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Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke-induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
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Phosphorus (P) release from sediment poses a severe challenge for eutrophication management in the aquatic environment. The dissolved organic carbon (DOC) concentrations in riverine ecosystems have shown an increasing trend due to intensified climate change and anthropogenic activities, while their impact on sediment P cycling remains unclear. To investigate the effects of different DOC loads on sediment P release and the underlying mechanisms, we conducted a two-month experiment in 15 plexiglass tanks, with five gradient-increasing target DOC concentrations set according to reality: control (S0), 5 mg/L (S5), 10 mg/L (S10), 15 mg/L (S15), and 20 mg/L (S20). The results demonstrated that: i) DOC enrichment promoted the sediment P mobilization and release, with the underlying mechanisms exhibited periodic characteristics. ii) reduced dissolved oxygen (DO) concentration and stimulated alkaline phosphatase activity (APA) were likely the primary and sustained facilitating mechanisms. While after the termination of DOC load, elevated pH level was also considered a contributing factor when chlorophyll a (Chl a) ranged between 5.9 µg/L and 7.7 µg/L iii) ultimate concentration of total P (TP) in the overlying water depended on DOC load. After DOC addition was terminated, decreased TP concentrations were observed when DOC concentration was in the range of 5-15 mg/L, which may be attributed to the direct uptake of P by phytoplankton counteracting the minor promotion of P release induced by anoxic conditions. However, when DOC concentrations exceeded 15-20 mg/L, there were notable increments in TP concentrations. Our findings provide further insight into the response mechanisms of sediment P release to the increasing organic C load in natural ecosystems. The impact of broader C forms or C loads on sediment P cycling needs to be fully elucidated and even quantified in future studies, especially through large-scale field investigations to further clarify the coupled roles between C and P.
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The aroma profile of fermented chili pepper was analyzed using gas chromatography-mass spectrometry (GC-MS) coupled with chromatography-olfactometry (GC-O). A total of 19 aroma-active compounds were detected, exhibiting aroma intensities spanning from 1.8 to 4.2. And 12 aroma-active compounds were determined as pivotal odorants through odor activity value (OAV) calculation. Concentrations of these aroma-active compounds were quantified and subsequently employed in reconstructing the aroma profile of fermented chili pepper. Quantitative descriptive sensory analysis and electronic nose analysis proved that the aroma profile of fermented chili pepper was basically reconstituted. Omission experiments confirmed that methyl salicylate, linalool, 2-methoxy-3-isobutylpyrazine, and phenylethyl alcohol were the key aroma-active compounds of fermented chili pepper. Moreover, the perceptual interactions between the key aroma-active compounds were investigated. It was found that methyl salicylate masked the floral aroma, while phenylethyl alcohol had an additive effect on the aroma of linalool and 2-methoxy-3-isobutylpyrazine.
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PURPOSE: This study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer. METHODS: Early-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan-Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer. RESULTS: Seventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan-Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm. CONCLUSION: Patients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.
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Idade de Início , Neoplasias do Colo , Neoplasias Retais , Carga Tumoral , Humanos , Masculino , Feminino , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Estimativa de Kaplan-Meier , Programa de SEER , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , IdosoRESUMO
Purpose: This study aimed to identify prognostic factors and develop a nomogram for predicting overall survival (OS) in stage III/IV early-onset colorectal cancer (EO-CRC). Methods: Stage III/IV EO-CRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The datasets were randomly divided (2:1) into training and validation sets. A nomogram predicting OS was developed based on the prognostic factors identified by Cox regression analysis in the training cohort. Moreover, the predictive performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Subsequently, the internal validation was performed using the validation cohort. Finally, a risk stratification system was established based on the constructed nomogram. Results: Of the 10,387 patients diagnosed with stage III/IV EO-CRC between 2010 and 2015 in the SEER database, 8,130 patients were included. In the training cohort (n=3,071), sex, marital status, race/ethnicity, primary site, histologic subtypes, grade, T stage, and N stage were identified as independent prognostic variables for OS. The 1-, 3-, and 5-year area under the curve (AUC) values of the nomogram were robust in both the training (0.751, 0.739, and 0.723) and validation cohorts (0.748, 0.733, and 0.720). ROC, calibration plots, and DCA indicated good predictive performance of the nomogram in both the training and validation sets. Furthermore, patients were categorized into low-, middle-, and high-risk groups based on the nomogram risk score. Kaplan-Meier curve showed significant survival differences between the three groups. Conclusion: We developed a prognostic nomogram and risk stratification system for stage III/IV EO-CRC, which may facilitate clinical decision-making and individual prognosis prediction.
