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Disrupted connectivity in the default mode network (DMN) during resting-state functional MRI (rs-fMRI) is well-documented in schizophrenia (SCZ). The amygdala, a key component in the neurobiology of SCZ, comprises distinct subregions that may exert varying effects on the disorder. This study aimed to investigate variations in functional connectivity (FC) between distinct amygdala subregions and the DMN in SCZ individuals and explore the effects of treatment on these connections. Fifty-six SCZ patients and 51 healthy controls underwent FC analysis and questionnaire surveys during resting state. The amygdala was selected as the region of interest (ROI) and subdivided into four parts. Changes in FC were examined, and correlations between questionnaire scores and brain activity were explored. Pre-treatment, SCZ patients exhibited reduced FC between the amygdala and DMN compared to HCs. After treatment, significant differences persisted in the right medial amygdala, while other regions did not differ significantly from controls. In addition, PANSS scores positively correlated with FC between the Right Medial Amygdala and the left SMFC (r = .347, p = .009), while RBANS5A scores showed a positive correlation with FC between the Left Lateral Amygdala and the right MTG (rho = -.347, p = .009). The rsFC between the amygdala and the DMN plays a crucial role in the treatment mechanisms of SCZ. This could provide a promising predictive indicator for understanding the neural mechanisms behind treatment and symptomatic improvement.
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Amígdala del Cerebelo , Red en Modo Predeterminado , Imagen por Resonancia Magnética , Esquizofrenia , Humanos , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiopatología , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Esquizofrenia/tratamiento farmacológico , Masculino , Femenino , Adulto , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Adulto Joven , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Mapeo Encefálico , Antipsicóticos/uso terapéuticoRESUMEN
The clearance of apoptotic cell debris, containing professional phagocytosis and non-professional phagocytosis, is essential for maintaining the homeostasis of healthy tissues. Here, we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque. Single-cell RNA sequencing (RNA-seq) has revealed a unique endothelial cell subpopulation in atherosclerosis, which was strongly associated with vascular injury-related pathways. Moreover, integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1 (SR-B1) was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances. Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis. Furthermore, SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta. Overall, this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.
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Pursuing high-performance conductive hydrogels is still hot topic in development of advanced flexible wearable devices. Herein, a tough, self-healing, adhesive double network (DN) conductive hydrogel (named as OSA-(Gelatin/PAM)-Ca, O-(G/P)-Ca) was prepared by bridging gelatin and polyacrylamide network with functionalized polysaccharide (oxidized sodium alginate, OSA) through Schiff base reaction. Thanks to the presence of multiple interactions (Schiff base bond, hydrogen bond, and metal coordination) within the network, the prepared hydrogel showed outstanding mechanical properties (tensile strain of 2800 % and stress of 630 kPa), high conductivity (0.72 S/m), repeatable adhesion performance and excellent self-healing ability (83.6 %/79.0 % of the original tensile strain/stress after self-healing). Moreover, the hydrogel-based sensor exhibited high strain sensitivity (GF = 3.66) and fast response time (<0.5 s), which can be used to monitor a wide range of human physiological signals. Based on this, excellent compression sensitivity (GF = 0.41 kPa-1 in the range of 90-120 kPa), a three-dimensional (3D) array of flexible sensor was designed to monitor the intensity of pressure and spatial force distribution. In addition, a gel-based wearable sensor was accurately classified and recognized ten types of gestures, achieving an accuracy rate of >96.33 % both before and after self-healing under three machine learning models (the decision tree, SVM, and KNN). This paper provides a simple method to prepare tough and self-healing conductive hydrogel as flexible multifunctional sensor devices for versatile applications in fields such as healthcare monitoring, human-computer interaction, and artificial intelligence.
