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1.
Nanomicro Lett ; 16(1): 236, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963539

RESUMO

Inspired by the Chinese Knotting weave structure, an electromagnetic interference (EMI) nanofiber composite membrane with a twill surface was prepared. Poly(vinyl alcohol-co-ethylene) (Pva-co-PE) nanofibers and twill nylon fabric were used as the matrix and filter templates, respectively. A Pva-co-PE-MXene/silver nanowire (Pva-co-PE-MXene/AgNW, PMxAg) membrane was successfully prepared using a template method. When the MXene/AgNW content was only 7.4 wt% (PM7.4Ag), the EMI shielding efficiency (SE) of the composite membrane with the oblique twill structure on the surface was 103.9 dB and the surface twill structure improved the EMI by 38.5%. This result was attributed to the pre-interference of the oblique twill structure in the direction of the incident EM wave, which enhanced the probability of the electromagnetic waves randomly colliding with the MXene nanosheets. Simultaneously, the internal reflection and ohmic and resonance losses were enhanced. The PM7.4Ag membrane with the twill structure exhibited both an outstanding tensile strength of 22.8 MPa and EMI SE/t of 3925.2 dB cm-1. Moreover, the PMxAg nanocomposite membranes demonstrated an excellent thermal management performance, hydrophobicity, non-flammability, and performance stability, which was demonstrated by an EMI SE of 97.3% in a high-temperature environment of 140 °C. The successful preparation of surface-twill composite membranes makes it difficult to achieve both a low filler content and a high EMI SE in electromagnetic shielding materials. This strategy provides a new approach for preparing thin membranes with excellent EMI properties.

2.
IEEE Trans Cybern ; PP2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963742

RESUMO

This article investigates an adaptive neural network (NN) control technique with fixed-time tracking capabilities, employing composite learning, for manipulators under constrained position error. The first step involves integrating the composite learning method into the NN to address the dynamic uncertainties that inevitably arise in manipulators. A composite adaptive updating law of NN weights is formulated, requiring adherence solely to the relaxed interval excitation (IE) conditions. In addition, for the output error, instead of knowing the initial conditions, this article integrates the error transfer function and asymmetric barrier function to achieve the specific performance for position error in both steady and transient states. Furthermore, the fixed-time control methodology and Lyapunov stability criterion are synergistically employed in order to guarantee the convergence of all signals in the manipulators to a compact neighborhood around the origin within a fixed-time. Finally, numerical simulation and experiments with the Baxter robot results both determine the capability of the NN composite learning technique and fixed-time control strategy.

3.
Plant Sci ; 346: 112162, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901780

RESUMO

CrRLK1L subfamily members are involved in diverse growth- and development-related processes in Arabidopsis. However, the functions of their counterparts in rice are unknown. Here, OsANX expression was detected in developing inflorescences, mature pollen grains, and growing pollen tubes, and it was localized to the plasma membrane in pollen grains and tobacco epidermal cells. Homozygous osanx progeny could not be segregated from the CRISPR/Cas9-edited mutants osanx-c1+/- and osanx-c2+/-, and such progeny were segregated only occasionally from osanx-c3+/-. Further, all three alleles showed osanx male but not female gamete transmission defects, in line with premature pollen tube rupture in osanx-c3. Additionally, osanx-c3 exhibited precocious flowering, excessively branched inflorescences, and an extremely low seed setting rate of 1.4 %, while osanx-c2+/- and osanx-c3+/- had no obvious defects in inflorescence development or the seed setting rate compared to wild-type Nipponbare (Nip). Consistent with this, the complemented line pPS1:OsANX-GFP/osanx-c2 (PSC), in which the lack of OsANX expression was inflorescence-specific, showed slightly earlier flowering and overly-branched panicles. Multiple inflorescence meristem transition-related and inflorescence architecture-related genes were expressed at higher levels in osanx-c3 than in Nip; thus, they may partially account for the aforementioned mutant phenotypes. Our findings broaden our understanding of the biological functions of OsANX in rice.


Assuntos
Inflorescência , Oryza , Proteínas de Plantas , Tubo Polínico , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Oryza/enzimologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inflorescência/genética , Inflorescência/crescimento & desenvolvimento , Tubo Polínico/crescimento & desenvolvimento , Tubo Polínico/genética , Flores/crescimento & desenvolvimento , Flores/genética , Regulação da Expressão Gênica de Plantas
4.
Virol J ; 21(1): 131, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840200

RESUMO

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.


