Assuntos
Fibrose Pulmonar , Fibrose Pulmonar/genética , Fibrose Pulmonar/tratamento farmacológico , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Montagem e Desmontagem da Cromatina/genética , Animais , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Camundongos , DNA Helicases/genética , DNA Helicases/metabolismoRESUMO
Scaffolds with multiphasic structures are considered to be superior for guided tissue regeneration. Two types of tilapia skin collagen gradient membranes (stepped gradient and linear gradient) with multiphasic structures were prepared by controlling the collagen concentrations and the freezing rates. The results revealed that collagen gradient membranes were more capable of guiding tissue regeneration compared to homogeneous membranes. These two gradient membranes featured a dense outer layer and a loose inner layer, with good mechanical properties as indicated by tensile strengths of more than 250 Kpa and porosities exceeding 85â¯%. Additionally, these membranes also showed good hydrophilicity and water absorption, with an inner layer contact angle of less than 91° and a water absorption ratio greater than 40 times. Furthermore, the multiphasic scaffolds were proved to be biocompatible by the acute toxicity assay, the intradermal irritation test and so on. Gradient membranes could effectively promote the adhesion and proliferation of fibroblasts and osteoblasts, through elevating the TGF-ß/Smad signaling pathway by TGF-ß and Smads, and activating the Wnt/ß-catenin signaling pathway by LRP5 and ß-catenin, similar to homogenous membranes. Therefore, collagen gradient membranes from tilapia skin show important application value in guiding tissue regeneration.
RESUMO
Inchworm piezoelectric actuators have attracted much attention in the field of precision positioning due to the advantages of a large stroke, high output force, and high resolution. However, traditional inchworm piezoelectric actuators use two sets of clamps and a set of drive structures to achieve stepping motion, which generally requires at least three piezoelectric stacks, resulting in a complex structure and the control system. Several methodologies have been advanced to minimize the utilization of piezoelectric stacks. However, there still exists the issue of excessive volume. Therefore, an inchworm piezoelectric actuator with a single-clamp and single drive structure is proposed in the study, which provides a compact size and smaller volume. The clamping mechanism comprises two sets of clamping feet with opposite displacement, which alternate contact with the guide frame and adjustable plate to ensure that the clamping mechanism always has frictional force and accomplishes the stepping motion. The testing of the actuator's step distance, output force, and other parameters was conducted utilizing a displacement sensor. Experimental results indicate that the actuator achieved a maximum speed of 174.3 µm/s and an output force of 8.6 N when the frequency and voltage were 19 Hz and 150 V.
RESUMO
Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray's competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000-1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312-1.710, P < 0.001), and sarcopenia (HR 1.802, 95% CI 1.062-3.060, P = 0.029) were independently associated with increased 90-day mortality. Subgroup analysis of male patients with HBV-ACLF revealed that myosteatosis (HR 2.119, 95% CI 1.101-4.078, P = 0.025) was promising prognostic factors for 90-day mortality after being adjusted for ascites, acute kidney injury, AARC score, and sarcopenia. Myosteatosis is predictive of short-term outcomes in male patients with HBV-ACLF. Our results emphasise the importance of focusing on muscle fat infiltration in patients with HBV-ACLF. Further studies are warranted to investigate the underlying mechanisms and potential therapies for myosteatosis.
Assuntos
Insuficiência Hepática Crônica Agudizada , Sarcopenia , Humanos , Masculino , Feminino , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/etiologia , Pessoa de Meia-Idade , Sarcopenia/complicações , Estudos Retrospectivos , Prognóstico , Adulto , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Composição Corporal , Tecido Adiposo/patologia , Fatores de Risco , IdosoRESUMO
With the intensification of human activities, the amount of phosphorus (P)-containing waste has increased. When such waste is not recycled, P is released into the environment, leading to environmental issues such as the eutrophication of water bodies. In this study, based on the material flow analysis method, a P Waste Flow analysis model (P-WFA) was developed to analyze the P flow in the waste system of Poyang Lake, the largest freshwater lake in China. To address the research gap in long-term P flow analysis at the watershed scale, this study quantified the P content in the waste system of the Poyang Lake Watershed from 1950 to 2020. The analysis revealed that from 1950 to 2020, the total P input into the waste system increased from 5.49 × 104 tons in 1950 to 2.28 × 105 tons in 2020. The breeding industry system was identified as the primary source, accounting for 25.19-41.59 % of the total waste system. Over the past 70 years, P loss to surface water from waste systems has been primarily facilitated by manure from the breeding industry, as well as drainage from crop farming systems (77.74 % in 2020). At the same time, the P recycling rate (PRR) of the waste system exhibited an initial increase followed by a decrease, increasing from 44.14 % to 47.75 % before dropping to 44.41 %. Population growth, urbanization, and changes in consumption levels in Jiangxi Province have led to changes in the dietary structure and fertilizer use, consequently affecting the P cycling pattern. This study presents a comprehensive P flow model for waste systems in the Poyang Lake Watershed. This model can be used as a reference to enhance P cycling and manage P loss in other large freshwater lakes.