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Resinas Acrílicas , Alginatos , Conductividad Eléctrica , Gelatina , Hidrogeles , Dispositivos Electrónicos Vestibles , Alginatos/química , Resinas Acrílicas/química , Hidrogeles/química , Gelatina/química , Humanos , Oxidación-Reducción , Adhesivos/química , Resistencia a la Tracción , Técnicas Biosensibles/métodosRESUMEN
BACKGROUND: Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of these cancers, and circulating inflammatory proteins may play a role in their development. However, the causal relationship between specific plasma proteins and urological malignancies remains unclear. METHODS: We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS). Instrumental variables representing genetic variants associated with circulating inflammatory proteins were used to infer causality on the risk of kidney, bladder, and prostate cancer. Four MR methods were utilized to provide robust effect estimates. RESULTS: Our analysis identified several plasma proteins associated with a lower risk of kidney and bladder cancer, including Eukaryotic translation initiation factor 4E-binding protein 1, Caspase 8, Natural killer cell receptor 2B4, and Tumor necrosis factor ligand superfamily member 12. However, after adjusting for multiple testing, these associations did not remain statistically significant. For prostate cancer, CUB domain-containing protein 1 and Interleukin-10 receptor subunit beta were found to be protective, while Glial cell line-derived neurotrophic factor and SIR2-like protein 2 were identified as risk factors. After FDR adjustment, none of the inflammatory proteins were found to be significantly associated with a lower risk of prostate cancer. CONCLUSION: Our findings suggest that certain plasma proteins may be involved in the development of urological malignancies. Mendelian randomization provides a useful framework for investigating causal relationships between inflammatory proteins and urological cancers, offering potential insights into their underlying biology and therapeutic targets.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Masculino , Neoplasias Urológicas/genética , Neoplasias Urológicas/sangre , Neoplasias Urológicas/epidemiología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/sangre , Inflamación/genética , Inflamación/sangre , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Proteínas Sanguíneas/genética , Neoplasias Renales/genética , Neoplasias Renales/sangre , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/sangreRESUMEN
Oxidative stress can induce inflammation and tight junction disruption in enterocytes. The initiation of inflammation is thought to commence with the activation of the ROS/NLRP3/IL-1ß signaling pathway, marking a crucial starting point in the process. In our previous studies, we found that microbe-derived antioxidants (MAs) showed significant potential in enhancing both antioxidant capabilities and anti-inflammatory effects. The main aim of this research was to investigate the ability of MAs to protect cells from oxidative stress caused by H2O2, to reduce inflammatory responses, and to maintain the integrity of tight junction proteins by modulating the ROS/NLRP3/IL-1ß signaling pathway. IPEC-1 cells (1 × 104 cells/well) were initially exposed to 100 mg/L of MAs for 12 h, after which they were subjected to 1 mM H2O2 treatment for 1 h. We utilized small interfering RNA (siRNA) to inhibit the expression of NLRP3 and Nrf2. Inflammatory factors such as IL-1ß and antioxidant enzyme activity levels were detected by ELISA. Oxidative stress marker ROS was examined by fluorescence analysis. The NLRP3/IL-1ß signaling pathway, Nrf2/HO-1 signaling pathway and tight junction proteins (ZO-1 and Occludin) were detected by RT-qPCR or Western blotting. In our research, it was observed that MA treatment effectively suppressed the notable increase in H2O2-induced inflammatory markers (TNF-α, IL-1ß, and IL-18), decreased ROS accumulation, mitigated the expression of NLRP3, ASC, and caspase-1, and promoted the expression of ZO-1 and Occludin. After silencing the NLRP3 gene with siRNA, the protective influence of MAs was observed to be linked with the NLRP3 inflammasome. Additional investigations demonstrated that the treatment with MAs triggered the activation of Nrf2, facilitating its translocation into the nucleus. This process resulted in a notable upregulation of Nrf2, NQO1, and HO-1 expression, along with the initiation of the Nrf2-HO-1 signaling pathway. Consequently, there was an enhancement in the activities of antioxidant enzymes like SOD, GSH-Px, and CAT, which effectively mitigated the accumulation of ROS, thereby ameliorating the oxidative stress state. The antioxidant effectiveness of MAs was additionally heightened in the presence of SFN, an activator of Nrf2. The antioxidant and anti-inflammatory functions of MAs and their role in regulating intestinal epithelial tight junction protein disruption were significantly affected after siRNA knockdown of the Nrf2 gene. These findings suggest that MAs have the potential to reduce H2O2-triggered oxidative stress, inflammation, and disruption of intestinal epithelial tight junction proteins in IPEC-1 cells. This reduction is achieved by blocking the ROS/NLRP3/IL-1ß signaling pathway through the activation of the Nrf2 pathway.
