

20.
Sensors (Basel) ; 24(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38894450

RESUMO

Robust face clustering enjoys a wide range of applications for gate passes, surveillance systems and security analysis in embedded sensors. Nevertheless, existing algorithms have limitations in finding accurate clusters when data contain noise (e.g., occluded face clustering and recognition). It is known that in subspace clustering, the ℓ1- and ℓ2-norm regularizers can improve subspace preservation and connectivity, respectively, and the elastic net regularizer (i.e., the mixture of the ℓ1- and ℓ2-norms) provides a balance between the two properties. However, existing deterministic methods have high per iteration computational complexities, making them inapplicable to large-scale problems. To address this issue, this paper proposes the first accelerated stochastic variance reduction gradient (RASVRG) algorithm for robust subspace clustering. We also introduce a new momentum acceleration technique for the RASVRG algorithm. As a result of the involvement of this momentum, the RASVRG algorithm achieves both the best oracle complexity and the fastest convergence rate, and it reaches higher efficiency in practice for both strongly convex and not strongly convex models. Various experimental results show that the RASVRG algorithm outperformed existing state-of-the-art methods with elastic net and ℓ1-norm regularizers in terms of accuracy in most cases. As demonstrated on real-world face datasets with different manually added levels of pixel corruption and occlusion situations, the RASVRG algorithm achieved much better performance in terms of accuracy and robustness.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...