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Electroactive organic electrode materials exhibit remarkable potential in aqueous zinc ion batteries (AZIBs) due to their abundant availability, customizable structures, sustainability, and high reversibility. However, the research on AZIBs has predominantly concentrated on unraveling the storage mechanism of zinc cations, often neglecting the significance of anions in this regard. Herein, bipolar poly(thionine) is synthesized by a simple and efficient polymerization reaction, and the kinetics of different anions are investigated using poly(thionine) as the cathode of AZIBs. Notably, poly(thionine) is a bipolar organic polymer electrode material and exhibits enhanced stability in aqueous solutions compared to thionine monomers. Kinetic analysis reveals that ClO4 - exhibits the fastest kinetics among SO4 2-, Cl-, and OTF-, demonstrating excellent rate performance (109 mAh g-1 @ 0.5 A g-1 and 92 mAh g-1 @ 20 A g-1). Mechanism studies reveal that the poly(thionine) cathode facilitates the co-storage of both anions and cations in Zn(ClO4)2. Furthermore, the lower electrostatic potential of ClO4 - influences the strength of hydrogen bonding with water molecules, thereby enhancing the overall kinetics in aqueous electrolytes. This work provides an effective strategy for synthesizing high-quality organic materials and offers new insights into the kinetic behavior of anions in AZIBs.
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Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.
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Colecalciferol , Pez Cebra , Animales , Femenino , Colecalciferol/farmacología , Vitelogeninas/genética , Atresia Folicular , Vitamina D , Hormonas Esteroides Gonadales , OocitosRESUMEN
AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.
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Glucemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Persona de Mediana Edad , Glucemia/análisis , Estudios de Seguimiento , Estudios Prospectivos , Factores de Riesgo , Pronóstico , Anciano , Hemoglobina Glucada/análisis , Automonitorización de la Glucosa Sanguínea , Causas de Muerte , Biomarcadores/análisis , Biomarcadores/sangre , Ritmo Circadiano/fisiología , Hipoglucemia/mortalidad , Tasa de Supervivencia , AdultoRESUMEN
To ensure prolonged functionality of transpiration-driven electrokinetic power generators (TEPGs) in saltwater environments, it is imperative to mitigate salt accumulation. This study presents a salt pathway transpiration-driven electrokinetic power generator (SPTEPG), incorporating MXene, graphene oxide (GO), and carbon nanotubes (CNTs) as active materials, along with cellulose nanofibers (CNF) and poly(vinyl alcohol) (PVA) as aqueous binders and nonwoven fabrics. This unique combination confers exceptional hydrophilicity and enhances the energy generation performance. When tested with deionized water, the SPTEPG achieved a maximum voltage of 0.6 V and a current of 4.2 µA. In simulated seawater conditions, the presence of conductive ions in the solution boosted these values to 0.64 V and 42 µA. The incorporation of the salt pathway mechanism facilitates the return of excess salt deposits to the bulk solution, thus extending the SPTEPG's service life in saltwater environments. This research offers a straightforward yet effective strategy for designing transpiration-driven power generators suitable for saline water applications.
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INTRODUCTION: Ischemic stroke (IS) is a global health concern, often tied to dyslipidemia and vascular endothelial dysfunction. MicroRNA-34a (miR-34a) was reported to be up-regulated in the blood samples of patients with IS, but the specific role of miR-34a and methylenetetrahydrofolate reductase (MTHFR) in IS remains to be elucidated. METHODS: We studied 143 subjects: 71 IS patients, and 72 healthy controls. Human umbilical vein endothelial cells (HUVECs) were cultured and transfected with a miR-34a mimic, inhibitor, or negative control. The miR-34a expression in serum and HUVECs was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Viability and apoptosis of HUVECs were assessed using CCK-8 assay and flow cytometry. The expression levels of bcl-2, bax, cyt-c, cleaved caspase 3, MTHFR, and homocysteine were measured by Western blot or enzyme-linked immunosorbent assay (ELISA). The relationship between miR-34a and MTHFR was verified by luciferase reporter assay. The levels of MTHFR and homocysteine in serum were examined by ELISA. RESULTS: MiR-34a expression was increased in IS patients and inhibited viability of HUVECs while promoting their apoptosis. Overexpression of miR-34a up-regulated pro-apoptotic proteins (bax, cyt-c and cleaved caspase 3) and down-regulated anti-apoptotic protein bcl-2 in HUVECs. MTHFR was identified as the downstream target of miR-34a and its expression was reduced by miR-34a overexpression, while homocysteine levels increased. Consistently, MTHFR levels were lower and homocysteine levels were higher in IS patients compared with controls. DISCUSSION: Our results suggest that up-regulated miR-34a plays a role in the pathogenesis of IS, potentially through inhibiting MTHFR expression and increasing homocysteine in endothelial cells. Therefore, miR-34a might be a therapeutic target for IS.
