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Phosphate-solubilizing bacteria (PSB) are crucial for enhancing phosphorus bioavailability and regulating phosphorus transformation processes. However, the in situ phosphorus-solubilizing activity and the link between phenotypes and genotypes for PSB remain unidentified. Here we employed single-cell Raman spectroscopy combined with heavy water to discern and quantify soil active PSB. Our results reveal that PSB abundance and in situ activity differed significantly between soil types and fertilization treatments. Inorganic fertilizer input was the key driver for active PSB distribution. Targeted single-cell sorting and metagenomic sequencing of active PSB uncovered several low-abundance genera that are easily overlooked within bulk soil microbiota. We elucidate the underlying functional genes and metabolic pathway, and the interplay between phosphorus and carbon cycling involved in high phosphorus solubilization activity. Our study provides a single-cell approach to exploring PSB from native environments, enabling the development of a microbial solution for the efficient agronomic use of phosphorus and mitigating the phosphorus crisis.
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Bacterias , Fertilizantes , Fosfatos , Fósforo , Microbiología del Suelo , Suelo , Fósforo/metabolismo , Bacterias/metabolismo , Bacterias/genética , Fosfatos/metabolismo , Suelo/química , Fertilizantes/análisis , Análisis de la Célula Individual , Microbiota/fisiología , SolubilidadRESUMEN
Polyploidization plays a crucial role in plant evolution and is becoming increasingly important in breeding. Structural variations and epigenomic repatterning have been observed in synthetic polyploidizations. However, the mechanisms underlying the occurrence and their effects on gene expression and phenotype remain unknown. Here, we investigated genome-wide large deletion/duplication regions (DelDups) and genomic methylation dynamics in leaf organs of progeny from the first eight generations of synthetic tetraploids derived from Chinese cabbage (Brassica rapa L. ssp. pekinensis) and cabbage (Brassica oleracea L. var. capitata). One- or two-copy DelDups, with a mean size of 5.70 Mb (400 kb - 65.85 Mb), occurred from the first generation of selfing and thereafter. The duplication of a fragment in one subgenome consistently coincided with the deletion of its syntenic fragment in the other subgenome, and vice versa, indicating that these DelDups were generated by homoeologous exchanges (HEs). Interestingly, the larger the genomic syntenic region, the higher the frequency of DelDups, further suggesting that the pairing of large homoeologous fragments is crucial for HEs. Moreover, we found that the active transcription of continuously distributed genes in local regions is positively associated with the occurrence of HE breakpoints. In addition, the expression of genes within DelDups exhibited a dosage effect, and plants with extra parental genomic fragments generally displayed phenotypes biased towards the corresponding parent. Genome-wide methylation fluctuated remarkably, which did not clearly affect gene expression on a large scale. Our findings provide insights into the early evolution of polyploid genomes, offering valuable knowledge for polyploidization-based breeding.
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Despite a few recent reports on Rashba effects in two-dimensional (2D) Ruddlesden-Popper (RP) hybrid perovskites, the precise role of organic spacer cations in influencing Rashba band splitting remains unclear. Here, using a combination of temperature-dependent two-photon photoluminescence (2PPL) and time-resolved photoluminescence spectroscopy, alongside density functional theory (DFT) calculations, we contribute to significant insights into the Rashba band splitting found for 2D RP hybrid perovskites. The results demonstrate that the polarity of the organic spacer cation is crucial in inducing structural distortions that lead to Rashba-type band splitting. Our investigations show that the intricate details of the Rashba band splitting occur for organic cations with low polarity but not for more polar ones. Furthermore, we have observed stronger exciton-phonon interactions due to the Rashba-type band splitting effect. These findings clarify the importance of selecting appropriate organic spacer cations to manipulate the electronic properties of 2D perovskites.
