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INTRODUCTION: Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. OBJECTIVES: N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. METHODS AND RESULTS: This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi-omics analysis revealed that HSC-specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split-1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%-62% and protein levels to 28%-35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%-38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. CONCLUSION: These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. KEY POINTS/HIGHLIGHTS: IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency-mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.
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Ferroptose , Células Estreladas do Fígado , Proteína Jagged-1 , Cirrose Hepática , Proteínas de Ligação a RNA , Receptores Notch , Transdução de Sinais , Ferroptose/genética , Células Estreladas do Fígado/metabolismo , Animais , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Camundongos Knockout , Masculino , HumanosRESUMO
Memristive systems have potential applications in nonvolatile memories and even unexplored functionalities in electronics. However, progress has been delayed by difficulties in the controllability of memory behaviors and the dependence on material conductivity. Considering this, a new depletion-region width modulation model is proposed to realize and explain memory characteristics. The coexistence of memristive and memcapacitive behaviors is demonstrated in p-CuAlO2/n-ZnO, p+-Si/n-ZnO and p-NiO/n-ZnO heterostructure devices. A high external electric field induces the migration of oxygen ions and electrons/holes between the p-type and n-type semiconductor layers. It can regulate the oxygen vacancy concentration of the n-type side and cation vacancy concentration of the p-type side, changing the depletion-region width and modulating device conductivity and capacitance. Several essential synaptic functions were accurately imitated, including spike-timing-dependent plasticity (STDP) and "learning-experience" behaviors. This work provides new opportunities in fabricating a memristor and memcapacitor based on a PN heterostructure for synaptic simulation.
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BACKGROUND: Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. RESULTS: The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. CONCLUSIONS: Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.
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Frutas , Perfilação da Expressão Gênica , Metabolômica , Folhas de Planta , Prunus persica , Folhas de Planta/metabolismo , Folhas de Planta/genética , Prunus persica/genética , Prunus persica/metabolismo , Prunus persica/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Metaboloma , Transcriptoma , Flavonoides/metabolismo , Ácidos Indolacéticos/metabolismoRESUMO
Introduction: Peach (Prunus persica) has a high nutritional and economic value. However, its overgrowth can lead to yield loss. Regulating the growth of peach trees is challenging. The small auxin-up RNA (SAUR) gene family is the largest family of auxin-responsive genes, which play important roles in plant growth and development. However, members of this gene family are rarely reported in peach. Methods: In this study, we measured leaf area, chlorophyll and lignin content to detect the role of PpSAUR5 on growth through transgenic Arabidopsis. Results: PpSAUR5 responds to auxin and gibberellin, promoting and inhibiting the synthesis of gibberellin and auxin, respectively. The heterologous transformation of PpSAUR5 in Arabidopsis led to enhanced growth of leaves and siliques, lightening of leaf color, decrease in chlorophyll content, increase in lignin content, abnormalities in the floral organs, and distortion of the inflorescence axis. Transcriptome data analysis of PpSAUR5 overexpression and wild-type lines revealed 854 differentially expressed genes (DEGs). GO and KEGG analyses showed that the DEGs were primarily involved in biological processes, such as cellular processes, metabolic processes, response to stimuli, and catalytic activity. These genes were mainly enriched in pathways, such as phenylalanine biosynthesis, phytohormone signaling, and MAPK signaling. Discussion: In summary, these results suggested that PpSAUR5 might regulate tree vigor by modulating the synthesis of auxin and gibberellin. Future studies can use PpSAUR5 as a candidate gene to elucidate the potential regulatory mechanisms underlying peach tree vigor.
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As a vital factor in technological innovation, patentee plays a significant role in the process of scientific and technological innovation, researching patentee has attracted the attention of experts and scholars. Previously, scholars have mainly quantified patent indicators or constructed homogeneous information networks to analyze patentees, but these methods cannot objectively measure the impact of patentees. Therefore, this study proposes a novel approach to assessing patentee impact based on a heterogeneous information network. The proposed method distinguishes the weight of different types of nodes using a weighted mechanism and extracts three types of fine-grained characteristics of network nodes. This approach results in the construction of a heterogeneous patent innovation network and the development of a new patentee impact assessment algorithm called CWAPN. Using Chinese green patents in the field of energy conservation and environmental protection as an example, experimental results show that the CWAPN algorithm can effectively assess the impact of patentees. Thereby identifying patentees who have made outstanding contributions to sustainable development in China.
