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ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Macrófagos , SARS-CoV-2 , Replicación Viral , Animales , Ratones , Células RAW 264.7 , Replicación Viral/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Ratones Transgénicos , Pogostemon/química , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/virología , Pulmón/patología , Glucósidos/farmacología , Glucósidos/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Antiinflamatorios/farmacología , Masculino , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , HumanosRESUMEN
Vanadium (V)-based oxides have garnered significant attention as cathode materials for aqueous zinc-ion batteries (AZIBs) due to their multiple valences and high theoretical capacity. However, their sluggish kinetics and low conductivity remain major obstacles to practical applications. In this study, Mo-doped V2O3 with oxygen vacancies (OVs, Mo-V2O3-x@NC) is prepared from a Mo-doped V-metal organic framework. Ex situ characterizations reveal that the cathode undergoes an irreversible phase transformation from Mo-V2O3-x to Mo-V2O5-x·nH2O and serves as an active material exhibiting excellent Zn2+ storage in subsequent charge-discharge cycles. Mo-doped helps to further improve cycling stability and increases with increasing content. More importantly, the synergistic effect of Mo-doped and OVs not only effectively reduces the Zn2+ migration energy barrier, but also enhances reaction kinetics, and electrochemical performance. Consequently, the cathode demonstrates ultrafast electrochemical kinetics, showing a superior rate performance (190.9 mAh g-1 at 20 A g-1) and excellent long-term cycling stability (147.9 mAh g-1 at 20 A g-1 after 10000 cycles). Furthermore, the assembled pouch cell exhibits excellent cycling stability (313.6 mAh g-1 at 1 A g-1 after 1000 cycles), indicating promising application prospects. This work presents an effective strategy for designing and fabricating metal and OVs co-doped cathodes for high-performance AZIBs.
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Extracellular vesicles (EVs) derived from cancer cells are crucial mediators of intercellular communication during tumor progression. The cargo in tumor-derived EVs that facilitates the establishment of a tumor-supportive microenvironment could serve as a therapeutic target to improve cancer treatment. Here, we demonstrated that hepatocellular carcinoma (HCC) cells secreted the acyl-CoA synthetase ACSL4 in large extracellular vesicles (lEVs) to modulate tumor-microenvironment interactions that promote HCC progression. HCC-derived lEV ACSL4 increased the intracellular abundance of polyunsaturated fatty acid-containing lipids and remodeled the lipid profile to potentiate lipid peroxidation in peritumoral hepatocytes, resulting in hepatocyte senescence accompanied by the senescence-associated secretory phenotype (SASP). Depletion of senescent hepatocytes by senolytic treatment suppressed tumor progression. In HCC cells, SREBP2-mediated transcriptional activation upregulated ACSL4 expression, and Akt-mediated phosphorylation of ACSL4 induced its packaging into lEVs by augmenting its interaction with Annexin A2. This study identified the critical regulatory function of ACSL4 secreted from HCC cells in inducing lipid remodeling and senescence in hepatocytes to support HCC progression, suggesting that targeting lEV ACSL4 is a potential therapeutic strategy for HCC.
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RATIONALE: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. METHODS: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. RESULTS: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K a = 1.89×107 M-1) and decamethonium (K a = 1.01×107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. CONCLUSION: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.
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Antídotos , Tetracaína , Animales , Tetracaína/farmacología , Tetracaína/química , Ratones , Antídotos/farmacología , Antídotos/química , Amidas/química , Amidas/farmacología , Masculino , Anestésicos Locales/farmacología , Anestésicos Locales/química , Humanos , Bloqueantes Neuromusculares/química , Bloqueantes Neuromusculares/farmacologíaRESUMEN
The widespread application of metal additive manufacturing (AM) is limited by the ability to control the complex interactions between the energy source and the feedstock material. Here, we develop a generalizable process to introduce nanoscale grooves to the surface of metal powders which increases the powder absorptivity by up to 70% during laser powder bed fusion. Absorptivity enhancements in copper, copper-silver, and tungsten enable energy-efficient manufacturing, with printing of pure copper at relative densities up to 92% using laser energy densities as low as 83 joules per cubic millimeter. Simulations show that the enhanced powder absorptivity results from plasmon-enabled light concentration in nanoscale grooves combined with multiple scattering events. The approach taken here demonstrates a general method to enhance the absorptivity and printability of reflective and refractory metal powders by changing the surface morphology of the feedstock without altering its composition.
