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Soluble redox-active polymers (RAPs) enable size-exclusion nonaqueous redox flow batteries (NaRFBs) which promise high energy density. Pendants along the RAPs not only store charge but also engage in electron transfer to varying extents based on their designs. Here, we explore these phenomena in Metal-containing Redox Active Polymers (M-RAPs, M = Ru, Fe, Co). We assess by using cyclic voltammetry and chronoamperometry with ultramicroelectrodes the current response to electrolyte concentration spanning 3 orders of magnitude. Currents scaled as Ru-RAP > Fe-RAP â« Co-RAP, consistent with electron self-exchange trends in the small molecule analogues of the MII/III redox pair. Varying the ionic strength of the electrolyte also revealed nonmonotonic behavior, evidencing the impact of polyelectrolytic dynamics on M-RAP redox response. We developed a model to account for the behavior by combining kinetic Monte Carlo and Brownian dynamics near a boundary representing an electrode. While 1D pendant-to-pendant charge transfer along the chain is not a strong function of electrolyte concentration, the microstructure of the RAP at different electrolyte concentrations is decisively impacted, yielding qualitative trends to those observed experimentally. M-RAP size-exclusion NaRFBs using a poly viologen as negolyte varied in average potential with â¼1.54 V for Ru-RAP, â¼1.37 V for Fe-RAP, and â¼0.52 V for Co-RAP. Comparison of batteries at their optimal and suboptimal solution conditions as gauged from analytical experiments showed clear correlations in performance. This work provides a blueprint for understanding the factors underpinning charge transfer in solutions of RAPs for batteries and beyond.
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MAIN CONCLUSION: The SpHsfA8a upregulated expression can induce the expression of multiple heat-tolerance genes, and increase the tolerance of Arabidopsis thaliana to high-temperature stress. Sorbus pohuashanensis is an ornamental tree used in courtyards. However, given its poor thermotolerance, the leaves experience sunburn owing to high temperatures in summer, severely affecting its ornamental value. Heat-shock transcription factors play a critical regulatory role in the plant response to heat stress. To explore the heat-tolerance-related genes of S. pohuashanensis to increase the tree's high-temperature tolerance, the SpHsfA8a gene was cloned from S. pohuashanensis, and its structure and expression patterns in different tissues and under abiotic stress were analyzed, as well as its function in heat tolerance, was determined via overexpression in Arabidopsis thaliana. The results showed that SpHsfA8a encodes 416 amino acids with a predicted molecular weight of 47.18 kDa and an isoelectric point of 4.63. SpHsfA8a is a hydrophilic protein without a signal peptide and multiple phosphorylation sites. It also contains a typical DNA-binding domain and is similar to MdHsfA8a in Malus domestica and PbHsfA8 in Pyrus bretschneideri. In S. pohuashanensis, SpHsfA8a is highly expressed in the roots and fruits and is strongly induced under high-temperature stress in leaves. The heterologous expression of SpHsfA8a in A. thaliana resulted in a considerably stronger growth status than that of the wild type after 6 h of treatment at 45 °C. Its proline content, catalase and peroxidase activities also significantly increased, indicating that the SpHsfA8a gene increased the tolerance of A. thaliana to high-temperature stress. SpHsfA8a could induce the expression of multiple heat-tolerance genes in A. thaliana, indicating that SpHsfA8a could strengthen the tolerance of A. thaliana to high-temperature stress through a complex regulatory network. The results of this study lay the foundation for further elucidation of the regulatory mechanism of SpHsfA8a in response of S. pohuashanensis to high-temperature stress.