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BACKGROUND: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. METHODS: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. RESULTS: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. CONCLUSIONS: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.
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Células Epiteliais , Pólipos Nasais , Rinite , Fator de Transcrição STAT6 , Transdução de Sinais , Sinusite , Humanos , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/genética , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Pólipos Nasais/imunologia , Sinusite/metabolismo , Sinusite/patologia , Sinusite/imunologia , Rinite/metabolismo , Rinite/patologia , Doença Crônica , Células Epiteliais/metabolismo , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/genética , Feminino , Masculino , Quimiocina CCL26/metabolismo , Quimiocina CCL26/genética , Adulto , Pessoa de Meia-Idade , Eosinofilia/metabolismo , Eosinofilia/patologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Mucosa Nasal/imunologia , Regulação da Expressão Gênica , RinossinusiteRESUMO
Corneal damage contributes to blindness in millions of people. Simulating natural corneas with artificial corneas is challenging due to material and manufacturing limitations, including poor mechanical properties, complex manufacturing processes, and ocular histocompatibility. In this study, electrospun micro-nanofibrous decellularized extracellular matrix (dECM) is combined with digital light processing 3D bioprinting and validated as a bioartificial cornea for the first time. Electrospinning gives the material a controllable shape, and the electrospun micro-nanofibrous dECM, with preserved inherent biochemical components, can better mimic the natural ECM native microenvironment. An efficient platform can be developed for creating novel structural materials, when combined with intelligent manufacturing. Artificial biological corneas developed using this method showed five-fold improvements in mechanical properties (248.5 ± 35.67 kPa vs. 56.91 ± 3.68 kPa,p< 0.001), superior guidance for cell organization and adhesion, and better maintenance of the cellular phenotype of keratocytes. In animal studies,in vivotransplantation of this artificial cornea showed better regeneration, which accelerated corneal epithelialization and maintained corneal transparency. This method has potential for biomedical applications, and bioartificial corneas manufactured by this method have ideal properties as an alternative to lamellar keratoplasty, with promise for clinical transformation.
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Bioimpressão , Nanofibras , Animais , Humanos , Matriz Extracelular Descelularizada , Bioimpressão/métodos , Córnea , Matriz Extracelular/química , Alicerces Teciduais/química , Engenharia Tecidual/métodosRESUMO
The rapid evolution of gene editing technology has markedly improved the outlook for treating genetic diseases. Base editing, recognized as an exceptionally precise genetic modification tool, is emerging as a focus in the realm of genetic disease therapy. We provide a comprehensive overview of the fundamental principles and delivery methods of cytosine base editors (CBE), adenine base editors (ABE), and RNA base editors, with a particular focus on their applications and recent research advances in the treatment of genetic diseases. We have also explored the potential challenges faced by base editing technology in treatment, including aspects such as targeting specificity, safety, and efficacy, and have enumerated a series of possible solutions to propel the clinical translation of base editing technology. In conclusion, this article not only underscores the present state of base editing technology but also envisions its tremendous potential in the future, providing a novel perspective on the treatment of genetic diseases. It underscores the vast potential of base editing technology in the realm of genetic medicine, providing support for the progression of gene medicine and the development of innovative approaches to genetic disease therapy.