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Biomechanical forces, including vascular shear stress, cyclic stretching, and extracellular matrix stiffness, which influence mechanosensitive channels in the plasma membrane, determine cell function in atherosclerosis. Being highly associated with the formation of atherosclerotic plaques, endocytosis is the key point in molecule and macromolecule trafficking, which plays an important role in lipid transportation. The process of endocytosis relies on the mobility and tension of the plasma membrane, which is sensitive to biomechanical forces. Several studies have advanced the signal transduction between endocytosis and biomechanics to elaborate the developmental role of atherosclerosis. Meanwhile, increased plaque growth also results in changes in the structure, composition and morphology of the coronary artery that contribute to the alteration of arterial biomechanics. These cross-links of biomechanics and endocytosis in atherosclerotic plaques play an important role in cell function, such as cell phenotype switching, foam cell formation, and lipoprotein transportation. We propose that biomechanical force activates the endocytosis of vascular cells and plays an important role in the development of atherosclerosis.
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This research investigated the presence of Burkholderia gladioli pathovar cocovenenans (BGC) in wet rice and starch products, Tremella, and Auricularia auricula in Guangzhou, China. It examined BGC growth and bongkrekic acid (BA) production in wet rice noodles and vermicelli with varying rice flour, edible starch ratios, and oil concentrations. A qualitative analysis of 482 samples revealed a detection rate of 0.62%, with three positive for BGC. Rice flour-based wet rice noodles had BA concentrations of 13.67 ± 0.64 mg/kg, 2.92 times higher than 100% corn starch samples (4.68 ± 0.54 mg/kg). Wet rice noodles with 4% soybean oil had a BA concentration of 31.72 ± 9.41 mg/kg, 5.74 times higher than those without soybean oil (5.53 ± 1.23 mg/kg). The BA concentration correlated positively (r = 0.707, P < 0.05) with BGC contamination levels. Low temperatures (4 °C and -18 °C) inhibited BGC growth and BA production, while higher storage temperatures (26 °C and 32 °C) promoted BGC proliferation and increased BA production. Reducing edible oil use and increasing edible starch can mitigate the risk of BGC-related food poisoning in wet rice noodles and vermicelli production. Further research is needed to find alternative oils that do not enhance BA production. Strengthening prevention and control measures is crucial across the entire production chain to address BGC contamination and BA production.
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Burkholderia gladioli , Oryza , Ácido Bongcréquico/análisis , Aceite de Soja/análisis , Almidón , Contaminación de Alimentos/análisis , Harina/análisisRESUMEN
BACKGROUND: Weaning usually causes low feed intake and weight loss in piglets, which mobilizes lipid to energize. The microbe-derived antioxidants (MAs) exhibit great potential in antioxidation, anti-inflammation, and metabolic regulation. OBJECTIVES: We aimed to investigate the changes of lipid metabolism postweaning and effects of MA on growth performance and hepatic lipid metabolism in weanling piglets. METHODS: In the first experiment, piglets weaned at 21 d of age were slaughtered on weaning day (d0), 4 (d4), and 14 (d14) postweaning (6 piglets per day). In the second experiment, piglets were divided into 2 groups, receiving MA (MA) and saline gavage (CON), respectively. All piglets were weaned at 21 d of age and 6 piglets from each group were slaughtered at 25 d of age. RESULTS: In experiment 1, the serum triglyceride, total cholesterol (TC), and LDL cholesterol on d4 and d14 declined significantly compared with d0 (P < 0.05). The serum leptin on d0 was higher than that on d4 and d14 (P < 0.05). The serum ghrelin kept increasing from d0 to d14 (P < 0.05). The hepatic hormone-sensitive lipase and adipose triglyceride lipase first increased from d0 to d4 and then decreased from d4 to d14 (P < 0.05). In experiment 2, the average daily gain and average daily feed intake from 21 to 25 d of age increased in the MA group compared with the CON group (P < 0.05). The serum TC, hepatic TC, and glucose of MA group showed a significant increase than that of the CON group (P < 0.05). The expression of SCD1, ACAT2, and PPARγ were upregulated in the MA group (P < 0.05). Contrary to the decreased expression of phosphorylation of adenosine 5'-monophosphate-activated protein kinase alfa subunit (Thr172), the nuclear sterol regulatory element-binding protein 1c, fatty acid synthase, and peroxisome proliferator-activated receptor gamma of MA group increased than that of CON group (P < 0.05). CONCLUSIONS: Weaning promoted hepatic lipolysis and MA could enhance lipid synthesis by regulating adenosine 5'-monophosphate-activated protein kinase alfa subunit-sterol regulatory element-binding protein 1c pathway, thus improving growth performance of weanling piglets.
