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The purpose of this study is to investigate the risk factors for postoperative deep vein thrombosis (DVT) in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed using ultrasound. Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bedrest, and MA values of TEG were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bedrest, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer > 5.065 mg/l, lower extremity < 3, duration of bedrest, and MA value of TEG are independent risk factors for postoperative DVT in SCI patients, D-dimer having the highest diagnostic value. When the above risk factors occur, clinicians need to be vigilant and take appropriate prevention and treatment measures.
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Complicaciones Posoperatorias , Traumatismos de la Médula Espinal , Fracturas de la Columna Vertebral , Trombosis de la Vena , Humanos , Trombosis de la Vena/etiología , Trombosis de la Vena/sangre , Factores de Riesgo , Masculino , Femenino , Traumatismos de la Médula Espinal/complicaciones , Persona de Mediana Edad , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Adulto , Estudios Retrospectivos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , AncianoRESUMEN
Cabotegravir (CAB-LA), the first long-acting injectable pre-exposure prophylaxis (PrEP), has been approved for use in the USA and is not currently on the market in China. However, willingness to use CAB-LA and associated factors among men who have sex with men (MSM) have not yet been evaluated in China. A cross-sectional study was conducted in Guangxi, China, in 2022 recruiting 1,006 MSM. Their mean age was 30.2 years, 74.2% had college or above education, and 48.6% had a monthly income between 3,000 and 5,999 Chinese yuan (CNY). Most (73.4%) had previously heard of PrEP while few (8.3%) had ever used this type of preventative medication. Willingness to use CAB-LA was 79.8% and was positively associated with eight variables: younger age, being married to a woman, having a low monthly income, having six or more male partners in the past six months, having only regular male partners in the past month, having a high perceived risk of HIV infection, and history of using PrEP. Ten other variables were not significantly associated with willingness to use CAB-LA. Among 894 participants who were willing to use or did not definitely reject using CAB-LA, the main concerns about CAB-LA were its side effects (90.2%), efficacy (63.6%), and high cost (58.2%). Only 14.7% were willing to pay more than 1,200 CNY (~US$180) every two months to use CAB-LA. The preferred injection places were centers for disease control facilities, hospitals, and social organizations. Many (89.0%) said that they would recommend CAB-LA to their male sexual partners. We conclude that willingness to use CAB-LA was high among MSM in Guangxi. However, implementation of CAB-LA faces tough challenges due to its high cost and the low use of PrEP. Peer education may play a large role in the implementation of CAB-LA in China.
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Infecciones por VIH , Homosexualidad Masculina , Profilaxis Pre-Exposición , Piridonas , Humanos , Masculino , China , Adulto , Estudios Transversales , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/psicología , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/estadística & datos numéricos , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Parejas Sexuales/psicología , Conocimientos, Actitudes y Práctica en Salud , Adulto Joven , Persona de Mediana Edad , DicetopiperazinasRESUMEN
BACKGROUND: The role of basal metabolic rate (BMR) in intervertebral disc degeneration (IVDD) is still uncertain. To address this gap, we conducted a Mendelian randomization (MR) study to comprehensively explore the causal relationship between BMR and IVDD. METHODS: BMR data were obtained from a large genome-wide association study (GWAS) database, while IVDD data were derived from the FinnGen project. The causal relationship between IVDD and BMR was investigated using MR, with inverse-variance weighting (IVW) as the primary estimate. MR-Egger weighed median and weighed mode were employed for robustness. Sensitivity analyses, including the Cochran Q test, leave-one-out analysis, and MR-Egger intercept analysis, were conducted. Furthermore, the study also identified causal relationships between IVDD and factors associated with BMR (hyperthyroidism, type 2 diabetes, standing height, weight, and body mass index). Multivariable MR was applied to further assess the direct effect of BMR on IVDD. RESULTS: Genetic predisposition to BMR (after removing outliers OR: 1.49; 95% CI: 1.37-1.63; P = 5.073e-21) were associated with an increased risk of IVDD. Additionally, IVDD risk increased with greater height, weight, and BMI. No causal relationship was observed between hy/thy and T2D and intervertebral disc degeneration (IVDD) (P > 0.05). In multivariable MR, a significant causal association between BMR and IVDD persisted, even after adjusting for BMI, height, and weight. CONCLUSION: In this study, we successfully identified that a higher BMR is independently and causally linked to IVDD, indicating an increased risk of developing IVDD. These findings suggest that managing BMR could potentially mitigate the risk of IVDD.
