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Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.

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INTRODUCTION: Acute promyelocytic leukemia (APL) is mainly due to the chromosome translocation t(15; 17) (q22; q12), leading to the formation of PML-RARα fusion protein. However, some patients carried rare translocation involving RARα gene, and they were referred to as variant APL caused by the RAR family (RARα, RARB, and RARG) and partner genes. PLZF-RARα was a rare type of molecular genetic abnormality with unfavorable prognosis that has been reported in few cases in variant APL. Knowledge of PLZF-RARα (+) APL treatment remains limited understood. CASE REPORT: We presented a case of variant APL in a 47-year-old female, who was PLZF-RARα positive detected by reverse transcription polymerase chain reaction (RT-PCR). The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. CONCLUSION: Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.

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Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Decitabina , Leucemia Promielocítica Aguda , Proteínas de Fusión Oncogénica , Sulfonamidas , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/genética , Femenino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Decitabina/uso terapéutico , Decitabina/administración & dosificación , Sulfonamidas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azacitidina/uso terapéutico

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BACKGROUND: The structure of proanthocyanidins (PC) contains a large number of active phenolic hydroxyl groups, which makes it have strong antioxidant capacity. This study investigated the structural and functional properties of ovalbumin (OVA) modified by its interaction with PC. RESULTS: It was found that on increasing the concentration ratio of PC to OVA from 10:1 to 40:1, the free amino and total sulfhydryl contents of OVA decreased from 470.59 ± 38.77 and 29.81 ± 0.31 nmol mg-1 to 96.61 ± 4.55 and 21.22 ± 0.78 nmol mg-1, respectively, and the free sulfhydryl content increased from 7.65 ± 0.41 to 9.48 ± 0.58 nmol mg-1. These results indicated that CN and CS bonds were formed and PC was covalently linked with OVA. The PC content in the OVA-PC conjugates increased from 281.93 ± 12.92 to 828.81 ± 46.09 nmol mg-1 on increasing the concentration ratio of PC to OVA from 10:1 to 40:1. The contents of α-helix and ß-turn of OVA decreased, and the contents of ß-sheet and random coil increased, confirmed by circular dichroism. The tertiary structure of OVA was also altered according to the results of fluorescence and ultraviolet absorption spectra. The surface hydrophobicity of OVA-PC conjugates decreased with increasing bound polyphenol content. The conjugation of OVA to PC significantly improved its emulsification and antioxidant activity and denaturation temperature. CONCLUSION: This study may provide valuable information for improving OVA's functional properties and its PC conjugates for applications in the food industry. © 2024 Society of Chemical Industry.

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OBJECTIVES: The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. METHODS: We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. RESULTS: The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). CONCLUSION: We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. CLINICAL RELEVANCE STATEMENT: The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. KEY POINTS: Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.

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In this study, deep eutectic solvent (DES) prepared from choline chloride, lactic acid, and one of the four polyols (ethylene glycol, glycerol, xylitol, and sorbitol) were compared and assessed for their effectiveness in extracting chitin from lobster shells. Our results revealed that as the number of hydroxyl groups in polyols increased, the hydrogen bond network within the DESs became denser. However, this led to a corresponding increase in viscosity, which impacted the efficiency of chitin extraction. Among all prepared DESs, choline chloride-lactic acid/glycerol (CCLaGly) exhibited superior extractive ability, resulting in the extraction of pure chitin from lobster shells. The purity, crystallinity, and molecular weight of the extracted chitin using CCLaGly DES were comparable to those of chemically-isolated chitin, with purity reaching 94.76 ± 0.33 %, crystallinity at 78.78 %, and a molecular weight of 655 kDa. Additionally, the physicochemical properties of the DES-extracted chitins were characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy. This study conducted a comparative analysis of polyol effects on chitin extraction from lobster shells, thereby opening a promising avenue for the utilization of various crustacean shells in sustainable biomaterial production.