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Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), a process associated with ferroptosis. Ginsenoside Rb1 (GRb1), a major active component extracted from Panax ginseng, inhibits HSC activation. However, the potential role of GRb1 in mediating HSC ferroptosis remains unclear. This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro, using CCl4-induced liver fibrosis mouse model and primary HSCs, LX-2 cells. The findings revealed that GRb1 effectively inactivated HSCs in vitro, reducing alpha-smooth muscle actin (α-SMA) and Type I collagen (Col1A1) levels. Moreover, GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo. From a mechanistic standpoint, the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1. Specifically, GRb1 promoted HSC ferroptosis both in vivo and in vitro, characterized by increased glutathione depletion, malondialdehyde production, iron overload, and accumulation of reactive oxygen species (ROS). Intriguingly, GRb1 increased Beclin 1 (BECN1) levels and decreased the System Xc-key subunit SLC7A11. Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1. Moreover, BECN1 could directly interact with SLC7A11, initiating HSC ferroptosis. In conclusion, the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro. Overall, this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation, at least partly through its modulation of BECN1 and SLC7A11.
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Optoelectronic memristors are new multifunctional devices with both electrically tunable and light-tunable synaptic plasticity, attracting great attention as key promising devices for optoelectronic neuromorphic computing systems. At present, the conductance modulation in most optoelectronic memristors is conducted in a hybrid photoelectric mode, suffering some problems such as heat generation and control complexity. Here, an optoelectronic memristor based on the p+-Si/n-ZnO heterojunction is proposed where the conductance can be reversibly modulated in an all-optically controlled mode. The electron detrapping/trapping mechanism at the p+-Si/n-ZnO interface barrier region is presented to explain the light-induced conductance potentiation/depression behavior. Furthermore, some synaptic functions, including excitatory postsynaptic current (EPSC), inhibitory postsynaptic current (IPSC), and paired-pulse facilitation (PPF), are successfully mimicked in the p+-Si/n-ZnO heterojunction memristor, instructing its application potential for optoelectronic neuromorphic computing.
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Cryptosporidium spp. and G. duodenalis often infect humans, cats, and other mammals, causing diarrhea and being responsible for numerous outbreaks of waterborne and foodborne infections worldwide. The rapid increase in the number of pet cats poses a substantial public health risk. However, there were few reports about the infection of Cryptosporidium spp. and G. duodenalis infections in pet cats in Henan Province, central China. Thus, to understand the prevalence and genetic distribution of Cryptosporidium spp. and G. duodenalis in pet cats, and to evaluate the zoonotic potential, possible transmission routes and public health implications of isolates, fecal samples (n = 898) were randomly collected from pet cats in 11 cities in Henan Province, central China. Nested PCR based on the SSU rRNA gene and bg gene was used to the prevalence of Cryptosporidium spp. and G. duodenalis, respectively. The prevalence was 0.8 % (7/898) and 2.0 % (18/898) for Cryptosporidium spp. and G. duodenalis respectively. Additionally, the Cryptosporidium spp. positive isolates were identified as C. parvum subtype IIdA19G1 by gp60 gene. In the present study, the IIdA19G1 subtype was discovered in pet cats for the first time in China, enriching the information on the host type and geographical distribution of Cryptosporidium spp. in China. For G. duodenalis, a total of 18 G. duodenalis positive samples were identified, belonging to four assemblages: a zoonotic assemblage A1 (4/898), three host-specific assemblages C (8/898), D (5/898), and F (1/898). Interestingly, we found that pet cats infected with Cryptosporidium spp. and G. duodenalis are more likely to experience emaciation symptoms compared to the negative group. More importantly, the prevalence of Cryptosporidium spp. and G. duodenalis detected in the present study were low, but the subtype IIdA19G1 of Cryptosporidium spp. and the assemblages A1, C, D, and F of G. duodenalis have the potential for zoonotic transmission. Thus, we should focus on preventing and controlling the risk of cross-species transmission that may occur in pet cats in Henan Province.