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The present study explored the effects of different lipid sources on growth performance, lipid deposition, antioxidant capacity, inflammatory response and disease resistance of largemouth bass (Micropterus salmoides). Four isonitrogenous (crude protein 50.46 %) and isolipidic (crude lipid 11.12 %) diets were formulated to contain 7 % of different oil sources including fish oil (FO) (control), soybean oil (SO), linseed oil (LO) and coconut oil (CO). Largemouth bass with initial body weight of 36.0 ± 0.2 g were randomly distributed into 12 tanks, with 30 fish per tank and 3 tanks per treatment. The fish were fed with the experiment diets twice daily for 8 weeks. The results indicated that the weight gain of largemouth bass fed the FO diet was significantly higher than that of fish fed the LO and CO diets. The liver crude lipid content in FO group was significantly higher than other groups, while the highest liver triglyceride content was showed in SO group and the lowest was detected in LO group. At transcriptional level, expression of lipogenesis related genes (pparγ, srebp1, fas, acc, dgat1 and dgat2) in the SO and CO group were significantly higher than the FO group. However, the expression of lipolysis and fatty acids oxidation related genes (pparα, cpt1, and aco) in vegetable oils groups were significantly higher than the FO group. As to the antioxidant capacity, vegetable oils significantly reduced the malondialdehyde content of largemouth bass. Total antioxidant capacity in the SO and LO groups were significantly increased compared with the FO group. Catalase in the LO group was significantly increased compared with the FO group. Furthermore, the ER stress related genes, such as grp78, atf6α, atf6ß, chop and xbp1 were significantly enhanced in the vegetable oil groups compared with the FO group. The activity of serum lysozyme in vegetable oil groups were significantly higher than in FO group. Additionally, the relative expression of non-specific immune related genes, including tlr2, mapk11, mapk13, mapk14, rela, tgf-ß1, tnfα, 5lox, il-1ß and il10, were all significantly increased in SO and CO groups compared to the other groups. In conclusion, based on the indexes including growth performance, lipid deposition, antioxidant capacity and inflammatory response, SO and LO could be alternative oil sources for largemouth bass.
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Alimentación Animal , Antioxidantes , Lubina , Dieta , Metabolismo de los Lípidos , Animales , Lubina/inmunología , Lubina/crecimiento & desarrollo , Dieta/veterinaria , Alimentación Animal/análisis , Antioxidantes/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Distribución Aleatoria , Suplementos Dietéticos/análisis , Grasas de la Dieta/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceite de Linaza/administración & dosificación , Enfermedades de los Peces/inmunología , Inflamación/veterinaria , Inflamación/inmunología , Aceite de Soja/administración & dosificación , Aceite de Coco/administración & dosificaciónRESUMEN
Micropolymorphism significantly shapes the peptide-binding characteristics of major histocompatibility complex class I (MHC-I) molecules, affecting the host's resistance to pathogens, which is particularly pronounced in avian species displaying the "minimal essential MHC" expression pattern. In this study, we compared two duck MHC-I alleles, Anpl-UAA*77 and Anpl-UAA*78, that exhibit markedly different peptide binding properties despite their high sequence homology. Through mutagenesis experiments and crystallographic analysis of complexes with the influenza virus-derived peptide AEAIIVAMV (AEV9), we identified a critical role for the residue at position 62 in regulating hydrogen-bonding interactions between the peptide backbone and the peptide-binding groove. This modulation affects the characteristics of the B pocket and the stability of the loop region between the 310 helix and the α1 helix, leading to significant changes in the structure and stability of the peptide-MHC-I complex (pMHC-I). Moreover, the proportion of different residues at position 62 among Anpl-UAAs may reflect the correlation between pAnpl-UAA stability and duck body temperature. This research not only advances our understanding of the Anpl-UAA structure but also deepens our insight into the impact of MHC-I micropolymorphism on peptide binding.