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Traditional deicing methods are increasingly insufficient for modern technologies like 5G infrastructure, photovoltaic systems, nearspace aerocraft, and terrestrial observatories. To address the challenge of combining anti-icing efficiency with operational performance, an innovative, spectrally selective, photo/electrothermic, ice-phobic film was prepared through a cost-effective mist deposition method. By manipulating the diameter ratio and density of nanowires, the local density of free electrons within this film is controlled to precisely dictate the position and intensity of surface plasmon resonance to achieve spectrally selective photo/electrothermal conversion. Additionally, the synthesized hydrophobic N-Boroxine-PDMS/SiO2 layer improves thermal stability and accelerates the deicing process. It achieves rapid deicing within 86 s under photothermal conditions and 65 s with Joule heating while maintaining high optical transmittance. The film improves the operational efficiency and thermal safety of equipment while preserving aesthetics and stability, thereby underscoring its broad suitability for advanced outdoor installations in cold environments.
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Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.
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ETHNOPHARMACOLOGICAL RELEVANCE: Blossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. AIM OF THE STUDY: This study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. MATERIALS AND METHODS: The pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, Western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. RESULTS: In vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. CONCLUSION: Eriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. METHODS: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). RESULTS: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product-vaccarin (VAC)-that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. CONCLUSIONS: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.
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The incidence of thyroid cancer is increasing worldwide. Fine-needle aspiration (FNA) cytology is widely applied with the use of extracted biological cell samples, but current FNA cytology is labor-intensive, time-consuming, and can lead to the risk of false-negative results. Surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms holds promise for cancer diagnosis. In this study, we develop a label-free SERS liquid biopsy method with machine learning for the rapid and accurate diagnosis of thyroid cancer by using thyroid FNA washout fluids. These liquid supernatants are mixed with silver nanoparticle colloids, and dispersed in quartz capillary for SERS measurements to discriminate between healthy and malignant samples. We collect Raman spectra of 36 thyroid FNA samples (18 malignant and 18 benign) and compare four classification models: Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA), Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN). The results show that the CNN algorithm is the most precise, with a high accuracy of 88.1%, sensitivity of 87.8%, and the area under the receiver operating characteristic curve of 0.953. Our approach is simple, convenient, and cost-effective. This study indicates that label-free SERS liquid biopsy assisted by deep learning models holds great promise for the early detection and screening of thyroid cancer.
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Aprendizaje Automático , Espectrometría Raman , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biopsia con Aguja Fina , Plata/química , Máquina de Vectores de Soporte , Nanopartículas del Metal/química , Análisis de Componente Principal , Algoritmos , Redes Neurales de la Computación , Biopsia Líquida , Análisis DiscriminanteRESUMEN
A novel strategy for the catalyst-free domino cross-olefination and intramolecular cyclization of Morita-Baylis-Hillman carbonates with sulfur ylides has been established, resulting in the synthesis of 1,2-dihydroquinolines with a broad scope, excellent chemoselectivity, and high efficiency. Mechanistic experiments revealed the process of 1,1-dipole cross-olefination and highlighted the assistance of the amino group in achieving successful transformations.
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BACKGROUND: Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5-10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage. METHODS: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group. RESULTS: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group. CONCLUSION: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.