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Arabidopsis , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción del Choque Térmico , Respuesta al Choque Térmico , Proteínas de Plantas , Sorbus , Sorbus/genética , Sorbus/fisiología , Sorbus/metabolismo , Respuesta al Choque Térmico/genética , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción del Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismo , Plantas Modificadas Genéticamente , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Calor , Termotolerancia/genéticaRESUMEN
Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in pigs of all ages and reproductive failure in sows, resulting in great economic losses to the swine industry. In this work, we identified the interaction between PSMB4 and PRRSV Nsp1α by yeast two-hybrid screening. The PSMB4-Nsp1α interaction was further confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown, and laser confocal experiments. The PCPα domain (amino acids 66 to 166) of Nsp1α and the C-terminal domain (amino acids 250 to 264) of PSMB4 were shown to be critical for the PSMB4-Nsp1α interaction. PSMB4 overexpression reduced PRRSV replication, whereas PSMB4 knockdown elicited opposing effects. Mechanistically, PSMB4 targeted K169 in Nsp1α for K63-linked ubiquitination and targeted Nsp1α for autolysosomal degradation by interacting with LC3 to enhance the activation of the lysosomal pathway. Meanwhile, we found that PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. In conclusion, our data revealed a new mechanism of PSMB4-mediated restriction of PRRSV replication, whereby PSMB4 was found to induce Nsp1α degradation and type I interferon expression, in order to impede the replication of PRRSV. IMPORTANCE In the swine industry, PRRSV is a continuous threat, and the current vaccines are not effective enough to block it. This study determined that PSMB4 plays an antiviral role against PRRSV. PSMB4 was found to interact with PRRSV Nsp1α, mediate K63-linked ubiquitination of Nsp1α at K169, and thus trigger its degradation via the lysosomal pathway. Additionally, PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. This study extends our understanding of the proteasome subunit PSMB4 against PRRSV replication and will contribute to the development of new antiviral strategies.
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Interferón Tipo I , Virus del Síndrome Respiratorio y Reproductivo Porcino , Complejo de la Endopetidasa Proteasomal , Proteínas no Estructurales Virales , Expresión Génica/inmunología , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón beta/genética , Lisosomas/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/inmunología , Dominios Proteicos , Proteolisis , Porcinos , Ubiquitinación , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/genética , AnimalesRESUMEN
In June 2020, Lumpy Skin Disease Virus (LSDV) was first discovered in Guangdong, China. Whole-genome sequencing and evolutionary analysis indicate that this strain represents a novel recombinant vaccine strain. Our investigation has identified regions affected by LSD outbreaks prior to 2024, revealing widespread prevalence of LSDV across East Asia and Southeast Asia. Subsequent analysis of the physical and chemical characteristics of the strain revealed LSDV's resilience to high temperatures, varying pH levels, humidity, UV radiation, and light exposure. Among the tested disinfectants, potassium persulfate, glutaraldehyde, and benzalkonium bromide have demonstrated the most potent virucidal efficacy against LSDV while maintaining high safety profiles. Utilizing the Syrian hamster model, infection with this strain has resulted in the formation of skin nodules and testicular damage, providing valuable insights into the pathogenesis of LSDV. In conclusion, the comprehensive experimental data presented herein serve as a cornerstone for advancing biosafety protocols, facilitating effective prevention and control strategies, and fostering the development of small animal model for LSDV.
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Porcine reproductive and respiratory syndrome virus (PRRSV) is a viral pathogen with substantial economic implications for the global swine industry. The existing vaccination strategies and antiviral drugs offer limited protection. Replication of the viral RNA genome encompasses a complex series of steps, wherein a replication complex is assembled from various components derived from both viral and cellular sources, as well as from the viral genomic RNA template. In this study, we found that ZNF283, a Krüppel-associated box (KRAB) containing zinc finger protein, was upregulated in PRRSV-infected Marc-145 cells and porcine alveolar macrophages and that ZNF283 inhibited PRRSV replication and RNA synthesis. We also found that ZNF283 interacts with the viral proteins Nsp9, an RNA-dependent RNA polymerase, and Nsp10, a helicase. The main regions involved in the interaction between ZNF283 and Nsp9 were determined to be the KRAB domain of ZNF283 and amino acids 178-449 of Nsp9. The KRAB domain of ZNF283 plays a role in facilitating Nsp10 binding. In addition, ZNF283 may have an affinity for the 3' untranslated region of PRRSV. These findings suggest that ZNF283 is an antiviral factor that inhibits PRRSV infection and extend our understanding of the interactions between KRAB-containing zinc finger proteins and viruses.