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Apoptosis , Supervivencia Celular , Homocisteína , Accidente Cerebrovascular Isquémico , Metilenotetrahidrofolato Reductasa (NADPH2) , MicroARNs , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Homocisteína/sangre , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/patología , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , MicroARNs/metabolismo , MicroARNs/genéticaRESUMEN
BACKGROUND: Vaginectomy has been shown to be effective for select patients with vaginal high-grade squamous intraepithelial lesions (HSIL) and is favored by gynecologists, while there are few reports on the robotic-assisted laparoscopic vaginectomy (RALV). The aim of this study was to evaluate the safety and treatment outcomes between RALV and the conventional laparoscopic vaginectomy (CLV) for patients with vaginal HSIL. METHODS: This retrospective cohort study was conducted in 109 patients with vaginal HSIL who underwent either RALV (RALV group) or CLV (CLV group) from December 2013 to May 2022. The operative data, homogeneous HPV infection regression rate and vaginal HSIL regression rate were compared between the two groups. Student's t-test, the Mann-Whitney U test, Pearson χ2 test or the Fisher exact test, Kaplan-Meier survival analysis and Cox proportional-hazards models were used for data analysis. RESULTS: There were 32 patients in the RALV group and 77 patients in the CLV group. Compared with the CLV group, patients in the RALV group demonstrated less estimated blood loss (41.6 ± 40.3 mL vs. 68.1 ± 56.4 mL, P = 0.017), lower intraoperative complications rate (6.3% vs. 24.7%, P = 0.026), and shorter flatus passing time (2.0 (1.0-2.0) vs. 2.0 (2.0-2.0), P < 0.001), postoperative catheterization time (2.0 (2.0-3.0) vs. 4.0 (2.0-6.0), P = 0.001) and postoperative hospitalization time (4.0 (4.0-5.0) vs. 5.0 (4.0-6.0), P = 0.020). In addition, the treatment outcomes showed that both RALV group and CLV group had high homogeneous HPV infection regression rate (90.0% vs. 92.0%, P > 0.999) and vaginal HSIL regression rate (96.7% vs. 94.7%, P = 0.805) after vaginectomy. However, the RALV group had significantly higher hospital costs than that in the CLV group (53035.1 ± 9539.0 yuan vs. 32706.8 ± 6659.2 yuan, P < 0.001). CONCLUSIONS: Both RALV and CLV can achieve satisfactory treatment outcomes, while RALV has the advantages of less intraoperative blood loss, fewer intraoperative complications rate and faster postoperative recovery. Robotic-assisted surgery has the potential to become a better choice for vaginectomy in patients with vaginal HSIL without regard to the burden of hospital costs.
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Laparoscopía , Infecciones por Papillomavirus , Procedimientos Quirúrgicos Robotizados , Lesiones Intraepiteliales Escamosas , Femenino , Embarazo , Humanos , Estudios Retrospectivos , Colpotomía , Pérdida de Sangre QuirúrgicaRESUMEN
BACKGROUND: The Onyx™ Liquid Embolic System is a non-adhesive liquid embolic agent, which has been proved by the US FDA for embolization of lesions in the peripheral and neurovasculature since 2005. We reported a case of ischemic optic neuropathy after using Onyx-18 to embolize the anterior ethmoid arteries that feeding dural arteriovenous fistulas (DAVF). CASE PRESENTATION: A 57-year-old Asian male presented with anterior cranial fossa DAVF underwent embolotherapy by delivering Onyx-18 through a microcatheter into the anterior ethmoid arteries under angiography guidance. The interventional procedure was successful and no clear evidence was found pointing to untargeted occlusive embolus. But after the surgery the patient experienced delayed painless vision loss in the right eye (RE). The fundoscopy showed unilateral papilledema with pale optic disc in RE, accompanied by significant edema and thickening in the retinal nerve fiber layer (RNFL) of macula. The fundus fluorescence angiography showed that most of the optic disc in RE had postponed or absent fluorescence filling. Visual evoked potential (VEP) confirmed that the amplitude of the P100 component was decreased in RE without significant prolongation of the latency. The patient was diagnosed with anterior ischemic optic neuropathy, but immediate pulse steroid therapy failed to rescue his vision. CONCLUSION: Preoperative evaluation of the patient's hemodynamic status and fundus examination are essential for assessing the risk of ischemic ocular complications, and the non-adhesive liquid embolic agent Onyx-18 should be used cautiously during endovascular embolization of intracranial artery.