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Doenças do Gato , Criptosporidiose , Cryptosporidium , Fezes , Giardia lamblia , Giardíase , Animais de Estimação , Animais , Gatos , China/epidemiologia , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Criptosporidiose/transmissão , Doenças do Gato/parasitologia , Doenças do Gato/epidemiologia , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , Cryptosporidium/classificação , Fezes/parasitologia , Giardia lamblia/genética , Giardia lamblia/isolamento & purificação , Giardia lamblia/classificação , Animais de Estimação/parasitologia , Prevalência , Giardíase/epidemiologia , Giardíase/veterinária , Giardíase/parasitologia , Giardíase/transmissão , DNA de Protozoário/genética , Filogenia , Reação em Cadeia da Polimerase , Genótipo , Zoonoses/parasitologia , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
Electrochemical conversion of nitrogen into ammonia at ambient conditions as a sustainable approach has gained significant attention, but it is still extremely challenging to simultaneously obtain a high faradaic efficiency (FE) and NH3 yield. In this work, the interstitial boron-doped porous Pd nanotubes (B-Pd PNTs) are constructed by combining the self-template reduction method with boron doping. Benefiting from distinctive one-dimensional porous nanotube architectonics and the incorporation of the interstitial B atoms, the resulting B-Pd PNTs exhibit high NH3 yield (18.36 µg h-1 mgcat.-1) and FE (21.95%) in neutral conditions, outperforming the Pd/PdO PNTs (10.4 µg h-1 mgcat.-1 and 8.47%). The present study provides an attractive method to enhance the efficiency of the electroreduction of nitrogen into ammonia by incorporating interstitial boron into porous Pd-based catalysts.
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BACKGROUND: Enterocytozoon bieneusi is a zoonotic pathogen widely distributed in animals and humans. It can cause diarrhea and even death in immunocompromised hosts. Approximately 800 internal transcribed spacer (ITS) genotypes have been identified in E. bieneusi. Farmed foxes and raccoon dogs are closely associated to humans and might be the reservoir of E. bieneusi which is known to have zoonotic potential. However, there are only a few studies about E. bieneusi genotype identification and epidemiological survey in foxes and raccoon dogs in Henan and Hebei province. Thus, the present study investigated the infection rates and genotypes of E. bieneusi in farmed foxes and raccoon dogs in the Henan and Hebei provinces. RESULT: A total of 704 and 884 fecal specimens were collected from foxes and raccoon dogs, respectively. Nested PCR was conducted based on ITS of ribosomal RNA (rRNA), and then multilocus sequence typing (MLST) was conducted to analyze the genotypes. The result showed that infection rates of E. bieneusi in foxes and raccoon dogs were 18.32% and 5.54%, respectively. Ten E. bieneusi genotypes with zoonotic potential (NCF2, NCF3, D, EbpC, CHN-DC1, SCF2, CHN-F1, Type IV, BEB4, and BEB6) were identified in foxes and raccoon dogs. Totally 178 ITS-positive DNA specimens were identified from foxes and raccoon dogs and these specimens were then subjected to MLST analysis. In the MLST analysis, 12, 2, 7 and 8 genotypes were identified in at the mini-/ micro-satellite loci MS1, MS3, MS4 and MS7, respectively. A total of 14 multilocus genotypes were generated using ClustalX 2.1 software. Overall, the present study evaluated the infection of E. bieneusi in foxes and raccoon dogs in the Henan and Hebei province, and investigated the zoonotic potential of the E. bieneusi in foxes and raccoon dogs. CONCLUSIONS: These findings expand the geographic distribution information of E. bieneusi' host in China and was helpful in preventing against the infection of E. bieneusi with zoonotic potential in foxes and raccoon dogs.
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Enterocytozoon , Microsporidiose , Humanos , Animais , Tipagem de Sequências Multilocus/veterinária , Enterocytozoon/genética , Raposas/genética , Cães Guaxinins , Epidemiologia Molecular , Microsporidiose/epidemiologia , Microsporidiose/veterinária , Fezes , Prevalência , Filogenia , China/epidemiologia , GenótipoRESUMO
Replacing the slow oxygen evolution reaction with favorable hydrazine oxidation reaction (HzOR) is a green and efficient way to produce hydrogen. In this work, we synthesize amorphous/crystalline RhFeP metallene via phase engineering and heteroatom doping. RhFeP metallene has good catalytic activity and stability for HER and HzOR, and only an ultralow voltage of 18 mV is required to achieve 10 mA cm-2in a two-electrode hydrazine-assisted water splitting system. The superior result is mainly ascribed to the co-doping of Fe and P and the formation of amorphous/crystalline RhFeP metallene with abundant phase boundaries, thereby adjusting electronic structure and increasing active sites.