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Necroptosis is a recently identified caspase-independent form of cell death which plays a significant role in the onset and progression of cancer. MicroRNAs (miRNAs) are vital for the development of uterine corpus endometrial carcinoma (UCEC) because they are an important regulatory component in necroptosis. This study developed a new necroptosis-related miRNAs profile to predict the prognosis of patients with UCEC. The TCGA-UCEC cohort's RNA sequencing data, consisting of 534 tumor samples and 33 normal samples, was downloaded. Ten differentially expressed miRNAs related to necroptosis were identified. A prediction model for necroptosis-related miRNAs was then created through COX regression and nomograms analysis. Clinical and pathological parameters were integrated to construct a nomogram and evaluate the model. Prognosis-related miRNAs were further used to predict target genes, and functional analysis was conducted to explore the potential mechanisms of these target genes. Subsequently, immune infiltration analysis was performed using transcriptome data to identify immune genes associated with prognosis, and the expression levels of target gene was validated using UCEC tissues. We identified 7 up-regulated miRNAs (hsa-miR-577, hsa-miR-7-5p, hsa-miR-210-3p, hsa-miR-210-5p, hsa-miR-200a-5p, hsa-miR-141-3p, hsa-miR-425-5p) and 3 down-regulated miRNAs (hsa-miR-7-2-3p, hsa-miR-383-5p, hsa-miR-29a-3p). The risk signature was based on univariate and multivariate COX analyses, constructed using 2 independent prognostic factors and miRNAs (hsa-miR-425-5p, hsa-miR-7-5p) associated with necroptosis. Nomograms demonstrated the prognostic value of risk level, age, FIGO stage, and histological type. Kaplan-Meier analysis revealed significant differences in overall survival (OS) outcomes associated with the expression of hsa-miR-425-5p (P < 0.001) and hsa-miR-7-5p (P = 0.015). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations indicated that these miRNAs play crucial roles in tumor development, metastasis, and prognosis. Immune infiltration analysis showed decreased infiltration of CD8+ T cells, CD8+ T cells, NK cells, and M1 macrophages in normal tissues. Subsequently, a necroptosis-related immune gene significantly associated with prognosis (THRB) was identified, western blot and immunohistochemical staining confirmed the differential expression of THRB in normal endometrial tissues and tumor. Our findings demonstrate a close association between necroptosis and UCEC. The two necroptosis-related miRNAs used in this study may serve as valuable prognostic markers for UCEC patients, and are associated with immune cell infiltration. This suggests that necroptosis may be involved in the development of UCEC through its interaction with immune responses.
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Neoplasias do Endométrio , MicroRNAs , Feminino , Humanos , Prognóstico , Necroptose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Transcriptoma , Neoplasias do Endométrio/genéticaRESUMO
This study employed adaptive laboratory evolution to improve the acid tolerance of Lactiplantibacillus plantarum, a vital strain in food fermentation and a potential probiotic. Phenotype and genomic analyses identified the overexpression of stress response proteins, ATP synthases, and transporters as pivotal in conferring acid tolerance to the evolved strains. These adaptations led to a shorter lag phase, improved survival rates, and higher intracellular pH values compared to the wild-type strain under acid stress conditions. Additionally, the evolved strains showed an increased expression of genes in the fatty acid synthesis pathway, resulting in a higher production of unsaturated fatty acids. The changes in cell membrane composition possibly prevented H+ influx, while mutant genes related to cell surface structure contributed to observed elongated cells and thicker cell surface. These alterations in cell wall and membrane composition, along with improved transporter efficiency, were key factors contributing to the enhanced acid tolerance in the evolved strains.
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Lactobacillus plantarum , Probióticos , Membrana Celular , Parede Celular , Fermentação , Genômica , Proteínas de Choque Térmico , Proteínas de Membrana TransportadorasRESUMO
Fine particulate matter (PM2.5) represents a prevalent environmental pollutant in the atmosphere, capable of exerting deleterious effects on human health. Numerous studies have indicated a correlation between PM2.5 exposure and the development of chronic upper airway inflammatory diseases. The objective of this study was to investigate the impact of PM2.5 on the transcriptome of fibroblasts derived from nasal mucosa. Initially, nasal mucosa-derived fibroblasts were isolated, cultured, and subsequently stimulated with PM2.5 (100 µg/mL) or an equivalent volume of normal culture medium for a duration of 24 h. Following this, total RNA from these cells was extracted, purified, and subjected to sequencing using next-generation RNA sequencing technology. Differentially expressed genes (DEGs) were then identified and utilized for functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed, and validation of key genes and proteins was carried out using quantitative real-time PCR and ELISA methods. Results revealed 426 DEGs, comprising 276 up-regulated genes and 150 down-regulated genes in nasal mucosa-derived fibroblasts treated with PM2.5 compared to control cells. Functional enrichment analysis indicated that DEGs were predominantly associated with inflammation-related pathways, including the IL-17 signaling pathway. In alignment with this, PPI analysis highlighted that hub genes were primarily involved in the regulation of the IL-17 signaling pathway. Subsequent validation through quantitative real-time PCR and ELISA confirmed significant alterations in the relative expressions of IL-17 signaling pathway-related genes and concentrations of IL-17 signaling pathway related proteins in nasal mucosa-derived fibroblasts treated with PM2.5 compared to control cells. In conclusion, PM2.5 intervention substantially altered the transcriptome of nasal mucosa-derived fibroblasts. Furthermore, PM2.5 has the potential to exacerbate the inflammatory responses of these fibroblasts by modulating the expression of key genes in the IL-17 signaling pathway.