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Malformaciones Vasculares del Sistema Nervioso Central , Arterias Ciliares , Embolización Terapéutica , Polivinilos , Humanos , Masculino , Persona de Mediana Edad , Embolización Terapéutica/métodos , Embolización Terapéutica/efectos adversos , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico , Polivinilos/uso terapéutico , Neuropatía Óptica Isquémica/etiología , Neuropatía Óptica Isquémica/diagnóstico , Dimetilsulfóxido/efectos adversos , Dimetilsulfóxido/administración & dosificación , Angiografía con Fluoresceína , Combinación de Medicamentos , TantalioRESUMEN
Anterior and inferior ST elevation on electrocardiography (ECG) in patients with acute myocardial infarction is uncommon. ST-segment elevation due to right ventricular infarction induced by right coronary occlusion may extend from V1 to V3/V4, resembling the pattern of transmural ischemia of the anterior wall of the left ventricle. In addition, a wraparound left anterior descending (LAD) artery can produce ischemia manifesting as ST-segment elevation in the anterior and inferior leads. Our case report reveals dynamic ST-segment changes in acute inferior myocardial infarction, including the appearance of the shark fin ECG pattern, unlike what has been reported before.
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Electrocardiografía , Humanos , Masculino , Infarto de la Pared Inferior del Miocardio/fisiopatología , Infarto de la Pared Inferior del Miocardio/diagnóstico , Infarto de la Pared Inferior del Miocardio/complicaciones , Diagnóstico Diferencial , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/complicaciones , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5-10 on various types of cerebrovascular disease. METHODS: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. RESULTS: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10⯵g/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10⯵g/m3 rise in PM2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. CONCLUSIONS: Short-term exposures to both PM2.5 and PM2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.
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Contaminantes Atmosféricos , Trastornos Cerebrovasculares , Estudios Cruzados , Material Particulado , Material Particulado/análisis , Material Particulado/toxicidad , Humanos , Masculino , China/epidemiología , Femenino , Persona de Mediana Edad , Anciano , Trastornos Cerebrovasculares/mortalidad , Trastornos Cerebrovasculares/inducido químicamente , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/efectos adversos , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Tamaño de la Partícula , Anciano de 80 o más Años , Adulto , Estaciones del AñoRESUMEN
A molecularly imprinted electrochemiluminescent sensor is developed for the sensitive detection of tetracycline in environmental and food samples. The sensor uses an ionic liquid (i.e. [APMIM]Br) modified graphene-carbon nanotube composite (GMI) material as substrate, a double-layered core-shell metal-organic framework NH2-UiO-66@ZIF-8 (NUZ) loaded bipyridyl ruthenium (NUZ@Ru) as luminescent material, and a molecularly imprinted copolymer of o-phenylenediamine and hydroquinone as recognition element. The ionic liquid-modified graphene-carbon nanotube composite has a favorable three-dimensional structure, high specific surface area, and good hydrophilicity; the core-shell structured metal-organic framework has high stability and plentiful reaction sites for loading; the molecularly imprinted copolymer film has enhanced stability and recognition effect. Hence, the resulting sensor combines the merits of several materials and presents improved performance. Under the optimum detection conditions, it shows a wide linear range of 0.05 µM - 1 mM, a low detection limit of 20 nM, high selectivity, and excellent stability. It has been successfully applied to the detection of tetracycline in different samples.