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The estuarine plastisphere, a novel ecological habitat in the Anthropocene, has garnered global concerns. Recent geochemical evidence has pointed out its potential role in influencing nitrogen biogeochemistry. However, the biogeochemical significance of the plastisphere and its mechanisms regulating nitrogen cycling remain elusive. Using 15N- and 13C-labelling coupled with metagenomics and metatranscriptomics, here we unveil that the plastisphere likely acts as an underappreciated nitrifying niche in estuarine ecosystems, exhibiting a 0.9 ~ 12-fold higher activity of bacteria-mediated nitrification compared to surrounding seawater and other biofilms (stone, wood and glass biofilms). The shift of active nitrifiers from O2-sensitive nitrifiers in the seawater to nitrifiers with versatile metabolisms in the plastisphere, combined with the potential interspecific cooperation of nitrifying substrate exchange observed among the plastisphere nitrifiers, collectively results in the unique nitrifying niche. Our findings highlight the plastisphere as an emerging nitrifying niche in estuarine environment, and deepen the mechanistic understanding of its contribution to marine biogeochemistry.
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Bacterias , Biopelículas , Estuarios , Nitrificación , Agua de Mar , Agua de Mar/microbiología , Bacterias/metabolismo , Bacterias/genética , Biopelículas/crecimiento & desarrollo , Ecosistema , Microbiota/fisiología , Metagenómica , Filogenia , Ciclo del Nitrógeno , Nitrógeno/metabolismo , Isótopos de Nitrógeno/metabolismoRESUMEN
The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.
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Proteómica , Humanos , Proteómica/métodos , Espectrometría de Masas/métodos , Biomarcadores/análisis , Estados Unidos , Tratamiento Basado en Trasplante de Células y Tejidos , Terapia Genética , Cromatografía/métodos , BlancoRESUMEN
Whether information in working memory (WM) is stored in a domain-independent or domain-specific system is still the subject of intense debate. This study used the delayed match-to-sample paradigm, the dual-task paradigm, and the selective interference paradigm to investigate the mechanism of cross-modal storage in visual and vibrotactile WM. We postulated that WM may store cross-modal data from haptics and vision independently, and we proposed domain-specific WM storage. According to the findings, the WM can store cross-modal information from vision and haptics independently, and the storage of visual and tactile WM may be domain-specific. This study provides early support for the hypothesis that haptic and visuospatial sketchpads are dissociated. In addition, the current study provides evidence to elucidate the mechanisms by which WM stores and processes data from different modalities and content. The results also indicate that a cross-modal approach can broaden the cognitive processing bandwidth of WM.
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Coronary artery lesions (CALs) are the most common complications of Kawasaki disease (KD) and play a crucial role in determining the prognosis of the disease. Consequently, the early identification of children with KD who are at risk of developing coronary artery damage is vitally important. We sought to investigate the relationship between the Systemic Immune-Inflammation Index (SII) and CALs in patients with KD and to assess its predictive value. We carried out a retrospective review and analysis of medical records for KD patients treated at the First Affiliated Hospital of Anhui Medical University between January 2017 and January 2023. We utilized single-variable tests, binary logistic regression analysis, ROC curve analysis, restricted cubic spline tests, and curve fitting to evaluate the association between SII and CALs. In our study, 364 patients were included, with 63 (17.3%) presenting with CALs at the time of admission. The binary logistic regression analysis indicated that SII was a significant risk factor for CALs at admission, evident in both unadjusted and models adjusted for confounders. The ROC curve analysis revealed an AUC (Area Under the Curve) value of 0.789 (95%CI 0.723-0.855, P < 0.001) for SII's predictive ability regarding CALs at admission. A consistent positive linear relationship between SII and the risk of CALs at admission was observed in both the raw and adjusted models. Our research findings suggest that SII serves as a risk factor for CALs and can be used as an auxiliary laboratory biomarker for predicting CALs.
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Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Vasos Coronarios , Inflamación , Factores de Riesgo , Curva ROCRESUMEN
Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec+ cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpß transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.