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Antioxidantes , Metabolismo de los Lípidos , Animales , Antioxidantes/metabolismo , Proteínas Quinasas/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Porcinos , DesteteRESUMEN
This study aimed to investigate the dynamic changes in hepatic glucose metabolism in response to early weaning. A total of 60 piglets were randomly selected and weaned at 21 days old. Six piglets were slaughtered on the weaning day (d0) and at 1 (d1), 4 (d4), 7 (d7), and 14 (d14) days postweaning. The results illustrated that body weight significantly increased from d4 to d14 (p < 0.001). Serum glucose fell sharply after weaning and then remained at a low level from d1 to d14 (p < 0.001). Serum insulin decreased from d4 (p < 0.001), which caused hepatic glycogen to be broken down (p = 0.007). The glucose-6-phosphatase activity increased from d0 to d4 and then decreased from d4 to d14 (p = 0.039). The pyruvate carboxylase activity presented a significant sustained increase from d0 to d14 (p < 0.001). The succinate (p = 0.006) and oxaloacetate (p = 0.003) content on d4 was lower than that on d0. The succinate dehydrogenase activity (p = 0.008) and ATP (p = 0.016) production decreased significantly on d4 compared to that on d0. Taken together, these findings reveal the dynamic changes of metabolites and enzymes related to hepatic glycometabolism and the TCA (tricarboxylic acid) cycle in piglets after weaning. Our findings enrich weaning stress theory and might provide a reference for dietary intervention.
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This paper presents an innovative, minimally invasive, battery-free, wireless, peripheral nervous system (PNS) neural interface, which seamlessly integrates a millimeter-scale, fascicle-selective integrated circuit (IC) with extraneural recording and stimulating channels. The system also incorporates a wearable interrogator equipped with integrated machine-learning capabilities. This PNS interface is specifically tailored for adaptive neuromodulation therapy, targeting individuals with paralysis, amputation, or chronic medical conditions. By employing a neural pathway classifier and temporal interference stimulation, the proposed interface achieves precise deep fascicle selectivity for recording and stimulation without the need for nerve penetration or compression. Ultrasonic energy harvesters facilitate wireless power harvesting and data reception, enhancing the usability of the system. Key circuit performance metrics encompass a 2.2 µVrms input-referred noise, 14-bit ENOB, and a 173 dB Schreier figure of merit (FOM) for the neural analog-to-digital converter (ADC). Additionally, the ultra-low-power radio-frequency (RF) transmitter boasts a remarkable 1.38 pJ/bit energy efficiency. In vivo experiments conducted on rat sciatic nerves provide compelling evidence of the interface's ability to selectively stimulate and record neural fascicles. The proposed PNS neural interface offers alternative treatment options for diagnosing and treating neurological disorders, as well as restoring or repairing neural functions, improving the quality of life for patients with neurological and sensory deficits.
