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Background: The link between glymphatic system function in the brain and alterations in white-matter microstructure among individuals with major depressive disorder (MDD) remains unclear. This study aimed to examine the assessment of glymphatic system function in patients with MDD using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and to evaluate its association with cerebral-white-matter abnormalities and neuropsychological scores. Methods: From February 2023 to November 2023, this cross-sectional study recruited 35 patients with MDD from the Psychosomatic Diseases Department of the First Affiliated Hospital of Dalian Medical University. In this time period, 23 healthy controls (HCs) were enlisted from the community and matched with the MDD cohort in terms of years of education, gender, and age. All participants underwent magnetic resonance imaging, depression, anxiety, and cognitive assessments. The tract-based spatial statistics (TBSS) analyzed DTI parameters and identified significant clusters. Automated fiber quantification (AFQ) was used to automatically identify fiber bundles with statistical differences. Mann-Whitney tests or two-sample t-tests were used for comparisons. Interobserver consistency of the DTI-ALPS measurements was evaluated using the interclass correlation coefficient (ICC). Partial correlation analyses and linear regression analyses were used to examine relationships. A comparison of the DTI-ALPS index was made between the two groups. Correlations among diffusion characteristics, neuropsychological scores, and the DTI-ALPS index were analyzed. Results: Compared to HCs, patients with MDD exhibited a lower DTI-ALPS score (P=0.001). According to using linear regression analysis, the ALPS index was found to be an independent predictor of the Hamilton Depression Rating Scale [B=-25.32; P=0.001; 95% confidence interval (CI): -40.35 to -11.55], Hamilton Anxiety Rating Scale (B=-33.48; P=0.003; 95% CI: -55.38 to -11.24), and Montreal Cognitive Assessment total score (B=8.59; P=0.008; 95% CI: 2.38 to 14.79). According to the TBSS analysis, there were clusters of increased axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in patients with MDD as compared to HCs (all P values <0.05). A lower DTI-ALPS score was correlated with higher AD (r=-0.592; P<0.001), MD (cluster 1: r=-0.567, P=0.001; cluster 2: r=-0.581, P<0.001), and RD (r=-0.491; P=0.004) values. AFQ analysis identified the significantly different diffusion indicators in the left cingulum bundle (CB_L), left inferior longitudinal fasciculus (ILF_L), and left uncinate fasciculus (UF_L) between the two groups (all false discovery rate P values <0.05). DTI-ALPS score was negatively correlated with the AD value of CB_L (r=-0.304; P=0.024), ILF_L (r=-0.35; P=0.008), and UF_L (r=-0.354; P=0.008) in AFQ tract-level analysis. In point-wise analysis, the MD value of CB_L at nodes 33 to 36 was negatively correlated with DTI-ALPS score (r ranging from -0.504 to -0.535; P<0.01). Conclusions: Our results indicated a decrease in DTI-ALPS index score in patients with MDD. DTI-ALPS score was associated with depression, anxiety, declined cognitive ability, and white-matter microstructural abnormalities and may thus be a promising biomarker for the partial evaluation of glymphatic system function in patients with MDD.
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BACKGROUND: The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. METHODS: Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7-65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. RESULTS: Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. LIMITATIONS: The sample size is small. CONCLUSION: MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity.
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Hormona Adrenocorticotrópica , Antioxidantes , Trastorno Depresivo Mayor , Giro del Cíngulo , Neurotransmisores , Ácido gamma-Aminobutírico , Humanos , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Hormona Adrenocorticotrópica/sangre , Femenino , Masculino , Adulto , Antioxidantes/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/sangre , Persona de Mediana Edad , Neurotransmisores/sangre , Neurotransmisores/metabolismo , Giro del Cíngulo/metabolismo , Glutatión/sangre , Glutatión/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Estrés Oxidativo/fisiología , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. CASE PRESENTATION: A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. CONCLUSIONS: This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.