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Patos , Antígenos de Histocompatibilidad Clase I , Animales , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Péptidos/química , Péptidos/genética , Polimorfismo Genético , Estabilidad Proteica , Secuencia de Aminoácidos , Unión Proteica , Alelos , Presentación de Antígeno , Modelos MolecularesRESUMEN
Nitrogen-doped carbon dots (NCD) with high fluorescence retention and good stability were successfully fabricated using citric acid and urea via a facile and eco-friendly one-step microwave method, which exhibited superior specificity for detection of nitrofurantoin (NFT). Upon the addition of NFT, the fluorescence intensity of NCD at 450 nm was significantly decreased. Besides, a satisfactory linear relationship between the fluorescence quenching efficiency and concentrations of NFT was obtained. Especially, NCD was qualitatively and quantitatively applied for detection NFT in milk and meat extract samples with a high recovery rate. Consequently, it was suggested that the detection method had potential application in the specific detection of NFT, offering a novel approach for veterinary drug residue detection.
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Vibrio parahaemolyticus is a significant cause of foodborne illness, and its incidence worldwide is on the rise. It is thus imperative to develop a straightforward and efficient method for typing strains of this pathogen. In this study, we conducted a pangenome analysis of 75 complete genomes of V. parahaemolyticus and identified the core gene mtlA with the highest degree of variation, which distinguished 44 strains and outperformed traditional seven-gene-based MLST when combined with aer, another core gene with high degree of variation. The mtlA gene had higher resolution to type strains with a close relationship compared to the traditional MLST genes in the phylogenetic tree built by core genomes. Strong positive selection was also detected in the gene mtlA (ω > 1), representing adaptive and evolution in response to the environment. Therefore, the panel of gene mtlA and aer may serve as a tool for the typing of V. parahaemolyticus, potentially contributing to the prevention and control of this foodborne disease.
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A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3-4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.
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Lubina , Clostridium butyricum , Humanos , Animales , Antioxidantes/metabolismo , Lubina/metabolismo , Clostridium butyricum/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , ARN Ribosómico 16S/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Dieta/veterinaria , CarbohidratosRESUMEN
Previous studies have indicated that iron disorder, inflammation, and autophagy play an important role in traumatic brain injury (TBI). The triggering receptor expressed on myeloid cells 2 (TREM2), an immunoglobulin superfamily transmembrane receptor, is involved in inflammation. However, the role of TREM2 in modulating the microglia response in TBI has been rarely investigated. The present study aimed to investigate if the iron chelator deferoxamine (DFO) could ameliorate TBI through autophagy mediated by the TREM2. TBI was developed by the controlled cortical impact (CCI) mouse model and stretching of individual primary cortical microglia taken from the tissue of the rat brain. DFO was intraperitoneally used for intervention. Western blotting assay, qRT-PCR, TUNEL staining, immunofluorescence staining, confocal microscopy analysis, transmission electron microscopy, H&E staining, brain water content measurement, and the neurobehavioral assessments were performed. TREM2 expression was up-regulated in cortex of TBI mice model and in microglia stretching model, which was attenuated by DFO. After the mice were subjected to CCI, DFO treatment significantly up-regulated the protein levels of autophagy compared with the TBI group at 3 days and caused an increase of autophagic vacuoles. Treatment with DFO reduced TBI-induced cell apoptosis, cerebral edema, neuroinflammation, and motor function impairment in mice, at least partly via the mTOR signaling pathway that facilitates the TREM2 activity. The results indicated that the maintenance of iron homeostasis by DFO plays neuroprotection by modulating the inflammatory response to TBI through TREM2-mediated autophagy. This study suggested that TREM2-mediated autophagy might be a potential target for therapeutic intervention in TBI.