Assuntos
Infecções por Citomegalovirus , Hemorragia , Humanos , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Recém-Nascido , Masculino , Evolução Fatal , Hemorragia/etiologia , Citomegalovirus , Pulmão/patologia , Pulmão/diagnóstico por imagem , Pulmão/virologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Autopsia , Pneumopatias/virologia , Pneumopatias/etiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38743538

RESUMO

Learning an autonomous dynamic system (ADS) encoding human motion rules has been shown as an effective way for human motion skills transfer. However, most existing approaches focus on goal-directed motion skills transfer, and the study on periodic motion skills transfer is rare. One popular approach for periodic motion skills transfer is learning periodic dynamic movement primitive (DMP); however, periodic DMP is sensitive to spatial disturbances due to the introduction of the phase parameters. To solve this issue, this brief presents a novel approach to learn an ADS with a stable limit cycle without introducing phase parameters. First, a data-driven Lyapunov function (energy function) is learned, such that one of its level surfaces is consistent with periodic human demonstration trajectories. Then, an ADS is learned by sequentially solving energy function-related constrained optimization problems. With a proper design of constraint functions, we can ensure that the trajectory generated by the ADS will converge to an energy function-level surface, of which the shape is similar to periodic human demonstration trajectories. Experiments are conducted to show the effectiveness of the proposed approach (PA).

6.
Plants (Basel) ; 13(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38592851

RESUMO

Receptor kinases DRUS1 (Dwarf and Runtish Spikelet1) and DRUS2 are orthologues of the renowned Arabidopsis thaliana gene FERONIA, which play redundant roles in rice growth and development. Whether the two duplicated genes perform distinct functions in response to environmental stress is largely unknown. Here, we found that osmotic stress (OS) and ABA increased DRUS1 expression while decreasing DRUS2. When subjected to osmotic stress, the increased DRUS1 in drus2 mutants suppresses the OsIAA repressors, resulting in a robust root system with an increased number of adventitious and lateral roots as well as elongated primary, adventitious, and lateral roots, conferring OS tolerance. In contrast, the decreased DRUS2 in drus1-1 mutants are not sufficient to suppress OsIAA repressors, leading to a feeble root system with fewer adventitious and lateral roots and hindering seminal root growth, rendering OS intolerance. All these findings offer valuable insights into the biological significance of the duplication of two homologous genes in rice, wherein, if one is impaired, the other one is able to continue auxin-signaling-mediated root growth and development to favor resilience to environmental stress, such as water shortage.

7.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(2): 335-341, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38686415

RESUMO

Place cell with location tuning characteristics play an important role in brain spatial cognition and navigation, but there is relatively little research on place cell screening and its influencing factors. Taking pigeons as model animals, the screening process of pigeon place cell was given by using the spike signal in pigeon hippocampus under free activity. The effects of grid number and filter kernel size on the place field of place cells during the screening process were analyzed. The results from the real and simulation data showed that the proposed place cell screening method presented in this study could effectively screen out place cell, and the research found that the size of place field was basically inversely proportional to the number of grids divided, and was basically proportional to the size of Gaussian filter kernel in the overall trend. This result will not only help to determine the appropriate parameters in the place cell screening process, but also promote the research on the neural mechanism of spatial cognition and navigation of birds such as pigeons.


Assuntos
Columbidae , Hipocampo , Columbidae/fisiologia , Animais , Hipocampo/citologia , Hipocampo/fisiologia , Células de Lugar/fisiologia , Navegação Espacial/fisiologia , Cognição , Potenciais de Ação
8.
Proc Natl Acad Sci U S A ; 121(16): e2314359121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38557166

RESUMO

Suction is a highly evolved biological adhesion strategy for soft-body organisms to achieve strong grasping on various objects. Biological suckers can adaptively attach to dry complex surfaces such as rocks and shells, which are extremely challenging for current artificial suction cups. Although the adaptive suction of biological suckers is believed to be the result of their soft body's mechanical deformation, some studies imply that in-sucker mucus secretion may be another critical factor in helping attach to complex surfaces, thanks to its high viscosity. Inspired by the combined action of biological suckers' soft bodies and mucus secretion, we propose a multiscale suction mechanism which successfully achieves strong adaptive suction on dry complex surfaces which are both highly curved and rough, such as a stone. The proposed multiscale suction mechanism is an organic combination of mechanical conformation and regulated water seal. Multilayer soft materials first generate a rough mechanical conformation to the substrate, reducing leaking apertures to micrometres (~10 µm). The remaining micron-sized apertures are then sealed by regulated water secretion from an artificial fluidic system based on the physical model, thereby the suction cup achieves long suction longevity on complex surfaces but minimal overflow. We discuss its physical principles and demonstrate its practical application as a robotic gripper on a wide range of complex dry surfaces. We believe the presented multiscale adaptive suction mechanism is a powerful unique adaptive suction strategy which may be instrumental in the development of versatile soft adhesion.