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Técnicas Electroquímicas , Límite de Detección , Mediciones Luminiscentes , Estructuras Metalorgánicas , Polímeros Impresos Molecularmente , Tetraciclina , Tetraciclina/análisis , Tetraciclina/química , Polímeros Impresos Molecularmente/química , Estructuras Metalorgánicas/química , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Grafito/química , Nanotubos de Carbono/química , Contaminación de Alimentos/análisis , Líquidos Iónicos/química , Antibacterianos/análisis , Antibacterianos/química , Contaminantes Químicos del Agua/análisis , Impresión MolecularRESUMEN
In order to evaluate the effects of the interaction between different proteins and feeding frequency on largemouth bass (Micropterus salmoides) and to provide scientific guidance for the application of novel proteins and the corresponding optimal feeding strategy, a two-factorial design (5 × 3) with five protein feeds (fishmeal (FM), Clostridium autoethanogenum protein (CAP), Tenebrio molitor (TM), Chlorella meal (ChM), cottonseed protein concentrate (CPC)), and three feeding frequency (1, 2, and 3 times/d; FF1, FF2, FF3) was designed in culturing largemouth bass (initial weight, 2.98 ± 0.22 g/fish) for 8 weeks. Z-score combined with cluster analysis was used to analyze and compare the effects of different treatments on different indicators, such as growth performance, feed utilization, antioxidant capacity, and immune response to draw a general picture of the relationship among all these massive biomarkers. The results showed that different protein sources and feeding frequencies had significant interactive effects on growth performance, feed utilization efficiency, body lipid, and health status of largemouth bass. Fish fed with ChM feed showed similar performance to that in FM group, implying its potential for complete replacement of fishmeal in largemouth bass. Fish fed with CAP, TM, and CPC feeds showed worse performance compared to FM and ChM groups, characterized by poor growth and feed utilization, enhanced stress, chronic inflammation, and varying symptoms of histological changes in the liver and intestine, which demonstrated the adverse effects of the complete replacement of fishmeal by these three proteins. In terms of feeding frequency, fish fed with FM feed in FF3 group led to liver hypertrophy, fat accumulation, and the risk of fatty liver, while inducing liver inflammation. In addition, the TM and CAP group had the higher expression levels of inflammatory factors at FF3 group, which displayed that the interactions between FM, CAP, TM feeds and feeding frequency at FF3 might aggravate the occurrence of liver inflammation and oxidative damage of hepatocytes. Overall, FF2 had higher feed efficiency, protein efficiency, antioxidant enzyme and lysozyme activities, lower MDA content, and lower gene expression of inflammatory cytokines and could be considered as the optimum feeding frequency for largemouth bass fed with different protein feeds.
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Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group ( P < 0.01); the peak time, half-wave width, threshold and maximum descending slope of the action potential were significantly higher than those in the control group ( P < 0.01). The time-frequency energy values of LFPs signals in the θ and γ bands of mice in the ischemia and reperfusion groups were significantly reduced ( P < 0.01), and the time-frequency energy values in the reperfusion group were increased compared with the ischemia group ( P < 0.01). The signal complexity of LFPs in the ischemia and reperfusion group was significantly reduced ( P < 0.05), and the signal complexity in the reperfusion group was increased compared with the ischemia group ( P < 0.05). In summary, cerebral ischemia-reperfusion reduced the excitability of nerve cells in the DG area of the mouse hippocampus; cerebral ischemia reduced the discharge activity and signal complexity of nerve cells, and the electrophysiological indicators recovered after reperfusion, but it failed to reach the healthy state during the experiment period.
