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Background: Drug-coated balloons (DCBs) have become increasingly vital to percutaneous coronary intervention, offering many advantages. However, a significant challenge is that many patients are intolerant to the myocardial ischemia caused by DCB dilation. Remote ischemic preconditioning (RIPC) is known to enhance heart's tolerance to ischemia and hypoxia. This study investigated whether preoperative RIPC could extend the tolerated DCB inflation time and improve the long-term prognosis of patients with coronary artery disease (CAD). Methods: A total of 653 patients with CAD were recruited and randomized into a RIPC group (n = 323) and a control (n = 330) group. The RIPC group underwent RIPC on the left upper limb twice daily, starting three days before the DCB implantation. The patients were followed up for one year after the operation, and 197 patients returned for coronary angiography (CAG) examination where the quantitative flow ratio (QFR) of the target vessels was measured. The primary endpoint of the study was the incidence of target lesion failure (TLF), which included target lesion revascularization (TLR), target vessel myocardial infarction, and cardiac death. The secondary endpoint was the rate of QFR loss in the target vessels. Results: The findings revealed a significantly lower incidence of TLR in the RIPC group compared to the control group. Additionally, at the one-year follow-up, the rate of QFR loss in target vessels was lower in the RIPC group than in the control group. Conclusions: The preoperative application of RIPC effectively extended the duration patients could tolerate DCB inflation. Furthermore, this approach positively impacted the long-term prognosis of CAD patients undergoing DCB treatment. Clinical Trial Registration Information: NCT04766749.
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The hedgehog signaling pathway plays an important role in early development and growth of most vertebrates. Sonic hedgehog (shh) gene is a critical regulator of embryonic development in many species, including humans. However, it is not clear what roles shh can play in the development of fish. In this paper, shh gene was cloned from Pseudopleuronectes yokohamae. The full-length complementary DNA (cDNA) of P. yokohamae sonic hedgehog gene (Pyshh) comprises 3194 bp, with a 1317-bp open reading frame (ORF) that encodes a polypeptide of 438 amino acids with a typical HH-signal domain and Hint-N domain. The conserved sequences of the protein among species were predicted by using multiple sequence comparison. The phylogenetic tree construction showed that PySHH is clustered in a branch of Pleuronectidae. To explore the expression of Pyshh gene in various tissues of P. yokohamae, we used real-time fluorescence quantitative PCR technology to detect it. The results showed that Pyshh gene is widely distributed in various tissues of P. yokohamae juveniles, different tissues of adult males and females, and is particularly expressed in immune organs. The Pyshh gene expression was higher in the muscle and brain of juvenile fish, and higher in bone, gill, and skin of male fish than that of female fish, suggesting that Pyshh might be involved in the formation of immune organs of P. yokohamae. The expression of Pyshh gene significantly upregulated from the gastrula stage to the hatching stage. Western blotting of the expression levels of PySHH during different embryonic development stages revealed that PySHH levels increased gradually during development stages from oosperm stage to hatching stage. These results indicate that Pyshh is highly conserved among species and plays a critical role in the complex process of embryonic development. Its precise regulation is essential for the proper formation of many organs and tissues in the body, and disruptions in its function may have serious consequences for the formation of immune organs in fish.
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A protein mixture was prepared using a blend of soybean protein isolate, soybean protein concentrate, and wheat protein through high-moisture extrusion. This study investigated the effects of soybean oil/coconut oil additions (2%, 5%, and 8%) on the physiochemical properties of a soy protein-wheat protein mixture subjected to high-moisture extrusion. The protein extrudates underwent assessment for textural properties, fiber degree, sensory evaluation, microstructure, protein solubility, and protein secondary structure. The findings indicated that plant oils significantly reduced the hardness, springiness, and chewiness of the extrudates, and 5% plant oil significantly increased the fiber degree of the extrudates. In addition, the highest fiber degree and sensory evaluation score were achieved with 5% coconut oil. Observation of the macro- and microstructure indicated that the presence of unsaturated fatty acids in soybean oil did not benefit the improvement of the fibrous structure of protein extrudates during high-moisture extrusion processing. SDS-PAGE and FTIR results revealed that coconut oil, rich in saturated fatty acids, caused the clustering of medium- and low-molecular-weight subunits in texturized protein. Additionally, coconut oil elevated the ratio of 11S protein subunits containing sulfur-based amino acids and facilitated a shift from ß-turn to ß-sheet. The inclusion of plant oils increased the development of hydrogen and disulfide bonds, resulting in a denser, fibrous structure. DSC demonstrated that plant oils reduced the thermal stability of the texturized proteins but enhanced the order of protein structure.