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Exoesqueleto , Quitina , Disolventes Eutécticos Profundos , Polímeros , Quitina/química , Quitina/aislamiento & purificación , Animales , Polímeros/química , Exoesqueleto/química , Disolventes Eutécticos Profundos/química , Viscosidad , Peso Molecular , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Nephropidae/química

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BACKGROUND: Chronic diseases, such as heart disease, cancer, and diabetes, are the leading causes of death and disability. Loneliness is linked to a greater risk of chronic disease. However, the lack of loneliness may change this relationship. METHODS: The 4th Survey of the Aged Population in Urban and Rural China (SSAPUR) was performed. 222,179 people over 60 years old were recruited. Chronic disease was defined by self-reported tumble incidents using the fourth SSAPUR questionnaire. We found that the residuals were well normally distributed. Subsequently, we analyzed the association between each studied factor and chronic disease by univariate logistic regression analysis. Finally, we stratified the population by age, gender, and urban and rural. RESULTS: 77,448 individuals experienced loneliness, while 137,593 did not. Loneliness correlated significantly with urban-rural classification, age, and gender (P < 0.001). There was a significant association between chronic diseases and loneliness (P < 0.05). Compared to lonely individuals, those with low level of loneliness had a lower incidence of gastric diseases (OR = 0.752, 95% CI, 0.736-0.769, P < 0.001), osteoarthritis (OR = 0.685, 95% CI, 0.673-0.697, P < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 0.678, 95% CI, 0.659-0.698, P < 0.001), asthma (OR = 0.608, 95% CI, 0.583-0.633, P < 0.001), malignant tumors (OR = 0.892, 95% CI, 0.822-0.968, P = 0.006), and reproductive system diseases (OR = 0.871, 95% CI, 0.826-0.918, P < 0.001). CONCLUSION: In summary, loneliness is an important risk factor in the occurrence and development of chronic diseases in the elderly in China, and it has adverse effects on hypertension, stomach disease, cataract or glaucoma, osteoarthrosis, chronic lung disease, asthma, malignant tumor, and reproductive system diseases.

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Soledad , Humanos , Soledad/psicología , Masculino , Femenino , China/epidemiología , Anciano , Enfermedad Crónica/epidemiología , Enfermedad Crónica/psicología , Persona de Mediana Edad , Anciano de 80 o más Años , Población Rural , Población Urbana , Epidemias

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Importance: There is a burgeoning interest in therapeutic development for cutaneous neurofibromas (cNFs), a major cause of morbidity in persons with neurofibromatosis type 1 (NF1). To determine meaningful clinical trial outcomes, deeper understanding is needed regarding how cNFs are associated with quality of life (QoL). However, this understanding has been hampered by challenges in recruiting participants with this rare genetic disease. Objective: To develop a large, crowdsourced validated registry of persons with NF1 and determine the association of specific cNF features with QoL, pain, and itch. Design, Setting, and Participants: From May 2021 to December 2023, a decentralized platform was developed and recruited persons 40 years or older with NF1 and at least 1 cNF from 49 states and 12 countries, who provided clinical survey data, detailed photographs, and genetic sequencing data. Photographs from 583 participants were scored on 12 features of cNFs, including general severity, number, size, facial severity, color, and subtypes. Exposure: cNF features derived from participant-supplied photographs. Main Outcomes and Measures: Total Skindex scores and subdomain scores (symptoms, emotion, function, pain, and itch). Results: Of 583 participants, 384 (65.9%) were female, and the mean (range) age was 51.7 (40.0-83.0) years. Female sex, general severity, number, size, and facial severity of cNFs were negatively associated with QoL, as demonstrated by increased total Skindex scores. QoL had the largest association with the number of cNFs and presence of facial cNFs. Increasing number of cNFs was associated with worse QoL, and even individuals with a low cNF burden (<10 total cNFs) experienced a decrease in QoL. Conclusions and Relevance: The results of this study suggest that reducing cNF number, particularly on the face, may be associated with improved QoL in individuals with NF1. In addition, early intervention before the development of numerous tumors may lead to the highest benefit in QoL. These data potentially provide insight into which individuals and cNF tumors may benefit most from therapy and highlights the utility of a completely decentralized, photograph-validated and age-controlled study for rare genetic disease. This cohort will allow analysis of disease and tumor heterogeneity after full phenotypic expression is achieved in NF1 and potentially serves as an example in its design for other rare diseases that struggle from poor recruitment.

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Background: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL. Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs). Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively. Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.