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Proteínas Potenciadoras de Unión a CCAAT , Eosinófilos , Pez Cebra , Animales , Humanos , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/genética , Eosinófilos/metabolismo , Neutrófilos/metabolismo , Pez Cebra/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismoRESUMEN
The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases. It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage. In this study, we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos, enabling us to identify and define the molecular features of human hematopoietic mesoderm (HM) cells biased towards hematopoietic lineages. We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells. Mechanistically, BMP4 acts as a downstream target of HDAC1, which modulates the expression of BMP4 by deacetylating its enhancer. Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation. In conclusion, our study identifies human HM cells and describes new mechanisms for human hematopoietic development.
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Células Madre Embrionarias , Mesodermo , Humanos , Diferenciación Celular/genética , Mesodermo/metabolismo , Linaje de la Célula/genéticaRESUMEN
Bacterial infections with emerging resistance to antibiotics require urgent development of antibacterial agents with new core skeletons. Recently, a series of antibacterial agents have been reported based on positively charged organic groups, such as ammonium, guanidine, and phosphonium groups, which can selectively bind and destroy negatively charged bacterial membranes. To achieve imaging-guided precise antibacterial therapy, these positively charged organic groups usually require further decoration with imaging modalities, such as fluorescence. However, most fluorophores with electron-closed shell structures usually suffer from tedious synthetic procedures for preparation. We herein prepare a series of positively charged and deep-red fluorescent supramolecular pyrrole radical cations (PË+-CB[7]) based on the simple mixing of pyrroles and CB[7] in water under air. The readily available deep-red fluorescent PË+-CB[7] can not only be used for selective imaging and killing of live Gram-positive bacteria with excellent biocompatibility, but also for imaging of dead Gram-negative bacteria killed by drugs and in vivo monitoring of phagocytosis of bacteria by innate immune cells in zebrafish. It is believed that the deep-red fluorescent pyrrole radical cations as a new core skeleton are promising in bacterial theranostics.
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Medicina de Precisión , Pirroles , Animales , Pez Cebra , Antibacterianos/farmacología , Antibacterianos/química , Bacterias , Cationes/químicaRESUMEN
To investigate the diversity and community structure of gut microbiome of the invasive species, Achatina fulica, along an urbanization gradient, we collected 30 A. fulica samples from five parks in the urban, suburban, and rural areas of Xiamen City. Using full-length 16S rRNA gene sequencing performed by the third generation PacBio sequencing platform, we analyzed the community characteristics of gut microbiome and soil microbiome in different habitats. We found a significant disparity between the composition of gut microbiome of A. fulica and that of the soil microbiome in their habitats. Furthermore, the gut microbiome of A. fulica were more sensitive to urbanization. The microbial α-diversity indices (Sobs, Chao, Shannon indices) in the soil of A. fulica habitats were consistently higher than those within their guts. Despite the similar ß-diversity indices of microbial communities in urban, suburban, and rural soils, we found a significant discrepancy in gut microbiome composition. Urbanization significantly influenced A. fulica gut microbiome composition. Gut microbiome of A. fulica in urban and suburban regions primarily consisted of Enterobacteriaceae, Xanthomonadaceae, and Mycoplasmataceae, while that in rural areas chiefly composed of Streptococcaceae and Paenibacillaceae. The diversity and abundance of potential human pathogenic bacteria within the gut microbiome of A. fulica significantly increased in urban environments, suggesting that urbanization escalated the risk of A. fulica transmitting potential pathogens.
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Microbioma Gastrointestinal , Microbiota , Humanos , Animales , Urbanización , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Caracoles/genética , Caracoles/microbiología , Suelo/químicaRESUMEN
Polyploidization is important to the evolution of plants. Subgenome dominance is a distinct phenomenon associated with most allopolyploids. A gene on the dominant subgenome tends to express to higher RNA levels in all organs as compared to the expression of its syntenic paralogue (homoeolog). The mechanism that underlies the formation of subgenome dominance remains unknown, but there is evidence for the involvement of transposon/DNA methylation density differences nearby the genes of parents as being causal. The subgenome with lower density of transposon and methylation near genes is positively associated with subgenome dominance. Here, we generated eight generations of allotetraploid progenies from the merging of parental genomes Brassica rapa and Brassica oleracea. We found that transposon/methylation density differ near genes between the parental (rapa:oleracea) existed in the wide hybrid, persisted in the neotetraploids (the synthetic Brassica napus), but these neotetraploids expressed no expected subgenome dominance. This absence of B. rapa vs. B. oleracea subgenome dominance is particularly significant because, while there is no negative relationship between transposon/methylation level and subgenome dominance in the neotetraploids, the more ancient parental subgenomes for all Brassica did show differences in transposon/methylation densities near genes and did express, in the same samples of cells, biased gene expression diagnostic of subgenome dominance. We conclude that subgenome differences in methylated transposon near genes are not sufficient to initiate the biased gene expressions defining subgenome dominance. Our result was unexpected, and we suggest a "nuclear chimera" model to explain our data.