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BACKGROUND: Delayed spinal epidural hematoma (SEH) following central neuraxial block (CNB) is a rare but serious complication. The underlying causes of SEH associated with neuraxial anesthesia are still unclear. Furthermore, the decision between surgical intervention and conservative management for SEH remains a complex and unresolved issue. CASE PRESENTATION: We report a case of delayed SEH in a 73-year-old woman who underwent vaginal hysterectomy under combined spinal-epidural anesthesia, with the administration of postoperative anticoagulants to prevent deep vein thrombosis on the 1st postoperative day (POD). She experienced symptoms 56 h after CNB. Magnetic resonance imaging (MRI) revealed a dorsal SEH at the L1-L4 level with compression of the thecal sac. On conservative treatment, full recovery was achieved after six months. CONCLUSIONS: This case reminds anesthesiologists should be alert to the possible occurrence of a delayed SEH following CNB, particularly with the administration of anticoagulants. Immediate neurological evaluation of neurological deficit and MRI are advised. Conservative treatment combined with close and dynamic neurological function monitoring may be feasible for patients with mild or nonprogressive symptoms even spontaneous recovery.
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Anestesia Epidural , Raquianestesia , Tratamento Conservador , Hematoma Epidural Espinal , Humanos , Feminino , Idoso , Hematoma Epidural Espinal/etiologia , Hematoma Epidural Espinal/diagnóstico por imagem , Anestesia Epidural/efeitos adversos , Raquianestesia/efeitos adversos , Tratamento Conservador/métodos , Histerectomia Vaginal , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
Parvimonas micra, a gram-positive anaerobic bacterium, has garnered increased attention due to its role in infective endocarditis. We present a challenging prosthetic valve endocarditis caused by Parvimonas micra in a patient with a complex cardiac history involving multiple surgeries. The case highlights the difficulties in diagnosis and treatment, emphasizing the importance of advanced diagnostic techniques, including metagenomics next-generation sequencing (mNGS). Additionally, it underscores the need for heightened vigilance regarding oral symptoms and the potential risk of bacteremia in post-valvular surgery patients. This report contributes to a better understanding of Parvimonas micra-associated endocarditis and its unique characteristics.
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Endocardite Bacteriana , Firmicutes , Infecções por Bactérias Gram-Positivas , Próteses Valvulares Cardíacas , Infecções Relacionadas à Prótese , Humanos , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Próteses Valvulares Cardíacas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Firmicutes/isolamento & purificação , Firmicutes/genética , Masculino , Antibacterianos/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Pessoa de Meia-IdadeRESUMO
Alzheimer's disease (AD) starts decades before cognitive symptoms develop. Easily accessible and cost-effective biomarkers that accurately reflect AD pathology are essential for both monitoring and therapeutics of AD. Neurofilament light chain (NfL) levels in blood and cerebrospinal fluid are increased in AD more than a decade before the expected onset, thus providing one of the most promising blood biomarkers for monitoring of AD. The clinical practice of employing single-molecule array (Simoa) technology for routine use in patient care is limited by the high costs. Herein, we developed a microarray chip-based high-throughput screening method and screened an attractive self-assembling peptide targeting NfL. Through directly "imprinting" and further analyzing the sequences, morphology, and affinity of the identified self-assembling peptides, the Pep-NfL peptide nanosheet with high binding affinity toward NfL (KD = 1.39 × 10-9 mol/L), high specificity, and low cost was characterized. The superior binding ability of Pep-NfL was confirmed in AD mouse models and cell lines. In the clinical setting, the Pep-NfL peptide nanosheets hold great potential for discriminating between patients with AD (P < 0.001, n = 37), mild cognitive impairment (P < 0.05, n = 26), and control groups (n = 30). This work provides a high-throughput, high-sensitivity, and economical system for noninvasive tracking of AD to monitor neurodegeneration at different stages of disease. The obtained Pep-NfL peptide nanosheet may be useful for assessing dynamic changes in plasma NfL concentrations to evaluate disease-modifying therapies as a surrogate end point of neurodegeneration in clinical trials.