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Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Enfermedades de los Porcinos , Animales , Porcinos , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Unión Proteica , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , ARN Viral/metabolismo , Dedos de Zinc , Replicación ViralRESUMEN
BACKGROUND: SHP1 has been documented as a tumor suppressor and it was thought to play an antagonistic role in the pathogenesis of Helicobacter pylori infection. In this study, the exact mechanism of this antagonistic action was studied. MATERIALS AND METHODS: AGS, MGC803, and GES-1 cells were infected with H. pylori, intracellular distribution changes of SHP1 were first detected by immunofluorescence. SHP1 overexpression and knockdown were then constructed in these cells to investigate its antagonistic roles in H. pylori infection. Migration and invasion of infected cells were detected by transwell assay, secretion of IL-8 was examined via ELISA, the cells with hummingbird-like alteration were determined by microexamination, and activation of JAK2/STAT3, PI3K/Akt, and ERK pathways were detected by immunoblotting. Mice infection model was established and gastric pathological changes were evaluated. Finally, the SHP1 activator sorafenib was used to analyze the attenuating effect of SHP1 activation on H. pylori pathogenesis in vitro and in vivo. RESULTS: The sub-localization of SHP1 changed after H. pylori infection, specifically that the majority of the cytoplasmic SHP1 was transferred to the cell membrane. SHP1 inhibited H. pylori-induced activation of JAK2/STAT3 pathway, PI3K/Akt pathway, nuclear translocation of NF-κB, and then reduced EMT, migration, invasion, and IL-8 secretion. In addition, SHP1 inhibited the formation of CagA-SHP2 complex by dephosphorylating phosphorylated CagA, reduced ERK phosphorylation and the formation of CagA-dependent hummingbird-like cells. In the mice infection model, gastric pathological changes were observed and increased IL-8 secretion, indicators of cell proliferation and EMT progression were also detected. By activating SHP1 with sorafenib, a significant curative effect against H. pylori infection was obtained in vitro and in vivo. CONCLUSIONS: SHP1 plays an antagonistic role in H. pylori pathogenesis by inhibiting JAK2/STAT3 and PI3K/Akt pathways, NF-κB nuclear translocation, and CagA phosphorylation, thereby reducing cell EMT, migration, invasion, IL-8 secretion, and hummingbird-like changes.
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Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Proteínas Bacterianas/metabolismo , Antígenos Bacterianos/metabolismo , Helicobacter pylori/fisiología , FN-kappa B/metabolismo , Interleucina-8/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Infecciones por Helicobacter/patología , Sorafenib/metabolismo , Células Epiteliales/metabolismoRESUMEN
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a severe complication of CTD, being one of the leading causes of mortality for patients with this condition. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker associated with adverse clinical outcomes in cardiovascular patients. In this study, we investigated the role of sST2 as a predictor of poor clinical outcome in patients with CTD associated with pulmonary hypertension (CTD-PH). METHODS: This retrospective cohort study enrolled 71 CTD-PH patients diagnosed by echocardiography. Twenty-one CTD patients without PH were selected for a control group. A receiver operating characteristic (ROC) curve assessed the predictive value of sST2 in assessing 3-year clinical worsening. Hazard ratios associated with potential predictors of clinical worsening were estimated using Cox proportional hazard models. The primary end point was clinical worsening. RESULTS: The level of sST2 was significantly elevated in CTD-PH patients compared with the control group. After a mean follow-up of 25.29 (1.88) months, end point events occurred in 26 patients. sST2 was an independent predictor of clinical worsening and all-cause death in patients with CTD-PH. sST2 ≥ 39.99 ng/ml discriminated 3-year clinical worsening with a sensitivity and specificity of 100% and 84.9%, respectively. The patients with both higher levels of sST2 (≥39.99 ng/ml) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (≥300 ng/l) had the worst prognosis. CONCLUSION: sST2 ≥ 39.99 ng/ml predicts higher incidence of clinical worsening events in CTD-PH patients. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.