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Aminoácidos , Blastocisto , Desarrollo Embrionario , Glutatión , Síndrome del Ovario Poliquístico , Animales , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/patología , Femenino , Ratones , Blastocisto/metabolismo , Desarrollo Embrionario/genética , Glutatión/metabolismo , Aminoácidos/metabolismo , Análisis de Secuencia de ARN , Modelos Animales de Enfermedad , Regulación del Desarrollo de la Expresión GénicaRESUMEN
BACKGROUND: Non-Small Cell Lung Cancer (NSCLC), a prevalent type of lung cancer, has a poor prognosis and contributes to a high mortality rate. Agrimonolide, which belongs to the Rosaceae family, possesses various biomedical activities. This study aimed to explore the efficacy and mechanism of agrimonolide in NSCLC. METHODS: The viability, proliferation, and tumor-forming ability of A549 cells were detected using the Cell Counting Kit-8 assay (CCK-8) assay, EdU staining, and colony formation assay. The cell cycle was detected using flow cytometry. Cell migration and invasion were detected using wound healing and transwell assays. Western blot was used to detect Epithelial-Mesenchymal Transition (EMT)-, ferroptosis-, and mechanistic targets of rapamycin (mTOR) signaling pathway-related proteins. Lipid peroxidation was detected using the thiobarbituric acid reactive substances (TBARS) assay kit, while lipid Reactive Oxygen Species (ROS) was detected using a BODIPY 581/591 C11 kit. The level of Fe2+ was detected using corresponding assay kits. RESULTS: In this study, agrimonolide with varying concentrations (10, 20, and 40 µM] could inhibit the proliferation, induce cycle arrest, suppress metastasis, induce ferroptosis, and block the mTOR signaling pathway in NSCLC cells. To further reveal the mechanism of agrimonolide associated with the mTOR signaling pathway in NSCLC, mTOR agonist MHY1485 (10 µM) was used to pre-treat A549 cells, and functional experiments were conducted again. It was found that the protective effects of AM on NSCLC cells were all partially abolished by MHY1485 pre-treatment. CONCLUSION: Agrimonolide inhibited the malignant progression of NSCLC and induced ferroptosis by blocking the mTOR signaling pathway, thus indicating the potential of agrimonolide as a prospective candidate for treating NSCLC.
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The aesthetic demand has become an imperative challenge to advance the practical and commercial application of daytime radiative cooling technology toward mitigating climate change. Meanwhile, the application of radiative cooling materials usually focuses on the building surface, related tightly to fire safety. Herein, the absorption and reflection spectra of organic and inorganic colorants are first compared in solar waveband, finding that iron oxides have higher reflectivity in NIR region. Second, three kinds of iron oxides-based colorants are selected to combine porous structure and silicon-modified ammonium polyphosphate (Si-APP) to engineer colored polyurethane-based (PU) coating, thus enhancing the reflectivity and flame retardancy. Together with reflectivity of more than 90% in near-infrared waveband and infrared emissivity of ≈91%, average temperature drops of ≈5.7, ≈7.9, and ≈3.8 °C are achieved in porous PU/Fe2O3/Si-APP, porous PU/Fe2O3·H2O/Si-APP, and porous PU/Fe3O4·H2O/Si-APP, compared with dense control samples. The catalysis effect of iron oxides in the cross-linking reaction of pyrolysis products and dehydration mechanism of Si-APP enable PU coating to produce an intumescent and protective char residue. Consequently, PU composite coatings demonstrate desirable fire safety. The ingenious choice of colorants effectively minimizes the solar heating effect and trades off the daytime radiative cooling and aesthetic appearance requirement.
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The ocean has absorbed anthropogenic carbon dioxide (Canthro) from the atmosphere and played an important role in mitigating global warming. However, how much Canthro is accumulated in coastal oceans and where it comes from have rarely been addressed with observational data. Here, we use a high-quality carbonate dataset (1996-2018) in the U.S. East Coast to address these questions. Our work shows that the offshore slope waters have the highest Canthro accumulation changes (ΔCanthro) consistent with water mass age and properties. From offshore to nearshore, ΔCanthro decreases with salinity to near zero in the subsurface, indicating no net increase in the export of Canthro from estuaries and wetlands. Excesses over the conservative mixing baseline also reveal an uptake of Canthro from the atmosphere within the shelf. Our analysis suggests that the continental shelf exports most of its absorbed Canthro from the atmosphere to the open ocean and acts as an essential pathway for global ocean Canthro storage and acidification.
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The spoilage of refrigerated pork involves nutrient depletion and the production of spoilage metabolites by spoilage bacteria, yet the microbe-metabolite interactions during this process remain unclear. This study employed 16S rRNA high-throughput sequencing and non-targeted metabolomics based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to reveal the core microbiota and metabolite profiles of pork during refrigeration. A total of 45 potential biomarkers were screened through random forest model analysis. Metabolic pathway analysis indicated that eleven pathways, including biogenic amine metabolism, pentose metabolism, purine metabolism, pyrimidine metabolism, phospholipid metabolism, and fatty acid degradation, were potential mechanisms of pork spoilage. Correlation analysis revealed nine metabolites-histamine, tyramine, tryptamine, D-gluconic acid, UDP-d-glucose, xanthine, glutamine, phosphatidylcholine, and hexadecanoic acid-as spoilage biomarkers, with Pseudomonas, Serratia, and Photobacterium playing significant roles. This study provides new insights into the changes in microbial and metabolic characteristics during the spoilage of refrigerated pork.