Assuntos
Robótica , Água , Sucção , Desenho de Equipamento
10.
Nat Commun ; 15(1): 2488, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509071

RESUMO

Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by dynamin-like GTPase atlastin (ATL). This fundamental process relies on GTP-dependent domain rearrangements in the N-terminal region of ATL (ATLcyto), including the GTPase domain and three-helix bundle (3HB). However, its conformational dynamics during the GTPase cycle remain elusive. Here, we combine single-molecule FRET imaging and molecular dynamics simulations to address this conundrum. Different from the prevailing model, ATLcyto can form a loose crossover dimer upon GTP binding, which is tightened by GTP hydrolysis for membrane fusion. Furthermore, the α-helical motif between the 3HB and transmembrane domain, which is embedded in the surface of the lipid bilayer and self-associates in the crossover dimer, is required for ATL function. To recycle the proteins, Pi release, which disassembles the dimer, activates frequent relative movements between the GTPase domain and 3HB, and subsequent GDP dissociation alters the conformational preference of the ATLcyto monomer for entering the next reaction cycle. Finally, we found that two disease-causing mutations affect human ATL1 activity by destabilizing GTP binding-induced loose crossover dimer formation and the membrane-embedded helix, respectively. These results provide insights into ATL-mediated homotypic membrane fusion and the pathological mechanisms of related disease.


Assuntos
Proteínas de Drosophila , Humanos , Proteínas de Drosophila/metabolismo , Fusão de Membrana/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Hidrólise , Guanosina Trifosfato/metabolismo
11.
J Affect Disord ; 354: 500-508, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484883

RESUMO

BACKGROUND: The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD). METHODS: This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety. RESULTS: The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD. LIMITATIONS: Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects. CONCLUSION: Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico/métodos , Lobo Temporal
13.
BMC Cardiovasc Disord ; 24(1): 117, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373881

RESUMO

BACKGROUND: To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST segment elevation myocardial infarction (STEMI) patients. METHODS: This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients [hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046]. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027). CONCLUSION: The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Estudos de Coortes , Estudos Retrospectivos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Fatores de Risco , Prognóstico , Arritmias Cardíacas/complicações , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco
14.
Front Bioeng Biotechnol ; 12: 1336692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375454

RESUMO

Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth. Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques. Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages. Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38357951

RESUMO

INTRODUCTION: Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However, whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD+ and LCZ696. METHOD: Cardiac function, hemodynamics, and biomarkers were evaluated during the treatment period. Heart weight, myocardial fibrosis, and MI rate were measured eventually. RESULT: Compared with the HF groups, groups treated with LCZ696 and different doses of NAD+ showed increased ejection fractions, fractional shortening, cardiac output, and stroke volume and decreased end-systolic volume, end-systolic dimension, creatine kinase, and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group, but this decrease was significantly greater in the medium and high NAD+ dose groups. CONCLUSION: The ratios of heart weight indexes, fibrotic areas, and MI rates in the CZ696 and medium and high NAD+ dose groups were lower than those in the HF group. Medium and high-dose NAD+ showed superior positive effects on myocardial hypertrophy, cardiac function, and myocardial fibrosis and reduced the MI rate.

16.
Soft Matter ; 20(5): 1089-1099, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38221881

RESUMO

An exciting result is reported in this study where a polypropylene (PP) foam with a high open-cell content was achieved by constructing a thermally conductive network for the first time. PP and nano-graphite particles were used as substrate and filler, respectively, to prepare the PP-graphite (PP-G) composite foam by twin-screw blending, hot pressing, and supercritical CO2 foaming. The nano-graphite particles can effectively adjust the microstructure of the PP-G foam and achieve a high porosity. When the amount of nano-graphite is 10.0 wt%, the PP-G foam exhibits optimal sound absorption performance, compression resistance, heat insulation, and hydrophobic properties. In the human-sensitive frequency range of 1000-6000 Hz, the corresponding average SAC is above 0.9, and the internal tortuosity is 5.27. After 50 cycles of compression, the compressive stress is 980 kPa and the SAC loss is only 7.8%. This study also innovatively proposed a new strategy to achieve the simple and rapid preparation of open-cell PP foams by increasing the thermal conductivity of the foaming substrate.