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Enfermedades del Tejido Conjuntivo , Hipertensión Pulmonar , Biomarcadores , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Pronóstico , Estudios RetrospectivosRESUMEN
A novel Gram-negative, motile, aerobic, spiral-shaped bacterium designated D5T, was isolated from a coastal sediment collected in the Yellow Sea. Optimal growth occurred at 30 °C, pH 7.0-8.0 and in the presence of 1-3% (w/v) NaCl. Strain D5T contained ubiquinone 8 (Q-8) as the predominant respiratory quinone. The major fatty acids (> 10%) were C16:0, C16:1 ω7c/C16:1 ω6c and C18:1w7c/C18:1w6c. The main polar lipids were phosphatidylglycerol and phosphatidylethanolamine. The draft genome is 5.6 Mb in length, and DNA G + C content is 47.2 mol%. 16S rRNA gene sequences showed that strain D5T is most closely related to Oceanospirillum beijerinckii NBRC 15445T (97.8%, sequence similarity). However, the digital DNA-DNA hybridization (dDDH) value and average nucleotide identity (ANI) between strain D5T and O. beijerinckii is only 27.8% and 77.1%. Phylogenetic trees based on 16S rRNA gene sequences and whole genomes all indicated that strain D5T formed a separate branch in the genus Oceanospirillum. Combined results of the polyphasic analyses suggested that strain D5T represents a novel species in the genus Oceanospirillum, for which the name Oceanospirillum sediminis sp. nov. is proposed. The type strain is D5T (= MCCC 1K06061T = KCTC 62987T).
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Sedimentos Geológicos , Oceanospirillaceae , Filogenia , Agua de Mar , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos/química , Sedimentos Geológicos/microbiología , Oceanospirillaceae/clasificación , Oceanospirillaceae/aislamiento & purificación , Fosfolípidos/química , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN , Ubiquinona/químicaRESUMEN
The triplet-triplet annihilation (TTA) effect of sensitizers themselves can lead to the additional quenching of lifetimes of triplet states; therefore, how to weaken the TTA effect of sensitizers is an urgent issue to be resolved for their further applications. Besides, it remains a tremendous challenge for constructing supramolecular systems of photosensitizers based on photosensitizer-functionalized pillararenes because there have been very few investigations on them. Thus, 2,6-diiodo-1,3,5,7-tetramethyl-8-phenyl-4,4-difluoroboradiazaindacene (DIBDP) and ethoxy pillar[5]arene (EtP5) were utilized to synthesize a DIBDP-functionalized pillar[5]arene (EtP5-DIBDP), a cyano-containing DIBDP (G) used as a guest molecule was also prepared, and they were used to investigate the electron-transfer mechanism between EtP5 and DIBDP moieties and weaken the TTA effect of DIBDP moieties. The theoretical computational results of frontier molecular orbitals and isosurfaces of spin density preliminarily predicted that the cavities of the EtP5 moiety had influence on the fluorescence emission of DIBDP units but not on their triplet states in EtP5-DIBDP. The fluorescence emission intensities in a variety of solvents with different polarities and electrochemical studies revealed that there was electron transfer from EtP5 to the DIBDP units, and the electron-transfer process had influence on the fluorescence emission but not on the triplet states of DIBDP moieties in EtP5-DIBDP, which verified the results of density functional theory calculations. The triplet state lifetimes of EtP5-DIBDP were longer than those of DIBDP and G and the photooxidation abilities of EtP5-DIBDP were better than those of DIBDP and G at a high concentration (1.0 × 10-5 M) in various solvents; in contrast, the intrinsic triplet state lifetimes and singlet oxygen quantum yields (ΦΔ) of DIBDP, G, and EtP5-DIBDP were very similar. This was because the steric hindrance of EtP5 moieties could weaken the TTA effect of DIBDP moieties without influencing their intrinsic triplet state lifetimes in EtP5-DIBDP.