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Isquemia Encefálica , Giro Dentado , Daño por Reperfusión , Animales , Giro Dentado/fisiopatología , Ratones , Daño por Reperfusión/fisiopatología , Isquemia Encefálica/fisiopatología , Potenciales de Acción , Potenciales de la Membrana , Modelos Animales de Enfermedad , Hipocampo/fisiopatología , Infarto Cerebral/fisiopatología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Masculino , Neuronas , ReperfusiónRESUMEN
The DOMAINS REARRANGED METHYLTRANSFERASEs (DRMs) are crucial for RNA-directed DNA methylation (RdDM) in plant species. Setaria viridis is a model monocot species with a relatively compact genome that has limited transposable element (TE) content. CRISPR-based genome editing approaches were used to create loss-of-function alleles for the two putative functional DRM genes in S. viridis to probe the role of RdDM. Double mutant (drm1ab) plants exhibit some morphological abnormalities but are fully viable. Whole-genome methylation profiling provided evidence for the widespread loss of methylation in CHH sequence contexts, particularly in regions with high CHH methylation in wild-type plants. Evidence was also found for the locus-specific loss of CG and CHG methylation, even in some regions that lack CHH methylation. Transcriptome profiling identified genes with altered expression in the drm1ab mutants. However, the majority of genes with high levels of CHH methylation directly surrounding the transcription start site or in nearby promoter regions in wild-type plants do not have altered expression in the drm1ab mutant, even when this methylation is lost, suggesting limited regulation of gene expression by RdDM. Detailed analysis of the expression of TEs identified several transposons that are transcriptionally activated in drm1ab mutants. These transposons are likely to require active RdDM for the maintenance of transcriptional repression.
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Setaria (Planta) , Metilación de ADN/genética , Regulación de la Expresión Génica de las Plantas/genética , Metiltransferasas/genética , Setaria (Planta)/genética , TranscriptomaRESUMEN
Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA.
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Atherosclerosis is a complex pathological process that results from the chronic inflammatory reaction of the blood vessel wall and involves various immune cells and cytokines. An imbalance in the proportion and function of the effector CD4+ T-cell (Teff) and regulatory T-cell (Treg) subsets is an important cause of the occurrence and development of atherosclerotic plaques. Teff cells depend on glycolytic metabolism and glutamine catabolic metabolism for energy, while Treg cells mainly rely on fatty acid oxidation (FAO), which is crucial for determining the fate of CD4+ T cells during differentiation and maintaining their respective immune functions. Here, we review recent research achievements in the field of immunometabolism related to CD4+ T cells, focusing on the cellular metabolic pathways and metabolic reprogramming involved in the activation, proliferation, and differentiation of CD4+ T cells. Subsequently, we discuss the important roles of mTOR and AMPK signaling in regulating CD4+ T-cell differentiation. Finally, we evaluated the links between CD4+ T-cell metabolism and atherosclerosis, highlighting the potential of targeted modulation of CD4+ T-cell metabolism in the prevention and treatment of atherosclerosis in the future.
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BACKGROUND: Pathological cardiac hypertrophy is linked to immune-inflammatory injury, and regulatory T cells (Tregs) play a crucial role in suppressing immune-inflammatory responses. However, the precise role of Tregs in pathological cardiac hypertrophy remains unclear. OBJECTIVE: To summarize the current knowledge on the role and mechanisms of Tregs in pathological cardiac hypertrophy and explore their perspectives and challenges as a new therapeutic approach. RESULTS: Treg cells may play an important protective role in pressure overload (hypertension, aortic stenosis), myocardial infarction, metabolic disorders (diabetes, obesity), acute myocarditis, cardiomyopathy (hypertrophic cardiomyopathy, storage diseases), and chronic obstructive pulmonary disease-related pathological cardiac hypertrophy. Although some challenges remain, the safety and efficacy of Treg-based therapies have been confirmed in some clinical trials, and engineered antigen-specific Treg cells may have better clinical application prospects due to stronger immunosuppressive function and stability. CONCLUSION: Targeting the immune-inflammatory response via Treg-based therapies might provide a promising and novel future approach to the prevention and treatment of pathological cardiac hypertrophy.