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Autofagia , Lesiones Traumáticas del Encéfalo , Deferoxamina , Glicoproteínas de Membrana , Microglía , Receptores Inmunológicos , Animales , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Autofagia/efectos de los fármacos , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Masculino , Ratones , Deferoxamina/farmacología , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Modelos Animales de Enfermedad , RatasRESUMEN
Ultracompact devices engineered for second-harmonic generation (SHG) hold a significant promise across a diverse spectrum of applications. Here, we propose a merging bound state in the continuum at an off-Γ point in a reciprocal space with the anisotropic materials lithium niobate. Such a merging BIC yields a profound reduction in radiative loss and scattering losses while concurrently exhibiting a substantial enhancement in the quality factor. As a result, we achieved a noteworthy SHG efficiency (η = 3.7%) at the incident angle θ = 10° when the pump intensity I0 = 2â kW/cm2, outperforming alternative nanostructures designed for SHG. This research contributes valuable insights into the feasibility of metadevices founded on the principles of nanoengineering applied to traditional nonlinear crystals. Such advancements hold a considerable promise for the development of compact, high-performance SHG devices across a range of applications.
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Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of "COVID-19 epidemic", "Novel Coronavirus" and "COVID-19" can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0-28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5-8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1-3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70-0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase.
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COVID-19 , Epidemias , Ácidos Nucleicos , Humanos , COVID-19/epidemiología , China/epidemiología , SARS-CoV-2RESUMEN
Background: Hippocampus impairment is a common condition encountered in the clinical diagnosis and treatment of traumatic brain injury (TBI). Several studies have investigated this phenomenon. However, its molecular mechanism remains unclear. Methods: In this study, Illumina RNA-seq technology was used to determine the gene expression profile in mice hippocampus after TBI. We then conducted bioinformatics analysis to identify the altered gene expression signatures and mechanisms related to TBI-induced pathology in the hippocampus. Real-time quantitative polymerase chain reaction and western blot were adopted to verify the sequencing results. Results: The controlled cortical impact was adopted as the TBI model. Hippocampal specimens were removed for sequencing. Bioinformatics analysis identified 27 upregulated and 17 downregulated differentially expressed genes (DEGs) in post-TBI mouse models. Potential biological functions of the genes were determined via Gene Set Enrichment Analysis (GSEA)-based Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, which suggested a series of functional changes in the nervous system. Specifically, the nucleoporin 62 (Nup62) DEG was discussed and verified. Gene ontology biological process enriched analysis suggests that the cell division was upregulated significantly. The present study may be helpful for the treatment of impaired hippocampus after TBI in the future.
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Lesiones Traumáticas del Encéfalo , Perfilación de la Expresión Génica , Animales , Ratones , Lesiones Traumáticas del Encéfalo/genética , División Celular , Perfilación de la Expresión Génica/métodos , Hipocampo/metabolismo , RNA-SeqRESUMEN
PIEZO1 is ubiquitously expressed in cells in different kinds of tissues throughout the body, which can sense physical or mechanical stimuli and translate them into intracellular electrochemical signals to regulate organism functions. In particular, PIEZO1 appears in complex interactive regulatory networks as a central node, governing normal and pathological functions in the body. However, the effect and mechanism of the activation or expression of PIEZO1 in diseases of the central nervous system (CNS) remain unclear. On one hand, in CNS diseases, pathophysiological processes in neurons and glial are often accompanied by variations in the mechanical properties of the cellular and extracellular matrix stiffness. The expression of PIEZO1 can therefore be upregulated, in responding to mechanical stimulation, to drive the biological process in cells, which in turns indirectly affects the cellular microenvironment, resulting in alterations of the cellular status. On the other hand, it may have contradictory effects with the change of active patterns and/or subcellular location. This review highlights the biological processes involved with PIEZO1 in CNS cells, with special emphasis on its multiple roles in glioma-associated phenotypes. In conclusion, PIEZO1 can be used as an indicator to assess the malignancy and prognosis of patients with gliomas, as well as a therapeutic target for clinical application following fully exploring the potential mechanism of PIEZO1 in CNS diseases.