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BACKGROUND: Ginsenoside Rg3 (G-Rg3), extracted from Panax notoginseng, possesses hepatoprotective properties. Hepatic stellate cells (HSCs) activation is responsible for liver fibrosis. Recent studies have reported the suppressive effects of G-Rg3 on HSC activation and proliferation. Ferroptosis is a novel iron regulated cell death. ACSL4, a key indicator of ferroptosis, is commonly methylated in various diseases. PURPOSE: However, the role of ACSL4 methylation-mediated HSC ferroptosis in G-Rg3 inhibition of hepatic fibrosis needs to be explored. METHODS: Effects of G-Rg3 on inhibiting fibrosis were evaluated in vivo and in vitro. The impact of G-Rg3 on HSC ferroptosis was assessed in vitro. Furthermore, the expression of ACSL4, ACSL4 methylation and microRNA-6945-3p (miR-6945-3p) levels were determined. RESULTS: G-Rg3 significantly alleviated CCl4-induced liver fibrosis, accompanied by collagen downregulation. In vitro, G-Rg3 contributed to HSC inactivation, leading to decreased collagen production. G-Rg3 induced HSC ferroptosis, characterized by increased iron accumulation, depletion of glutathione, malondialdehyde levels, and generation of lipid reactive oxygen species. Moreover, G-Rg3 promoted ACSL4 demethylation and restored its expression. Notably, DNMT3B counteracted the effect of G-Rg3-mediated inhibition of ACSL4 methylation and was targeted by miR-6945-3p. Further investigations revealed that G-Rg3 suppressed ACSL4 methylation through miR-6945-3p-mediated DNMT3B inhibition. Consistent with this, miR-6945-3p inhibition reversed G-Rg3-induced ACSL4 expression and HSC ferroptosis. CONCLUSION: G-Rg3 inhibits ACSL4 methylation by miR-6945-3p-mediated DNMT3B inhibition, thereby promoting HSC ferroptosis and mitigating liver fibrosis.
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Ferroptose , Ginsenosídeos , MicroRNAs , Humanos , Células Estreladas do Fígado , Transdução de Sinais , Cirrose Hepática/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ferro/metabolismo , Colágeno/metabolismoRESUMO
Hepatic stellate cell (HSC) activation is considered as a central driver of liver fibrosis and effective suppression of HSC activation contributes to the treatment of liver fibrosis. Circular RNAs (circRNAs) have been reported to be important in tumor progression. However, the contributions of circRNAs in liver fibrosis remain largely unclear. The liver fibrosis-specific circRNA was explored by a circRNA microarray and cVIM (a circRNA derived from exons 4 to 8 of the vimentin gene mmu_circ_32994) was selected as the research object. Further studies revealed that cVIM, mainly expressed in the cytoplasm, may act as a sponge for miR-122-5p and miR-9-5p to enhance expression of type I TGF-ß receptor (TGFBR1) and TGFBR2 and promotes activation of the TGF-ß/Smad pathway, thereby accelerating the progression of liver fibrosis. Our results demonstrate a vital role for cVIM in promoting liver fibrosis progression and provide a fresh perspective on circRNAs in liver fibrosis.
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MicroRNAs , RNA Circular , Vimentina , Humanos , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Vimentina/genéticaRESUMO
Skeletal muscle growth and development in livestock and poultry play a pivotal role in determining the quality and yield of meat production. However, the mechanisms of myogenesis are remained unclear due to it finely regulated by a complex network of biological macromolecules. In this study, leveraging previous sequencing data, we investigated a differentially expressed circular RNA (circSGCB) present in fetal and adult muscle tissues among various ruminant species, including cattle, goat, and sheep. Our analysis revealed that circSGCB is a single exon circRNA, potentially regulated by an adjacent bovine enhancer. Functional analysis through loss-of-function tests demonstrated that circSGCB exerts inhibitory effects on bovine myoblast proliferation while promoting myocytes generation. Furthermore, we discovered that circSGCB primarily localizes to the cytoplasm, where it functions as a molecular sponge by binding to bta-miR-27a-3p. This interaction releases the mRNAs of KLF3 gene and further activates downstream functional pathways. In vivo, studies provided evidence that up-regulation of KLF3 contributes to muscle regeneration. These findings collectively suggest that circSGCB operates via a competing endogenous RNA (ceRNA) mechanism to regulate KLF3, thereby influencing myogenesis in ruminants and highlights it may as potential molecular targets for enhancing meat production in livestock and poultry industries.