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COVID-19 , Leucoencefalitis Hemorrágica Aguda , Miocarditis , Humanos , Femenino , COVID-19/complicaciones , Adulto , Miocarditis/diagnóstico por imagen , Miocarditis/diagnóstico , Miocarditis/complicaciones , Leucoencefalitis Hemorrágica Aguda/diagnóstico , Leucoencefalitis Hemorrágica Aguda/diagnóstico por imagen , SARS-CoV-2 , Imagen por Resonancia Magnética , Oxigenación por Membrana Extracorpórea/métodosRESUMEN
Background: Chemodynamic therapy (CDT) faces challenges of low catalytic ion efficiency and ROS production. We developed a ROS nano-bomb, Cu/ZIF-8@GA-Fe, to address these issues. Methods: The nano-bomb was synthesized by doping copper into ZIF-8 and assembling Fe3+ and gallic acid (GA). It was tested for reactive oxygen species (ROS) generation in acidic conditions and its photothermal properties. Results: In an acidic micro environment, Cu/ZIF-8@GA-Fe effectively released Fe3+ and Cu2+, depleting GSH and generating ROS. The GA-Fe coating provided photothermal heat and was used to enhance Fenton reactions via dual ions for increasing ROS production. In vivo and in vitro experiments, Cu/ZIF-8@GA-Fe inhibited tumor growth with minimal side effects. Conclusion: Cu/ZIF-8@GA-Fe shows promise for safe and effective CDT, offering a synergistic approach to tumor therapy.
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Cobre , Ácido Gálico , Glutatión , Especies Reactivas de Oxígeno , Ácido Gálico/química , Ácido Gálico/farmacología , Cobre/química , Cobre/farmacología , Animales , Glutatión/química , Especies Reactivas de Oxígeno/metabolismo , Humanos , Ratones , Línea Celular Tumoral , Terapia Fototérmica/métodos , Hierro/química , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Ratones Endogámicos BALB C , Nanopartículas del Metal/química , Terapia Combinada , Femenino , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Global release of plastics exerts various impacts on the ecological cycle, particularly on primary photosynthesis, while the impacts of plastic additives are unknown. As a carrier of fluorescent brightener, plastic particles co-modify Chlorella pyrenoidosa (C. pyrenoidosa) growth and its photosynthetic parameters. In general, adding to the oxidative damage induced by polystyrene, fluorescent brightener-doped polystyrene produces stronger visible light and the amount of negative charge is more likely to cause photodamage in C. pyrenoidosa leading to higher energy dissipation through conditioning than in the control group with a date of ETR (II) inhibition rate of 33 %, Fv/Fm inhibition rate of 8.3 % and Pm inhibition rate of 48.8 %. To elucidate the ecological effect of fluorescent brightener doping in plastic particles, a machine learning method is performed to establish a Gradient Boosting Machine model for predicting the impact of environmental factors on algal growth. Upon validation, the model achieved an average fitting degree of 88 %. Relative concentration of plastic particles and algae claimed the most significant factor by interpretability analysis of the machine learning. Additionally, both Gradient Boosting Machine prediction and experimental results indicate a matching result that plastic additives have an inhibitive effect on algal growth.
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Chlorella , Aprendizaje Automático , Fotosíntesis , Chlorella/crecimiento & desarrollo , Chlorella/efectos de los fármacos , Chlorella/metabolismo , Fotosíntesis/efectos de los fármacos , Plásticos/química , Plásticos/toxicidad , Poliestirenos/química , Contaminantes Químicos del Agua/toxicidad , Colorantes Fluorescentes/químicaRESUMEN
Highly acidic citrus pomace (CP) is a byproduct of Pericarpium Citri Reticulatae production and causes significant environmental damage. In this study, a newly isolated acid-tolerant strain of Serratia sp. JS-043 was used to treat CP and evaluate the effect of reduced acid citrus pomace (RACP) in passivating heavy metals. The results showed that biological treatment could remove 97.56% of citric acid in CP, the organic matter in the soil increased by 202.60% and the catalase activity in the soil increased from 0 to 0.117 U g-1. Adding RACP into soil can increase the stabilization of Cu, Zn, As, Co, and Pb. Specifically, through the metabolism of strain JS-043, RACP was also involved in the stabilization of Zn and Pb, and Residual Fraction in the total pool of these metals increased by 10.73% and 10.54%, respectively. Finally, the genome sequence of Serratia sp. JS-043 was completed, and the genetic basis of its acid-resistant and acid-reducing characteristics was preliminarily revealed. JS-043 also contains many genes encoding proteins associated with heavy metal ion tolerance and transport. These findings suggest that JS-043 may be a high-potential strain to improve the quality of acidic organic wastes that can then be useful for soil bioremediation.