RESUMO
INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.
Assuntos
Medicamentos de Ervas Chinesas , Fumigação , Paeonia , Enxofre , Espectrometria de Massas em Tandem , Paeonia/química , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Enxofre/química , Fumigação/métodos , Glucosídeos/química , Monoterpenos/química , Metabolômica/métodosRESUMO
Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. Cortical slow oscillations drive the repeated reactivation of hippocampal memory representations together with SWRs and thalamo-cortical spindles, inducing long-lasting cellular and network modifications responsible for memory stabilization.In this review, we aim to comprehensively cover the field of "reactivation and memory consolidation" research by detailing the physiological mechanisms of neuronal reactivation and firing patterns during SWRs and providing a discussion of more recent key findings. Several mechanistic explanations of neuropsychiatric diseases propose that impaired neural replay may underlie some of the symptoms of the disorders. Abnormalities in neuronal reactivation are a common phenomenon and cause pathological impairment in several diseases, such as Alzheimer's disease (AD), epilepsy and schizophrenia. However, the specific pathological changes and mechanisms of reactivation in each disease are different. Recent work has also enlightened some of the underlying pathological mechanisms of neuronal reactivation in these diseases. In this review, we further describe how SWRs, ripples and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response.
Assuntos
Consolidação da Memória , Neurônios , Humanos , Consolidação da Memória/fisiologia , Animais , Neurônios/fisiologia , Hipocampo/fisiopatologia , Hipocampo/fisiologia , Ondas Encefálicas/fisiologia , Epilepsia/fisiopatologia , Doença de Alzheimer/fisiopatologiaRESUMO
Currently, the method of establishing the correspondence between the flame light field image and the temperature field by deep learning is widely used. Based on convolutional neural networks (CNNs), the reconstruction accuracy has been improved by increasing the depth of the network. However, as the depth of the network increases, it will lead to gradient explosion and network degradation. To further improve the reconstruction accuracy of the flame temperature field, this paper proposes an ES-ResNet18 model, in which SoftPool is used instead of MaxPool to preserve feature information more completely and efficient channel attention (ECA) is introduced in the residual block to reassign more weights to feature maps of critical channels. The reconstruction results of our method were compared with the CNN model and the original ResNet18 network. The results show that the average relative error and the maximum relative error of the temperature field reconstructed by the ES-ResNet18 model are 0.0203% and 0.1805%, respectively, which are reduced by one order of magnitude compared to the CNN model. Compared to the original ResNet18 network, they have decreased by 17.1% and 43.1%, respectively. Adding Gaussian noise to the flame light field images, when the standard deviation exceeds 0.03, the increase in reconstruction error of the ES-ResNet18 model is lower than that of ResNet18, demonstrating stronger anti-noise performance.
RESUMO
The significant threat of antibiotic resistance genes (ARGs) to aquatic environments health has been widely acknowledged. To date, several studies have focused on the distribution and diversity of ARGs in a single river while their profiles in complex river networks are largely known. Here, the spatiotemporal dynamics of ARG profiles in a canal network were examined using high-throughput quantitative PCR, and the underlying assembly processes and its main environmental influencing factors were elucidated using multiple statistical analyses. The results demonstrated significant seasonal dynamics with greater richness and relative abundance of ARGs observed during the dry season compared to the wet season. ARG profiles exhibited a pronounced distance-decay pattern in the dry season, whereas no such pattern was evident in the wet season. Null model analysis indicated that deterministic processes, in contrast to stochastic processes, had a significant impact on shaping the ARG profiles. Furthermore, it was found that Firmicutes and pH emerged as the foremost factors influencing these profiles. This study enhanced our comprehension of the variations in ARG profiles within canal networks, which may contribute to the design of efficient management approaches aimed at restraining the propagation of ARGs.