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Brassica napus , Brassica rapa , Brassica , Brassica/genética , Genoma de Planta/genética , Brassica rapa/genética , Brassica napus/genética , Metilación de ADN/genética , PoliploidíaRESUMEN
BACKGROUND: COVID-19 has had an enormous impact on the mental health of people around the world, particularly adolescents. Non-suicidal self-injury (NSSI) is one of the most prominent and dangerous behaviors associated with suicide. However, few meta-analyses of the NSSI prevalence have ever been conducted since the COVID-19 outbreak. Here, we conducted a meta-analysis to estimate the pooled prevalence and elucidate the influencing factors for NSSI. METHODS: We searched PubMed, Web of Science, Embase, APA PsycINFO, CNKI and Wanfang Database for relevant literature published before April 2022. Pooled prevalence and 95 % confidence interval (CI) were used to assess NSSI prevalence. Subgroup and meta-regression analyses were performed to clarify the potential influencing factors. RESULTS: A total of 15 studies with 24,055 participants were eventually included. The results showed that the pooled overall prevalence of NSSI among overall samples during the COVID-19 pandemic was 22.5 % (95 % CI: 17.2 % to 28.9 %). Subgroup and meta-regression analyses revealed that the crucial influencing factors for NSSI included gender, age, regional distribution, and suicidal ideation. Specifically, the NSSI prevalence among adolescents and adults during the pandemic was 32.40 % and 15.70 %, respectively. Most importantly, gender is a significant influencing factor for NSSI among adolescents. CONCLUSIONS: The pooled prevalence of NSSI during the COVID-19 outbreak has surged to alarming heights, especially among adolescents. The prevalence of NSSI may be influenced by complex factors such as gender and age. Therefore, it is critical to pay attention to NSSI behaviors in the adolescent population, particularly male adolescents who appear to be susceptible.
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COVID-19 , Conducta Autodestructiva , Adolescente , Adulto , Humanos , Masculino , COVID-19/epidemiología , Pandemias , Prevalencia , Factores de Riesgo , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Ideación Suicida , Intento de Suicidio/psicología , FemeninoRESUMEN
Nonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.
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Sulindac , Pez Cebra , Animales , Ratones , Sulindac/farmacología , Apoptosis , Antiinflamatorios no Esteroideos , Neuronas GABAérgicas , LarvaRESUMEN
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis. In ischemic stroke mice, telaprevir reduced infarct volume, improved the long-term survival rate, and enhanced sensorimotor, memory, and cognitive functions. In hypoxia-treated nerve cells, telaprevir decreased the intracellular calcium concentrations and reduced LDH release. Mechanistically, telaprevir inhibited MALT1 protease activity, thus decreasing the membrane protein level of GluN2B and its phosphorylation through reducing the level of STEP61. Moreover, telaprevir was able to inhibit the levels of necroptosis-associated proteins. According to these results, it can be concluded that telaprevir alleviates neuronal brain injury in stroke mice via restraining GluN2B activation and suppresses the receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway through inhibiting MALT1. Thus, telaprevir might have a novel indication for treating patients with ischemic stroke.
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Lesiones Encefálicas , Accidente Cerebrovascular Isquémico , Ratones , Animales , Calcio , Proteínas Quinasas/metabolismo , Necroptosis , CogniciónRESUMEN
Hyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 109/L (full adjusted ß, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34+ cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor (Mpl) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk.Trial Registration clinicaltrials.gov Identifier: NCT00794885.
