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BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.
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Astrocitos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Modelos Animales de Enfermedad , Proteínas del Tejido Nervioso , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Astrocitos/fisiología , Proteínas del Tejido Nervioso/metabolismo , Ratones , Regeneración Nerviosa/fisiología , Neuronas , Femenino , Ratones Endogámicos C57BL , Médula Espinal/metabolismoRESUMEN
BACKGROUND: Under the background of the increasing trend of population aging, the health and quality of life of older adults have become the focus of social concern. As an important part of older adults' daily life, the design and configuration of the built environment may positively or negatively affect older adults' health behaviors. Therefore, this study aims to explore the relationship between older adults' perceived built environments and health behaviors, which is the association between perceived built environments and older adults' physical activity (PA) and social interactions. This is important for optimizing the community built environment and improving the quality of life of older adults. METHODS: In this study, a questionnaire was surveyed on 916 Chinese older adults aged 60 and above. The questionnaire was used to collect demographic information and social interaction from the participants, and the Physical Activity Neighborhood Environment Scale (PANES) and the Physical Activity Scale for the Elderly (PASE) were used to assess older adults' subjective perceptions of the built environment in their neighborhoods and their levels of PA, respectively. In data analysis, ANOVA and chi-square tests were used to compare the significance of differences between groups, and multiple linear regression model were used to estimate the association between older adults' perceived characteristics of the built environment and their PA and social interaction. RESULTS: After controlling for confounders such as gender, age, BMI, and education level, the multiple linear regression model showed that perceived destination accessibility, neighborhood infrastructure, aesthetic qualities, and neighborhood environment indices were significantly correlated with PA (ß = 0.083 ~ 0.095, P < 0.05) and social interaction (ß = 0.087 ~ 0.144, P < 0.05) among older adults. In addition, neighborhood safety (ß = -0.084, P < 0.05), social environment (ß = 0.091, P < 0.01), and street connectivity (ß = 0.112, P < 0.001) were also strongly associated with older adults' social interaction. CONCLUSIONS: Different perceived built environment attributes are correlated with the health behaviors of Chinese older adults to different degrees. This finding helps to guide community planning and construction, provides an empirical basis for improving health behaviors of older adults, and provides an important reference for building healthy communities for older adults and realizing comprehensive healthy development of older adults. TRIAL REGISTRATION: There was no trial registration for this study, but the study was approved by the Institutional Review Board of Tsinghua University (No. THU0120230196).
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Entorno Construido , Ejercicio Físico , Conductas Relacionadas con la Salud , Humanos , Anciano , Masculino , Femenino , Estudios Transversales , Conductas Relacionadas con la Salud/fisiología , Persona de Mediana Edad , Beijing/epidemiología , Ejercicio Físico/psicología , Ejercicio Físico/fisiología , Encuestas y Cuestionarios , Anciano de 80 o más Años , Interacción Social , Características del Vecindario , China/epidemiología , Características de la ResidenciaRESUMEN
Objective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.
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HIV disease remains prevalent in the United States and is particularly prevalent in sub-Saharan Africa. Recent investigations revealed that mitochondrial dysfunction in kidney contributes to HIV-associated nephropathy (HIVAN) in Tg26 transgenic mice. We hypothesized that nicotinamide adenine dinucleotide (NAD) deficiency contributes to energetic dysfunction and progressive tubular injury. We investigated metabolomic mechanisms of HIVAN tubulopathy. Tg26 and wild-type (WT) mice were treated with the farnesoid X receptor (FXR) agonist INT-747 or nicotinamide riboside (NR) from 6 to 12 wk of age. Multiomic approaches were used to characterize kidney tissue transcriptomes and metabolomes. Treatment with INT-747 or NR ameliorated kidney tubular injury, as shown by serum creatinine, the tubular injury marker urinary neutrophil-associated lipocalin, and tubular morphometry. Integrated analysis of metabolomic and transcriptomic measurements showed that NAD levels and production were globally downregulated in Tg26 mouse kidneys, especially nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. Furthermore, NAD-dependent deacetylase sirtuin3 activity and mitochondrial oxidative phosphorylation activity were lower in ex vivo proximal tubules from Tg26 mouse kidneys compared with those of WT mice. Restoration of NAD levels in the kidney improved these abnormalities. These data suggest that NAD deficiency might be a treatable target for HIVAN.NEW & NOTEWORTHY The study describes a novel investigation that identified nicotinamide adenine dinucleotide (NAD) deficiency in a widely used HIV-associated nephropathy (HIVAN) transgenic mouse model. We show that INT-747, a farnesoid X receptor agonist, and nicotinamide riboside (NR), a precursor of nicotinamide, each ameliorated HIVAN tubulopathy. Multiomic analysis of mouse kidneys revealed that NAD deficiency was an upstream metabolomic mechanism contributing to HIVAN tubulopathy.