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Doença de Alzheimer , Proteínas de Neurofilamentos , Peptídeos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/sangue , Proteínas de Neurofilamentos/sangue , Animais , Humanos , Camundongos , Peptídeos/química , Ensaios de Triagem em Larga Escala , Biomarcadores/sangue , Biomarcadores/metabolismo , Análise Serial de ProteínasRESUMO
As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development.
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Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Parede Celular , Infecções Estafilocócicas , Staphylococcus aureus , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Staphylococcus aureus/genética , Humanos , Infecções Estafilocócicas/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Parede Celular/metabolismo , Animais , Peptidoglicano/metabolismoRESUMO
Circulating tumor cells (CTCs) have significant clinical value in early tumor detection, dynamic monitoring and immunotherapy. CTC detection stands out as a leading non-invasive approach for tumor diagnostics and therapeutics. However, the high heterogeneity of CTCs and the occurrence of epithelial-mesenchymal transition (EMT) during metastasis pose challenges to methods relying on EpCAM-positive enrichment. To address these limitations, a method based on negative enrichment of CTCs using specific leukocyte targets has been developed. In this study, aiming to overcome the low purity associated with immunomagnetic beads targeting solely the leukocyte common antigen CD45, we introduced CD66b-modified immunomagnetic beads. CD66b, a specific target for neutrophils with abundant residues, was chosen as a complementary approach. The process involved initial collection of nucleated cells from whole blood samples using density gradient centrifugation. Subsequently, magnetically labeled leukocytes were removed by magnetic field, enabling the capture of CTCs with higher sensitivity and purity while retaining their activity. Finally, we selected 20 clinical blood samples from patients with various cancers to validate the effectiveness of this strategy, providing a new generalized tool for the clinical detection of CTCs.
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BACKGROUND: The KRAS, NRAS, and BRAF genotypes are critical for selecting targeted therapies for patients with metastatic colorectal cancer (mCRC). Here, we aimed to develop a deep learning model that utilizes pathologic whole-slide images (WSIs) to accurately predict the status of KRAS, NRAS, and BRAFV600E. METHODS: 129 patients with left-sided colon cancer and rectal cancer from the Third Affiliated Hospital of Sun Yat-sen University were assigned to the training and testing cohorts. Utilizing three convolutional neural networks (ResNet18, ResNet50, and Inception v3), we extracted 206 pathological features from H&E-stained WSIs, serving as the foundation for constructing specific pathological models. A clinical feature model was then developed, with carcinoembryonic antigen (CEA) identified through comprehensive multiple regression analysis as the key biomarker. Subsequently, these two models were combined to create a clinical-pathological integrated model, resulting in a total of three genetic prediction models. RESULT: 103 patients were evaluated in the training cohort (1782,302 image tiles), while the remaining 26 patients were enrolled in the testing cohort (489,481 image tiles). Compared with the clinical model and the pathology model, the combined model which incorporated CEA levels and pathological signatures, showed increased predictive ability, with an area under the curve (AUC) of 0.96 in the training and an AUC of 0.83 in the testing cohort, accompanied by a high positive predictive value (PPV 0.92). CONCLUSION: The combined model demonstrated a considerable ability to accurately predict the status of KRAS, NRAS, and BRAFV600E in patients with left-sided colorectal cancer, with potential application to assist doctors in developing targeted treatment strategies for mCRC patients, and effectively identifying mutations and eliminating the need for confirmatory genetic testing.
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Neoplasias Colorretais , GTP Fosfo-Hidrolases , Genótipo , Proteínas de Membrana , Redes Neurais de Computação , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Aprendizado Profundo , Adulto , MutaçãoRESUMO
To evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case-control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.