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Tejido Nervioso , Calidad de Vida , Humanos , Ratas , Animales , Diseño de Equipo , Tecnología Inalámbrica , Nervio CiáticoRESUMEN
The modification of titanium dioxide (TiO2) is a strategy to maximize the utilization of sunlight. Carbon quantum dots (CQDs) are carbon nanomaterials with outstanding optical and electronic properties that are suitable for that purpose. In this work, three types of hybrid TiO2/CQD photoelectrodes were synthesized following different methods: 1) deposition of a CQD layer on top of TiO2 (labelled as TiO2-CQD); 2) deposition of a TiO2 layer on top of CQDs (labelled as CQD-TiO2) and; 3) deposition of a mixed CQD + TiO2 layer (labelled as CQD + TiO2). The photoelectrodes were investigated for the photoelectrocatalytic degradation of phenol as model pollutant under simulated solar light and TiO2-CQD showed the highest apparent reaction rate constant of kapp = 0.0117 min-1 with 40% of TOC removal in 6 h of treatment. CQDs were found to enhance photon absorption in the visible region of the electromagnetic spectrum and in turn phenol degradation by promoting the separation of photogenerated charge carriers through electron transfer via the Ti-O-C bonds formed at the TiO2-CQD interface. Finally, the performance of the TiO2-CQD photoanode was evaluated for the treatment of real wastewater from the membrane fabrication sector, confirming its photoelectrocatalytic efficiency under solar radiation with 93% of TOC removal in 8 h of treatment and kapp = 0.0058 min-1.
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Puntos Cuánticos , Luz Solar , Carbono , FenolesRESUMEN
Biocompatible chitosan-based hydrogels have attracted extensive attention in wound dressing due to their human skin-like tissue characteristics. However, it is a crucial challenge to fabricate chitosan-based hydrogels with versatile properties, including flexibility, stretchability, adhesivity, and antibacterial activity. In this work, a kind of chitosan-based hydrogels with integrated functionalities are facilely prepared by solution polymerization of acrylamide (AAm) and sodium p-styrene sulfonate (SS) in the presence of quaternized carboxymethyl chitosan (QCMCS). Due to the dual cross-linking between QCMCS and P(AAm-co-SS), the optimized QCMCS/P(AAm-co-SS) hydrogel exhibits tough mechanical properties (0.767 MPa tensile stress and 1100% fracture strain) and moderate tissue adhesion (11.4 kPa). Moreover, biological evaluation in vitro illustrated that as-prepared hydrogel possesses satisfactory biocompatibility, hemocompatibility, and excellent antibacterial ability (against S. aureus and E. coli are 98.8% and 97.3%, respectively). Then, the hydrogels are tested in a rat model for bacterial infection incision in vivo, and the results show that they can significantly accelerate epidermal regeneration and wound closure. This is due to their ability to reduce the inflammatory response, promote the formation of collagen deposition and granulation tissue. The proposed chitosan-based antibacterial hydrogels have the potential to be a highly effective wound dressing in clinical wound healing.
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Quitosano , Ratas , Animales , Humanos , Hidrogeles/farmacología , Adhesivos , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , VendajesRESUMEN
Endothelial cells (ECs) angiogenesis is the process of sprouting new vessels from the existing ones, playing critical roles in physiological and pathological processes such as wound healing, placentation, ischemia/reperfusion, cardiovascular diseases and cancer metastasis. Although mitochondria are not the major sites of energy source in ECs, they function as important biosynthetic and signaling hubs to regulate ECs metabolism and adaptations to local environment, thus affecting ECs migration, proliferation and angiogenic process. The understanding of the importance and potential mechanisms of mitochondria in regulating ECs metabolism, function and the process of angiogenesis has developed in the past decades. Thus, in this review, we discuss the current understanding of mitochondrial proteins and signaling molecules in ECs metabolism, function and angiogeneic signaling, to provide new and therapeutic targets for treatment of diverse cardiovascular and angiogenesis-dependent diseases.
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Células Endoteliales , Transducción de Señal , Células Endoteliales/metabolismo , Transducción de Señal/fisiología , Neovascularización Fisiológica , MitocondriasRESUMEN
The burden of foodborne diseases is of serious concern. More effective and localized intervention policies for outbreak prevention and management are required; however, policy modification is hampered due to a lack of information on the epidemiological characteristics of outbreaks in Guangzhou. We collected data from 182 foodborne disease outbreaks reported in Guangzhou, China from 2017 to 2021 to investigate the epidemiological characteristics and associated factors. Nine outbreaks were serious enough to be labelled as level IV public health emergencies, all of which were associated with canteens. In terms of the number of outbreaks, morbidity and clinical medical needs, bacteria and poisonous plants/fungi were the primary causative hazards of outbreaks, and were found mostly in foodservice establishments (96 %, 95/99) and private homes (86 %, 37/43) respectively. Surprisingly, Vibrio parahaemolyticus was primarily identified in meat and poultry products rather than in aquatic products in these outbreaks. Patient specimens and food samples were among the most common sources of detected pathogens in foodservice establishments and private homes. Cross-contamination (35 %), improper processing (32 %) and equipment/utensil contamination (30 %) were the top three risk factors for outbreaks related to foodservice establishments, while accidental ingestion of poisonous food (78 %) was the most common risk factor in private homes. Based on the above epidemiological characteristics of the outbreaks, key foodborne disease intervention policy points should be to raise public awareness of harmful food and avoid risk behaviour, improve handler hygiene training, and strengthen the hygiene management and supervision of kitchens, especially canteens in collective units.