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Interleucina-17 , Mucosa Nasal , Humanos , Interleucina-17/metabolismo , Mucosa Nasal/metabolismo , Transdução de Sinais , Material Particulado/metabolismo , Fibroblastos/metabolismoRESUMO
Epilepsy is a prevalent neurological disorder characterized by unprovoked seizures. γ-Aminobutyric acid (GABA) serves as the primary fast inhibitory neurotransmitter in the brain, and GABA binding to the GABAA receptor (GABAAR) regulates Cl- and bicarbonate (HCO3-) influx or efflux through the channel pore, leading to GABAergic inhibition or excitation, respectively. The neuron-specific K+-Cl- cotransporter 2 (KCC2) is essential for maintaining a low intracellular Cl- concentration, ensuring GABAAR-mediated inhibition. Impaired KCC2 function results in GABAergic excitation associated with epileptic activity. Loss-of-function mutations and altered expression of KCC2 lead to elevated [Cl-]i and compromised synaptic inhibition, contributing to epilepsy pathogenesis in human patients. KCC2 antagonism studies demonstrate the necessity of limiting neuronal hyperexcitability within the brain, as reduced KCC2 functioning leads to seizure activity. Strategies focusing on direct (enhancing KCC2 activation) and indirect KCC2 modulation (altering KCC2 phosphorylation and transcription) have proven effective in attenuating seizure severity and exhibiting anti-convulsant properties. These findings highlight KCC2 as a promising therapeutic target for treating epilepsy. Recent advances in understanding KCC2 regulatory mechanisms, particularly via signaling pathways such as WNK, PKC, BDNF, and its receptor TrkB, have led to the discovery of novel small molecules that modulate KCC2. Inhibiting WNK kinase or utilizing newly discovered KCC2 agonists has demonstrated KCC2 activation and seizure attenuation in animal models. This review discusses the role of KCC2 in epilepsy and evaluates its potential as a drug target for epilepsy treatment by exploring various strategies to regulate KCC2 activity.
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Epilepsia , Simportadores , Animais , Humanos , Cotransportadores de K e Cl- , Simportadores/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Neurônios/metabolismo , Ácido gama-Aminobutírico/metabolismo , ConvulsõesRESUMO
BACKGROUND: Aspiration pneumonitis (AP) secondary to cerebrospinal fluid (CSF) leak is underestimated and rarely discussed. This study aimed to evaluate the association between AP and CSF leaks. METHODS: Clinical and surgical characteristics of CSF leak patients with and without AP between January 2010 and December 2022 were included and compared. RESULTS: This study included 159 patients, 16 with CSF otorrhea and 143 with CSF rhinorrhea. Among them, 40 (25.2%) had AP. Bilateral pneumonitis was identified in 32 cases, of which 11 showed severe pneumonitis in the right upper lung lobe. Twenty-one (52.5%) asymptomatic and 19 (47.5%) symptomatic cases were documented. The major clinical manifestations included cough (n = 19, 47.5%) and expectoration (n = 9, 22.5%). The prevalence of pneumonitis was significantly higher in the spontaneous group than in the traumatic group. High-flow CSF leak was associated with AP (42.5% vs. 16.8%, p = 0.001). No significant differences were identified in defect locations between patients with and without AP. Patients with pneumonitis had a higher prevalence of meningitis (32.5% vs. 12.6%, p = 0.003). Multiple logistic regression results revealed that meningitis, spontaneous and high-flow CSF leaks are independent factors for AP occurrence. Both the CSF leak and pulmonary complications resolved following successful surgical repair. CONCLUSIONS: AP secondary to CSF leaks is frequently underdiagnosed, with a higher incidence identified in spontaneous cases. The occurrence of AP was associated with high-flow CSF leak.
