Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 220
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-39126287

RESUMO

OBJECTIVE: To evaluate the impact of smoking statuses on disease severity and subcutaneous immunotherapy (SCIT) efficacy in allergic rhinitis (AR). STUDY DESIGN: Open observational cohort study. SETTING: Tertiary referral center. METHODS: Five hundred and five AR patients undergoing dust mite allergen SCIT were categorized into never smokers, former smokers, and current smokers. AR severity was assessed using widely employed questionnaires. The changes in questionnaire scores pre- and post-SCIT were evaluated for SCIT efficacy. The differences in disease severity and SCIT efficacy were compared for different smoking statuses among AR patients. RESULTS: Compared to never smokers, former and current smokers exhibited higher proportion of male, alcohol, and asthma (P < .05). Current smokers had a greater prevalence of allergic conjunctivitis than former smokers (P < .05). Before SCIT, AR severity was similar across 3 groups, even after adjusting for confounders (P > .05). Current smokers reported lower SCIT efficacy in the first year (P < .05). By the third year, 3 groups showed comparable long-term efficacy (P > .05). However, current smokers experienced a significant decrease in benefits 2 years post-SCIT (P < .05) and lower improvement rates at the end of the 3-years SCIT period and 2 years following SCIT (P < .05). CONCLUSION: AR patients across different smoking statuses demonstrated similar baseline disease severity and long-time SCIT efficacy. Active smoking was associated with increased asthma risk, delayed early SCIT efficacy perception, reduced improvement over 3 years, and diminished benefits 2 years after SCIT. Prompt smoking cessation is crucial to mitigate these effects.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39100210

RESUMO

Asthma is a prevalent respiratory condition with multifaceted pathomechanisms, presenting challenges for therapeutic development. The SLC (Solute Carrier) gene family, encompassing diverse membrane transport proteins, plays pivotal roles in various human diseases by facilitating solute movement across biological membranes. These solutes include ions, sugars, amino acids, neurotransmitters, and drugs. Mutations in these ion channels have been associated with numerous disorders, underscoring the significance of SLC gene families in physiological processes. Among these, the SLC26A4 gene encodes pendrin, an anion exchange protein involved in transmembrane transport of chloride, iodide, and bicarbonate. Mutations in SLC26A4 are associated with Pendred syndrome. Elevated SLC26A4 expression has been linked to airway inflammation, hyperreactivity, and mucus production in asthma. Here, we review novel insights from SLC gene family members into the mechanisms of substrate transport and disease associations, with specific emphasis on SLC26A4. We explore triggers inducing SLC26A4 expression and its contributions to the pathogenesis of pulmonary diseases, particularly asthma. We summarize the inhibitors of SLC26A4 that have shown promise in the treatment of different phenotypes of diseases. While SLC26A4 inhibitors present potential treatments for asthma, further research is imperative to delineate their precise role in asthma pathogenesis and develop efficacious therapeutic strategies targeting this protein.

3.
Sci Rep ; 14(1): 19425, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169054

RESUMO

This paper introduces the efficient medical-images-aimed segment anything model (EMedSAM), addressing the high computational demands and limited adaptability of using SAM for medical image segmentation tasks. We present a novel, compact image encoder, DD-TinyViT, designed to enhance segmentation efficiency through an innovative parameter tuning method called med-adapter. The lightweight DD-TinyViT encoder is derived from the well-known ViT-H using a decoupled distillation approach.The segmentation and recognition capabilities of EMedSAM for specific structures are improved by med-adapter, which dynamically adjusts the model parameters specifically for medical imaging. We conducted extensive testing on EMedSAM using the public FLARE 2022 dataset and datasets from the First Hospital of Zhejiang University School of Medicine. The results demonstrate that our model outperforms existing state-of-the-art models in both multi-organ and lung segmentation tasks.