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Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

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Biodiversidad , Medicina Tradicional China , Plantas Medicinales , Plantas Medicinales/química , Plantas Medicinales/clasificación , Plantas Medicinales/crecimiento & desarrollo , China , Encuestas y Cuestionarios

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We developed a protocol for the synthesis of highly functionalized 5,6-dihydro-imidazo[1,2-c][1,2,3]triazole derivatives 4-5 (DHITs) from 1-diazonaphthalen-2(1H)-one derivatives with heterocyclic ketene aminals (HKAs). This strategy involved cycloaddition and skeletal rearrangement entailing the heating of a mixture of substrates 1 with HKAs 2-3 and THF without any catalyst. As a result, a series of DHITs 4-5 were produced by cleaving one bond (1 C═N bond) and forming three bonds (1 N-N and 2 C-N bonds) in a single step. This protocol achieved the dual functionalization of diazo building blocks involving both the aromatic nitrogen alkylation reaction to form an ArC-N bond without any metal catalyst and the intermolecular cycloaddition of the N═N bond. These strategies can be used to synthesize functionalized DHITs for combinatorial and parallel syntheses via one-pot reactions without any catalyst.

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Detecting roads in automatic driving environments poses a challenge due to issues such as boundary fuzziness, occlusion, and glare from light. We believe that two factors are instrumental in addressing these challenges and enhancing detection performance: global context dependency and effective feature representation that prioritizes important feature channels. To tackle these issues, we introduce DTRoadseg, a novel duplex Transformer-based heterogeneous feature fusion network designed for road segmentation. DTRoadseg leverages a duplex encoder architecture to extract heterogeneous features from both RGB images and point-cloud depth images. Subsequently, we introduce a multi-source Heterogeneous Feature Reinforcement Block (HFRB) for fusion of the encoded features, comprising a Heterogeneous Feature Fusion Module (HFFM) and a Reinforcement Fusion Module (RFM). The HFFM leverages the self-attention mechanisms of Transformers to achieve effective fusion through token interactions, while the RFM focuses on emphasizing informative features while downplaying less important ones, thereby reinforcing feature fusion. Finally, a Transformer decoder is utilized to produce the final semantic prediction. Furthermore, we employ a boundary loss function to optimize the segmentation structure area, reduce false detection areas, and improve model accuracy. Extensive experiments are carried out on the KITTI road dataset. The results demonstrate that, compared with state-of-the-art methods, DTRoadseg exhibits superior performance, achieving an average accuracy of 97.01%, a Recall of 96.35%, and runs at a speed of 0.09 s per picture.

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Protein-based subunit vaccines like RBD-Fc are promising tools to fight COVID-19. RBD-Fc fuses the receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein with the Fc region of human IgG1, making it more immunogenic than RBD alone. Earlier work showed that combining RBD-Fc with iNKT cell agonists as adjuvants improved neutralizing antibodies but did not sufficiently enhance T cell responses, a limitation RBD-Fc vaccines share with common adjuvants. Here we demonstrate that aluminum hydroxide combined with α-C-GC, a C-glycoside iNKT cell agonist, significantly improved the RBD-Fc vaccine's induction of RBD-specific T-cell responses. Additionally, aluminum hydroxide with α-GC-CPOEt, a phosphonate diester derivative, synergistically elicited more robust neutralizing antibodies. Remarkably, modifying αGC with phosphate (OPO3H2) or phosphonate (CPO3H2) to potentially enhance aluminum hydroxide interaction did not improve efficacy over unmodified αGC with aluminum hydroxide. These findings underscore the straightforward yet potent potential of this approach in advancing COVID-19 vaccine development and provide insights for iNKT cell-based immunotherapy.

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Adyuvantes Inmunológicos , Hidróxido de Aluminio , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas de Subunidad , Vacunas contra la COVID-19/inmunología , Hidróxido de Aluminio/inmunología , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/química , Anticuerpos Neutralizantes/inmunología , Vacunas de Subunidad/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Ratones , Inmunogenicidad Vacunal , Humanos , Células T Asesinas Naturales/inmunología , Glucolípidos/inmunología , Glucolípidos/química , Femenino , Adyuvantes de Vacunas , Ratones Endogámicos BALB C