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Glycyrrhizae Radix et Rhizoma is regarded as one of the most popular and commonly used herbal medicines and has been used in traditional Chinese medicine (TCM) prescriptions for over 2000 years. Pentacyclic triterpene saponins are common secondary metabolites in these plants, which are synthesized via the isoprenoid pathway to produce a hydrophobic triterpenoid aglycone containing a hydrophilic sugar chain. This paper systematically summarizes the chemical structures of triterpene saponins in Glycyrrhizae Radix et Rhizoma and reviews and updates their main biological activities studies. Furthermore, the solubilization characteristics, influences, and mechanisms of Glycyrrhizae Radix et Rhizoma are elaborated. Solubilization of the triterpene saponins from Glycyrrhizae Radix et Rhizoma occurs because they contain the nonpolar sapogenin and water-soluble sidechain. The possible factors affecting the solubilization of Glycyrrhizae Radix et Rhizoma are mainly other crude drugs and the pH of the decoction. Triterpene saponins represented by glycyrrhizin from Glycyrrhizae Radix et Rhizoma characteristically form micelles due to amphiphilicity, which makes solubilization possible. This overview provides guidance regarding a better understanding of GlycyrrhizaeRadix et Rhizoma and its TCM compatibility, alongside a theoretical basis for the further development and utilization of Glycyrrhizae Radix et Rhizoma.
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Medicamentos Herbarios Chinos/química , Glycyrrhiza/química , Saponinas/química , Antiinfecciosos/química , Antiinflamatorios/química , Antineoplásicos/química , Estructura MolecularRESUMEN
Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity than BA. Remarkably, the most potent compound 7e (the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 µM) was 12-fold more toxic in vitro than BA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound 7e could induce the early apoptosis of Hela cells. Structure-activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.
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Antineoplásicos , Citotoxinas , Neoplasias/tratamiento farmacológico , Triterpenos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Células Hep G2 , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Triterpenos Pentacíclicos , Relación Estructura-Actividad , Ácido BetulínicoRESUMEN
Through resources investigation and sample collection,a total number of 392 Dendrobium officinale from 38 different populations,9 provinces were processed for measuring and observing.Fourteen agronomy characterizations like stem height,stem diameter,number of node in stem were selected for further classification.The cluster analysis was performed using Ward and Euclidean method.The results showed that the threshold of genetic distance was 2.77.Thirtyeight populations were divided into 6 groups.The factor analysis showed that,the leaf shape,stem shape,pitch length and leaf color were very important factors for classification.This study establish the foundation for analyzing the genetic relationship of D.officinale from different populations.
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Dendrobium/anatomía & histología , Dendrobium/clasificación , Análisis por Conglomerados , Hojas de la Planta , Plantas Medicinales/anatomía & histología , Plantas Medicinales/clasificaciónRESUMEN
BACKGROUND Many heart failure (HF) cases are caused by idiopathic dilated cardiomyopathy (iDCM). This study explored the mechanisms of the development and progression of HF caused by iDCM. MATERIAL AND METHODS The gene expression profiles of 102 samples were downloaded from the GEO database (GSE5406). Differentially expressed genes (DEGs) were identified through GO analysis and a KEGG pathway analysis, respectively. A protein-protein interaction (PPI) network was constructed and analyzed to screen potential regulatory proteins. In addition, MCODE and a cytoHubba plugin were used to identify the module and hub genes of DEGs. Finally, transcription factors (TFs) were predicted using PASTAA. We did not perform whole-exome sequencing (WES) for detecting mitochondrial DNA (mtDNA). RESULTS A total of 197 DEGs were screened, and 3 modules, and 4 upregulated and 11 downregulated hub genes were screened. The GO analysis focused on the terms and 12 KEGG pathways were enriched. The FOS, TIMP1, and SERPINE1 hub genes, as well as some key TFs, demonstrated important roles in the progression of HF caused by iDCM. CEBPD, CEBOB, CDC37L1, and SRGN may be new targets for HF in iDCM patients. CONCLUSIONS The identified DEGs and their enriched pathways provide references for exploring the mechanisms of the development and progression of HF patients with iDCM. Moreover, modules, hub genes, and TFs may be useful in the treatment and diagnosis of HF patients with iDCM. However, mtDNA was not investigated.