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BACKGROUND: Although highly heterogeneous among countries, the incidence rates of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) have been increasing globally over the past two decades. To better understand the cause of these secular trends, this study aimed to investigate the effects of age, period, and birth cohort on LBW, PTB, and SGA rates in Shanghai. METHODS: Data from 2,958,695 singleton live births at 24-41 gestational weeks between 2004 and 2020 were obtained for this study. Age-period-cohort models based on Poisson regression were used to evaluate the independent effects of maternal age, delivery period, and maternal birth cohort on the trends in LBW, PTB, and SGA. RESULTS: The overall prevalence rates of LBW, PTB, and SGA were 2.9%, 4.7%, and 9.3%, respectively, and significant changes were observed (average annual change: + 10.7, + 9.1, -11.9) from 2004 to 2020. Cohort effect increased steadily, from 1960 (risk ratio [RR] = 0.71, 95% confidence interval [CI]: 0.65-0.78) to 1993 (RR = 0.97, 95% CI: 0.94-1.01) for LBW and from 1960 (RR = 0.69, 95% CI: 0.64-0.75) to 2004 (RR = 1.02, 95% CI: 0.94-1.12) for PTB. A strong cohort effect was found with the highest risk of SGA (RR = 1.82, 95% CI: 1.72-1.93) in 1960 and the lowest risk (RR = 0.57, 95% CI: 0.54-0.61) in 2004, compared with the reference cohort of 1985. There was a "U-shaped" maternal age effect on LBW and PTB and a weak period effect on the three birth outcomes. CONCLUSIONS: Our findings suggested a significant independent effect of age, period, and birth cohort on the three birth outcomes. The increasing rates of LBW and PTB motivated us to focus on young and advanced pregnant women. Meanwhile, the prevalence of SGA decreased steadily, illustrating the need for further research on the mechanisms underlying these trends.
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Nacimiento Prematuro , Recién Nacido , Femenino , Embarazo , Humanos , Nacimiento Prematuro/epidemiología , Edad Gestacional , China/epidemiología , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Estudios de Cohortes , Peso al Nacer , Factores de RiesgoRESUMEN
Wellen's syndrome, a STEMI equivalent, is associated with severe stenosis of the proximal left anterior descending (LAD) in a patient with chest pain who needs emergency coronary angiography with the possibility of intervention. Due to only T wave changes in the electrocardiograph (ECG), Wellen's syndrome was easily ignored. Moreover, it may progress to acute myocardial infarction or even cardiac arrest. Therefore, clinicians should improve their understanding of this ECG pattern and appropriately dilate the coronary angiography indication. In addition, more dangerous narrowing of a coronary artery, as in our case, the left main artery stenosis, should also be considered.
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Electrocardiografía , Paro Cardíaco , Humanos , Constricción Patológica , Síndrome , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Paro Cardíaco/diagnóstico , Paro Cardíaco/etiología , Paro Cardíaco/terapiaRESUMEN
OBJECTIVE: To assess the association of rs55829688 and rs75315904 polymorphisms of the lncRNA-GAS5 gene with susceptibility to systemic lupus erythematosus (SLE) in Guangxi population. METHODS: Peripheral venous blood samples were collected from the SLE group and control group. Following extraction of genomic DNA, SNPscan and Sanger sequencing were carried out to determine the genotypes for the rs55829688 and rs75315904 loci of the lncRNA-GAS5 gene. RESULTS: No difference was found between the two groups with regard to the genotypic frequencies for rs55829688 and rs75315904 (P > 0.05). However, the frequencies of C allele of rs55829688 between the two groups was significantly different (P < 0.05). In the SLE group, the frequencies of C allele and CT+CC genotype for rs55829688 among SLE patients with nephritis were significantly lower than those of SLE patients without nephritis (P < 0.05). In addition, haplotype analysis showed that the frequency of rs55829688 C/rs75315904 A allele in the SLE group was lower than that of the control group (P < 0.05). CONCLUSION: In Guangxi population, the carrier status of rs55829688 C allele of the lncRNA-GAS5 gene may reduce the risk of SLE and its complicated nephritis, and the rs55829688 C/rs75315904 A haplotype may reduce the risk for SLE.
Asunto(s)
Lupus Eritematoso Sistémico , Nefritis , ARN Largo no Codificante , Humanos , Estudios de Casos y Controles , China/epidemiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/genéticaRESUMEN
We numerically investigate the transfer of optical information from a vector-vortex control beam to an unstructured probe beam, as mediated by an atomic vapour. The right and left circular components of these beams drive the atomic transitions of a double-V system, with the atoms acting as a spatially varying circular birefringent medium. Modeling the propagation of the light fields, we find that, for short distances, the vectorial light structure is transferred from the control field to the probe. However, for larger propagation lengths, diffraction causes the circular components of the probe field to spatially separate. We model this system for the D1 line of cold rubidium atoms and demonstrate that four wave mixing can lead to correlations between the optical polarization structure and the diffraction of light, generating coupled dynamics of the internal and external degrees of freedom.