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Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) 'resets' these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices-which do not have the constraints of bioprinted scaffolds-the 'reset' vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call 'Organ-On-VascularNet'. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting.
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Vasos Sanguíneos/citología , Carcinogénesis , Células Endoteliales/citología , Hemodinámica , Neoplasias/irrigación sanguínea , Organogénesis , Organoides/irrigación sanguínea , Vasos Sanguíneos/crecimiento & desarrollo , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Cromatina/metabolismo , Epigénesis Genética , Epigenómica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Técnicas In Vitro , Islotes Pancreáticos/irrigación sanguínea , Modelos Biológicos , Especificidad de Órganos , RNA-Seq , Análisis de la Célula Individual , Factores de Transcripción , TranscriptomaRESUMEN
VarCards, an online database, combines comprehensive variant- and gene-level annotation data to streamline genetic counselling for coding variants. Recognising the increasing clinical relevance of non-coding variations, there has been an accelerated development of bioinformatics tools dedicated to interpreting non-coding variations, including single-nucleotide variants and copy number variations. Regrettably, most tools remain as either locally installed databases or command-line tools dispersed across diverse online platforms. Such a landscape poses inconveniences and challenges for genetic counsellors seeking to utilise these resources without advanced bioinformatics expertise. Consequently, we developed VarCards2, which incorporates nearly nine billion artificially generated single-nucleotide variants (including those from mitochondrial DNA) and compiles vital annotation information for genetic counselling based on ACMG-AMP variant-interpretation guidelines. These annotations include (I) functional effects; (II) minor allele frequencies; (III) comprehensive function and pathogenicity predictions covering all potential variants, such as non-synonymous substitutions, non-canonical splicing variants, and non-coding variations and (IV) gene-level information. Furthermore, VarCards2 incorporates 368 820 266 documented short insertions and deletions and 2 773 555 documented copy number variations, complemented by their corresponding annotation and prediction tools. In conclusion, VarCards2, by integrating over 150 variant- and gene-level annotation sources, significantly enhances the efficiency of genetic counselling and can be freely accessed at http://www.genemed.tech/varcards2/.
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Bases de Datos Factuales , Variación Genética , Genoma Humano , Programas Informáticos , Humanos , Bases de Datos Genéticas , Variaciones en el Número de Copia de ADN , Nucleótidos , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism. METHODS: In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis. We also generated Glp1r-/- mice to detect whether GLP-1R is required for angiogenic function of GLP-1(32-36). In in vitro experiments, EPCs isolated from the mouse bone marrow and human umbilical cord blood samples were used to detect GLP-1(32-36)-mediated angiogenic capability under high glucose treatment. RESULTS: We demonstrated that GLP-1(32-36) did not affect insulin secretion but could significantly rescue angiogenic function and blood perfusion in ischemic limb of streptozocin-induced T1DM mice, a function similar to its parental GLP-1. We also found that GLP-1(32-36) promotes angiogenesis in EPCs exposed to high glucose. Specifically, GLP-1(32-36) has a causal role in improving fragile mitochondrial function and metabolism via the GLP-1R-mediated pathway. We further demonstrated that GLP-1(32-36) rescued diabetic ischemic lower limbs by activating the GLP-1R-dependent eNOS (endothelial NO synthase)/cGMP/PKG (protein kinase G) pathway. CONCLUSIONS: Our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming toward glycolytic flux in partnership with GLP-1R for improved angiogenesis in high glucose-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral artery disease. REGISTRATION: URL: www.ebi.ac.uk/metabolights/; Unique identifier: MTBLS9543.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliales , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón , Glucólisis , Miembro Posterior , Isquemia , Ratones Endogámicos C57BL , Ratones Noqueados , Neovascularización Fisiológica , Transducción de Señal , Animales , Isquemia/tratamiento farmacológico , Isquemia/fisiopatología , Isquemia/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Neovascularización Fisiológica/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glucólisis/efectos de los fármacos , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/farmacología , Humanos , Miembro Posterior/irrigación sanguínea , Masculino , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/efectos de los fármacos , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/etiología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Células Cultivadas , Inductores de la Angiogénesis/farmacología , Fragmentos de Péptidos/farmacología , Ratones , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Modelos Animales de Enfermedad , Incretinas/farmacología , AngiogénesisRESUMEN
Increasing evidences suggest that mitochondrial dysfunction is implicated in diseases and aging, and whole-genome sequencing (WGS) is the most unbiased method in analyzing the mitochondrial genome (mtDNA). However, the genetic landscape of mtDNA in the Chinese population has not been fully examined. Here, we described the genetic landscape of mtDNA using WGS data from Chinese individuals (n = 3241). We identified 3892 mtDNA variants, of which 3349 (86%) were rare variants. Interestingly, we observed a trend toward extreme heterogeneity of mtDNA variants. Our study observed a distinct purifying selection on mtDNA, which inhibits the accumulation of harmful heteroplasmies at the individual level: (1) mitochondrial dN/dS ratios were much <1; (2) the dN/dS ratio of heteroplasmies was higher than homoplasmies; (3) heteroplasmies had more indels and predicted deleterious variants than homoplasmies. Furthermore, we found that haplogroup M (20.27%) and D (20.15%) had the highest frequencies in the Chinese population, followed by B (18.51%) and F (16.45%). The number of variants per individual differed across haplogroup groups, with a higher number of homoplasmies for the M lineage. Meanwhile, mtDNA copy number was negatively correlated with age but positively correlated with the female sex. Finally, we developed an mtDNA variation database of Chinese populations called MTCards (http://genemed.tech/mtcards/) to facilitate the query of mtDNA variants in this study. In summary, these findings contribute to different aspects of understanding mtDNA, providing a better understanding of the genetic basis of mitochondrial-related diseases.