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Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased. However, when phosphatase actin regulatory factor 1 was knocked down, the water content decreased. We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway, decreased blood-brain barrier permeability, reduced aquaporin 4 and intercellular adhesion molecule 1 expression, inhibited neuroinflammation, and neuronal apoptosis, thereby improving neurological function. The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.
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Traumatic brain injury (TBI) has been found as the primary cause of morbidity and disability worldwide, which has posed a significant social and economic burden. The first stage of TBI produces brain edema, axonal damage, and hypoxia, thus having an effect on the blood-brain barrier function, promoting inflammatory responses, and increasing oxidative stress. Patients with TBI are more likely to develop post-traumatic epilepsy, behavioral issues, as well as mental illnesses. The long-term effects arising from TBI have aroused rising attention over the past few years. Microglia in the brain can express the triggering receptor expressed on myeloid cells 2 (TREM2), which is a single transmembrane receptor pertaining to the immunoglobulin superfamily. The receptor has been correlated with a number of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and other relevant diseases. In this review, it is demonstrated that TREM2 is promising to serve as a neuroprotective factor for neurodegenerative disorders following TBI by modulating the function of microglial cells. Accordingly, it has potential avenues for TREM2-related therapies to improve long-term recovery after TBI.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/etiología , Lesiones Traumáticas del Encéfalo/complicaciones , Microglía/fisiología , Enfermedad de Alzheimer/complicaciones , Encéfalo , Glicoproteínas de Membrana , Receptores InmunológicosRESUMEN
Yeast ß-glucan (YG) possess an extensive range of biological activities, such as the inhibition of oxidation, but the poor water solubility of macromolecular YG limits its application. In this study, through the combined degradation of ultrasonic waves and H2O2, and the optimization of the main process parameters for solubilizing YG by response surface methodology (RSM), a new product of YGUH was generated. The molecular weight, structural characteristics and degradation kinetics before and after solubilization were evaluated. The results showed that the optimal solubilization conditions were reaction time: 4 h, ultrasonic power: 3 W/mL, H2O2 concentration: 24 %. Under these conditions, ultrasound-assisted H2O2 increased the solubility (from 13.60 % to 70.00 %) and reduced molecular weight (from 6.73 × 106 Da to 1.22 × 106 Da). Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), Congo red (CR), scanning electron microscopy (SEM) revealed that ultrasound-assisted H2O2 increased the conformation's flexibility greatly, without changing the main structure of YG. More importantly, solubilization of YG improved free radical scavenging activity with YGUH exhibiting the highest levels of DPPH and ABTS+ free radical scavenging activity. These results revealed that ultrasound-assisted H2O2 degradation could be a suitable way to increase the solubility of YG for producing value-added YG.
