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Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.
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Reparación del ADN , Ubiquitina-Proteína Ligasas , Humanos , Roturas del ADN de Doble Cadena , Histonas/metabolismo , Histonas/genética , Poliubiquitina/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
Magic-angle twisted bilayer graphene exhibits correlated phenomena such as superconductivity and Mott insulating states related to the weakly dispersing flat band near the Fermi energy. Such a flat band is expected to be sensitive to both the moiré period and lattice relaxations. Thus, clarifying the evolution of the electronic structure with the twist angle is critical for understanding the physics of magic-angle twisted bilayer graphene. Here we combine nano-spot angle-resolved photoemission spectroscopy and atomic force microscopy to resolve the fine electronic structure of the flat band and remote bands, as well as their evolution with twist angle from 1.07° to 2.60°. Near the magic angle, the dispersion is characterized by a flat band near the Fermi energy with a strongly reduced band width. Moreover, we observe a spectral weight transfer between remote bands at higher binding energy, which allows to extract the modulated interlayer spacing near the magic angle. Our work provides direct spectroscopic information on flat band physics and highlights the important role of lattice relaxations.
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OBJECTIVE: Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. METHODS: This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. RESULTS: In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). CONCLUSION: In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.
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Aterosclerosis , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/etiología , Resultado del Tratamiento , Estudios Retrospectivos , Trombectomía/efectos adversos , Accidente Cerebrovascular/etiología , Aterosclerosis/etiología , Colesterol , Isquemia Encefálica/etiologíaRESUMEN
Arsenic is a well-known environmental toxicant and emerging evidence suggests that arsenic exposure has potential skeletal muscle toxicity; however, the underlying mechanism has not yet been clarified. The aim of this study was to investigate the correlation among adverse effects of subchronic and chronic environmental arsenic exposure on skeletal muscle as well as specific myokines secretion and angiotensin II (AngII)-melatonin (MT) axis in rats. Four-week-old rats were exposed to arsenite (iAs) in drinking water at environmental relevant concentration of 10 ppm for 3 or 9 months. Results indicated that the gastrocnemius muscle had atrophied and its mass was decreased in rats exposed to arsenite for 9 months, whereas, they had no significant changes in rats exposed to arsenite for 3 months. The levels of serum-specific myokine irisin and gastrocnemius muscle insulin-like growth factor-1 (IGF-1) were increased in 3-month exposure group and decreased in 9-month exposure group, while serum myostatin (MSTN) was increased significantly in 9-month exposure group. In addition, serum AngII level increased both in 3- and 9-month exposure groups, while serum MT level increased in 3-month exposure group and decreased in 9-month exposure group. Importantly, the ratio of AngII to MT level in serum increased gradually with the prolongation of arsenite exposure. It showed a certain correlation between AngII-MT axis and gastrocnemius muscle mass, gastrocnemius muscle level of IGF-1 or serum levels of irisin and MSTN. In conclusion, the disruption of AngII-MT axis balance may be a significant factor for skeletal muscle atrophy induced by chronic environmental arsenic exposure.
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Arsénico , Arsenitos , Melatonina , Ratas , Animales , Angiotensina II , Factor I del Crecimiento Similar a la Insulina , Melatonina/farmacología , Arsenitos/toxicidad , Fibronectinas , Músculo Esquelético , AtrofiaRESUMEN
INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/tratamiento farmacológico , Análisis de la Aleatorización Mendeliana/métodos , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple/genética , Glutatión Transferasa/genética , Predisposición Genética a la Enfermedad/genética , MultiómicaRESUMEN
Antisense transcription of protein-coding genes has been increasingly recognized as an important regulatory mechanism of gene expression. However, less is known about the extent and importance of antisense transcription of noncoding genes. Here, we investigate the breadth and dynamics of antisense transcription of miRNAs, a class of important noncoding RNAs. Because the antisense transcript of a miRNA is likely to form a hairpin suitable as the substrate of ADARs, which convert adenosine to inosine in double-stranded RNAs, we used A-to-I RNA editing as ultrasensitive readout for antisense transcription of the miRNAs. Through examining the unstranded targeted RNA-seq libraries covering all miRNA loci in 25 types of human tissues, we identified 7275 editing events located in 81% of the antisense strand of the miRNA loci, thus uncovering the previously unknown prevalent antisense transcription of the miRNAs. We found that antisense transcripts are tightly regulated, and a substantial fraction of miRNAs and their antisense transcripts are coexpressed. Sense miRNAs have been shown to down-regulate the coexpressed antisense transcripts, whereas the act of antisense transcription, rather than the transcripts themselves, regulates the expression of sense miRNAs. RNA editing tends to decrease the miRNA accessibility of the antisense transcripts, therefore protecting them from being degraded by the sense-mature miRNAs. Altogether, our study reveals the landscape of antisense transcription and editing of miRNAs, as well as a previously unknown reciprocal regulatory circuit of sense-antisense miRNA pairs.