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Genoma Mitocondrial , ADN Mitocondrial/genética , Femenino , Genoma Humano/genética , Genoma Mitocondrial/genética , Humanos , Mitocondrias/genética , Secuenciación Completa del GenomaRESUMEN
Biomolecular and physical cues of the extracellular matrix environment regulate collective cell dynamics and tissue patterning. Nonetheless, how the viscoelastic properties of the matrix regulate collective cell spatial and temporal organization is not fully understood. Here we show that the passive viscoelastic properties of the matrix encapsulating a spheroidal tissue of breast epithelial cells guide tissue proliferation in space and in time. Matrix viscoelasticity prompts symmetry breaking of the spheroid, leading to the formation of invading finger-like protrusions, YAP nuclear translocation and epithelial-to-mesenchymal transition both in vitro and in vivo in a Arp2/3-complex-dependent manner. Computational modelling of these observations allows us to establish a phase diagram relating morphological stability with matrix viscoelasticity, tissue viscosity, cell motility and cell division rate, which is experimentally validated by biochemical assays and in vitro experiments with an intestinal organoid. Altogether, this work highlights the role of stress relaxation mechanisms in tissue growth dynamics, a fundamental process in morphogenesis and oncogenesis.
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Células Epiteliales , Matriz Extracelular , Viscosidad , ElasticidadRESUMEN
BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.
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Biomarcadores , Glucemia , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Medición de Riesgo , Incidencia , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/sangre , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Triglicéridos/sangre , Factores de Riesgo Cardiometabólico , Estudios Transversales , Valor Predictivo de las Pruebas , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVES: To determine the value of the whole-blood inflammatory response index as an emerging biomarker for the assessment of disease activity in osteoarthritis (OA). METHODS: Extensive analysis of the literature on OA and whole-blood inflammatory indicators were provided through a bibliometric approach. Clinical characteristics and indicators of OA patients and healthy controls (HC) were retrospectively analysed. Four whole-blood inflammatory response indices - neutrophil/lymphocyte count (NLR), platelet/lymphocyte count (PLR), monocyte/lymphocyte count (MLR), and systemic inflammation response index (SIRI), as well as clinical traits like the OA patient's self-perception and immune-inflammatory indicators were analysed for correlations. Cut-off values were determined using receiver operating characteristic (ROC) curves, and they were subsequently employed in logistic regression models to work out whole-blood inflammatory indices and disease activity. RESULTS: The pathophysiology of osteoarthritis has received most of the spotlight in literature studies of OA and whole-blood inflammation indicators. The "inflammation", "osteoarthritis" and "disease activity" were the top 3 key word clusters. Retrospective analysis showed that MLR, NLR, PLR, and SIRI were markedly higher in OA subjects compared to HC subjects. ROC curve consequences manifested that SIRI and NLR could separate OA from healthy controls. NLR, PLR, MLR, and SIRI proved to be related to immune-inflammatory markers, visual analogue scale (VAS) scores, and short-form (SF)-36 scores with regard to correlation analysis and association criteria. Logistic regression manifested that SIRI, NLR, and C-reactive protein (CRP) forecasted disease activity, however, the model that combined SIRI and CRP was superior to CRP alone. CONCLUSIONS: SIRI may serve as a non-invasive, appropriate biomarker to correlate with disease activity.