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Cardiomiopatía Dilatada/genética , Perfilación de la Expresión Génica/métodos , Insuficiencia Cardíaca/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Mapas de Interacción de Proteínas , Transducción de Señal/genética , Factores de Transcripción/genética , TranscriptomaRESUMEN
Korean red pine (Pinus densiflora) bark has been traditionally used in Korea and other parts of East Asia to relieve inflammatory diseases. Although many studies using P. densiflora bark have been reported, its effect on atopic dermatitis (AD) has not been elucidated. Thus, we investigated whether the P. densiflora bark extract (PBE) has potential to attenuate AD symptoms and elucidated the molecular mechanism. Oral administration of PBE to mice with 2,4-dinitrochlorobenzene (DNCB)-induced AD lessened dermatitis scores and scratching behavior and significantly reduced measures of epidermal thickness, infiltration of mast cells and eosinophils, levels of immunoglobulin E (IgE), and IgG1 /IgG2a ratio in serum. PBE not only inhibited IL-4, IL-5, and IL-13 but also increased IFN-γ in splenic production. Furthermore, PBE significantly suppressed mRNA expression of thymic stromal lymphopoietin and further downregulated the mRNA expression of Th2 and Th17 cytokines such as IL-4, IL-13, IL-17, IL-31, and TNF-α. In addition, the protein expressions of filaggrin, involucrin, and loricrin in lesional skin were recovered by PBE. These results suggest that PBE attenuates DNCB-induced AD via regulating Th1/Th2 balance and skin barrier function.
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Dermatitis Atópica/inducido químicamente , Dinitroclorobenceno/efectos adversos , Piel/efectos de los fármacos , Balance Th1 - Th2/genética , Animales , Masculino , RatonesRESUMEN
Viral diarrhea is the predominant digestive tract sickness in piglings, resulting in substantial profit losses in the porcine industry. Porcine rotavirus A (PoRVA) and porcine epidemic diarrhea virus (PEDV) are the main causes of grave gastroenteritis and massive dysentery, especially in piglets. PoRVA and PEDV have high transmissibility, exhibit similar clinical symptoms, and frequently co-occur. Therefore, to avoid financial losses, a quick, highly efficient, objective diagnostic test for the prevention and detection of these diseases is required. Enzymatic recombinase amplification (ERA) is a novel technology based on isothermal nucleic acid amplification. It demonstrates high sensitivity and excellent specificity, with a short processing time and easy operability, compared with other in vitro nucleic acid amplification technologies. In this study, a dual ERA method to detect and distinguish between PEDV and PoRVA nucleic acids was established. The method shows high sensitivity, as the detection limits were 101 copies/µL for both viruses. To test the usefulness of this method in clinical settings, we tested 64 swine clinical samples. Our results were 100% matched with those acquired using a commercially available kit. Therefore, we have successfully developed a dual diagnostic ERA nucleic acids method for detecting and distinguishing between PEDV and PoRVA.
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Infecciones por Coronavirus , Ácidos Nucleicos , Virus de la Diarrea Epidémica Porcina , Rotavirus , Enfermedades de los Porcinos , Animales , Porcinos , Virus de la Diarrea Epidémica Porcina/genética , Recombinasas/genética , Enfermedades de los Porcinos/diagnóstico , Sensibilidad y Especificidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/veterinaria , Diarrea/diagnóstico , Diarrea/veterinariaRESUMEN
CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.
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Secuencias de Aminoácidos , Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas , Humanos , Antígenos Bacterianos/metabolismo , Antígenos Bacterianos/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Carcinogénesis , Pueblos del Este de Asia , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Unión Proteica , Transducción de SeñalRESUMEN
Abnormal aggregation and fibrillogenesis of amyloid-ß protein (Aß) can cause Alzheimer's disease (AD). Thus, the discovery of effective drugs that inhibit Aß fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating Aß aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on Aß1-42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-ß-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of Aß1-42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of Aß1-42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with Aß1-42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of Aß, and promote further exploration of the therapeutic strategy against AD.