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Regulación de la Expresión Génica , MicroARNs/biosíntesis , ARN sin Sentido/biosíntesis , Adenosina/metabolismo , Humanos , Inosina/metabolismo , MicroARNs/química , MicroARNs/genética , MicroARNs/metabolismo , Edición de ARN , ARN sin Sentido/química , ARN sin Sentido/genética , ARN sin Sentido/metabolismo , RNA-SeqRESUMEN
Ambient fine particulate matter (PM2.5) has severe adverse health impacts, making it crucial to reduce PM2.5 exposure for public health. Meteorological and emissions factors, which considerably affect the PM2.5 concentrations in the atmosphere, vary substantially under different climate change scenarios. In this work, global PM2.5 concentrations from 2021 to 2100 were generated by combining the deep learning technique, reanalysis data, emission data, and bias-corrected CMIP6 future climate scenario data. Based on the estimated PM2.5 concentrations, the future premature mortality burden was assessed using the Global Exposure Mortality Model. Our results reveal that SSP3-7.0 scenario is associated with the highest PM2.5 exposure, with a global concentration of 34.5 µg/m3 in 2100, while SSP1-2.6 scenario has the lowest exposure, with an estimated of 15.7 µg/m3 in 2100. PM2.5-related deaths for individuals under 75 years will decrease by 16.3 and 10.5% under SSP1-2.6 and SSP5-8.5, respectively, from 2030s to 2090s. However, premature mortality for elderly individuals (>75 years) will increase, causing the contrary trends of improved air quality and increased total PM2.5-related deaths in the four SSPs. Our results emphasize the need for stronger air pollution mitigation measures to offset the future burden posed by population age.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Anciano , Contaminantes Atmosféricos/análisis , Cambio Climático , Contaminación del Aire/análisis , Material Particulado/análisis , Atmósfera/análisis , Mortalidad PrematuraRESUMEN
OBJECTIVE: To analyze the effect of a new type of tension-reduced suture named "double W tension-reduced suture technique" on the abdominal scars following the da Vinci robot-assisted gastrectomy for severely obese patients. METHODS: 40 abdominal incisions following the da Vinci robot-assisted gastrectomy on severely obese patients from September 1st, 2021 to March 1st, 2022 were comprised in the study. 20 incisions were closed by the conventional full-thickness surgical suture as the control group, and 20 incisions were sewn up by double W tension-reduced suture as the double W group. The scars were assessed at the 1-month follow-up visit using the Vancouver scar scale (VSS), ultrasound and patient satisfaction. Meanwhile, digital photographs of scars were taken as well. RESULTS: The VSS score was 6.80 ± 2.16 in the control group, while that of the double W group was 2.60 ± 1.89. The difference between groups was significant. Digital photographs showed that the scar color was not only light and close to the skin color, but also flat and soft in the double W group. Ultrasound showed that the fibers of subcutaneous tissue in the double W group were arranged neatly, the ultrasonic signal intensity was relatively uniform, and the tunnel was small without obvious lacunae. More patients were satisfied and very satisfied with scars in the double W group. CONCLUSION: Double W tension-reduced suture technique could significantly improve the appearance and reduce comorbidities of scars following the da Vinci robot-assisted gastrectomy for severely obese patients.