Assuntos
Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Pulmão/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Tomografia Computadorizada por Raios X/métodos , Modelos Teóricos
4.
Neuroreport ; 35(14): 875-882, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39166397

RESUMO

Emotional information can be seen everywhere in daily life. Research on emotional words often employs lexical decision tasks to judge the veracity of words, involving only superficial processing and not the deep processing of emotional significance. Therefore, the purpose of this study is to explore the effect of types of emotional words on the processing of emotional pictures. Participants were publicly recruited for a button-press experiment to discuss the impact of emotional words on the processing of emotional pictures from both behavioral and physiological mechanisms. The results of experiment 1 show: (a) in terms of reaction time, the processing speed for negative emotional words was slower, with longer reaction times; (b) In terms of accuracy, positive emotional words had a higher correct rate than negative emotional words. The results of experiment 2 found: (a) a significant main effect of emotional word type in the late processing stage; (b) a significant interaction between emotional word type and congruency. Previously presented emotional words affect the processing of subsequently presented emotional pictures, with differences in the processing of the four types of words, indicating a significant role of language in emotional processing.


Assuntos
Emoções , Potenciais Evocados , Estimulação Luminosa , Tempo de Reação , Humanos , Emoções/fisiologia , Feminino , Masculino , Tempo de Reação/fisiologia , Adulto Jovem , Potenciais Evocados/fisiologia , Adulto , Estimulação Luminosa/métodos , Eletroencefalografia , Reconhecimento Visual de Modelos/fisiologia , Encéfalo/fisiologia
5.
Environ Pollut ; 361: 124806, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39182815

RESUMO

Elemental mercury (Hg0) removal is a crucial target for mercury pollution control in flue gas. This article focuses on Hg0 removal in flue gas using corona discharge (CD) and dielectric barrier discharge (DBD) technologies, and provides a mechanistic perspective on the development and influencing factors of non-thermal plasma (NTP) technology for Hg0 removal. The influence factors include reactor configurations, power supplies, energy density, residence time, oxidation methods, gas composition, and the synergy between NTP and catalysis/adsorption, etc. This study reveals that the use of a pulsating electrical power supply significantly increases electron densities in both CD and DBD systems, thereby ensuring high energy efficiency and economic viability. Cl2 proves to be more effective than HCl as a chlorine source for Hg0 removal. NO significantly reduces Hg0 oxidation efficiency, while the effects of SO2 and H2O remain unclear. Energy density distribution is closely related to plasma devices, power supplies, and overall reactor configurations. Direct oxidation proves to be more effective than indirect oxidation for Hg0 removal. The combination of NTP with adsorption/catalysis technologies shows significantly better Hg0 removal efficiency compared to using NTP alone. This study can provide theoretical support for enhancing Hg0 removal mechanisms and optimizing process control parameters in industrial applications of NTP technology.

6.
FASEB J ; 38(16): e70024, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39190024

RESUMO

The role of programmed cell death 4 (PDCD4) in multiple myeloma (MM) development remains unknown. Here, we investigated its role and action mechanism in MM. Bioinformatic analysis indicated that patients with MM and high PDCD4 expression had higher overall survival than those with low PDCD4 expression. PDCD4 expression promoted MM cell apoptosis and inhibited their viability in vitro and tumor growth in vivo. RNA-binding protein immunoprecipitation sequencing analysis showed that PDCD4 is bound to the 5' UTR of the apoptosis-related genes PIK3CB, Cathepsin Z (CTSZ), and X-chromosome-linked apoptosis inhibitor (XIAP). PDCD4 knockdown reduced the cell apoptosis rate, which was rescued by adding PIK3CB, CTSZ, or XIAP inhibitors. Dual luciferase reporter assays confirmed the internal ribosome entry site (IRES) activity of the 5' UTRs of PIK3CB and CTSZ. An RNA pull-down assay confirmed binding of the 5' UTR of PIK3CB and CTSZ to PDCD4, identifying the specific binding fragments. PDCD4 is expected to promote MM cell apoptosis by binding to the IRES domain in the 5' UTR of PIK3CB and CTSZ and inhibiting their translation. Our findings suggest that PDCD4 plays an important role in MM development by regulating the expression of PIK3CB, CTSZ, and XIAP, and highlight new potential molecular targets for MM treatment.