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Nefropatía Asociada a SIDA , Ratones Transgénicos , NAD , Niacinamida , Compuestos de Piridinio , Sirtuina 3 , Animales , NAD/metabolismo , Nefropatía Asociada a SIDA/metabolismo , Nefropatía Asociada a SIDA/genética , Nefropatía Asociada a SIDA/patología , Niacinamida/análogos & derivados , Niacinamida/farmacología , Compuestos de Piridinio/farmacología , Sirtuina 3/metabolismo , Sirtuina 3/genética , Sirtuina 3/deficiencia , Modelos Animales de Enfermedad , Nicotinamida Fosforribosiltransferasa/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Ratones , Mitocondrias/metabolismo , Mitocondrias/patología , Progresión de la Enfermedad , Metabolómica , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/deficiencia , Riñón/metabolismo , Riñón/patología , Riñón/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Citocinas/metabolismoRESUMEN
α-Sn, a new elemental topological quantum material, has drawn substantial attention lately. Unique transport properties and intriguing spintronics applications of α-Sn are demonstrated, resurrecting this material from its notorious "tin pest" infamy. With a diamond cubic crystal structure, group-IV α-Sn holds the potential for integrated topological quantum devices on Si. However, directly growing α-Sn on Si is still challenging due to the ≈20% lattice mismatch. Here, a new method is demonstrated to grow 200 nm-thick α-Sn microstructures on a 2 nm-thick Ge seed layer on Si substrate by physical vapor deposition. In situ Raman spectroscopy reveals that the as-deposited ß-Sn melts upon rapid thermal annealing at 350-450 °C and solidifies to α-Sn after cooling back to room temperature, seeded by heterogeneous nucleation on the Ge layer. Cooling condition and HCl etching are tuned to achieve phase-pure α-Sn microstructures toward quantum devices. Approximately 1 at.% Ge is alloyed into α-Sn due to diffusion from the Ge seed layer, which helps stabilize α-Sn thermodynamically to facilitate device processing. A compressive strain is incorporated into these α-Sn microstructures, making them 3D topological Dirac semimetals for integrated quantum devices on Si.
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BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (nâ =â 445) and Kyung Hee University (nâ =â 63), respectively. Fang JQ (nâ =â 27) and Evidence-Based Complementary and Alternative Medicine (nâ =â 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.
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Bibliometría , Terapias Complementarias , Neuralgia , Terapias Complementarias/estadística & datos numéricos , Terapias Complementarias/métodos , Terapias Complementarias/tendencias , Humanos , Neuralgia/terapiaRESUMEN
In this work, iron-phosphorus based composite biochar (FPBC) was prepared by modification with potassium phosphate and iron oxides for the removal of heavy metal ions from single and mixed heavy metal (Pb and Cd) solutions. FTIR and XPS characterization experiments showed that the novel modified biochar had a greater number of surface functional groups compared to the pristine biochar. The maximum adsorption capacities of FPBC for Pb(II) and Cd(II) were 211.66 mg·g-1 and 94.08 mg·g-1 at 293 K. The adsorption of Pb(II) and Cd(II) by FPBC followed the proposed two-step adsorption kinetic model and the Freundlich isothermal adsorption model, suggesting that the mechanism of adsorption of Pb(II) and Cd(II) by FPBC involved chemical adsorption of multiple layers. Mechanistic studies showed that the introduction of -PO4 and -PO3 chemisorbed with Pb(II) and Cd(II), and the introduction of -Fe-O increased the ion exchange with Pb(II) and Cd(II) during the adsorption process and produced precipitates such as Pb3Fe(PO4)3 and Cd5Fe2(P2O7)4. Additionally, the abundant -OH and -COOH groups also participated in the removal of Pb(II) and Cd(II). In addition, FPBC demonstrated strong selective adsorption of Pb(II) in mixed heavy metal solutions. The Response Surface Methodology(RSM) analysis determined the optimal adsorption conditions for FPBC as pH 5.31, temperature 26.01 °C, and Pb(II) concentration 306.30 mg·L-1 for Pb(II). Similarly, the optimal adsorption conditions for Cd(II) were found to be pH 5.66, temperature 39.34 °C, and Cd(II) concentration 267.68 mg·L-1. Therefore, FPBC has the potential for application as a composite-modified adsorbent for the adsorption of multiple heavy metal ions.