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Ultrasound Localization Microscopy (ULM) surpasses the constraints imposed by acoustic diffraction, achieving sub-wavelength resolution visualization of microvasculature through the precise localization of minute microbubbles (MBs). Nonetheless, the analysis of densely populated regions with overlapping MB point spread responses introduces significant localization errors, limiting the use of technique to low-concentration conditions. This raises a trade-off issue between localization efficiency and MB density. In this work, we present a new deep learning framework that combines Transformer and U-Net architectures, termed ULM-TransUNet. As a non-linear model, it is able to learn the complex data patterns of overlapping MBs in dense conditions for accurate localization. To evaluate the performance of ULM-TransUNet, a series of numerical simulations and in vivo experiments are carried out. Numerical simulation results indicate that ULM-TransUNet achieves high-quality ULM imaging, with improvements of 21.93 % in detection rate, 17.36 % in detection precision, and 20.53 % in detection sensitivity, compared to previous state-of-the-art deep learning (DL) method (e.g., ULM-UNet). For the in vivo experiments, ULM-TransUNet achieves the highest spatial resolution (9.4 µm) and rapid inference speed (26.04 ms/frame). Furthermore, it consistently detects more small vessels and resolves closely spaced vessels more effectively. The outcomes of this work imply that ULM-TransUNet can potentially enhance the microvascular imaging performance on high-density MB conditions.

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Microburbujas , Ultrasonografía , Animales , Ultrasonografía/métodos , Microscopía/métodos , Aprendizaje Profundo , Microvasos/diagnóstico por imagen , Ratones , Simulación por Computador

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Lentiviral vectors have markedly enhanced gene therapy efficiency in treating congenital diseases, but their long-term safety remains controversial. Most gene therapies for congenital eye diseases need to be carried out at early ages, yet the assessment of related risks to ocular development posed by lentiviral vectors is challenging. Utilizing single-cell transcriptomic profiling on human retinal organoids, this study explored the impact of lentiviral vectors on the retinal development and found that lentiviral vectors can cause retinal precursor cells to shift toward photoreceptor fate through the up-regulation of key fate-determining genes such as PRDM1. Further investigation demonstrated that the intron and intergenic region of PRDM1 was bound by PHLDA1, which was also up-regulated by lentiviral vectors exposure. Importantly, knockdown of PHLDA1 successfully suppressed the lentivirus-induced differentiation bias of photoreceptor cells. The findings also suggest that while lentiviral vectors may disrupt the fate determination of retinal precursor cells, posing risks in early-stage retinal gene therapy, these risks could potentially be reduced by inhibiting the PHLDA1-PRDM1 axis.

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Diferenciación Celular , Vectores Genéticos , Lentivirus , Retina , Células Madre , Factores de Transcripción , Humanos , Retina/metabolismo , Retina/citología , Lentivirus/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Vectores Genéticos/metabolismo , Vectores Genéticos/genética , Diferenciación Celular/genética , Células Madre/metabolismo , Células Madre/citología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Organoides/metabolismo , Organoides/citología , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Terapia Genética/métodos

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Aim: To examine the prevalence and potential risk factors of multimorbidity among older adult in China. In addition, we investigated the pattern of multimorbidity. Methods: This study is based on data from the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) in 2015, a comprehensive survey of individuals aged 60 years or older in China. We calculated baseline data and prevalence rates for comorbidities, stratified by household registration, age, sex, education, exercise, and health insurance. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for comorbidities. Furthermore, we determined the prevalence rates for the three most frequent disease combinations. Results: A total of 215,040 participants were included in our analysis. The prevalence of multimorbidity was 50.5% among the older adult in China. The prevalence rate was slightly higher in rural areas than in urban areas, with rates of 51.5 and 49.6%, respectively (p < 0.001). Moreover, the prevalence rate was higher in females than in males, with rates of 55.2 and 45.3%, respectively (p < 0.001). Multivariate logistic regression analysis revealed that individuals aged 70-79 years (OR:1.40, 95% CI: 1.38-1.43, p < 0.001) and over 80 years (OR:1.41, 95% CI: 1.38-1.45, p < 0.001) had a higher prevalence of multimorbidity than those aged 60-69 years. The most prevalent pair of comorbidities was hypertension and osteoarthropathy, with 19.6% of the participants having these two conditions, accounting for 5.4% of the total participants. Conclusion: Our findings indicate a high prevalence of multimorbidity among the older adult in China. Increased expenditure on preventive health care, popularization of general medicine and popular medical education may be adopted by the Government to cope with the high prevalence of multimorbidity.