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Biodegradación Ambiental , Metales Pesados , Serratia , Microbiología del Suelo , Contaminantes del Suelo , Serratia/metabolismo , Serratia/genética , Metales Pesados/metabolismo , Contaminantes del Suelo/metabolismo , Concentración de Iones de Hidrógeno , CitrusRESUMEN
[This retracts the article DOI: 10.21037/tcr-22-346.].
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Background: The heterogeneity and dynamic changes of endometrial cells have a significant impact on health as they determine the normal function of the endometrium during the menstrual cycle. Dysfunction of the endometrium can lead to the occurrence of various gynecological diseases. Therefore, deconvolution of immune microenvironment that drives transcriptional programs throughout the menstrual cycle is key to understand regulatory biology of endometrium. Methods: Herein, we comprehensively analyzed single-cell transcriptome of 59,397 cells across ten human endometrium samples and revealed the dynamic cellular heterogeneity throughout the menstrual cycle. Results: We identified two perivascular cell subtypes, four epithelial subtypes and four fibroblast cell types in endometrium. Moreover, we inferred the cell type-specific transcription factor (TF) activities and linked critical TFs to transcriptional output of diverse immune cell types, highlighting the importance of transcriptional regulation in endometrium. Dynamic interactions between various types of cells in endometrium contribute to a range of biological pathways regulating differentiation of secretory. Integration of the molecular biomarkers identified in endometrium and bulk transcriptome of 535 endometrial cancers (EC), we revealed five RNA-based molecular subtypes of EC with highly intratumoral heterogeneity and different clinical manifestations. Mechanism analysis uncovered clinically relevant pathways for pathogenesis of EC. Conclusion: In summary, our results revealed the dynamic immune microenvironment of endometrium and provided novel insights into future development of RNA-based treatments for endometriosis and endometrial carcinoma.
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PURPOSE: This study aims to compare the effectiveness of pencil push-up training and binocular vision training in treating post-operative mild under-correction in patients with intermittent exotropia. METHODS: A prospective cohort study was conducted, including patients who underwent surgery for intermittent exotropia at Children's Hospital of Nanjing Medical University between June 2022 and January 2023 and experienced post-operative mild under-correction (-8∆ to -15∆). Patients were divided into two groups: pencil push-up training group and binocular vision training group. All patients underwent measurements of exodeviation and stereoacuity at distance and near, sensory fusion, and fusion convergence amplitude. The data were analyzed using independent sample t-tests, repeated measures analysis of variance, and Chi-square tests. RESULTS: There were no statistically significant differences in exodeviation at distance and near between the two training groups before the training. After 6 months of training, the exodeviation at distance and near achieved a significant decrease in both groups (P < 0.05), and the pencil push-up training group showed a similar distance and near exodeviation compared to the binocular vision training group (t = 1.58, P ï¼ 0.05; t = 0.43, P ï¼ 0.05). After 6 months of training, the binocular vision training group exhibited significantly superior stereoacuity and fusion convergence amplitude compared to the pencil push-up training group (P < 0.001). CONCLUSION: Both pencil push-up training and binocular vision training are effective in reducing exodeviation in patients with post-operative mild under-correction of intermittent exotropia. However, binocular vision training demonstrates superior efficacy in restoring stereopsis and fusion convergence amplitude compared to pencil push-up training.
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Exotropía , Músculos Oculomotores , Procedimientos Quirúrgicos Oftalmológicos , Visión Binocular , Agudeza Visual , Humanos , Exotropía/cirugía , Exotropía/fisiopatología , Estudios Prospectivos , Visión Binocular/fisiología , Femenino , Masculino , Agudeza Visual/fisiología , Procedimientos Quirúrgicos Oftalmológicos/métodos , Niño , Músculos Oculomotores/cirugía , Músculos Oculomotores/fisiopatología , Preescolar , Estudios de Seguimiento , Resultado del Tratamiento , Periodo Posoperatorio , Percepción de Profundidad/fisiologíaRESUMEN
OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa ( κ ) of 0.14 ( p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.
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Diferencia Mínima Clínicamente Importante , Otitis Media , Calidad de Vida , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Enfermedad Crónica , Encuestas y Cuestionarios/normas , Otitis Media/cirugía , Timpanoplastia/métodos , Anciano , China , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).