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Linfocitos , Osteoartritis , Humanos , Estudios Retrospectivos , Biomarcadores , Recuento de Leucocitos , Inflamación/diagnóstico , Proteína C-Reactiva/análisis , Osteoartritis/diagnósticoRESUMEN
ABSTRACTLittle is known about gender differences in the symptom burden of people living with HIV/AIDS (PLWHA) on antiretroviral therapy in China. This study was conducted based on a biopsychosocial-medical model to describe gender differences in symptom burden among 1035 PLWHA in Yunnan Province, China. After propensity score matching, 798 PLWHA were included in this analysis. Feeling stressed, poor sleep, and memory loss were the most burdensome symptoms among men, while feeling stressed, memory loss, and dizziness were the most burdensome symptoms among women. Among men PLWHA, factors associated with symptom burden were being of the ethnic minority, CD4 count ≥ 500 cells/mm3, physical functioning, and social support. Among women PLWHA, factors associated with symptom burden were being an inpatient, physical functioning, psychological functioning, and social support. Our findings suggest that healthcare providers need to take into account gender differences when developing optimal prevention, treatment, and care programs that provide individualized care to reduce patients' symptom burden.
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Infecciones por VIH , Apoyo Social , Humanos , Masculino , Femenino , China/epidemiología , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Factores Sexuales , Persona de Mediana Edad , Costo de Enfermedad , Recuento de Linfocito CD4 , Calidad de Vida , Fármacos Anti-VIH/uso terapéutico , Estrés Psicológico/psicología , Carga SintomáticaRESUMEN
BACKGROUND: The adverse events (AEs) after a Coronavirus disease 2019 (Covid-19) Pfizer-Biotech mRNA vaccination present a medical and epidemiological issue of increasing interest. Headache is the most frequent neurological adverse effect and generally the third most common adverse event after a Covid-19 vaccination, but only a few studies focus on the link between headache and other AEs after vaccination. This study aims to investigate the correlation between headaches and Covid-19 vaccination, as well as the possible links between headaches and other AEs after Covid-19 vaccination, thereby helping the management of AEs and avoiding further occurrences. METHODS: This study is based on a published questionnaire survey of 1,402 healthcare workers. Our study focused on the 5 questions including 12 AEs and headaches extracted from the questionnaire post the first and second Covid-19 vaccination. The severity of the 12 AEs and headaches could be classified by the participants on a five-step scale: "Not at all", "Little", "Average", "Quite", and "Very" (abbreviated as "N", "L", "A", "Q", "V"). We used the Bowker test to study the comparison of headache severity, indicated on a 5-point Likert scale between the first and second vaccinations. We applied an ordinal logistic regression to the 5 categories with headache severity serving as the dependent variable and the ratings of the other 12 AEs serving as the independent variable to further explore to what extent the severity of the 12 AEs is associated with the severity of headaches. Receiver Operating Characteristic (ROC) analysis was conducted to evaluate the predictive value of the ratings of the 12 AEs to headache severity. RESULTS: We found that participants rated their headaches as more severe after the second vaccination, and participants who reported experiencing fatigue, flu-like symptoms, pain at the injection site, known tension-type headache, fever, dizziness/balance problems and known migraine are associated with headache symptoms. CONCLUSIONS: There are clusters of headache-associated AEs post Covid-19 vaccination. The association of various AEs with headaches may be due to similar causative mechanisms.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Cefalea/epidemiología , Cefalea/etiología , Encuestas y Cuestionarios , Vacunación/efectos adversosRESUMEN
The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet ß-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of ß-cell mass is through the generation and transplantation of new ß-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous ß-cell proliferation, reprogramming non-ß-cells to ß-like cells, and harvesting islets from genetically engineered animals. Together these approaches form a rich pipeline of therapeutic development for pancreatic regeneration.
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Páncreas/fisiología , Regeneración/fisiología , Medicina Regenerativa/métodos , Células Madre Adultas/citología , Células Madre Adultas/trasplante , Animales , Proliferación Celular , Reprogramación Celular , Humanos , Islotes Pancreáticos/citología , Islotes Pancreáticos/crecimiento & desarrollo , Islotes Pancreáticos/patología , Islotes Pancreáticos/fisiología , Páncreas/citología , Páncreas/crecimiento & desarrollo , Páncreas/patología , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/trasplanteRESUMEN
Change history: In this Insight Review, '1989' has been changed to '1998' in the sentence "This deep understanding of pancreatic development was put to the service of regenerative medicine in 1998, when human embryonic stem cells (hES cells) were successfully cultured and opened the door to developing methods of deriving pancreatic islets from hES cells66.". This error has been corrected online.