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The influence of Pichia spp. on flavor formation and metabolic pathways during chili pepper fermentation was investigated in this study. Multiple omics approaches were employed, including metabolomics analysis to identify volatile and non-volatile flavor compounds, and genomic analysis to gain insights into the underlying molecular mechanism driving flavor formation of chili peppers inoculated with Pichia spp. The results showed that inoculation with Pichia spp. accelerated fermentation process of chili peppers compared to spontaneous fermentation. Metabolomics analysis showed P. fermentans promoted characteristic terpenes [e.g., (Z)-ß-ocimene and linalool], L-glutamate, gamma-aminobutyric acid, and succinate production, while P. manshurica produced more alcohols (e.g., isoamyl alcohol and phenylethyl alcohol) and phenols (e.g., 4-ethylguaiacol and 2-methoxy-4-methylphenol). Genomics analysis revealed that a substantial portion of the genes in Pichia spp. were associated with amino acid and carbohydrate metabolism. Specifically, the pathways involved in amino acid metabolism and the release of glycoside-bound aromatic compounds were identified as the primary drivers behind the unique flavor of fermented chili peppers, facilitated by Pichia spp.
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Capsicum , Pichia , Pichia/genética , Pichia/metabolismo , Capsicum/metabolismo , Álcoois/metabolismo , Genômica , Cânfora/metabolismo , Aminoácidos/metabolismoRESUMO
The softening of acidified chili peppers induced by processing and storage has become a major challenge for the food industry. This study aims to explore the impact of pasteurization techniques, thermal processing (TP), high-pressure processing (HPP), addition of sodium metabisulfite (SMS), and storage conditions (25 °C, 37 °C, and 42 °C for 30 days) on the texture-related properties of acidified chili pepper. The results showed that the textural properties of samples were destructed by TP (the hardness of samples decreased by 19.43 %) but were less affected by HPP and SMS. Compared with processing, storage temperature had a more dominant impact on texture and pectin characteristics. With increased storage temperature, water-solubilized pectin fraction content increased (increased by 160.99 %, 136.74 %, and 13.01 % in TP, HPP, and SMS-stored groups, respectively), but sodium carbonate-solubilized pectin fraction content decreased (decreased by 29.84 %, 26.81 %, and 8.60 % in TP-, HPP-, and SMS-stored groups, respectively), especially in TP-stored groups. Multivariate data analysis showed that softening was more closely related to pectin conversion induced by acid hydrolysis and pectinase depolymerization. This finding offers new perspectives for the production of acidified chili pepper.
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Capsicum , Pasteurização , Pectinas , Temperatura , Antioxidantes/análiseRESUMO
Escherichia coli (E. coli) is a major environmental pathogen that causes mammary tissue damage and cell death, which results in substantial economic losses. Pyroptosis, a novel form of programmed cell death characterized by DNA fragmentation, chromatin condensation, cell swelling and leakage of cell contents, often occurs after inflammatory apoptotic pathways activation. Our objective was to investigate the intraction between E. coli infection and bovine mammary epithelial cells (bMECs) with pyroptosis and to explore the underlying regulatory mechanism. bMECs were infected with E. coli for 6 h. Lactic dehydrogenase activities, interleukin (IL)-10, IL-1ß, IL-18 and tumor necrosis factor-α concentrations, total apoptosis indexes, and protein expressions of P-cdc25c, P-CDK1, cleaved caspase 9, cleaved caspase 3, cleaved PARP, P-NF-κB, NLRP3, ASC, caspase 1, gasdermin D N-terminal, IL-1ß and IL-18 were significantly increased in E. coli infected bMECs. Whereas, cell membrane potential, protein levels of cdc25c, CDK1, cyclin B1, and Bcl-2/Bax level were markedly reduced. Furthermore, Ac-DEVD-CHO (specific inhibitor of apoptosis) dramatically suppressed pyroptosis in bMECs. Moreover, expressions of p53 and p21 promptly improved after E. coli infection, however, Pifithrin-α (specific inhibitor of p53) inhibited p53-p21 pathway, apoptosis, cell cycle arrest and pyroptosis. These results elaborated that E. coli infection of bMECs induced pyroptosis through activating the p53-p21 pathway-mediated apoptosis and cell cycle arrest. Taken together, inhibition of pyroptosis via suppressing of p53-p21 pathway may be an effective therapeutic approach for treating E. coli-induced mastitis, offering efficient theoretical support for the protection and treatment of bovine mastitis.