17.
Int J Nanomedicine ; 18: 6901-6914, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026524

RESUMO

Purpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy. Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated. Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model. Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias do Colo do Útero , Humanos , Animais , Camundongos , Feminino , Antineoplásicos/uso terapêutico , Polietilenoglicóis/química , Ácido Glutâmico , Neoplasias do Colo do Útero/tratamento farmacológico , Nanopartículas/química
18.
Digit Health ; 9: 20552076231188206, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529540

RESUMO

Introduction: Sleep is vital to human health, and sleep staging is an essential process in sleep assessment. However, manual classification is an inefficient task. Along with the increased demand for portable sleep quality detection devices, lightweight automatic sleep staging needs to be developed. Methods: This study proposes a novel attention-based lightweight deep learning model called LWSleepNet. A depthwise separable multi-resolution convolutional neural network is introduced to analyze the input feature map and captures features at multiple frequencies using two different sized convolutional kernels. The temporal feature extraction module divides the input into patches and feeds them into a multi-head attention block to extract time-dependent information from sleep recordings. The model's convolution operations are replaced with depthwise separable convolutions to minimize its number of parameters and computational cost. The model's performance on two public datasets (Sleep-EDF-20 and Sleep-EDF-78) was evaluated and compared with those of previous studies. Then, an ablation study and sensitivity analysis were performed to evaluate further each module. Results: LWSleepNet achieves an accuracy of 86.6% and Macro-F1 score of 79.2% for the Sleep-EDF-20 dataset and an accuracy of 81.5% and Macro-F1 score of 74.3% for the Sleep-EDF-78 dataset with only 55.3 million floating-point operations per second and 180 K parameters. Conclusion: On two public datasets, LWSleepNet maintains excellent prediction performance while substantially reducing the number of parameters, demonstrating that our proposed Light multiresolution convolutional neural network and temporal feature extraction modules can provide excellent portability and accuracy and can be easily integrated into portable sleep monitoring devices.

19.
Front Cardiovasc Med ; 10: 1208370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469482

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) represents a syndrome involving multiple pathophysiologic disorders and clinical phenotypes. This complexity makes it challenging to develop a comprehensive preclinical model, which presents an obstacle to elucidating disease mechanisms and developing new drugs. Metabolic syndrome (MetS) is a major phenotype of HFpEF. Thus, we produced a rat model of the MetS-related HFpEF phenotype and explored the molecular mechanisms underpinning the observed pathological changes. Methods: A rat model of the MetS-related HFpEF phenotype was created by feeding spontaneously hypertensive rats a high-fat-salt-sugar diet and administering streptozotocin solution intraperitoneally. Subsequently, pathological changes in the rat heart and their possible molecular mechanisms were explored. Results: The HFpEF rats demonstrated primary features of MetS, such as hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and cardiac anomalies, such as left ventricular (LV) remodeling and diastolic impairment, and left atrial dilation. Additionally, inflammation, myocardial hypertrophy, and fibrosis were observed in LV myocardial tissue, which may be associated with diverse cellular and molecular signaling cascades. First, the inflammatory response might be related to the overexpression of inflammatory regulators (growth differentiation factor 15 (GDF-15), intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1)). Secondly, phosphorylated glycogen synthase kinase 3ß (GSK-3ß) may stimulate cardiac hypertrophy, which was regulated by activated -RAC-alpha serine/threonine-protein kinase (AKT). Finally, the transforming growth factor-ß1 (TGF-ß1)/Smads pathway might regulate collagen production and fibroblast activation, promoting myocardial fibrosis. Conclusion: The HFpEF rat replicates the pathology and clinical presentation of human HFpEF with MetS and may be a reliable preclinical model that helps elucidate HFpEF pathogenesis and develop effective treatment strategies.

20.
J Ethnopharmacol ; 317: 116849, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37385575

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown. AIM OF THE STUDY: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway from the perspective of animal experiments. MATERIALS AND METHODS: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-ß1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-ß1/Smads pathways. RESULTS: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-ß1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-ß1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-ß1/Smads pathway. CONCLUSION: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-ß1/Smads pathways in HFpEF rats.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Ratos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Simulação de Acoplamento Molecular , Volume Sistólico , Fibrose , Transdução de Sinais , Cardiomiopatias/metabolismo , RNA Mensageiro/metabolismo
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