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Angioplastia Coronaria con Balón , Catéteres Cardíacos , Fármacos Cardiovasculares , Materiales Biocompatibles Revestidos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Valor Predictivo de las Pruebas , Ultrasonografía Intervencional , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Resultado del Tratamiento , Factores de Tiempo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , Estudios Prospectivos , Factores de Riesgo , ChinaRESUMEN
Amphibians and reptiles, especially the critically endangered Chinese alligators, are vulnerable to climate change. Historically, the decline in suitable habitats and fragmentation has restricted the distribution of Chinese alligators to a small area in southeast Anhui Province in China. However, the effects of climate change on range-restricted Chinese alligator habitats are largely unknown. We aimed to predict current and future (2050s and 2070s) Chinese alligator distribution and identify priority conservation areas under climate change. We employed species distribution models, barycenter migration analyses, and the Marxian model to assess current and future Chinese alligator distribution and identify priority conservation areas under climate change. The results showed that the lowest temperature and rainfall seasonality in the coldest month were the two most important factors affecting the distribution of Chinese alligators. Future predictions indicate a reduction (3.39%-98.41%) in suitable habitats and a westward shift in their distribution. Further, the study emphasizes that suitable habitats for Chinese alligators are threatened by climate change. Despite the impact of the Anhui Chinese Alligator National Nature Reserve, protection gaps persist, with 78.27% of the area lacking priority protected area. Our study provides crucial data for Chinese alligator adaptation to climate change and underscores the need for improved conservation strategies. Future research should refine conservation efforts, consider individual plasticity, and address identified limitations to enhance the resilience of Chinese alligator populations in the face of ongoing climate change.
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Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products.
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In this issue, Li et al.1 report internal mRNA 2'-O-methyl (Nm) modification mapping by nanopore sequencing and the effect of Nm on mRNA stability and cancer cell progression.
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Secuenciación de Nanoporos , Neoplasias , Estabilidad del ARN , ARN Mensajero , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Secuenciación de Nanoporos/métodos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , MetilaciónRESUMEN
Sn-based materials with high capacity showcase great potential for next-generation lithium-ion batteries (LIBs). Yet, the large volume change and limited ion/electron transfer efficiency of Sn-based materials upon operation significantly compromises the battery performance. In this study, a unique 3D copper-nickel nanoporous column array current collector is rationally developed via a facile template-free galvanostatic electrodeposition method, followed by electrodepositing SnS active material onto it (denoted as 3D SnS@CNCA). Excitingly, the morphology of the 3D SnS@CNCA electrode perfectly inherited the nanoporous column array structure of the 3D current collector, which not only endows the electrode with a large specific surface area to provide more active sites and sufficient ion/electron transport pathways, but also effectively alleviates the volume expansion of SnS upon repeated charge-discharge cycles. Therefore, the binder-free 3D SnS@CNCA electrode showcases a significantly enhanced Li storage performance, showing a high initial reversible capacity of 1019.7 mAh g-1 with noteworthy cycling stability (a capacity retention rate of 89.4% after 200 cycles). Moreover, the designed electrode also manifests high rate performance with a high capacity of 570.6 mAh g-1 at 4 A g-1. This work provides a novel design idea for the preparation of high-performance electrodes beyond LIBs.
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tRNA modifications help maintain tRNA structure and facilitate translation and stress response. Found in all three kingdoms of life, m1A tRNA modification occurs in the T loop of many tRNAs, stabilizes tertiary tRNA structure, and impacts translation. M1A in the T loop is reversible by three mammalian demethylase enzymes, which bypasses the need of turning over the tRNA molecule to adjust its m1A levels in cells. However, no prokaryotic tRNA demethylase enzyme has been identified that acts on endogenous RNA modifications. Using Streptomyces venezuelae as a model organism, we confirmed the presence and quantitative m1A tRNA signatures using mass spectrometry and high-throughput tRNA sequencing. We identified two RNA demethylases that can remove m1A in tRNA and validated the activity of a previously annotated tRNA m1A writer. Using single-gene knockouts of these erasers and the m1A writer, we found dynamic changes of m1A levels in many tRNAs under stress conditions. Phenotypic characterization highlighted changes in their growth and altered antibiotic production. Our identification of the first prokaryotic tRNA demethylase enzyme paves the way for investigating new mechanisms of translational regulation in bacteria.