Assuntos
Rios , Estações do Ano , Rios/microbiologia , Resistência Microbiana a Medicamentos/genética , Hidrologia , Genes Bacterianos , Antibacterianos/farmacologiaRESUMO
Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.
Assuntos
Fumigação , Ginsenosídeos , Panax , Controle de Qualidade , Enxofre , Ginsenosídeos/química , Ginsenosídeos/análise , Panax/química , Enxofre/química , Sulfitos/química , Sulfitos/análise , Metais/química , Metais/análise , Extratos Vegetais/químicaRESUMO
As a vital component of blood, platelets play crucial roles in hemostasis and maintaining vascular integrity, and actively participate in inflammation and immune regulation. The unique biological properties of natural platelets have enabled their utilization as drug delivery vehicles. The advancement and integration of various techniques, including biological, chemical, and physicochemical methods, have enabled the preparation of engineered platelets. Platelets can serve as drug delivery platforms combined with immunotherapy and chemokine therapy to enhance their therapeutic impact. This review focuses on the recent advancements in the application of unactivated platelets for drug delivery. The construction strategies of engineered platelets are comprehensively summarized, encompassing internal loading, surface modification, and genetic engineering techniques. Engineered platelets hold vast potential for treating cardiovascular diseases, cancers, and infectious diseases. Furthermore, the challenges and potential considerations in creating engineered platelets with natural activity are discussed.
Assuntos
Plaquetas , Sistemas de Liberação de Medicamentos , Humanos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/química , Animais , Engenharia CelularRESUMO
OBJECTIVE: Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. DESIGN: HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat-Cre mice or the Postn-CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. RESULTS: We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice. More importantly, Suv39h1 inhibition by a small-molecule compound chaetocin dampened HSC-myofibroblast transition in cell culture and mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed HMOX1 transcription. HMOX1 depletion blunted the effects of Suv39h1 inhibition on HSC-myofibroblast transition in vitro and liver fibrosis in vivo. Transcriptomic analysis revealed that HMOX1 might contribute to HSC-myofibroblast transition by modulating retinol homeostasis. Finally, myofibroblast-specific HMOX1 overexpression attenuated liver fibrosis in both a preventive scheme and a therapeutic scheme. CONCLUSIONS: Our data demonstrate a previously unrecognised role for Suv39h1 in liver fibrosis and offer proof-of-concept of its targetability in the intervention of cirrhosis.
Assuntos
Células Estreladas do Fígado , Cirrose Hepática , Humanos , Camundongos , Animais , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/patologia , Fígado/metabolismo , MiofibroblastosRESUMO
Digital holography, recognized for its noncontact nature and high precision in three-dimensional imaging, is effectively employed to measure the morphology of bubbles and droplets. However, in terms of near-wall bubbles and droplets, such as confined bubbles in microfluidic chips, the measurement of the interface morphology of bubbles near the glass surface has not yet been resolved due to the coherent noise resulting from glass surface reflections in microfluidic chips. Accordingly, an off-axis digital holography system was devised by using Linnik interferometry. Measuring the confined bubble interface near the wall within a microfluidic chip and droplet evaporation on solid surfaces was studied. Partially coherent LED sources and reference light modulation techniques were employed in the optical setup to mitigate the coherent noise. Dual exposure and weighted least-squares unwrapping algorithms were introduced to correct phase distortions, enhancing image quality. Imaging two confined CO2 bubbles was done near the wall in silicon oil within a porous microfluidic chip, and contact angles of 4.7 and 4.5° were measured. Additionally, the measurement of the three-dimensional morphology of vertically evaporating deionized water droplets on a glass surface was done, due to which calculation of contact angles at various orientations was possible. This work offers a feasible new method for measuring the 3D interface morphology of bubbles and droplets, particularly in microfluidic visualization, addressing current measurement gaps.