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MicroRNAs , Bovinos , Animais , Ovinos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Endógeno Competitivo , RNA Circular/genética , RNA Mensageiro/metabolismo , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismoRESUMO
A key event in liver fibrosis is the activation of the hepatic stellate cell (HSC). Schisandrin B (Sch B), a major component extracted from Schisandra chinensis, has been shown to inhibit HSC activation. Recently, ferroptosis (FPT) has been reported to be involved in HSC activation. However, whether Sch B has an effect on the HSC FPT remains unclear. Herein, we explored the effects of Sch B on liver fibrosis in vivo and in vitro and the roles of Wnt agonist 1 and ferrostatin-1 in the antifibrotic effects of Sch B. Sch B effectively alleviated CCl4-induced liver fibrosis, with decreased collagen deposition and α-SMA level. Additionally, Sch B resulted in an increase in lymphocyte antigen 6 complex locus C low (Ly6Clo) macrophages, contributing to a reduced level of TIMP1 and increased MMP2. Notably, the Wnt pathway was involved in Sch B-mediated Ly6C macrophage phenotypic transformation. Further studies demonstrated that Sch B-treated macrophages had an inhibitory effect on HSC activation, which was associated with HSC FPT. GPX4, a negative regulator of FPT, was induced by Sch B and found to be involved in the crosstalk between macrophage and HSC FPT. Furthermore, HSC inactivation as well as FPT induced by Sch B-treated macrophages was blocked down by Wnt pathway agonist 1. Collectively, we demonstrate that Sch B inhibits liver fibrosis, at least partially, through mediating Ly6Clo macrophages and HSC FPT. Sch B enhances Wnt pathway inactivation, leading to the increase in Ly6Clo macrophages, which contributes to HSC FPT. Sch B may be a promising drug for liver fibrosis treatment.
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Porcine reproductive and respiratory syndrome (PRRS) has been prevalent for nearly forty years since it was first reported. It has been one of the major diseases jeopardizing the healthy development of the world swine industry, as well as causing great economic losses to the industry's economic development. Furthermore, no way has been found to combat the disease due to the immunosuppressive properties of its pathogen porcine reproductive and respiratory syndrome virus (PRRSV) infection. We previously examined the mRNA expression of IFN-I in PRRSV-infected Marc-145 cells at different time periods using qRT-PCR, and found that the mRNA expression of IFN-I in the late stage of PRRSV infection showed suppression. Naringenin is a flavonoid found in citrus fruits and has a very wide range of pharmacological activities. Therefore, the aim of the present study was to investigate the modulatory effect of naringenin on the suppressed innate immune response after PRRSV infection. The expression of IFN-I, IL-10, and ISGs in the late stage of PRRSV infection was examined using qRT-PCR, and the results showed that naringenin improved the expression of antiviral cytokines suppressed by PRRSV infection. Further results showed that naringenin treatment significantly up-regulated the expression of proteins related to the RIG-I-MAV immune signaling pathway, and that naringenin could not significantly activate the RIG-I-MAVS signaling pathway after the addition of the RIG-I inhibitor Cyclo. Overall, these data demonstrated that naringenin could improve the innate immune response suppressed by PRRSV infection by modulating the RIG-I-MAVS signaling pathway. Therefore, our study will provide a theoretical basis for the development of naringenin as a drug against immunosuppressive viral infectious disease infections.