Assuntos
Proteínas Reguladoras de Apoptose , Apoptose , Mieloma Múltiplo , Proteínas de Ligação a RNA , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Humanos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Animais , Camundongos , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Masculino
7.
Talanta ; 278: 126489, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38959667

RESUMO

Pyrazinamide (PZA) is a widely-used anti-tuberculosis pharmaceutical, but its poor solubility prompts us to optimize pharmaceutical performance. Cocrystallization is a promising technique to improve physiochemical properties of active pharmaceutical ingredient (API) by connecting it with cocrystal former (CCF) via intermolecular interactions. Even though a series of alkyl dicarboxylic acids are employed to form cocrystal structures, systematic understanding on the role of intermolecular interactions is still missing. Therefore, terahertz (THz) spectroscopy and quantum chemical calculation are combined to elucidate the behavior of ubiquitous supramolecular synthons, such as hetero-synthons of acid-pyrazine, acid-amide and homo-synthon of amide-amide, from energy's view. Potential energy is calculated to differentiate the stability within polymorphs of PZA-MA cocrystal and free energy is evaluated to compare the solubility of PZA-CCF cocrystals respectively. With regard to vibrational energy, THz spectral fingerprints are theoretically assigned to specific vibrations and attributed to the flexibility deformation of supramolecular synthons based on oscillation theory, where stretching and twisting modes dominate the collective vibrational behavior. It provides a promising tool to evaluate cocrystal performance from its driving force and insightful guidance to discover new pharmaceutical cocrystals.

8.
J Colloid Interface Sci ; 676: 52-60, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018810

RESUMO

The seawater electrolysis technology powered by renewable energy is recognized as the promising "green hydrogen" production method to solve serious energy and environmental problems. The lack of low-cost and ampere-level current OER (oxygen evolution reaction) and HER (hydrogen evolution reaction) catalysis limits their industrial application. In this work, a unique tri-metal (Co/Fe/Ni) layered double hydroxide hollow array anode catalyst (CFN-LDH/NF) and the CoP/FeNi2P heterojunction hollow array cathode are successfully prepared via one in-situ growth of Co-MOF on nickel foam (Co-MOF/NF) precursor, which exhibits excellent catalytic performance. The η1000 values of 352 and 392 mV are achieved for CFN-LDH/NF (OER catalyst) in 1.0 M KOH and alkaline seawater solution, respectively. The CFNP/NF with a low overpotential of 281 mV is required to reach 1000 mA cm-2 current density for HER in 1.0 M KOH solution, while the η1000 in alkaline seawater solution is 312 mV. The CFN-LDH/NF||CFNP/NF electrolyzer exhibits excellent long-term durability over 100 h, achieving current density of 500 mA cm-2 at 1.825 V in 1.0 M KOH solution. The construction of hollow tri-metal LDH and phosphides heterostructures may open a new and relatively unexplored path for fabricating high performance seawater splitting catalysis.

9.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001137

RESUMO

Low-light imaging capabilities are in urgent demand in many fields, such as security surveillance, night-time autonomous driving, wilderness rescue, and environmental monitoring. The excellent performance of SPAD devices gives them significant potential for applications in low-light imaging. This article presents a 64 (rows) × 128 (columns) SPAD image sensor designed for low-light imaging. The chip utilizes a three-dimensional stacking architecture and microlens technology, combined with compact gated pixel circuits designed with thick-gate MOS transistors, which further enhance the SPAD's photosensitivity. The configurable digital control circuit allows for the adjustment of exposure time, enabling the sensor to adapt to different lighting conditions. The chip exhibits very low dark noise levels, with an average DCR of 41.5 cps at 2.4 V excess bias voltage. Additionally, it employs a denoising algorithm specifically developed for the SPAD image sensor, achieving two-dimensional grayscale imaging under 6 × 10-4 lux illumination conditions, demonstrating excellent low-light imaging capabilities. The chip designed in this paper fully leverages the performance advantages of SPAD image sensors and holds promise for applications in various fields requiring low-light imaging capabilities.