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Biomarcadores , Fatores de Crescimento de Fibroblastos , Oclusão da Artéria Retiniana , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e Controles , Fatores de Crescimento de Fibroblastos/sangue , Prognóstico , Oclusão da Artéria Retiniana/sangue , Oclusão da Artéria Retiniana/diagnóstico , Fatores de RiscoRESUMO
The occurrence of microplastics (MPs) in aquatic ecosystems and their ability to absorb hydrophobic pollutants, such as persistent organic pollutants (POPs), is currently a significant concern. MPs, which are the main breakdown product of plastics, have been frequently detected in the environment, posing serious threats to organisms' health. One particular pollutant, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), is a dominant congener of PBDEs and is highly toxic to organisms. However, there is limited knowledge regarding the exposure of marine fishes to PBDEs through MPs and their combined toxic effects. In this study, the embryo toxicity of Hexagrammos otakii was conducted to investigate the combined effects of MPs and BDE-47. The results showed that MPs and BDE-47 co-exposure had detrimental effects on embryonic development, such as reduced hatchability, increased mortality, decreased heart rate, and body malformation. Moreover, the combined toxicity of these substances appeared more pronounced harmful effects compared to exposure to BDE-47 alone. Histopathological examination revealed that co-exposure can cause greater damage to hatching glands and yolk. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included phagosome, metabolism of xenobiotics by cytochrome P450, TCA cycle, and Wnt signaling pathway, which are closely related to embryonic growth. BDE-47 and MPs may activate the Wnt signaling pathway to affect the normal development of embryos. Our results suggest that MPs and BDE-47 exposure may cause growth disorders in the early life stages of H.otakii, leading to abnormal embryonic development. All these results will contribute to the further study of the ecological risk assessment and toxicity of MPs and organic pollutant mixtures in marine fish.
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Embrião não Mamífero , Éteres Difenil Halogenados , Microplásticos , Poluentes Químicos da Água , Animais , Éteres Difenil Halogenados/toxicidade , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Poliestirenos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacosRESUMO
BACKGROUND: Asymptomatic gallstones are commonly detected using preoperative imaging in patients with colorectal cancer (CRC), but its management remains a topic of debate. METHODS: Clinicopathologic characteristics of patients who had asymptomatic gallstones presenting during the colorectal procedure were retrospectively reviewed. Medical records, including postoperative morbidity, mortality, and long-term gallstone-related diseases, were assessed. RESULTS: Of 134 patients with CRC having asymptomatic gallstones, 89 underwent elective colorectal surgery only (observation group), and 45 underwent elective colorectal surgery with simultaneous cholecystectomy (cholecystectomy group). After propensity score matching (PSM), the complications were similar in the 2 groups. During the follow-up period, biliary complications were noted in 11 patients (12.4%) in the observation group within 2 years after the initial CRC surgery, but no case was found in the cholecystectomy group. After PSM, the incidence of long-term biliary complications remained significantly higher in the observation group than in the cholecystectomy group (26.5% vs 0.0%; P < .01). Multivariable logistic regression analysis identified female gender, old age (≥65 years old), and small multiple gallstones as independent risk factors for the development of long-term gallstone-related diseases in patients from the observation group. CONCLUSION: Simultaneous prophylactic cholecystectomy during prepared, elective CRC surgery did not increase postoperative morbidity or mortality but decreased the risk of subsequent gallstone-related complications. Hence, simultaneous cholecystectomy might be a preferred therapeutic option for patients with CRC having asymptomatic gallstones in cases of elective surgery, especially for older patients (≥65 years old), female patients, and those with small multiple calculi.