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Cicatriz , Robótica , Humanos , Cicatriz/etiología , Cicatriz/prevención & control , Obesidad/complicaciones , Obesidad/cirugía , Gastrectomía , Técnicas de SuturaRESUMEN
Sodium bicarbonate pretreatment and solid-state fermentation (SSF) were used to maximize the nutritional value of corn germ meal (CGM) by inoculating it with Bacillus velezensis CL-4 (isolated from chicken cecal contents and capable of degrading lignocellulose). Based on genome sequencing, B. velezensis CL-4 has a 4,063,558 bp ring chromosome and 46.27% GC content. Furthermore, genes associated with degradation of lignocellulose degradation were detected. Pretreatment of CGM (PCGM) with sodium bicarbonate (optimized to 0.06 g/mL) neutralized low pH. Fermented and pretreated CGM (FPCGM) contained more crude protein (CP), soluble protein of trichloroacetic acid (TCA-SP), and total amino acids (aa) than CGM and PCGM. Degradation rates of cellulose and hemicellulose were reduced by 21.33 and 71.35%, respectively, after 48 h fermentation. Based on electron microscopy, FPCGM destroys the surface structure and adds small debris of the CGM substrate, due to lignocellulose breakdown. Furthermore, 2-oxoadipic acid and dimethyl sulfone were the most important metabolites during pretreatment. Concentrations of adenosine, cytidine, guanosine, S-methyl-5'-thioadenosine, and adenine decreased significantly after 48 h fermentation, whereas concentrations of probiotics, enzymes, and fatty acids (including palmitic, 16-hydroxypalmitic, and linoleic acids) were significantly improved after fermentation. In conclusion, the novel pretreatment of CGM provided a proof of concept for using B. velezensis CL-4 to degrade lignocellulose components, improve nutritional characteristics of CGM, and expand CGM lignocellulosic biological feed production. KEY POINTS: ⢠Sodium bicarbonate (baking soda) can be used as an economical and green additive to pretreat corn germ meal; ⢠Fermentation with B. velezensis degrades the cellulose and hemicellulose component of corn germ meal and improves its feed quality; ⢠As a novel qualified presumption of safety (QPS) strain, B. velezensis should have broad potential applications in food and feed industries.
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Bicarbonato de Sodio , Zea mays , Bacillus , Celulosa/metabolismo , Fermentación , Lignina , Nutrientes , Bicarbonato de Sodio/metabolismo , Zea mays/metabolismoRESUMEN
m6A is a prevalent internal modification in mRNAs and has been linked to the diverse effects on mRNA fate. To explore the landscape and evolution of human m6A, we generated 27 m6A methylomes across major adult tissues. These data reveal dynamic m6A methylation across tissue types, uncover both broadly or tissue-specifically methylated sites, and identify an unexpected enrichment of m6A methylation at non-canonical cleavage sites. A comparison of fetal and adult m6A methylomes reveals that m6A preferentially occupies CDS regions in fetal tissues. Moreover, the m6A sub-motifs vary between fetal and adult tissues or across tissue types. From the evolutionary perspective, we uncover that the selection pressure on m6A sites varies and depends on their genic locations. Unexpectedly, we found that â¼40% of the 3'UTR m6A sites are under negative selection, which is higher than the evolutionary constraint on miRNA binding sites, and much higher than that on A-to-I RNA modification. Moreover, the recently gained m6A sites in human populations are clearly under positive selection and associated with traits or diseases. Our work provides a resource of human m6A profile for future studies of m6A functions, and suggests a role of m6A modification in human evolutionary adaptation and disease susceptibility.
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Adenosina/análogos & derivados , Metilación de ADN , Evolución Molecular , Regiones no Traducidas 3' , Adenosina/metabolismo , Adulto , Susceptibilidad a Enfermedades , Epigenoma , Feto/metabolismo , Genética de Población , Células HEK293 , Humanos , Metiltransferasas/deficiencia , Metiltransferasas/genética , Especificidad de ÓrganosRESUMEN
Adenosine-to-inosine (A-to-I) RNA editing regulates miRNA biogenesis and function. To date, fewer than 160 miRNA editing sites have been identified. Here, we present a quantitative atlas of miRNA A-to-I editing through the profiling of 201 pri-miRNA samples and 4694 mature miRNA samples in human, mouse, and Drosophila. We identified 4162 sites present in â¼80% of the pri-miRNAs and 574 sites in mature miRNAs. miRNA editing is prevalent in many tissue types in human. However, high-level editing is mostly found in neuronal tissues in mouse and Drosophila Interestingly, the edited miRNAs in neuronal and non-neuronal tissues in human gain two distinct sets of new targets, which are significantly associated with cognitive and organ developmental functions, respectively. Furthermore, we reveal that miRNA editing profoundly affects asymmetric strand selection. Altogether, these data provide insight into the impact of RNA editing on miRNA biology and suggest that miRNA editing has recently gained non-neuronal functions in human.