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Cadmio , Carbón Orgánico , Plomo , Fósforo , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico/química , Cadmio/química , Plomo/química , Contaminantes Químicos del Agua/química , Fósforo/química , Hierro/química , Cinética , Purificación del Agua/métodos , Metales Pesados/químicaRESUMEN
BACKGROUND: Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, and cellular roles are not completely understood. Sphingolipids are produced by the serine palmitoyltransferase enzyme, canonically composed of 2 subunits, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) and SPTLC2 (serine palmitoyltransferase long chain base subunit 2). Noncanonical sphingolipids are produced by a more recently described subunit, SPTLC3 (serine palmitoyltransferase long chain base subunit 3). METHODS: The noncanonical (d16) and canonical (d18) sphingolipidome profiles in cardiac tissues of patients with end-stage ischemic cardiomyopathy and in mice with ischemic cardiomyopathy were analyzed by targeted lipidomics. Regulation of SPTLC3 by HIF1α under ischemic conditions was determined with chromatin immunoprecipitation. Transcriptomics, lipidomics, metabolomics, echocardiography, mitochondrial electron transport chain, mitochondrial membrane fluidity, and mitochondrial membrane potential were assessed in the cSPTLC3KO transgenic mice we generated. Furthermore, morphological and functional studies were performed on cSPTLC3KO mice subjected to permanent nonreperfused myocardial infarction. RESULTS: Herein, we report that SPTLC3 is induced in both human and mouse models of ischemic cardiomyopathy and leads to production of atypical sphingolipids bearing 16-carbon sphingoid bases, resulting in broad changes in cell sphingolipid composition. This induction is in part attributable to transcriptional regulation by HIF1α under ischemic conditions. Furthermore, cardiomyocyte-specific depletion of SPTLC3 in mice attenuates oxidative stress, fibrosis, and hypertrophy in chronic ischemia, and mice demonstrate improved cardiac function and increased survival along with increased ketone and glucose substrate metabolism utilization. Depletion of SPTLC3 mechanistically alters the membrane environment and subunit composition of mitochondrial complex I of the electron transport chain, decreasing its activity. CONCLUSIONS: Our findings suggest a novel essential role for SPTLC3 in electron transport chain function and a contribution to ischemic injury by regulating complex I activity.
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Cardiomiopatías , Complejo I de Transporte de Electrón , Serina C-Palmitoiltransferasa , Animales , Serina C-Palmitoiltransferasa/metabolismo , Serina C-Palmitoiltransferasa/genética , Ratones , Humanos , Cardiomiopatías/metabolismo , Cardiomiopatías/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , Esfingolípidos/metabolismo , Ratones Noqueados , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/genética , Isquemia Miocárdica/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patologíaRESUMEN
Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.
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Células Espumosas , Traumatismos de la Médula Espinal , Humanos , Células Espumosas/patología , Traumatismos de la Médula Espinal/metabolismo , Macrófagos/metabolismo , Sistema Nervioso Central/metabolismoRESUMEN
The construction of ecological civilization emphasizes holistic protection of "mountain-water-forest-farmland-lake-grassland-sand", which has become an important concept of desertification prevention projects in arid and semi-arid areas of China. In the past, sandy land management and use have been neglected in desertification prevention and control, in that the links have not been effectively connected and the long-term and efficient desertification prevention has not been realized. Therefore, combining Qian Xuesen's understanding of "deserticulture", we comprehensively discussed the "long-term achievements" of China's desertification control miracle from the perspective of the historical evolution of the interaction of technology and practice, and the strategic development of policy guidance. Further, we defined the concepts of desertification prevention, desertification control, and sandy land management and use. We analyzed the coupling and coordination relationship between the four links and the scientific principle based on the development of ecological industry chain. Finally, we put forward the policy and market realization pathways, with efficient sandy land management as the core, desertification prevention as the basis, desertification control as the channel, and long-term sandy land use as the foundation. We expected to provide theoretical and practical guidance for creating a new miracle of China's desertification prevention and control.
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Conservación de los Recursos Naturales , Arena , Monitoreo del Ambiente , China , Bosques , EcosistemaRESUMEN
BACKGROUND: Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. RESULTS: In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus, which were positively correlated with gut barrier function, while suppressing Odoribacter, Rikenella, Oscillibacter and Parasutterella, which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. CONCLUSIONS: Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.