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Antioxidantes , beta-Glucanos , Antioxidantes/farmacología , Antioxidantes/química , Saccharomyces cerevisiae , Peróxido de Hidrógeno , SolubilidadRESUMEN
The clarity of taste sensation interaction is a key basis for promoting the food sensory science research and its application to the beverage and food additive industries. This study explored the synergy and antagonism effect of sucrose-citric acid mixture and established an optimized method to determine the human sweetness and sourness interactive response. Sucrose-citric acid mixtures were evaluated by the "close type" question. According to the sensory difference strength curves and Weber-Fechner law, citric acid increased the sucrose's absolute threshold (0.424-0.624%) and weber fraction (20.5-33.0%). Meanwhile, sucrose increased citric acid's absolute threshold (0.0057-0.0082%) and decreased its weber fraction (17.96-9.53%). By fitting absolute threshold and weber fraction variation equations, the sweet-sour taste sensory strength variation models (SSTVM) were derived, which could be used to explain the synergy and antagonism effect of sweet-sour taste. According to the SSTVM, the interactive response to sweet-sour taste could be quantitatively calculated. The high coincidence between SSTVM and human evaluation (1.02% of relative error) indicated that it could be applied in the food industry, health management, and intelligent sensory science.
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To evaluate the potential anticancer effects of 1175 FDA-approved drugs, cell viability screening was performed using 25 human cancer cell lines covering 14 human cancer types. Here, we focus on the action of paroxetine, which demonstrated greater toxicity toward human gastric adenocarcinoma cell-line AGS cells compared with the other FDA-approved drugs, exhibiting an IC50 value lower than 10 µM. Evaluation of the underlying novel mechanisms revealed that paroxetine can enhance DNA damage in gastric cancer cells and involves downregulation of Rad51, HR23B and ERCC1 expression and function, as well as nucleotide shortage. Enhancement of autophagy counteracted paroxetine-induced apoptosis but did not affect paroxetine-induced DNA damage. Paroxetine also enhanced ROS generation in AGS cells, but a ROS scavenger did not improve paroxetine-mediated DNA damage, apoptosis, or autophagy, suggesting ROS might play a minor role in paroxetine-induced cell toxicity. In contrast, paroxetine did not enhance DNA damage, apoptosis, or autophagy in another insensitive gastric adenocarcinoma cell-line MKN-45 cells. Interestingly, co-administration of paroxetine with conventional anticancer agents sensitized MKN-45 cells to these agents: co-treated cells showed increased apoptosis relative to MKN-45 cells treated with the anticancer agent alone. Unequivocally, these data suggest that for the first time that paroxetine triggers cytotoxicity and DNA damage in AGS cells at least partly by reducing the gene expression of Rad51, HR23B, and ERCC1. Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.
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A great number of pediatric patients undergoing varied procedures make neonatal surgery plus anesthesia become a matter of great concern owing to underlying neurotoxicity in developing brain. The authors set out to assess long-term effects of surgery plus anesthesia in mouse model. Six-day-old C57BL/6 mice were randomized to receive either anesthesia with 3% sevoflurane, abdominal surgery under the same anesthesia, or the control condition. These mice were examined of learning and memory at juvenile age in Morris water maze test. The brain tissues of mice were harvested for Western blot analysis, including purinergic receptors P2X family, CaMKII and NF-κB. Another battery of mice were administered with inhibitors of P2RX2/3 (e.g., A317491) into hippocampal dentate gyrus before behavioral testing. We found that neonatal surgery plus anesthesia, but not sevoflurane anesthesia alone, impaired the learning and memory of juvenile mice, as evidenced by delayed escape latency and reduced platform-crossing times. Immunoblotting analysis showed that behavioral abnormalities were associated with increased levels of P2RX2, phosphorylated-CaMKIIß and activated NF-κB in mouse hippocampus. Injection of A317491 ameliorated the impaired learning and memory of juvenile mice undergoing neonatal surgery plus anesthesia, and it also mitigated the neonatal surgery-induced signaling enhancement of P2RX2/CaMKII/NF-κB. Together, these results indicate that neonatal surgery plus anesthesia may cause long-term cognitive dysfunction, with potential mechanism of increasing P2RX2 and downstream signaling of phosphorylated-CaMKII and NF-κB. Our findings will promote more studies to assess detrimental effects of surgery and accompanying inflammation, diverse anesthetics and even sleeping deprivation on mouse neurodevelopment and neurobehavioral performance.