RESUMO
OBJECTIVES: Low muscle mass has been found to be associated with adverse outcomes in patients with acute-on-chronic liver failure. However, data regarding the prognostic role of low muscle function are limited. Therefore, we aimed to investigate the predictive effect of low muscle function on 90-d mortality in patients with acute-on-chronic liver failure. METHODS: This prospective study consecutively enrolled acute-on-chronic liver failure patients from March 2021 to October 2022. Muscle function was assessed using the liver frailty index, and the time-dependent receiver operating characteristic curve with the highest Youden index was used to determine the optimal cutoff values of liver frailty index for diagnosing low muscle function. RESULTS: The study included 126 acute-on-chronic liver failure patients. The median liver frailty index was 3.89 (0.83), with 51 (40.5) patients classified as having low muscle function. Multivariate Cox analysis identified low muscle function (hazard ratio = 4.309; 95% CI, 1.795-10.345; P = 0.001) and number of organ failures (hazard ratio = 4.202; 95% CI, 2.040-8.656; P < 0.001) as independent risk factors for 90-d mortality. However, the multivariate analysis did not retain the significant effect of low muscle mass. Furthermore, multivariable logistic analysis revealed that age (odds ratio = 1.042; 95% CI, 1.002-1.083; P = 0.038), organ failures (odds ratio = 2.572; 95% CI, 1.331-4.968; P = 0.005), and low muscle mass (odds ratio = 6.607; 95% CI, 2.579-16.927; P < 0.001) were independent risk factors for low muscle function. CONCLUSIONS: The prognostic value of low muscle function was found superior to that of low muscle mass in patients with acute-on-chronic liver failure. Therefore, it is important to assess the muscle function and develop potential targeted treatment strategies in this population.
Assuntos
Insuficiência Hepática Crônica Agudizada , Fragilidade , Humanos , Estudos Prospectivos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Músculos , Estudos RetrospectivosRESUMO
Bacterioplankton play a vital role in maintaining the functions and services of lake ecosystems. Understanding the diversity and distribution patterns of bacterioplankton, particularly the presence of potential pathogenic bacterial communities, is crucial for safeguarding human health. In this study, we employed 16S rRNA gene amplicon sequencing to investigate the diversity and geographic patterns of bacterioplankton communities, as well as potential pathogens, in eight volcanic lakes located in the Arxan UNESCO Global Geopark (in the Greater Khingan Mountains of China). Our results revealed that the bacterial communities primarily comprised Bacteroidota (45.3%), Proteobacteria (33.1%), and Actinobacteria (9.0%) at the phylum level. At the genus level, prominent taxa included Flavobacterium (31.5%), Acinetobacter (11.0%), Chryseobacterium (7.9%), and CL500-29 marine group (5.6%). Among the bacterioplankton, we identified 34 pathogen genera (165 amplicon sequence variants [ASVs]), with Acinetobacter (59.8%), Rahnella (18.3%), Brevundimonas (9.6%), and Pseudomonas (5.8%) being the most dominant. Our findings demonstrated distinct biogeographic patterns in the bacterial communities at the local scale, driven by a combination of dispersal limitation and environmental factors influenced by human activities. Notably, approximately 15.3% of the bacterioplankton reads in the Arxan lakes were identified as potential pathogens, underscoring the potential risks to public health in these popular tourist destinations. This study provides the first comprehensive insight into the diversity of bacterioplankton in mountain lake ecosystems affected by high tourist activity, laying the groundwork for effective control measures against bacterial pathogens.
Assuntos
Ecossistema , Lagos , Humanos , Lagos/microbiologia , RNA Ribossômico 16S/genética , Filogenia , Bactérias/genética , Organismos Aquáticos , Plâncton , ChinaRESUMO
Medical report generation can be treated as a process of doctors' observing, understanding, and describing images from different perspectives. Following this process, this paper innovatively proposes a Transformer-based Semantic Query learning paradigm (TranSQ). Briefly, this paradigm is to learn an intention embedding set and make a semantic query to the visual features, generate intent-compliant sentence candidates, and form a coherent report. We apply a bipartite matching mechanism during training to realize the dynamic correspondence between the intention embeddings and the sentences to induct medical concepts into the observation intentions. Experimental results on two major radiology reporting datasets (i.e., IU X-ray and MIMIC-CXR) demonstrate that our model outperforms state-of-the-art models regarding generation effectiveness and clinical efficacy. In addition, comprehensive ablation experiments fully validate the TranSQ model's innovation and interpretation. The code is available at https://github.com/zjukongming/TranSQ.