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Colitis Ulcerosa , Colitis , Enterococcus faecium , Microbioma Gastrointestinal , Humanos , Animales , Ratones , Funcion de la Barrera Intestinal , ARN Ribosómico 16S/genética , Colitis/inducido químicamente , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/terapia , Bacteroidetes , Escherichia coli , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , ColonRESUMEN
Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD + ) is a small molecule that participates in hundreds of metabolism-related reactions. NAD + levels are decreased in CKD, and NAD + supplementation is protective. However, both the mechanism of how NAD + supplementation protects from CKD, as well as the cell types most responsible, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD + precursor, stimulates renal peroxisome proliferator-activated receptor α signaling and restores FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing shows that renal metabolic pathways are impaired in Alport mice and dramatically activated by NR in both sexes. These transcriptional changes are confirmed by orthogonal imaging techniques and biochemical assays. Single nuclei RNA-sequencing and spatial transcriptomics, both the first of their kind from Alport mice, show that NAD + supplementation restores FAO in the proximal tubules with minimal effects on the podocytes. Finally, we also report, for the first time, sex differences at the transcriptional level in this Alport model. Male Alport mice had more severe inflammation and fibrosis than female mice at the transcriptional level. In summary, the data herein identify both the protective mechanism and location of NAD + supplementation in this model of CKD.
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BACKGROUND: Air pollution poses a significant health risk to the human population, especially for vulnerable groups such as the elderly, potentially discouraging their engagement in physical activity. However, there is a lack of sufficient objective and longitudinal data in current research on how air pollution affects physical activity among older adults. With these gaps, we aimed to explore the relationship between air pollution and objective measurement-based physical activity among older adults by engaging in a longitudinal study design. METHODS: A total of 184 older adults were recruited from three cities with varying levels of air quality. Mean daily minutes of physical activity were measured with 7 consecutive days of accelerometer monitoring (ActiGraph GT3X-BT). Corresponding air pollution data including daily PM2.5 (µg/m3), PM10 (µg/m3) and air quality index (AQI) were sourced from the China National Environmental Monitoring Centre at monitor locations close to older adults' addresses. Associations between air quality and physical activity were estimated using a fixed effect model, adjusting for average daytime temperature, rain, age and weight. RESULTS: AQI and PM2.5 were observed to exhibit significant, inverse, and linear associations with mean daily walk steps, minutes of light physical activity (LPA), moderate physical activity (MPA) and moderate-to-vigorous physical activity (MVPA) in the single variable models. A one-level increase in AQI corresponded to a decline in 550.04 steps (95% [CI] = -858.97, -241.10; p < 0.001), 10.43 min (95% [CI] = -17.07, -3.79; p < 0.001), 4.03 min (95% [CI] = -7.48, -0.59; p < 0.001) and 4.16 min (95% [CI] = -7.77, -0.56; p < 0.001) in daily walking steps, LPA, MPA, and MVPA, respectively. A one-level increase in PM2.5 correlated with a decline in daily walk steps, LPA, MPA and MVPA by 361.85 steps (95% [CI] = -516.53, -207.16; p < 0.001), 8.97 min (95% [CI] = -12.28, -5.66; p < 0.001), 3.73 min (95% [CI] = -5.46, -2.01; p < 0.001,) and 3.79 min (95% [CI] = -5.59, -1.98; p < 0.001), respectively. However, PM10 displayed a significant negative association exclusively with LPA, with one-level increase in PM10 resulting in a 3.7-minute reduction in LPA (95% [CI] = -6.81, -0.59, p < 0.05). CONCLUSION: Air pollution demonstrates an inverse association with physical activity levels among older adults, potentially discouraging their engagement in physical activity. Different air quality indicators may exert varying impacts on physical activity. Future studies are warranted to enhance policy interventions aimed at reducing air pollution and promoting physical activity.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Anciano , Estudios Longitudinales , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Ejercicio Físico , Monitoreo del Ambiente , Contaminantes Atmosféricos/análisisRESUMEN
Utilizing metal-organic framework (MOF) materials for the extraction of bromide ions (Br-) from aqueous solutions, as an alternative to chlorine gas oxidation technology, holds promising potential for future applications. However, the limitations of powdered MOFs, such as low utilization efficiency, ease of aggregation in water, and challenging recovery processes, have hindered their practical application. Shaping MOF materials into application-oriented forms represents an effective but challenging approach to address these drawbacks. In this work, a novel Ag-UiO-66-(OH)2@delignified wood cellulose aerogel (CA) adsorbent is synthesized using an oil bath impregnation method, involving the deposition of UiO-66-(OH)2 nanoparticles onto CA and the uniform dispersion of Ag0 nanoparticles across its surface. CA, characterized by the intertwined cellulose nanofiber structure and a highly hydrophilic surface, serves as an ideal substrate for the uniform growth of UiO-66-(OH)2 nanoparticles, which, in turn, spontaneously reduce Ag+ to form distributed Ag0 nanoparticles due to the abundant hydroxyl groups provided. Leveraging the well-defined biological structure of CA, which offers excellent mass transfer channels, and the highly dispersed Ag adsorption sites, Ag-UiO-(OH)2/CA exhibits remarkable adsorption capacity (642 mg/gAg) under optimized conditions. Furthermore, an integrated device is constructed by interconnecting Ag-UiO-(OH)2/CA adsorbents in series, affirming its potential application in the continuous recovery of Br-. This study not only presents an efficient Ag-UiO-(OH)2/CA adsorbent for Br- recovery but also sheds light on the extraction of other valuable elements from various liquid ores.