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Enfermedad de Alzheimer , Glucósidos , Luteolina , Fragmentos de Péptidos , Humanos , Simulación del Acoplamiento Molecular , Fragmentos de Péptidos/metabolismo , Amiloide/metabolismo , Péptidos beta-Amiloides/química , Enfermedad de Alzheimer/metabolismoRESUMEN
African swine fever has caused substantial economic losses to China`s pig industry in recent years. Currently, the highly pathogenic African swine fever virus strain of genotype II is predominantly circulating in China, accompanied by a series of emerging isolates displaying unique genetic variations. The pathogenicity of these emerging strains is still unclear. Recently, a novel ASFV strain with a distinguishable three-large-fragment gene deletion was obtained from the field specimens, and its in vivo pathogenicity and transmission were evaluated in this study. The animal experiment involved inoculating a high dose of YNFN202103 and comparing its effects with those of the highly pathogenic strain GZ201801_2. Results showed that pigs infected by YNFN202103 exhibited significantly prolonged onset and survival time, lower viremia levels, and less severe histopathological lesions compared to GZ201801_2. These findings contributed valuable insights into the pathogenicity and transmission of ASFV and its prevention and eradication strategies in practical settings.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Enfermedades de los Porcinos , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Virulencia/genética , Eliminación de Gen , China , Enfermedades de los Porcinos/genéticaRESUMEN
Advanced functional two-dimensional (2D) nanomaterials offer unique advantages in drug delivery systems for disease treatment. Kaolinite (Kaol), a nanoclay mineral, is a natural 2D nanomaterial because of its layered silicate structure with nanoscale layer spacing. Recently, Kaol nanoclay is used as a carrier for controlled drug release and improved drug dissolution owing to its advantageous properties such as surface charge, strong biocompatibility, and naturally layered structure, making it an essential development direction for nanoclay-based drug carriers. This review outlines the main physicochemical characteristics of Kaol and the modification methods used for its application in biomedicine. The safety and biocompatibility of Kaol are addressed, and details of the application of Kaol as a drug delivery nanomaterial in antibacterial, anti-inflammatory, and anticancer treatment are discussed. Furthermore, the challenges and prospects of Kaol-based drug delivery nanomaterials in biomedicine are discussed. This review recommends directions for the further development of Kaol nanocarriers by improving their physicochemical properties and expanding the bioapplication range of Kaol.
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Portadores de Fármacos , Nanoestructuras , Portadores de Fármacos/química , Caolín/química , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , AntibacterianosRESUMEN
Soldiers in the military are exposed to numerous stressors, including some that are of an extreme nature. The main objective of this military psychology research study was to evaluate soldiers' occupational stress. Even though several tools have been developed to measure stress in this population, to date, none have focused on occupational stress. Hence, we developed the Military Occupational Stress Response Scale (MOSRS) to provide a tool to objectively measure soldiers' occupational stress responses. An initial pool of 27 items was assembled from the literature, existing instruments, and interviews with soldiers. Of those 27, 17 were included in the MOSRS. The scale was subsequently completed by soldiers from one military region, and exploratory factor analysis (EFA) and confirmatory factor analysis were conducted using Mplus8.3 and IBM SPSS 28.0 software, respectively. A total of 847 officers and soldiers were selected for scale testing, and 670 subjects were retained after data cleaning and screening according to the set criteria. After performing the Kaiser-Meyer-Olkin (KMO) and Bartlett's test, principal components analysis (PCA) was appropriate. The PCA yielded a three-factor model (physiological, psychological, and behavioral responses) with the items and factors strongly correlated. The confirmatory factor analysis revealed loads ranging from between 0.499 and 0.878 for each item. The Cronbach's α coefficient of the MOSRS was between 0.710 and 0.900, and the Omega reliability was between 0.714 and 0.898, which were all higher than the critical standard value of 0.7, indicating that the scale has good reliability. Analysis of the discrimination validity of each dimension revealed that the scale has good discrimination validity. The MOSRS demonstrated sound psychometric characteristics with acceptable reliability and validity, suggesting that it could be used to assess occupational stress in military personnel.