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Enfermedades Transmitidas por los Alimentos , Plantas Tóxicas , Humanos , Enfermedades Transmitidas por los Alimentos/microbiología , Brotes de Enfermedades , Bacterias , Hongos , Contaminación de Alimentos/análisisRESUMEN
The composition of influenza vaccines is updated annually. To ensure vaccine safety, the coverage and adverse events following immunization (AEFI) of 6 manufacturers of trivalent inactivated influenza vaccine (TIV3) need to be evaluated. In January 2022, we analyzed data from more than 1.59 million children in the Childhood Vaccination Information Management System and the AEFI Surveillance Information Management System and evaluated influenza vaccines for children aged 6 to 35 months in Guangzhou from 2016/17 to 2019/20 Vaccination rates and AEFI reporting rates. From 2016/17 to 2019/20, the 1-dose influenza vaccination rate was 25.0% (range: 20.7%-30.2%), and the 2-dose (full course) influenza vaccination rate was 21.6% (range: 17.7%-26.4%). The full vaccination coverage rate has trended down since 2017/2018 (2017/18: 26.0%; 2018/19: 8.3; 2019/20: 17.7%). Fifty-two cases (13.1/100 000) and 24 cases (6.9/100 000) received AEFI reports for 1 dose and 2 doses, respectively, mainly due to fever ≥38.6°C (39 cases for 1 dose, 9.8/100 000; 15 cases for 2 dose, 4.3/100 000) and allergic rash (9 cases with 1 dose, 2.3/100 000; 5 cases with 2 doses, 1.4/100 000). Patients who received A and F manufacturers were more likely to report side effects. The safety of influenza vaccines from 6 manufacturers is good, and it is necessary to improve the recommended information on influenza vaccines to dispel people's concerns and increase the vaccination rate.
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Exantema , Vacunas contra la Influenza , Gripe Humana , Cobertura de Vacunación , Vacunas de Productos Inactivados , Niño , Humanos , Lactante , Exantema/inducido químicamente , Inmunización , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Vacunación , Vacunas de Productos Inactivados/efectos adversosRESUMEN
Nanoparticles (NPs) hold tremendous targeting potential in cardiovascular disease and regenerative medicine, and exciting clinical applications are coming into light. Vascular endothelial cells (ECs) exposure to different magnitudes and patterns of shear stress (SS) generated by blood flow could engulf NPs in the blood. However, an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies. Here, the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted. The mechanism of SS affecting NP uptake through regulating the cellular ROS level, endothelial glycocalyx and membrane fluidity is summarized, and the molecules containing clathrin and caveolin in the engulfment process are elucidated. SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine. This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
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In this work, high internal phase emulsions (HIPEs) stabilized by naturally derived cellulose nanocrystals (CNC) and gelatinized soluble starch (GSS) were fabricated to stabilize oregano essential oil (OEO) in the absence of surfactant. The physical properties, microstructures, rheological properties, and storage stability of HIPEs were investigated by adjusting CNC contents (0.2, 0.3, 0.4 and 0.5 wt%) and starch concentration (4.5 wt%). The results revealed that CNC-GSS stabilized HIPEs exhibited good storage stability within one month and the smallest droplets size at a CNC concentration of 0.4 wt%. The emulsion volume fractions of 0.2, 0.3, 0.4 and 0.5 wt% CNC-GSS stabilized HIPEs after centrifugation reached 77.58, 82.05, 94.22, and 91.41 %, respectively. The effect of native CNC and GSS were analyzed to understand the stability mechanisms of HIPEs. The results revealed that CNC could be used as an effective stabilizer and emulsifier to fabricate the stable and gel-like HIPEs with tunable microstructure and rheological properties.