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Doenças Assintomáticas , Colecistectomia , Neoplasias Colorretais , Procedimentos Cirúrgicos Eletivos , Cálculos Biliares , Humanos , Feminino , Masculino , Cálculos Biliares/cirurgia , Cálculos Biliares/complicações , Idoso , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Colecistectomia/efeitos adversos , Pontuação de Propensão , Fatores de Risco , Fatores Etários , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores SexuaisRESUMO
Triclosan is a widely used antibacterial agent and disinfectant, and its overuse endangered ecological safety and human health. Therefore, reducing residual TCS concentrations in the environment is an urgent issue. Bacillus sp. DL4, an aerobic bacterium with TCS biodegradability, was isolated from pharmaceutical wastewater samples. Response surface methodology (RSM) and artificial neural network (ANN) were carried out to optimize and verify the different condition variables, and the optimal growth conditions of strain DL4 were obtained (35 °C, initial pH 7.31, and 5% v/v). After 48 h of cultivation under the optimal conditions, the removal efficiency of strain DL4 on TCS was 95.89 ± 0.68%, which was consistent with the predicted values from RSM and ANN models. In addition, higher R2 value and lower MSE and ADD values indicated that the ANN model had a stronger predictive capability than the RSM model. Whole genome sequencing results showed that many functional genes were annotated in metabolic pathways related to TCS degradation (e.g., amino acid metabolism, xenobiotics biodegradation and metabolism, carbohydrate metabolism). Main intermediate metabolites were identified during the biodegradation process by liquid chromatography-mass spectrometry (LC-MS), and a possible pathway was hypothesized based on the metabolites. Overall, this study provides a theoretical foundation for the characterization and mechanism of TCS biodegradation in the environment by Bacillus sp. DL4.
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Bacillus , Biodegradação Ambiental , Triclosan , Bacillus/metabolismo , Triclosan/metabolismo , Cinética , Poluentes Químicos da Água/metabolismo , Águas Residuárias/microbiologia , Redes Neurais de ComputaçãoRESUMO
The loss of distinctive aromas due to sterilization significantly hinders efforts to enhance the sensory quality of fruit and vegetable juices. This study aimed to elucidate the impacts of high-hydrostatic pressure (HHP) and high-temperature short-time (HTST) sterilization methods on the loss of C6 aldehyde aroma-active compounds in red raspberry juice. External standard quantification and quantitative descriptive analysis (QDA) revealed a notable decline in the levels of hexanal and (Z)-3-hexenal following the HHP and HTST treatments (p < 0.05), resulting in a marked attenuation of the grassy aroma characteristic of red raspberry juice. Furthermore, a comprehensive examination of the precursors, pivotal enzymes, intermediates, and downstream aromas within the fatty acid metabolism pathway in different raspberry juice samples indicated that the C6 aldehydes loss induced by HHP and HTST sterilizations was primarily ascribed to the competitive inhibition of ß-oxidation and the hindered enzymatic oxidation of fatty acids. These insights suggest that modifying sterilization protocols and enhancing enzymatic stability may help preserve the aroma integrity of raspberry juice. Our findings offer practical guidance for optimizing juice processing techniques to maintain flavor.
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During the production of plant-based meat analogues (PBMA), a significant loss of flavor characteristic compounds in meat-flavor essences could be observed. Pickering emulsion-based encapsulation is an effective method to improve their stability. Therefore, a soy protein isolate (SPI)/chitosan (CS) complex Pickering emulsion was fabricated to encapsulate roast beef flavor (RBF) and further applied in the processing of PBMA. Our results indicated that the network structure of emulsions was dominated by elasticity, while hydrogen and covalent bonding interactions played important roles in the encapsulation process. The release rate of flavor compounds gradually increased with the increase of pH value, glutamine transaminase, NaCl content, heating temperature or heating time, while encapsulation significantly reduced the loss of characteristic aroma compounds. In addition, the releasing characteristics of aroma compounds and textural properties of PBMA were greatly improved by treating with RBF-loaded emulsions. Consequently, the emulsions were promising to improve the flavor quality of PBMA.