10.
Chem Asian J ; : e202400496, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037569

RESUMO

Innovations in wearable sweat sensors hold great promise to provide deeper insights into molecular level health information non-invasively. Lactate, a key metabolite present in sweat, holds immense significance in assessing physiological conditions and performance in sports physiology and health sensing. This paper presents the development and characterization of stretchable electrodes with ultrahigh active surface area of 648% for lactate sensing. The as-printed stretchable electrodes were functionalized with an electron transfer layer comprising of Toluidine Blue O and multi-walled carbon nanotubes (MWCNTs), and an enzymatic layer consisting of lactate dehydrogenase with ß-Nicotinamide adenine dinucleotide as the cofactor for lactate selectivity. This sensor achieves a dual-signal read-out in which both electrochemical and fluorescence signals were obtained during lactate detection, demonstrating promising sensor performance in terms of sensitivity and reliability. We demonstrate the robustness of the dual-signal sensor under simulated conditions of physical deformation and shifted excitation. Under these compromised conditions, the performance of the stretchable electrodes remained largely unaffected, showcasing their potential for robust and adaptable sensing platforms in wearable health monitoring applications.

11.
Polymers (Basel) ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000778

RESUMO

Lignins, naturally occurring aromatic polymers with phenylpropane units, are promising bio-based alternatives for petroleum-based products. Resole-type phenol formaldehyde (PF) adhesive is commonly used in wood composites requiring durability and weather-proofness. However, PF adhesive is a petroleum-based product. The objective of this study is to transform the low-reactivity hardwood kraft lignin (KL) as the phenol substitute in the PF adhesive formulation by acidic phenolation. The variations in the molecular weights, chemical structures, and functional groups in lignins were investigated before and after the phenolation. The results indicate that the KL can be cleaved, and phenols are crosslinked onto KL to produce phenolated kraft lignin (PKL) under the suitable phenolation condition, heating 3/5 (w/w) of KL/phenol at 90 °C for 2 h with 5% H2SO4 as the catalyst. Resole-type PKL-PF adhesives can be directly synthesized after the phenolation in the same reactor. Plywood laminated with this adhesive obtains satisfactory strength and low formaldehyde emission. This not only reduces the usage of petroleum-based phenol but also increases the reactivity and applications for hardwood KL.

12.
J Inflamm Res ; 17: 3815-3823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895142

RESUMO

Purpose: Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies. Patients and Methods: Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration. Results: PDM patients had a higher median age compared to GLM patients (38 vs 32, p<0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p<0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p<0.001), ductal wall thickening (47.93% vs 1.75%, p<0.001), and ductal rupture (44.63% vs 5.26%, p<0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p<0.001), microabscess (68.42% vs 28.93%, p<0.001), and lipid vacuole (40.35% vs 8.26%, p<0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy. Conclusion: PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.

13.
Int J Biol Sci ; 20(8): 2904-2921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904023

RESUMO

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the critical pathological mechanisms of pulmonary hypertension (PH), and therefore is gradually being adopted as an important direction for the treatment of PH. Metallothioneins (MTs) have been reported to be associated with PH, but the underlying mechanisms are not fully understood. Here, we demonstrated that the expression level of metallothionein 3 (MT3) was significantly increased in pulmonary arterioles from PH patients and chronic hypoxia-induced rat and mouse PH models, as well as in hypoxia-treated human PASMCs. Knockdown of MT3 significantly inhibited the proliferation of human PASMCs by arresting the cell cycle in the G1 phase, while overexpression of MT3 had the opposite effect. Mechanistically, we found that MT3 increased the intracellular zinc (Zn2+) concentration to enhance the transcriptional activity of metal-regulated transcription factor 1 (MTF1), which promoted the expression of autophagy-related gene 5 (ATG5), facilitating autophagosome formation. More importantly, MT3-induced autophagy and proliferation of human PASMCs were largely prevented by knockdown of MTF1 and ATG5. Therefore, in this study, we identified MT3-Zinc-MTF1-ATG5 as a novel pathway that affects PASMC proliferation by regulating autophagosome formation, suggesting that MT3 may be a novel target for the treatment of PH.