Assuntos
Aprendizagem , Semântica , Humanos , Raios X , Radiografia , LógicaRESUMO
Emerging contaminants, including antibiotics, antibiotic-resistant bacteria (ARB), and extracellular antibiotic resistance genes (eARGs), have been detected in large numbers in the aquatic environment. The effects of emerging contaminants on bacterial communities in marine sediments are not well studied. In this study, the effects of emerging contaminants (antibiotics, ARB, and eARGs) on the variations of bacterial populations in marine sediments of the Bohai Sea, Yellow Sea, East China Sea, and South China Sea were investigated. The results showed that the abundance of the host bacterial phylum Probacteria in the marine sediments of the Bohai Sea was the lowest among the four seas after exposure to different antibiotics, ARB, and eARGs. The inputs of exogenous antibiotics and resistance genes significantly affected the community function, resulting in significant differences in community abundance at the genus level. The abundance of Halomonas, Sulfitobacter, and Alcanivorax in the four sea areas displayed noteworthy differences in response to the addition of exogenous antibiotics and eARGs. These findings contribute to a more comprehensive understanding of the intricate interplay between emerging contaminants and the dynamics of bacterial communities in natural ecosystems.
Assuntos
Antagonistas de Receptores de Angiotensina , Ecossistema , Sedimentos Geológicos , Inibidores da Enzima Conversora de Angiotensina , Bactérias/genética , Genes Bacterianos , Resistência Microbiana a Medicamentos/genética , China , Antibacterianos/farmacologiaRESUMO
Excessive fibrogenic response in the liver disrupts normal hepatic anatomy and function heralding such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. Myofibroblasts, derived primarily from hepatic stellate cells (HSCs), are the effector of liver fibrosis. In the present study we investigated the mechanism by which Brahma-related gene 1 (BRG1, encoded by Smarca4) regulates HSC-myofibroblast transition and the implication in intervention against liver fibrosis. We report that BRG1 expression was elevated during HSC maturation in cell culture, in animal models, and in human cirrhotic liver biopsy specimens. HSC-specific deletion of BRG1 attenuated liver fibrosis in several different animal models. In addition, BRG1 ablation in myofibroblasts ameliorated liver fibrosis. RNA-seq identified IGFBP5 as a novel target for BRG1. Over-expression of IGFBP5 partially rescued the deficiency in myofibroblast activation when BRG1 was depleted. On the contrary, IGFBP5 knockdown suppressed HSC-myofibroblast transition in vitro and mollified liver fibrosis in mice. Mechanistically, IGFBP5 interacted with Bat3 to stabilize the Bat3-TßR complex and sustain TGF-ß signaling. In conclusion, our data provide compelling evidence that BRG1 is a pivotal regulator of liver fibrosis by programming HSC-myofibroblast transition.
Assuntos
Neoplasias Hepáticas , Miofibroblastos , Animais , Humanos , Camundongos , Células Cultivadas , Montagem e Desmontagem da Cromatina , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Miofibroblastos/metabolismoRESUMO
In this study, we prepared porous Au-Ag alloy nanoparticle arrays with hydrophobic surfaces through the polystyrene colloidal crystal template combined with the chemical etching method to realize rapid SERS detection for biochemical molecules. In the preparation process, the pore size of Au-Ag alloy nanoparticles could be adjusted by changing the deposition time of the Ag element. Furthermore, after depositing the Au film on the surface of the porous nanoparticle arrays, their surface changed from hydrophilic to hydrophobic. The hydrophobic surface can drive target molecules to locally aggregate. Meanwhile, the hydrophobic surface also possessed a large number of active "hot spots" due to the porous structure. For these reasons, the porous Au-Ag alloy nanoparticle arrays can enable rapid and trace SERS detection, which provide the material basis for the subsequent construction of the high-quality SERS substrate.