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Copper (Cu) is a necessary mineral nutrient for plant growth and development and is involved in several morphological, physiological, and biochemical processes; however, high concentrations of Cu can negatively impact these processes. The role of stomata in responding to various biotic and abiotic stimuli has not been studied in Bruguiera gymnorhiza, particularly in terms of their coordinated interactions at the molecular, physiological, and biochemical levels. Moreover, numerous plants employ strategies such as the presence of thick waxy cuticles on their leaf epidermis and the closing of stomata to reduce water loss. Thus, this study investigates the accumulation of Cu in B. gymnorhiza and its effect on leaf morphology and the molecular response under different Cu treatments (0, 200, and 400â¯mgâ¯L⻹, Cu0, Cu200, and Cu400, respectively) during a two years stress period. The results show that Cu stress affected accumulation and transport, increased the activities of peroxidase and ascorbate peroxidase, concentrations of soluble sugar, proline, and H2O2, and decreased the activity of catalase and content of malondialdehyde. Also, Cu-induced stress decreased the uptake of phosphorus and nitrogen and inhibited plant photosynthesis, which consequently led to reduced plant growth. Scanning electron microscopy combined with gas chromatography-mass spectrometry showed that B. gymnorhiza leaves had higher wax crystals and compositions under increased Cu stress, which forced the leaf's stomata to be closed. Also, the contents of alkanes, alcohols, primary alcohol levels (C26:0, C28:0, C30:0, and C32:0), n-Alkanes (C29 and C30), and other wax loads were significantly higher, while fatty acid (C12, C16, and C18) was lower in Cu200 and Cu400 compared to Cu0. Furthermore, the transcriptomic analyses revealed 1240 (771 up- and 469 downregulated), 1000 (723 up- and 277 down-regulated), and 1476 (808 up- and 668 downregulated) differentially expressed genes in Cu0 vs Cu200, Cu0 vs Cu400, and Cu200 vs Cu400, respectively. RNA-seq analyses showed that Cu mainly affected eight pathways, including photosynthesis, cutin, suberin, and wax biosynthesis. This study provides a reference for understanding mangrove response to heavy metal stress and developing novel management practices.
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Cobre , Hojas de la Planta , Estomas de Plantas , Ceras , Cobre/toxicidad , Hojas de la Planta/efectos de los fármacos , Estomas de Plantas/efectos de los fármacos , Estomas de Plantas/fisiología , Estrés Fisiológico/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Onagraceae/efectos de los fármacos , Onagraceae/fisiología , Transcriptoma/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacosRESUMEN
PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.
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Blastocisto , Nacimiento Vivo , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Índice de Embarazo , Transferencia de Embrión , Criopreservación , VitrificaciónRESUMEN
As an economical solar energy conversion technology, organic photovoltaics (OPVs) are regarded as a promising solution to environmental problems and energy challenges. With the highest efficiency of OPVs exceeding 20%, the research focus will shift from efficiency-oriented aspects to commercialization-oriented aspects in the near future. Semi-transparent OPVs (STOPVs) are one of the most possible commercialized forms of OPVs, and have achieved power conversion efficiency over 14% with average visible light transmittance over 20% so far. In this tutorial review, we first systematically summarize the device structures, operating principles and evaluation parameters of STOPVs, and compare them with those of opaque OPVs. Then, strategies to construct high-performance STOPVs by cooperatively optimizing materials and devices are proposed. Methods to realize the scale-up of STOPVs in terms of minimization of electrode and interconnect resistance are summarized. The potential applications of STOPVs in multifunctional windows, agrivoltaics and floating photovoltaics are also discussed. Finally, this review highlights major challenges and research directions that need to be addressed prior to the future commercialization of STOPVs.
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OBJECTIVES: We aimed to assess the sleep quality of patients with primary Sjögren's syndrome (pSS) and the associated factors. Moreover, Preliminary exploration of the clinical significance of serum brain-derived neurotrophic factor (BDNF) in pSS patients with sleep disorders. METHODS: A self-report survey was administered to 111 pSS patients and 40 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. General clinical information,the sleep quality and mental conditions were collected using on-site questionnaires and various scales. 40 healthy controls from the health examination center of the same hospital, who were age and sex matched. Detection of serum BDNF levels by ELISA method . Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Patients with pSS had higher scores on the PSQI than the healthy individuals. Abnormal sweating, high PHQ-9 and ESSPRI scores were independent risk factors for sleep disorders. pSS patients had lower serum BDNF than the healthy individuals, The area under the curve (AUC) of predicting sleep disorder in pSS patients using detection of serum BDNF level was 0.8470, and the sensitivity and specificity were 0.951 and 0.727, which were superior to PHQ-9 and GAD-7. CONCLUSION: Compared with the healthy individuals, pSS patients had a higher prevalence of sleep disorders and lower serum BNDF. Serum BDNF level demonstrated greater predictive advantage for sleep disorder in pSS patients.