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Quitosana , Emulsões , Aromatizantes , Proteínas de Soja , Paladar , Emulsões/química , Proteínas de Soja/química , Quitosana/química , Animais , Aromatizantes/química , Bovinos , Produtos da Carne/análise , Odorantes/análise , Manipulação de Alimentos , Culinária , Substitutos da CarneRESUMO
Purpose: To characterize features of central retinal artery occlusion (CRAO) using multicolor (MC) imaging and to assess the differences in CRAO grading between color fundus photography (CFP) and MC image qualitatively and quantitatively. Methods: We conducted a prospective, cross-sectional study in the Department of Ophthalmology of Renmin Hospital of Wuhan University. In total, 86 acute CRAO patients were included. Spectral-domain optical coherence tomography (SD-OCT), CFP, and MC examinations were taken at baseline. Based on the findings of these three examinations, CRAO was divided into three grades (incomplete, subtotal, and total). Based on OCT grading criteria, we qualitatively compared the ability of grading CRAO by CFP and MC. CRAO patient's visual acuity (VA) was obtained from the initial visit. The retinal thickness was measured by SD-OCT. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained from optical coherence tomography angiography (OCTA) examinations. Quantitative data were compared across the three acute CRAO subgroups and against three examination findings. Results: MC image had significantly higher power of acute CRAO detection than CFP (P = 0.03). In the same group of CRAO patients, there was no significant difference in VA when comparing OCT with the MC grading system or with the CFP grading system (all P > 0.05). Significant differences in VA were found between the three CRAO subgroups only under MC grading (P = 0.016). In incomplete CRAO patients, significant differences were found in central fovea thickness (CFT) when comparing OCT with the CFP grading system (P = 0.019). In the same group of CRAO patients, there was no significant difference in retinal thickness when comparing OCT with the MC grading system (All P > 0.05). Significance differences in CFT (P < 0.001), innermost retinal layer (IMRL; P < 0.01), middle retinal layer (MRL; P < 0.001), and outer retinal layer (ORL; P = 0.021) were found between the three CRAO subgroups by MC grading. Vessel density of SCP showed a statistically increased as the severity of three CRAO subgroups (P = 0.03), whereas DCP did not have significant differences (P = 0.745). Comparisons were made between the OCT grading method and the MC and CFP grading methods; there is no significant difference in vessel density of SCP and DCP (All P > 0.05). Conclusion: The images obtained by MC are superior to those obtained by CFP in CRAO grading, retinal thickness, and vessel density measurement. MC imaging may be more capable of CRAO grading than OCT. We recommend MC imaging to determine CRAO severity to guide disease treatment and predict visual prognosis.
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Central retinal artery occlusion (CRAO) is a kind of ophthalmic emergency which may cause loss of functional visual acuity. However, the limited treatment options emphasize the significance of early disease prevention. Metabolomics has the potential to be a powerful tool for early identification of individuals at risk of CRAO. The aim of the study was to identify potential biomarkers for CRAO through a comprehensive analysis. We employed metabolomics analysis to compare venous blood samples from CRAO patients with cataract patients for the venous difference, as well as arterial and venous blood from CRAO patients for the arteriovenous difference. The analysis of metabolites showed that PC(P-18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PC(P-18:0/20:4(5Z,8Z,11Z,14Z)) and octanoylcarnitine were strongly correlated with CRAO. We also used univariate logistic regression, random forest (RF), and support vector machine (SVM) to screen clinical parameters of patients and found that HDL-C and ApoA1 showed significant predictive efficacy in CRAO patients. We compared the predictive performance of the clinical parameter model with combined model. The prediction efficiency of the combined model was significantly better with area under the receiver operating characteristic curve (AUROC) of 0.815. Decision curve analysis (DCA) also exhibited a notably higher net benefit rate. These results underscored the potency of these three substances as robust predictors of CRAO occurrence.
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One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT). The results show that the median viral load (VL) was significantly higher in the HCMV persistent-infection group compared to the non-persistent-infection group (p = 0.002), and that the late-infection rate was considerably higher in the high-VL group compared to the low-VL group (p = 0.014). The uninfected group had a considerably higher median IFN-γ spot-forming cell (SFC) count than the persistent-infection group (p = 0.001), and IFN-γ SFC counts correlated negatively and linearly with VLs (r = -0.397, p = 0.002). The immune-response groups showed significantly difference in median VL (p = 0.018), and the high immune response group had a reduced late-infection rate than the no/low immune response groups (p = 0.049). Our study showed that allo-HSCT recipients with a high VL at an early transplantation stage were at high risk for late HCMV infection. Further HCMV reactivation can be prevented by HCMV-specific T cells secreting enough IFN-γ.
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Purpose There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. Methods Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. Results In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. Conclusion XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment (AU)