Assuntos
Proliferação de Células , Metalotioneína 3 , Miócitos de Músculo Liso , Artéria Pulmonar , Zinco , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Animais , Humanos , Zinco/metabolismo , Camundongos , Ratos , Miócitos de Músculo Liso/metabolismo , Masculino , Autofagossomos/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Autofagia , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fator MTF-1 de Transcrição , Metalotioneína/metabolismo , Metalotioneína/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-38861446

RESUMO

This paper presents a digital edge neuromorphic spiking neural network (SNN) processor chip for a variety of edge intelligent cognitive applications. This processor allows high-speed, high-accuracy and fully on-chip spike-timing-based multi-layer SNN learning. It is characteristic of hierarchical multi-core architecture, event-driven processing paradigm, meta-crossbar for efficient spike communication, and hybrid and reconfigurable parallelism. A prototype chip occupying an active silicon area of 7.2 mm2 was fabricated using a 65-nm 1P9M CMOS process. when running a 256-256-256-256-200 4-layer fully-connected SNN on downscaled 16 × 16 MNIST images. it typically achieved a high-speed throughput of 802 and 2270 frames/s for on-chip learning and inference, respectively, with a relatively low power dissipation of around 61 mW at a 100 MHz clock rate under a 1.0V core power supply, Our on-chip learning results in comparably high visual recognition accuracies of 96.06%, 83.38%, 84.53%, 99.22% and 100% on the MNIST, Fashion-MNIST, ETH-80, Yale-10 and ORL-10 datasets, respectively. In addition, we have successfully applied our neuromorphic chip to demonstrate high-resolution satellite cloud image segmentation and non-visual tasks including olfactory classification and textural news categorization. These results indicate that our neuromorphic chip is suitable for various intelligent edge systems under restricted cost, energy and latency budgets while requiring in-situ self-adaptative learning capability.

15.
Front Pharmacol ; 15: 1397029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910884

RESUMO

Background: Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight management in adults with obesity or overweight as an adjunct to a reduced-calorie diet and increased physical activity. However, the safety profile of Tirzepatide-associated adverse events requires comprehensive evaluation. Methods: The AE reports from the first quarter of 2022 to the third quarter of 2023 were selected by exploring the FDA Adverse Event Reporting System (FAERS) database. The new and unexpected potenial AE signals were detected using the disproportionality analysis, including reporting odds ratio(ROR), the proportional reporting ratio (PRR) the Bayesian confidence propagation neural network (BCPNN) and the empirical Bayes geometric mean(EBGM). Then the MedDRA was used to systematically classify the results. Results: A total of 1,904,481 case reports were obtained from 2022Q2 to 2023Q3. Forty-sixth tirzepatide-induced ADRs at the preferred terms (PTs) level are associated with 8 system organ class In addition, this study uncovered multiple anticipated ADRs, such as gastrooesophageal reflux disease, dyspepsia, and vomiting, in line with the drug labels. Moreover, unexpected and significant ADRs at PTs level, such as incorrect dose administered, injection site haemorrhage, and increased appetite, were discovered and linked to Injury, poisoning, and procedural complications, General disorders and administration site conditions, and Metabolism and nutrition disorders at the System Organ Class level. Conclusion: This study offered new perspectives on the monitoring, surveillance, and management of adverse drug reactions related to tirzepatide. The outcomes of severe adverse events and their respective detection signals, along with unexpected significant adverse event signals, are important to consider in efforts to enhance clinical medication safety when using tirzepatide.

16.
Circ Res ; 135(1): 93-109, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770649

RESUMO

BACKGROUND: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown. METHODS: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 (deformed epidural auto-regulatory factor-1) domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 (3-cyano-5-{2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]-phenyl}-N-[(3-pyrrolidin-1-yl)propyl]benzamide) were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism. RESULTS: We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH. CONCLUSIONS: Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.