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Adenosina , ARN de Transferencia , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/enzimología , ARN de Transferencia/metabolismo , ARN de Transferencia/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , ARN Bacteriano/metabolismo , Procesamiento Postranscripcional del ARNRESUMEN
Almost all elongator tRNAs (Transfer RNAs) harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, generated by the enzymes TrmA and TruB, respectively, in Escherichia coli. TrmA and TruB both act as tRNA chaperones, and strains lacking trmA or truB are outcompeted by wild type. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of trmA and truB in E. coli causes a global decrease in aminoacylation and alters other tRNA modifications such as acp3U47. While overall protein synthesis is not affected in ΔtrmA and ΔtruB strains, the translation of a subset of codons is significantly impaired. As a consequence, we observe translationally reduced expression of many specific proteins, that are either encoded with a high frequency of these codons or that are large proteins. The resulting proteome changes are not related to a specific growth phenotype, but overall cellular fitness is impaired upon deleting trmA and truB in accordance with a general protein synthesis impact. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness irrespective of the growth conditions which explains the conservation of trmA and truB.
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Escherichia coli , ARN de Transferencia , ARN de Transferencia/metabolismo , ARN de Transferencia/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Biosíntesis de Proteínas , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , ARNt Metiltransferasas/metabolismo , ARNt Metiltransferasas/genética , Procesamiento Postranscripcional del ARNRESUMEN
Organic electrochemical transistors (OECTs) are of great interest in low-power bioelectronics and neuromorphic computing, as they utilize organic mixed ionic-electronic conductors (OMIECs) to transduce ionic signals into electrical signals. However, the poor environmental stability of OMIEC materials significantly restricts the practical application of OECTs. Therefore, the non-fused planar naphthalenediimide (NDI)-dialkoxybithiazole (2Tz) copolymers are fine-tuned through varying ethylene glycol (EG) side chain lengths from tri(ethylene glycol) to hexa(ethylene glycol) (namely P-XO, X = 3-6) to achieve OECTs with high-stability and low threshold voltage. As a result, the NDI-2Tz copolymers exhibit ambipolarity, rapid response (<10 ms), and ultra-high n-type stability. Notably, the P-6O copolymers display a threshold voltage as low as 0.27 V. They can operate in n-type mode in an aqueous solution for over 60 h, maintaining an on-off ratio of over 105. This work sheds light on the design of exceptional n-type/ambipolar materials for OECTs. It demonstrates the potential of incorporating these ambipolar polymers into water-operational integrated circuits for long-term biosensing systems and energy-efficient brain-inspired computing.
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Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.
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Animales Recién Nacidos , Hipocampo , Hipoxia-Isquemia Encefálica , Mitofagia , Neuronas , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Supervivencia Celular/fisiología , Células Cultivadas , Hipocampo/metabolismo , Hipocampo/patología , Hipoxia-Isquemia Encefálica/metabolismo , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Mitofagia/fisiología , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Polycyclic aromatic hydrocarbons (PAHs), as persistent environmental pollutants, often reside in nonaqueous-phase liquids (NAPLs). Mycobacterium sp. WY10, boasting highly hydrophobic surfaces, can adsorb to the oil-water interface, stabilizing the Pickering emulsion and directly accessing PAHs for biodegradation. We investigated the impact of Triton X-100 (TX100) on this interfacial uptake of phenanthrene (PHE) by Mycobacteria, using n-tetradecane (TET) and bis-(2-ethylhexyl) phthalate (DEHP) as NAPLs. Interfacial tension, phase behavior, and emulsion stability studies, alongside confocal laser scanning microscopy and electron microscope observations, unveiled the intricate interplay. In surfactant-free systems, Mycobacteria formed stable W/O Pickering emulsions, directly degrading PHE within the NAPLs because of their intimate contact. Introducing low-dose TX100 disrupted this relationship. Preferentially binding to the cells, the surfactant drastically increased the cell hydrophobicity, triggering desorption from the interface and phase separation. Consequently, PAH degradation plummeted due to hindered NAPL access. Higher TX100 concentrations flipped the script, creating surfactant-stabilized O/W emulsions devoid of interfacial cells. Surprisingly, PAH degradation remained efficient. This paradox can be attributed to NAPL emulsification, driven by the surfactant, which enhanced mass transfer and brought the substrate closer to the cells, despite their absence at the interface. This study sheds light on the complex effect of surfactants on Mycobacteria and PAH uptake, revealing an antagonistic effect at low concentrations that ultimately leads to enhanced degradation through emulsification at higher doses. These findings offer valuable insights into optimizing bioremediation strategies in PAH-contaminated environments.