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Interferon Tipo I , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Linhagem Celular , Interferon Tipo I/metabolismo , Transdução de Sinais , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Imunidade Inata , RNA MensageiroRESUMO
AIM: This study sought to identify potential biomarkers and miRNA-mRNA networks within extracellular vesicles (EVs) for detecting severe acute pancreatitis-associated lung injury (SAPALI). METHODS: Blood-derived EVs were isolated, and their miRNA transcriptomic profiles were comprehensively analyzed using miRBase v.21 database along with miRDeep2 tool to predict novel miRNAs. DEGseq R package was deployed for the identification of differentially expressed miRNAs (DEMs). Protein-protein interaction (PPI) networks were assembled using STRING and Cytoscape. A lung injury model was established using Lipopolysaccharide (LPS)-induced BEAS-2B cells, chosen for their respiratory epithelial origin and pertinent association with lung injury. The expression levels of targeted miRNA and associated proteins, TLR4, NF-κB mRNA were quantified via RT-PCR and Western Blot. Levels of IL-6, IL-1ß, TNF-α, and ROS were measured using designated kits. Dual-luciferase reporter assay was conducted to examine the interaction between miRNA and proteins. RESULTS: The comparisons between the SAPALI and the control group revealed 10 DEM, including miR-503-5p and miR-483-5p. The cytoHubba plugin in Cytoscape identified three principal miRNA-mRNA interactions: miR-483-5p with PTK2 and HDAC2; miR-28-5p with MAPK1, TP53BP1, SEMA3A; and miR-503-5p with PPP1CB, SEMA6D, EPHB2, UNC5B. The SAPALI model exhibited elevated miR-503-5p, HDAC2 and inflammatory markers, with a decline UNC5B, miR-483-5p and miR-28-5p. Transfection with miR-503-5p and miR-483-5p inhibitors increased the levels of their supposed binding proteins but not miR-28-5p inhibitor. The Dual-luciferase reporter gene assay identified the interaction of miR-503-5p with UNC5B, and miR-483-5p with HDAC2, but not miR-28-5p with TP53BP1. CONCLUSIONS: Our study maps miRNA-mRNA interactions in SAPALI, identifying miR-503-5p and miR-483-5p as critical regulatory miRNAs.
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Lesão Pulmonar Aguda , Vesículas Extracelulares , MicroRNAs , Pancreatite , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transcriptoma , Doença Aguda , Pancreatite/genética , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , RNA Mensageiro , Luciferases/genética , Receptores de Netrina/genéticaRESUMO
It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.
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Hepatite B Crônica , Humanos , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Curva ROC , Cirrose Hepática , Fígado/patologia , Vírus da Hepatite B , Fibrose , Biomarcadores , Alanina TransaminaseRESUMO
Background: Isolated pulmonary nodules (SPNs) are small, circular lesions within lung tissue, often challenging to diagnose due to their size and lack of typical imaging features. Timely diagnosis is crucial for treatment decisions. However, the difficulty in qualitative diagnosis necessitates clinical biopsies. Objective: This study aimed to assess the diagnostic accuracy of CT-guided percutaneous lung biopsy for SPNs and identify potential risk factors for malignancy. Methods: We conducted a retrospective analysis of 112 patients with SPNs who underwent CT-guided core needle biopsy (CT-CNB) between June 2020 and June 2022. Histological and cytological results were obtained for all patients, and clinical data and imaging characteristics were compared between benign and malignant SPN groups. Binary logistic regression was used to analyze risk factors for malignancy, and complications were observed. Results: Cytological and histological specimens were successfully obtained for all patients. The cohort consisted of 43 patients with benign SPNs and 69 with malignant SPNs. Among the malignant SPN group, 67 cases were confirmed via CT-CNB and 2 through surgery, resulting in a sensitivity of 97.10% and specificity of 100.00%. The malignant nodules comprised 45 adenocarcinomas, 14 squamous cell carcinomas, 8 metastatic tumors, and 2 small cell carcinomas. Notably, 2 initially diagnosed as malignant cases were found to have chronic inflammation on preoperative biopsy but revealed adenocarcinoma and squamous cell carcinoma post-surgery. The benign nodules encompassed 20 granulomatous inflammation cases, 15 chronic inflammation, 3 fungal granulomas, 2 hamartomas, and 1 fibrous tissue. Cytological smears exhibited a sensitivity of 81.3% and a specificity of 100.0% for malignancy. Significantly, age ≥60, elevated tumor markers, and specific imaging signs (burr, foliation, pleural pull) were identified as risk factors for malignant SPNs using Binary Logistic regression (all P < .05). Conclusions: CT-guided percutaneous lung biopsy demonstrates excellent diagnostic efficacy and safety for distinguishing benign and malignant SPNs.