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Chronic kidney disease progresses through the replacement of functional tissue compartments with fibrosis, a maladaptive repair process. Shifting kidney repair toward a physiologically intact architecture, rather than fibrosis, is key to blocking chronic kidney disease progression. Much research into the mechanisms of fibrosis is performed in rodent models with less attention to the human genetic context. Recently, human induced pluripotent stem cell (iPSC)-derived organoids have shown promise in overcoming the limitation. In this study, we developed a fibrosis model that uses human iPSC-based 3-dimensional renal organoids, in which exogenous transforming growth factor-ß1 (TGF-ß1) induced the production of extracellular matrix. TGF-ß1-treated organoids showed tubulocentric collagen 1α1 production by regulating downstream transcriptional regulators, Farnesoid X receptor, phosphorylated mothers against decapentaplegic homolog 3 (p-SMAD3), and transcriptional coactivator with PDZ-binding motif (TAZ). Increased nuclear TAZ expression was confirmed in the tubular epithelium in human kidney biopsies with tubular injury and early fibrosis. A dual bile acid receptor agonist (INT-767) increased Farnesoid X receptor and reduced p-SMAD3 and TAZ, attenuating TGF-ß1-induced fibrosis in kidney organoids. Finally, we show that TAZ interacted with TEA-domain transcription factors and p-SMAD3 with TAZ and TEA-domain transcription factor 4 coregulating collagen 1α1 gene transcription. In summary, we establish a novel, readily manipulable fibrogenesis model and posit a role for bile acid receptor agonism early in renal parenchymal fibrosis.
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Fibrosis , Células Madre Pluripotentes Inducidas , Riñón , Organoides , Factor de Crecimiento Transformador beta1 , Humanos , Organoides/metabolismo , Organoides/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Riñón/metabolismo , Riñón/patologíaRESUMEN
Long noncoding RNAs (lncRNAs) have emerged as crucial regulators across diverse biological processes and diseases. While high-throughput sequencing has enabled lncRNA discovery, functional characterization remains limited. The EVLncRNAs database is the first and exclusive repository for all experimentally validated functional lncRNAs from various species. After previous releases in 2018 and 2021, this update marks a major expansion through exhaustive manual curation of nearly 25 000 publications from 15 May 2020, to 15 May 2023. It incorporates substantial growth across all categories: a 154% increase in functional lncRNAs, 160% in associated diseases, 186% in lncRNA-disease associations, 235% in interactions, 138% in structures, 234% in circular RNAs, 235% in resistant lncRNAs and 4724% in exosomal lncRNAs. More importantly, it incorporated additional information include functional classifications, detailed interaction pathways, homologous lncRNAs, lncRNA locations, COVID-19, phase-separation and organoid-related lncRNAs. The web interface was substantially improved for browsing, visualization, and searching. ChatGPT was tested for information extraction and functional overview with its limitation noted. EVLncRNAs 3.0 represents the most extensive curated resource of experimentally validated functional lncRNAs and will serve as an indispensable platform for unravelling emerging lncRNA functions. The updated database is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs3/.
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Bases de Datos de Ácidos Nucleicos , ARN Largo no Codificante , Manejo de Datos , Almacenamiento y Recuperación de la Información , ARN Largo no Codificante/genéticaRESUMEN
Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans, human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Humanos , Ratones , Caenorhabditis elegans/metabolismo , Longevidad/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Vitamina A/farmacología , Vitamina A/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Regulación hacia Arriba , Proteínas de Caenorhabditis elegans/metabolismo , Estrés Oxidativo , Mamíferos/metabolismo , Micronutrientes/metabolismo , Micronutrientes/farmacologíaRESUMEN
Background: Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated. Methods: We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR. Results: NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1ß (IL-1ß), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1ß, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI. Conclusion: The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.
RESUMEN
Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.