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Hiperhomocisteinemia , Melatonina , Humanos , Ratones , Animales , Trombopoyesis/genética , Megacariocitos , Plaquetas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/genética , Pez Cebra , Hormona del Crecimiento/farmacología , Melatonina/farmacología , Hiperhomocisteinemia/complicaciones , Diferenciación CelularRESUMEN
The dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and/or solute carrier family 7 member 11 (SLC7A11) is believed to contribute to ferroptosis in the hearts suffered ischemia/reperfusion (I/R), but the mechanisms behind the dysregulation of them are not fully elucidated. Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) can function as a paracaspase to cleave specified substrates and it is predicted to interact with Nrf2. This study aims to explore whether targeting MALT1 can reduce I/R-induced ferroptosis via enhancing the Nrf2/SLC7A11 pathway. The SD rat hearts were subjected to 1h-ischemia plus 3h-reperfusion to establish the I/R injury model, which showed myocardial injuries (increase in infarct size and creatine kinase release) and up-regulation of MALT1 while downregulation of Nrf2 and SLC7A11 concomitant with the increased ferroptosis, reflecting by an increase in glutathione peroxidase 4 (GPX4) level while decreases in the levels of acyl-CoA synthetase long chain family member 4 (ACSL4), total iron, Fe2+ and lipid peroxidation (LPO); these phenomena were reversed in the presence of MI-2, a specific inhibitor of MALT1. Consistently, similar results were achieved in the cultured cardiomyocytes subjected to 8h-hypoxia plus 12h-reoxygenation. Furthermore, micafungin, an antifungal drug, could also exert beneficial effect on mitigating myocardial I/R injury via inhibition of MALT1. Based on these observations, we conclud that inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.
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Ferroptosis , Daño por Reperfusión Miocárdica , Daño por Reperfusión , Animales , Ratas , Isquemia , Micafungina , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Factor 2 Relacionado con NF-E2 , Ratas Sprague-Dawley , ReperfusiónRESUMEN
Metal homeostasis is critical to normal neurophysiological activity. Metal ions are involved in the development, metabolism, redox and neurotransmitter transmission of the central nervous system (CNS). Thus, disturbance of homeostasis (such as metal deficiency or excess) can result in serious consequences, including neurooxidative stress, excitotoxicity, neuroinflammation, and nerve cell death. The uptake, transport and metabolism of metal ions are highly regulated by ion channels. There is growing evidence that metal ion disorders and/or the dysfunction of ion channels contribute to the progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, metal homeostasis-related signaling pathways are emerging as promising therapeutic targets for diverse neurological diseases. This review summarizes recent advances in the studies regarding the physiological and pathophysiological functions of metal ions and their channels, as well as their role in neurodegenerative diseases. In addition, currently available metal ion modulators and in vivo quantitative metal ion imaging methods are also discussed. Current work provides certain recommendations based on literatures and in-depth reflections to improve neurodegenerative diseases. Future studies should turn to crosstalk and interactions between different metal ions and their channels. Concomitant pharmacological interventions for two or more metal signaling pathways may offer clinical advantages in treating the neurodegenerative diseases.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Parkinson/metabolismo , Canales Iónicos/metabolismo , Canales Iónicos/uso terapéutico , HomeostasisRESUMEN
Authenticity refers to behaving in a manner that aligns with one's true self. The true self, though, is positive. From a self-enhancement standpoint, people exaggerate their strengths and overlook their shortcomings, forming positively-distorted views of themselves. We propose a self-enhancement framework of authenticity, advocating a reciprocal relation between the two constructs. Trait self-enhancement was associated with higher trait authenticity (Study 1), and day-to-day fluctuations in self-enhancement predicted corresponding variations in state authenticity (Study 2). Furthermore, manipulating self-enhancement elevated state authenticity (Studies 3-4), which was associated with meaning in life (Study 4), and manipulating authenticity augmented self-enhancement, which was associated with meaning in life and thriving (Study 5). The authentic self is largely the self-enhancing self.