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MicroARNs/biosíntesis , MicroARNs/genética , Edición de ARN/fisiología , Animales , Drosophila melanogaster , Femenino , Humanos , Masculino , RatonesRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth. METHODS: CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, microRNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. RESULTS: CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth. CONCLUSION: Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.
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BACKGROUND: Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance. METHODS: We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance. RESULTS: LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse-150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP. CONCLUSIONS: Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.
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The chemiluminescence (CL) of lucigenin (Luc(2+)) can be enhanced by different alcohols in alkaline solution. The effect of different fatty alcohols on the CL of lucigenin was related to the carbon chain length and the number of hydroxyl groups. Glycerol provides the greatest enhancement. UV/Vis absorption spectra and fluorescence spectra showed that N-methylacridone (NMA) was produced in the CL reaction in the presence of different alcohols. The peak of the CL spectrum was located at 470 nm in all cases, indicating that the luminophore was always the excited-state NMA. The quenching of lucigenin CL by superoxide dismutase (SOD) and the electron spin resonance (ESR) results with the spin trap of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) demonstrated that superoxide anions (O2 (â¢-)) were generated from dissolved oxygen in the CL reaction and that glycerol and dihydroxyacetone (DHA) can promote O2 (â¢-) production by the reduction of dissolved oxygen in alkaline solution. It was assumed that the enhancement provided by different alcohols was related to the solvent effect and reducing capacity. Glycerol and DHA can also reduce Luc(2+) into lucigenin cation radicals (Luc(â¢+) ), which react with O2 (â¢-) to produce CL, and glycerol can slowly transform into DHA, which is oxidized quickly in alkaline solution.
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Acridinas/química , Alcoholes/química , Álcalis/química , Luminiscencia , SolucionesRESUMEN
Constructing self-assembly with definite assembly structure-property correlation is of great significance for expanding the property richness and functional diversity of metal nanoclusters (NCs). Herein, a well-designed liquid reaction strategy was developed through which a highly ordered nanofiber superstructure with enhanced green photoluminescence (PL) was obtained via self-assembly of the individual silver nanoclusters (Ag NCs). By visual monitoring of the kinetic reaction process using time-dependent and in situ spectroscopy measurements, the assembling structure growth and the structure-determined luminescence mechanisms were revealed. The as-prepared nanofibers featured a series of advantages involving a high emission efficiency, large Stokes shift, homogeneous chromophore, excellent photostability, high temperature, and pH sensibility. By virtue of these merits, they were successfully employed in various fields of luminescent inks, encryption and anticounterfeiting platforms, and optoelectronic light-emitting diode (LED) devices.
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Because of the poor stability and rheological properties of fat-free stirred yogurt fortified with fruit pulp, new functional polysaccharides as a natural emulsifier, which can increase viscosity in the aqueous phase, may be needed. This study aimed to evaluate the effects of Exidia yadongensis polysaccharide (EYP) as emulsifier on the stability, aroma, and antioxidant activities of mango buffalo yogurt at 4 °C for 25 days. The yogurt with 15 g/L EYP gave a higher content of 215 g/L total solids, 11.3 g/L exopolysaccharides, 0.10 g/L total polyphenols, 630.5 g/L water-holding capacity, and 11.43 g/kg total free amino acids, and maintained better texture, DPPH scavenging activity of 54.05 % and OH scavenging rates of 67.16 %. Moreover, the EYP exhibited the expected ability to weaken postacidification, syneresis, and growth of microorganism, and greatly promote the textural, rheological properties, suspension stability, microstructure, and aroma profiles of stirred mango-flavored buffalo yogurt (p < 0.05). In addition, the addition of 15 g/L EYP can inhibit protein degradation and improve the stability of secondary structure of the protein complex in mango yogurt during 25 days of storage. Therefore, EYP (15 g/L) could be used as natural positive functional factors and emulsifiers in such fat-free stirred yogurt industry.