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Bacterias , Secuenciación de Nucleótidos de Alto Rendimiento , Metabolómica , Espectrometría de Masas en Tándem , Animales , Porcinos , Cromatografía Líquida de Alta Presión , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/crecimiento & desarrollo , Refrigeración , Microbiota , Carne de Cerdo/microbiología , Carne de Cerdo/análisis , ARN Ribosómico 16S/genéticaRESUMEN
Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1ß, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1ß to silence IL-1ß may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1ß and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1ß, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1ß (PM@siIL-1ß) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1ß were evaluated. A rat hind limb DVT model was established, and PM@siIL-1ß was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1ß, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1ß and t-PA were highly expressed in DVT patients, and IL-1ß treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1ß exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1ß and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1ß resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1ß, VWF, and t-PA levels. Furthermore, PM@siIL-1ß treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1ß can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1ß achieved efficient delivery and gene silencing of siIL-1ß, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.
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A shock-tube facility capable of generating a planar shock with the Mach number higher than 3.0 is developed for studying Richtmyer-Meshkov instability induced by a strong shock wave (referred to as strong-shock RMI). Shock enhancement is realized through the convergence of shock within a channel with the profile determined by using shock dynamics theory. The facility is designed considering the repeatability of shock generation, transition of shock profile, and effects of viscosity and flow choking. By measuring the dynamic pressure of the tube flow using pressure sensors and capturing the shock movement through the high-speed shadowing technique, the reliability and repeatability of the shock tube for generating a strong planar shock are first verified. Particular emphasis is then placed on the ability of the facility to study strong-shock RMI, for which a thin polyester film is adopted to form the initial interface separating gases of different densities. The results indicate that the shock tube is reliable for conducting strong-shock RMI experiments.
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This article aims to explore the most optimal pulsed laser energy density when using the pulsed laser deposition (PLD) process to prepare the MoS2 films. We gradually increased the pulsed laser energy density from 70 mJ·cm-2 to 110 mJ·cm-2 and finally determined that 100 mJ·cm-2 was the best-pulsed laser energy density for MoS2 films by PLD. The surface morphology and crystallization of the MoS2 films prepared under this condition are the best. The films consist of a high-crystallized 2H-MoS2 phase with strong (002) preferential orientation, and their direct optical band gap (Eg) is 1.614 eV. At the same time, the Si/MoS2 heterojunction prepared under the optimal pulsed laser energy density shows an opening voltage of 0.61 V and a rectification ratio of 457.0.
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AIMS: Hypoperfusion induces significant white matter injury in cerebral vascular disorders, including arteriosclerotic cerebral small vessel disease (aCSVD), which is prevalent among the elderly. Iron transport by blood vessel endothelial cells (BVECs) from the periphery supports oligodendrocyte maturation and white matter repair. This study aims to elucidate the association between iron homeostasis changes and white matter injury severity, and explore the crosstalk between BVECs and oligodendroglial lineage cells. METHODS: In vivo: C57BL/6 mice were subjected to unilateral common carotid artery occlusion (UCCAO). In vitro: BVECs with myelin pretreatment were co-cultured with oligodendrocyte progenitor cells (OPCs) or organotypic cerebellar slices subjected to oxygen and glucose deprivation. RESULTS: Circulatory iron tends to be stored in aCSVD patients with white matter injury. Myelin debris endocytosis by BVECs impairs iron transport, trapping iron in the blood and away from the brain, worsening oligodendrocyte iron deficiency in hypoperfusion-induced white matter injury. Iron accumulation in BVECs triggers ferroptosis, suppressing iron transport and hindering white matter regeneration. Intranasal holo-transferrin (hTF) administration bypassing the BBB alleviates oligodendrocyte iron deficiency and promotes myelin regeneration in hypoperfusion-induced white matter injury. CONCLUSION: The iron imbalance between BVECs and oligodendroglial lineage cells is a potential therapeutic target in hypoperfusion-induced white matter injury.