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Infecções por Escherichia coli , Piroptose , Feminino , Bovinos , Animais , Interleucina-18/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Escherichia coli/metabolismo , Apoptose , Células Epiteliais , Infecções por Escherichia coli/patologia , Pontos de Checagem do Ciclo CelularRESUMO
Millions of individuals across the world suffer from corneal stromal diseases that impair vision. Fortunately, three-dimensional (3D) bioprinting technology which has revolutionized the field of regenerative tissue engineering makes it feasible to create personalized corneas. In this study, an artificial cornea with a high degree of precision, smoothness, and programmable curvature was prepared by using digital light processing (DLP) 3D bioprinting in one piece with no support structure, and the construct was then confirmed by optical coherence tomography (OCT). On the basis of this approach, we developed a novel corneal decellularized extracellular matrix/gelatin methacryloyl (CECM-GelMA) bioink that can produce complex microenvironments with highly tunable mechanical properties while retaining high optical transmittance. Furthermore, the composite hydrogel was loaded with human corneal fibroblasts (hCFs), and in vitro experiments showed that the hydrogel maintained high cell viability and expressed core proteins. In vivo tests revealed that the hydrogel might promote epithelial regeneration, keep the matrix aligned, and restore clarity. This demonstrates how crucial a role CECM plays in establishing a favorable environment that encourages the transformation of cell function. Therefore, artificial corneas that can be rapidly customized have a huge potential in the development of in vitro corneal matrix analogs.
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PURPOSE: To assess the effect of anti-allergic therapy on sleep quality of children with allergic conjunctivitis (AC) and their parents. METHODS: This prospective single-arm intervention study included 54 AC child-parent dyads. Chinese versions of the Children's Sleep Habits Questionnaire (CSHQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess the sleep quality of children and their parents, respectively. RESULTS: CSHQ and PSQI total scores were significantly decreased after treatment, with fewer children and parents reporting poor sleep quality. Part impaired sleep behaviors of children and parents can recover to the normal levels. Sleep quality improved greater in children with a severe type of AC, those with worse baseline signs, and without other allergic diseases. For both children and parents, greater improvements in sleep quality were associated with longer treatment duration and with worse baseline sleep quality. CONCLUSION: Successful management of AC improves sleep quality for both children and their parents.
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Given the poor prognosis of metastatic colorectal cancer (mCRC), this research aimed to investigate the correlation between tumor size and prognosis, and develop a novel prediction model to guide individualized treatment. Patients pathologically diagnosed with mCRC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015, and were randomly divided (7:3 ratio) into a training cohort (n = 5597) and a validation cohort (n = 2398). Kaplan-Meier curves were used to analyze the relationship between tumor size and overall survival (OS). Univariate Cox analysis was applied to assess the factors associated with the prognosis of mCRC patients in the training cohort, and then multivariate Cox analysis was used to construct a nomogram model. The area under the receiver-operating characteristics curve (AUC) and calibration curve were used to evaluate the predictive ability of the model. Patients with larger tumors had a worse prognosis. While brain metastases were associated with larger tumors compared to liver or lung metastases, bone metastases tended to be associated with smaller tumors. Multivariate Cox analysis revealed that tumor size was an independent prognostic risk factor (HR 1.28, 95% CI 1.19-1.38), in addition to the other ten variables (age, race, primary site, grade, histology, T stage, N stage, chemotherapy, CEA level and metastases site). The 1-, 3-, and 5-year OS nomogram model yielded AUC values of more than 0.70 in both the training and validation cohorts, and its predictive performance was superior to that of the traditional TNM stage. Calibration plots demonstrated a good agreement between the predicted and observed 1-, 3-, and 5-year OS outcomes in both cohorts. The size of primary tumor was found to be significantly associated with prognosis of mCRC, and was also correlated with specific metastatic organ. In this study, we presented the first effort to create and validate a novel nomogram for predicting 1-, 3- and 5-year OS probabilities of mCRC. The prognostic nomogram was demonstrated to have an excellent predictive ability in estimating individualized OS of patients with mCRC.