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Objective: To identify inflamm-aging related biomarkers in osteoarthritis (OA). Methods: Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Results: A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1ß levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1ß, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model. Conclusion: FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.
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Envejecimiento , Biomarcadores , Biología Computacional , Aprendizaje Automático , Osteoartritis , Humanos , Osteoartritis/genética , Osteoartritis/diagnóstico , Osteoartritis/metabolismo , Biomarcadores/metabolismo , Biomarcadores/sangre , Biología Computacional/métodos , Envejecimiento/genética , Inflamación/genética , Inflamación/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Senescencia Celular/genética , Sirtuina 3/genética , Sirtuina 3/metabolismo , Perfilación de la Expresión Génica , Anciano , MasculinoRESUMEN
This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLâ ¡, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLâ ¡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.
Asunto(s)
Condrocitos , Medicamentos Herbarios Chinos , Osteoartritis , Ratas Sprague-Dawley , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Osteoartritis/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Ratas , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Masculino , Senescencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Cápsulas , Humanos , Apoptosis/efectos de los fármacosRESUMEN
Amyloidosis is a rare disease. This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom. The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough, sputum production, acid reflux, belching, and abdominal pain. Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis. Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx. Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue. The patient tested positive for anti-amyloid A antibodies, Congo red staining (+), and periodate Schiff staining (+). Amyloidosis commonly affects the digestive system and may have various etiologies, often presenting with symptoms that overlap with other digestive system diseases, leading to frequent misdiagnosis and missed optimal treatment opportunities. The hypopharynx, a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts, can be effectively evaluated for amyloidosis using digestive endoscopy.
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Amiloidosis , Hipofaringe , Humanos , Amiloidosis/diagnóstico , Amiloidosis/diagnóstico por imagen , Hipofaringe/patología , Hipofaringe/diagnóstico por imagen , Masculino , Endoscopía del Sistema Digestivo/métodosRESUMEN
The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2E2/E3 that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2E2/E3 functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3'UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2-repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2E2/E3 is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression-free and disease-specific survival in PCa patients. These findings show a novel autoenhancing EZH2-circEZH2E2/E3 -miR363/miR708-EZH2 regulatory loop, by which circEZH2E2/E3 plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.
Asunto(s)
MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , ARN Circular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/patología , Proliferación Celular/genética , Proteínas Activadoras de ras GTPasa/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: The homeodomain-containing transcription factor NANOG is overexpressed in prostate adenocarcinoma (PCa) and predicts poor prognosis. The SOX family transcription factor SOX9, as well as the transcription co-activator HMGB3 of the HMGB family, are also overexpressed and may play pivotal roles in PCa. However, it is unknown whether SOX9 and HMGB3 interact with each other, or if they regulate NANOG gene transcription. METHODS: We identified potential SOX9 responsive elements in NANOG promoter, and investigated if SOX9 regulated NANOG transcription in co-operation with HMGB3 by experimental analysis of potential SOX9 binding sites in NANOG promoter, reporter gene transcription assays with or without interference or artificial overexpression of SOX9 and/or HMGB3, and protein-binding assays of SOX9-HMGB3 interaction. Clinicopathologic and prognostic significance of SOX9-HMGB3 overexpression in PCa was analyzed. RESULTS: SOX9 activated NANOG gene transcription by preferentially binding to a highly conserved consensus cis-regulatory element (-573 to -568) in NANOG promoter, and promoted the expression of NANOG downstream oncogenic genes. Importantly, HMGB3 functioned as a partner of SOX9 to co-operatively enhance transactivation of NANOG by interacting with SOX9, predominantly via the HMG Box A domain of HMGB3. Overexpression of SOX9 and/or HMGB3 enhanced PCa cell survival and cell migration and were significantly associated with PCa progression. Notably, Cox proportional regression analysis showed that co-overexpression of both SOX9 and HMGB3 was an independent unfavorable prognosticator for both CRPC-free survival (relative risk [RR] = 3.779ï¼95% confidence interval [CI]: 1.159-12.322, p = 0.028) and overall survival (RR = 3.615ï¼95% CI: 1.101-11.876, p = 0.034). CONCLUSIONS: These findings showed a novel SOX9/HMGB3/NANOG regulatory mechanism, deregulation of which played important roles in PCa progression.