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Multimorbilidad , Población Rural , Humanos , China/epidemiología , Masculino , Femenino , Anciano , Estudios Transversales , Prevalencia , Persona de Mediana Edad , Anciano de 80 o más Años , Factores de Riesgo , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Encuestas y Cuestionarios

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The house fly is a significant pest in agriculture and human health that is increasingly difficult to manage due to multiple limitations including resistance development. To explore alternative pesticides, the topical toxicity and repellency profiles of 17 essential oil components (EOCs) were evaluated against a resistant and a susceptible strain of house fly, Musca domestica L., using topical application and Y-tube olfactometers, respectively. Six of the most toxic EOCs based on the LD50 were further investigated against a susceptible strain of house fly. Thymol, (+)-pulegone, eugenol, and carvacrol were always the top four most toxic chemicals tested against the resistant house fly strain. Little to no resistance was observed to the top six EOCs based on the comparison of the results between resistant and susceptible house fly strains. P-Cymene, citronellic acid, R-(+)-limonene, linalool, γ-terpinene, estragole, and eugenol were repellent to adult house flies at certain concentrations while (-)-carvone and thymol were attractive to adult house flies. This screening of a wide variety of individual EOCs provides a stronger foundation of information for further research. This should encourage further investigation into the topical toxicity and repellency in field studies, which will provide more insight into the performance of biopesticides for house fly management and potential commercialization.

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ETHNOPHARMACOLOGICAL RELEVANCE: Meibomian gland dysfunction (MGD), complicated by type 2 diabetes, is associated with a high incidence of ocular surface disease, and no effective drug treatment exists. Diabetes mellitus (DM) MGD shows a notable disturbance in lipid metabolism. Er-Dong-Xiao-Ke decoction (EDXKD) has important functions in nourishing yin, clearing heat, and removing blood stasis, which are effective in the treatment of DM MGD. AIM OF THE STUDY: To observe the therapeutic effect of EDXKD on DM MGD and its underlying molecular mechanism. MATERIALS AND METHODS: After establishing a type 2 DM (T2DM)-induced MGD rat model, different doses of EDXKD and T0070907 were administered. The chemical constituents of EDXKD were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the molecular mechanism of EDXKD in treating DM MGD was predicted using network pharmacology. Lipid metabolism in DM meibomian glands (MGs) was analyzed using LC-MS/MS, and lipid biomarkers were screened and identified. Histological changes and lipid accumulation in MGs were detected by staining, and Peroxisome proliferator-activated receptor gamma (PPARG) expression in MG acinar cells was detected by immunofluorescence. The expression of lipid metabolism-related factors was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blotting. RESULTS: EDXKD reduced lipid accumulation in the MGs and improved the ocular surface index in DM MGD rats. The main active components of EDXKD had advantages in lipid regulation. Additionally, the PPARG signaling pathway was the key pathway of EDXKD in the treatment of DM MGD. Twelve lipid metabolites were biomarkers of EDXKD in the treatment of DM MGD, and glycerophospholipid metabolism was the main pathway of lipid regulation. Moreover, EDXKD improved lipid deposition in the acini and upregulated the expression of PPARG. Further, EDXKD regulated the PPARG-mediated UCP2/AMPK signaling network, inhibited lipid production, and promoted lipid transport. CONCLUSION: EDXKD is an effective treatment for MGD in patients with T2DM. EDXKD can regulate lipids by regulating the PPARG-mediated UCP2/AMPK signaling network, as it reduced lipid accumulation in the MGs of DM MGD rats, promoted lipid metabolism, and improved MG function and ocular surface indices.

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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Metabolismo de los Lípidos , Disfunción de la Glándula de Meibomio , Transducción de Señal , Animales , Masculino , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Metabolismo de los Lípidos/efectos de los fármacos , Disfunción de la Glándula de Meibomio/tratamiento farmacológico , Disfunción de la Glándula de Meibomio/metabolismo , Glándulas Tarsales/efectos de los fármacos , Glándulas Tarsales/metabolismo , PPAR gamma/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos

RESUMEN

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Asunto(s)

Diabetes Mellitus Tipo 2 , Pie Diabético , Pie , Flujometría por Láser-Doppler , Microcirculación , Dispositivos Electrónicos Vestibles , Humanos , Pie Diabético/fisiopatología , Pie Diabético/diagnóstico por imagen , Masculino , Microcirculación/fisiología , Femenino , Flujometría por Láser-Doppler/métodos , Diabetes Mellitus Tipo 2/fisiopatología , Persona de Mediana Edad , Pie/irrigación sanguínea , Anciano , Análisis de Ondículas , Adulto

RESUMEN

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.