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Antioxidantes , Búfalos , Emulsionantes , Yogur , Antioxidantes/química , Antioxidantes/farmacología , Yogur/análisis , Emulsionantes/química , Animales , Reología , Viscosidad , Polisacáridos/química , Polisacáridos/farmacología , Odorantes/análisisRESUMEN
The foveal load hypothesis assumes that the ease (or difficulty) of processing the currently fixated word in a sentence can influence processing of the upcoming word(s), such that parafoveal preview is reduced when foveal load is high. Recent investigations using pseudo-character previews reported an absence of foveal load effects in Chinese reading. Substantial Chinese studies to date provide some evidence to show that parafoveal words may be processed orthographically, phonologically, or semantically. However, it has not yet been established whether parafoveal processing is equivalent in terms of the type of parafoveal information extracted (orthographic, phonological, semantic) under different foveal load conditions. Accordingly, the present study investigated this issue with two experiments. Participants' eye movements were recorded as they read sentences in which foveal load was manipulated by placing a low- or high-frequency word N preceding a critical word. The preview validity of the upcoming word N + 1 was manipulated in Experiment 1, and word N + 2 in Experiment 2. The parafoveal preview was either identical to word N + 1(or word N + 2); orthographically related; phonologically related; semantically related; or an unrelated pseudo-character. The results showed robust main effects of frequency and preview type on both N + 1 and N + 2. Crucially, however, interactions between foveal load and preview type were absent, indicating that foveal load does not modulate the types of parafoveal information processed during Chinese reading.
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Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca2+ -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect.
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Poscondicionamiento Isquémico , Fármacos Neuroprotectores , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Transducción de Señal , Apoptosis , Estrés del Retículo EndoplásmicoRESUMEN
OBJECTIVE: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted. RESULTS: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (ß:-0.76, P<0.05) and Digit Symbol Substitution tests (ß:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants. CONCLUSION: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.
Asunto(s)
Cognición , Inflamación , Encuestas Nutricionales , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios Transversales , Inflamación/sangre , Tasa de Supervivencia , Diabetes Mellitus/mortalidad , Diabetes Mellitus/inmunología , Diabetes Mellitus/epidemiología , Estados Unidos/epidemiología , Hiperglucemia/mortalidad , Glucemia/análisisRESUMEN
Thromboembolism is a possible consequence of underlying atrial cardiopathy, which can occur even before the onset of atrial fibrillation. Our objective was to examine the association between biomarkers of atrial cardiopathy and outcomes of acute ischemic stroke (AIS) following endovascular treatment (EVT). We conducted a retrospective study that collected data from patients with AIS who underwent EVT and compared the outcomes between those with and without atrial cardiopathy. Neurological function was assessed using the modified Rankin Scale (mRS), with an mRS score >2 indicating poor function at day 90. Additionally, we evaluated secondary consequences, including symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), and malignant cerebral edema (MCE). Our study included 87 patients (77.6 â% male; mean age 60.93 â± â12.47 years). Among these patients, 29 (33.3 â%) had atrial cardiopathy, while the remaining 58 (66.7 â%) did not. In the atrial cardiopathy group, 12 patients (41.4 â%) had poor functional outcomes (mRS>2), compared to 19 (32.8 â%) in the non-atrial cardiopathy group. We observed sICH in 22 (25.3 â%) patients, END in 14 (16.1 â%) patients, MCE in 11 (12.6 â%) patients, and two (2.3 â%) patients who died in the hospital. We found that patients with PTFV1>5000 âµV/ms (OR: 8.39, 95 â% CI: 1.43-105.95, P â= â0.02) and NT-proBNP>250 âpg/mL (OR: 5.09, 95 â% CI: 1.20-27.63, P â= â0.03) had significantly higher risk of END. After adjusting for covariates in the Firth logistic regression, we further found that atrial cardiopathy was significantly associated with END, as revealed by both univariate (OR: 6.31, 95 â% CI: 1.42-59.87, P â= â0.01) and multivariable firth regression models (Modle 1, OR: 7.10, 95 â% CI: 1.57-67.38, P â< â0.01; Modle 2, OR: 7.82, 95 â% CI: 1.69, 76.36, P â< â0.01; Modle 3, OR: 8.59, 95 â% CI: 1.72-91.70, P â< â0.01). Moreover, we observed that atrial cardiopathy was associated with an increased risk of END in AIS patients with large artery atherosclerosis (LAA) receiving EVT. Therefore, clinicians should consider atrial cardiopathy as a possible underlying cause of AIS in their patients. Further investigation is warranted to elucidate the relationship between atrial cardiopathy and AIS's occurrence, progression, and prognosis.