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Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-ß-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases.
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Senescencia Celular , Células Endoteliales , Placa Aterosclerótica , Animales , Humanos , Ratones , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Peróxido de Hidrógeno , Placa Aterosclerótica/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Endoteliales/metabolismoRESUMEN
Obesity induces lipodystrophy and metabolic inflammation. Microbe-derived antioxidants (MA) are novel small-molecule nutrients obtained from microbial fermentation, and have anti-oxidation, lipid-lowering and anti-inflammatory effects. Whether MA can regulate obesity-induced lipodystrophy and metabolic inflammation has not yet been investigated. The aim of this study was to investigate the effects of MA on oxidative stress, lipid disorders, and metabolic inflammation in liver and epididymal adipose tissues (EAT) of mice fed with a high-fat diet (HFD). Results showed that MA was able to reverse the HFD-induced increase in body weight, body fat rate and Lee's index in mice; reduce the fat content in serum, liver and EAT; and regulate the INS, LEP and resistin adipokines as well as free fatty acids to their normal levels. MA also reduced de novo synthesis of fat in the liver and EAT and promoted gene expression for lipolysis, fatty acid transport and ß-oxidation. MA decreased TNF-α and MCP1 content in serum, elevated SOD activity in liver and EAT, induced macrophage polarization toward the M2 type, inhibited the NLRP3 pathway, increased gene expression of the anti-inflammatory factors IL-4 and IL-13 and suppressed gene expression of the pro-inflammatory factors IL-6, TNF-α and MCP1, thereby attenuating oxidative stress and inflammation induced by HFD. In conclusion, MA can effectively reduce HFD-induced weight gain and alleviate obesity-induced oxidative stress, lipid disorders and metabolic inflammation in the liver and EAT, indicating that MA shows great promise as a functional food.
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Trastornos del Metabolismo de los Lípidos , Lipodistrofia , Ratones , Animales , Antioxidantes/farmacología , Dieta Alta en Grasa , Factor de Necrosis Tumoral alfa/metabolismo , Hígado/metabolismo , Inflamación/metabolismo , Tejido Adiposo/metabolismo , Obesidad/metabolismo , Trastornos del Metabolismo de los Lípidos/metabolismo , Antiinflamatorios/farmacología , Lipodistrofia/metabolismo , Lípidos/farmacología , Ratones Endogámicos C57BLRESUMEN
The emergence of protein hydrogel sensors has attracted intensive attention because of their biocompatibility and biodegradability, and potential application in wearable electronics. However, natural protein hydrogel sensors commonly exhibited low conductivity, weak mechanical strength, and unsatisfactory self-recovery performance. Herein, a fully physical crosslinked conductive BSA-MA-PPy/P(AM-co-AA)/Fe3+ hydrogel based on methacrylic anhydride (MA)-modified and polypyrrole (PPy)-functionalized bovine serum albumin (BSA) introduced into poly(acrylamide-co-acrylic acid) (P(AM-co-AA)) matrix was constructed. Due to the presence of the hydrogen bond complexation and the metal-ligand coordination between ferric ion (Fe3+) and the polymer chain, the as-prepared hydrogel showed outstanding mechanical strength (5.36 MPa tensile stress, 17.66 MJ/m3 toughness, and 1.61 MPa elastic modulus) and fast self-recovery performance (99.89 %/96.18 %/93.57 % stress/elastic modulus/dissipated energy within 10 min at room temperature). Meanwhile, the hydrogel exhibited outstanding conductivity (1.13 S/m) due to the presence of PPy and Fe3+ moieties, high strain sensitivity (GF = 4.98) and good biocompatibility without causing skin allergic reactions. Thus, the hydrogel can be fabricated into strain sensor to monitor the joint motion of the human body. Moreover, it can be used as soft electrode in electrocardiogram device to realize wireless heart-rate monitoring in the real-time conditions (relaxation and post-exercising), which exhibited excellent reusability, stability, and reliability simultaneously.