Assuntos
Histona-Lisina N-Metiltransferase , Hipertensão Pulmonar , Hipóxia , Mitofagia , Músculo Liso Vascular , Miócitos de Músculo Liso , PPAR gama , Artéria Pulmonar , Ratos Sprague-Dawley , Animais , Humanos , Masculino , Camundongos , Ratos , Proliferação de Células , Células Cultivadas , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Hipóxia/complicações , Hipóxia/metabolismo , Metilação , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , PPAR gama/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/metabolismo , Remodelação Vascular
17.
Environ Res ; 254: 119164, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38762005

RESUMO

The necessity for global engineering and technological solutions to address rural environmental challenges is paramount, particularly in improving rural waste treatment and infrastructure. This study presents a comprehensive quantitative analysis of 3901 SCI/SSCI and 3818 Chinese CSCD papers, spanning from 1989 to 2021, using tools like Derwent Data Analyzer and VOSviewer. Our key findings reveal a significant evolution in research focus, including a 716.67% increase in global publications from 1995 to 2008 and a 154.76% surge from 2015 to 2021, highlighting a growing research interest with technological hotspots in rural revitalization engineering and agricultural waste recycling. China and the USA are pivotal, contributing 784 and 714 publications respectively. Prominent institutions such as the Chinese Academy of Sciences play a crucial role, particularly in fecal waste treatment technology. These insights advocate for enhanced policy development and practical implementations to foster inclusive and sustainable rural environments globally.


Assuntos
População Rural , Engenharia , Reciclagem , China , Gerenciamento de Resíduos/métodos , Tecnologia , Agricultura/métodos
18.
Ecotoxicol Environ Saf ; 279: 116504, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795418

RESUMO

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.


Assuntos
Irradiação Craniana , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-kit , Espermatogênese , Animais , Masculino , Espermatogênese/efeitos da radiação , Camundongos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estresse Oxidativo/efeitos da radiação , Irradiação Craniana/efeitos adversos , Testículo/efeitos da radiação , Testículo/patologia , Transdução de Sinais/efeitos da radiação , Fator de Células-Tronco/metabolismo , Inflamação
19.
J Colloid Interface Sci ; 671: 67-77, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38788425

RESUMO

With the wide application of electromagnetic waves in national defense, communication, navigation and home appliances, the electromagnetic pollution problem is becoming more and more prominent. Therefore, high-performance, and low-density composite wave-absorbing materials have attracted much attention. In this paper, three-dimensional (3D) network structures of flower-like 1T/2H Molybdenum disulfide nanosheets anchored to carbon fibers (1T/2H MoS2/CNFs) were prepared by electrostatic spinning technique and calcination process. The morphology and electromagnetic wave absorption properties were tuned by changing the content of flower-like MoS2. The optimized 1T/2H MoS2/CNFs composite exhibits superior electromagnetic wave absorption with minimum reflection (RLmin) of -42.26 dB and effective absorption bandwidth (EAB) of 6.48 GHz at 2.5 mm. Multi-facts contribute to the super performance. First, the uniquely designed nanosheet and 3D interconnected networks leads to multiple reflection and scattering of electromagnetic waves, which promotes the attenuation of electromagnetic waves. Second, the propriate content of CNFs and MoS2 with different phase regulates its impedance matching characteristic. Third, Numerous heterogeneous interfaces existed between CNFs and MoS2, 1T and 2H MoS2 phase results in interface polarization. Besides, the 1T/2H MoS2 rich in defects induces defect polarization, improving the dielectric loss. Furthermore, the electromagnetic wave absorption performance was proved via radar reflectance cross section simulation. This work illustrates 1T/2H MoS2/CNFs is a promising material for electromagnetic absorption with wide bandwidth, strong absorption, low density, and high thermal stability.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124387, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704999

RESUMO

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.


Assuntos
Neoplasias da Mama , Jejum , Análise Espectral Raman , Microambiente Tumoral , Análise Espectral Raman/métodos , Animais , Feminino , Microambiente Tumoral/efeitos dos fármacos , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/patologia , Ratos , Modelos Animais de Doenças , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Neoplasias Mamárias Experimentais/prevenção & controle , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Ratos Sprague-Dawley , Jejum Intermitente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA