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1.
Age Ageing ; 53(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39324773

RESUMEN

BACKGROUND: To explore temporal trends and determine driving factors of age-related macular degeneration (AMD) burden in older adults aged 60-89 years at global, regional and national levels from 1990 to 2019. METHODS: Prevalence and years lived with disability (YLDs) were extracted. Joinpoint regression analysis was adopted to calculate average annual percentage change and to identify the year with the most significant changes. Global trends were stratified by sex, age and sociodemographic index, and regional and national trends were explored. Decomposition analysis was conducted to determine what extent the forces of population size, age structure and epidemiologic change driving alterations of AMD burden. RESULTS: Globally, prevalence rate slightly increased whereas YLDs rate decreased. The year 2005 marked a turning point where both prevalence and YLDs started to decline. Regionally, Western Sub-Saharan Africa had the highest prevalence and YLDs rates in 2019, with East Asia experiencing the most notable rise in prevalence from 1990 to 2019. Global decomposition revealed that the increased case number was primarily driven by population growth and ageing, and epidemiological change was only detected to lessen but far from offset these impacts. CONCLUSIONS: Although there was only slight increase or even decrease in prevalence and YLDs rates of AMD in older adults, the case number still nearly doubled, which may be primarily attributed to population growth and ageing, coupled with the emerging growing pattern of prevalence rate from 2015, collectively suggesting a huge challenge in control and management of AMD.


Asunto(s)
Salud Global , Degeneración Macular , Humanos , Anciano , Degeneración Macular/epidemiología , Degeneración Macular/diagnóstico , Masculino , Anciano de 80 o más Años , Femenino , Prevalencia , Persona de Mediana Edad , Salud Global/estadística & datos numéricos , Factores de Edad , Factores de Riesgo , Costo de Enfermedad , Factores de Tiempo
2.
Sci Total Environ ; 954: 176270, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278506

RESUMEN

Antibiotic contamination and eutrophication in mariculture have become problems that cannot be ignored, and enrofloxacin (ENR), as an example, is especially widely used in mariculture. This study firstly revealed that Sesuvium portulacastrum, a plant with world-wide distribution in coastal zones, with its rhizosphere microorganisms, could remove ENR as well as nutrients. The S. portulacastrum system could degrade ENR to small-molecule products 1,2,3,4-tetrahydroquinolin-4-ol and (2,4-dihydroxyphenyl)-cyclopropylamine. And there were 81.3-39.2 % removals of ENR with 0.01-100 mg/L. Although ENR significantly influenced functions of rhizosphere microbial community, like decreasing nitrogen fixation, shifting trophic strategies from phototrophy to chemoheterotrophy, nutrients (NH4+-N, NO2--N, NO3--N and total dissolved phosphorus) removal of S. portulacastrum system was essentially unaffected at low ENR concentration (< 1 mg/L). The removal mechanism of S. portulacastrum system was explored. Neither of the isolated root exudates and rhizosphere bacteria could degrade ENR, however, without rhizosphere bacteria, ENR removal rate would decrease. Root proteins including oxidase, decarboxylase, dehydrogenase, such as laccase, isocitrate dehydrogenase, delta-1-pyrroline-5-carboxylate dehydrogenase were overexpressed. Additionally, endocytosis is a pathway for antibiotics to enter S. portulacastrum. This study demonstrated that S. portulacastrum system could be used for remediation of antibiotics-nutrients combined pollution, and deepened understanding the antibiotic removal mechanism of macrophytes in mariculture, moreover, provided new macroplant species and a theoretical basis for antibiotics removal in aquatic systems.

3.
Naturwissenschaften ; 111(5): 50, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331084

RESUMEN

Biophotovoltaics (BPV) is a clean and sustainable solar energy generation technology that operates by utilizing photosynthetic autotrophic microorganisms to capture light energy and generate electricity. However, a major challenge faced by BPV systems is the relatively low electron transfer efficiency from the photosystem to the extracellular electrode, which limits its electrical output. Additionally, the transfer mechanisms of photosynthetic microorganism metabolites in the entire system are still not fully clear. In response to this, this article briefly introduces the basic BPV principles, reviews its development history, and summarizes measures to optimize its electrogenic efficiency. Furthermore, recent studies have found that constructing photosynthetic-electrogenic microbial consortia can achieve high power density and stability in BPV systems. Therefore, the article discusses the potential application of constructing photosynthetic-electrogenic microbial aggregates in BPV systems. Since photosynthetic-electrogenic microbial communities can also exist in natural ecosystems, their potential contribution to the carbon cycle is worth further attention.


Asunto(s)
Fotosíntesis , Fotosíntesis/fisiología , Secuestro de Carbono , Fuentes de Energía Bioeléctrica , Energía Solar
4.
Water Res ; 267: 122472, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39305525

RESUMEN

This study examined the influence of water periods on river nitrogen cycling by analysing nitrogen functional genes and bacterial communities in the Qingshui River, an upstream tributary of the Yellow River in China. Nitrate nitrogen predominated as inorganic nitrogen during the low-flow seasons, whereas salinity was highest during the high-flow seasons. Overall, the functional gene abundance increased with decreasing water volume, and nitrogen concentrations were determined by various specific gene groups. The relative abundance of bacteria carrying these genes varied significantly across water periods. The abundance of Pseudomona, Hydrogenophaga (carrying narGHI and nirB genes), and Flavobacterium (carrying nirK, norBC, and nosZ genes) significantly increased during the low-flow seasons. Nitrogen transformation bacteria exhibited both symbiotic and mutualistic relationships. Microbial network nodes and sizes decreased with decreasing water volume, whereas modularity increased. Additionally, the water period affected the functional microbial community structure by influencing specific environmental factors. Among them, SO42- primarily determined the denitrification, dissimilatory nitrate reduction to ammonium, and assimilatory nitrate reduction to ammonium communities, whereas NO2--N and Mg2+ were the main driving factors for the nitrogen-fixing and nitrifying communities, respectively. These findings have substantial implications for better understanding the reduction in river nitrogen loads in arid and semi-arid regions during different water periods.

5.
Water Res ; 266: 122408, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39260193

RESUMEN

The occurrence and risk of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), derived from the oxidation of the tire antidegradant 6PPD, has raised significant concern since it was found to cause acute mortality in coho salmon when exposed to urban runoff. Given the short half-life period and low solubility of 6PPD-Q, reliable in situ measurement techniques are required to accurately understand its occurrence and behaviour in aquatic environments. Here, using the diffusive gradients in thin-films (DGT) method with HLB as a binding agent, we developed a new methodology to measure 6PPD-Q in urban waters. 6PPD-Q was rapidly and strongly adsorbed on the HLB-binding gel and was efficiently extracted using organic solvents. The HLB-DGT accumulated 6PPD-Q linearly for >7 d and its performance was not significantly affected by pH (6.5-8.5), ionic strength (0.0001-0.5 M) or dissolved organic matter (0-20 mg L-1). Field evaluation of the DGT method demonstrated its effectiveness in urban runoff, detecting 6PPD-Q levels of 15.8-39.5 ng L-1 in rivers. In snowmelt, DGT detected 6PPD-Q levels of 210 ng L-1 which is two times higher than the value obtained by grab sampling. 6PPD-Q levels were much higher in snowmelt than those in rivers. This indicates that snowfall constitutes an important transport pathway for 6PPD-Q and that DGT effectively captured the fraction continuously released from dust particles in the snow samples. 6PPD-Q posed a substantial risk to migratory fish in urban waters, and its release from tire wear particles requires further investigation. This study is the first to develop a DGT-based method for 6PPD-Q determination in urban waters, and the method can ensure an accurate measurement of the release of 6PPD-Q to the environment, particularly in rainfall or snowmelt, important pathways for its entry into the aquatic environment.

6.
Elife ; 132024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259197

RESUMEN

The emergence of myelinating oligodendrocytes represents a pivotal developmental milestone in vertebrates, given their capacity to ensheath axons and facilitate the swift conduction of action potentials. It is widely accepted that cortical oligodendrocyte progenitor cells (OPCs) arise from medial ganglionic eminence (MGE), lateral/caudal ganglionic eminence (LGE/CGE), and cortical radial glial cells (RGCs). Here, we used two different fate mapping strategies to challenge the established notion that the LGE generates cortical OPCs. Furthermore, we used a Cre/loxP-dependent exclusion strategy to reveal that the LGE/CGE does not give rise to cortical OPCs. Additionally, we showed that specifically eliminating MGE-derived OPCs leads to a significant reduction of cortical OPCs. Together, our findings indicate that the LGE does not generate cortical OPCs, contrary to previous beliefs. These findings provide a new view of the developmental origins of cortical OPCs and a valuable foundation for future research on both normal development and oligodendrocyte-related disease.


Asunto(s)
Corteza Cerebral , Oligodendroglía , Animales , Oligodendroglía/fisiología , Oligodendroglía/citología , Ratones , Corteza Cerebral/embriología , Corteza Cerebral/fisiología , Corteza Cerebral/citología , Células Precursoras de Oligodendrocitos/fisiología , Células Precursoras de Oligodendrocitos/citología , Diferenciación Celular , Eminencia Ganglionar
7.
J Agric Food Chem ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39226078

RESUMEN

The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.

8.
J Clin Immunol ; 44(8): 184, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177867

RESUMEN

PURPOSE: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. METHODS: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. RESULTS: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. CONCLUSION: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease.


Asunto(s)
Candidiasis Mucocutánea Crónica , Mutación con Ganancia de Función , Inmunofenotipificación , Pirazoles , Factor de Transcripción STAT1 , Humanos , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/diagnóstico , Candidiasis Mucocutánea Crónica/terapia , Masculino , Femenino , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Azetidinas/uso terapéutico , Purinas/uso terapéutico , Niño , Adolescente , Taiwán , Adulto
9.
Bioresour Technol ; 409: 131234, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39117245

RESUMEN

To recycle the nutrients in spiramycin (SPM) fermentation residue (SFR) through biological methods, acid hydrothermal treatment (AHT) was employed as pretreatment to enhance SFR biodegradability. The results showed that the degradation rate of residual SPM in SFR reached 100% after 120 min at 100℃ and 0.30 M acid with a 30.5% and 89.7% increase in proteins and polysaccharides, respectively. The SPM degradation was faster at higher acidity and temperature. However, elevated SPM concentration and the presence of protein, humic acid, and polysaccharide inhibited SPM degradation. The disintegration of SFR was evidenced by changes in its microstructure and could be predicted through the release of dissolved organic matter. Eight major SPM intermediates were identified with lower mutagenicity and antibacterial activity testing against Staphylococcus aureus. These results demonstrate that AHT not only disintegrates SFR but also degrades the residual SPM antibiotics, which implies the possibility for practical applications.


Asunto(s)
Antibacterianos , Fermentación , Espiramicina , Antibacterianos/farmacología , Antibacterianos/química , Espiramicina/farmacología , Espiramicina/química , Staphylococcus aureus/efectos de los fármacos , Temperatura , Agua/química , Concentración de Iones de Hidrógeno , Ácidos/química , Biodegradación Ambiental
10.
Mol Cell Neurosci ; 130: 103958, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39151841

RESUMEN

Increasing evidence suggests that cannabinoid receptor 2 (CB2R) serves as a promising anti-inflammatory target. While inflammation is known to play crucial roles in the pathogenesis of epilepsy, the involvement of CB2R in epilepsy remains unclear. This study aimed to investigate the effects of a CB2R agonist, AM1241, on epileptic seizures and depressive-like behaviors in a mouse model of chronic epilepsy induced by pilocarpine. A chronic epilepsy mouse model was established by intraperitoneal administration of pilocarpine. The endogenous cannabinoid system (eCBs) in the hippocampus was examined after status epilepticus (SE). Animals were then treated with AM1241 and compared with a vehicle-treated control group. Additionally, the role of the AMPK/NLRP3 signaling pathway was explored using the selective AMPK inhibitor dorsomorphin. Following SE, CB2R expression increased significantly in hippocampal microglia. Administration of AM1241 significantly reduced seizure frequency, immobility time in the tail suspension test, and neuronal loss in the hippocampus. In addition, AM1241 treatment attenuated microglial activation, inhibited pro-inflammatory polarization of microglia, and suppressed NLRP3 inflammasome activation in the hippocampus after SE. Further, the therapeutic effects of AM1241 were abolished by the AMPK inhibitor dorsomorphin. Our findings suggest that CB2R agonist AM1241 may alleviate epileptic seizures and its associated depression by inhibiting neuroinflammation through the AMPK/NLRP3 signaling pathway. These results provide insight into a novel therapeutic approach for epilepsy.


Asunto(s)
Depresión , Modelos Animales de Enfermedad , Hipocampo , Pilocarpina , Receptor Cannabinoide CB2 , Convulsiones , Animales , Masculino , Ratones , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Depresión/etiología , Depresión/tratamiento farmacológico , Depresión/metabolismo , Epilepsia/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamente , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/metabolismo , Convulsiones/metabolismo , Convulsiones/tratamiento farmacológico
11.
Ann Hematol ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39105739

RESUMEN

ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.

12.
J Clin Immunol ; 44(8): 176, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133333

RESUMEN

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.


Asunto(s)
Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Nocardiosis , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Nocardiosis/inmunología , Nocardiosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/inmunología
13.
Acta Neuropathol ; 148(1): 21, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150562

RESUMEN

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by the expansion of GGC trinucleotide repeats in NOTCH2NLC gene. Despite identifying uN2CpolyG, a toxic polyglycine (polyG) protein translated by expanded GGC repeats, the exact pathogenic mechanisms of NIID remain unclear. In this study, we investigated the role of polyG by expressing various forms of NOTCH2NLC in mice: the wild-type, the expanded form with 100 GGC repeats (either translating or not translating into uN2CpolyG), and the mutated form that encodes a pure polyG without GGC-repeat RNA and the C-terminal stretch (uN2CpolyG-dCT). Both uN2CpolyG and uN2CpolyG-dCT induced the formation of inclusions composed by filamentous materials and resulted in neurodegenerative phenotypes in mice, including impaired motor and cognitive performance, shortened lifespan, and pathologic lesions such as white-matter lesions, microgliosis, and astrogliosis. In contrast, expressing GGC-repeat RNA alone was non-pathogenic. Through bulk and single-nuclei RNA sequencing, we identified common molecular signatures linked to the expression of uN2CpolyG and uN2CpolyG-dCT, particularly the upregulation of inflammation and microglia markers, and the downregulation of immediate early genes and splicing factors. Importantly, microglia-mediated inflammation was visualized in NIID patients using positron emission tomography, correlating with levels of white-matter atrophy. Furthermore, microglia ablation ameliorated neurodegenerative phenotypes and transcriptional alterations in uN2CpolyG-expressing mice but did not affect polyG inclusions. Together, these results demonstrate that polyG is crucial for the pathogenesis of NIID and highlight the significant role of microglia in polyG-induced neurodegeneration.


Asunto(s)
Cuerpos de Inclusión Intranucleares , Microglía , Enfermedades Neurodegenerativas , Animales , Microglía/patología , Microglía/metabolismo , Cuerpos de Inclusión Intranucleares/patología , Cuerpos de Inclusión Intranucleares/metabolismo , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Ratones , Ratones Transgénicos , Expansión de Repetición de Trinucleótido/genética , Humanos , Masculino , Femenino
14.
Hortic Res ; 11(8): uhae158, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108587

RESUMEN

Chromatin structure plays a critical role in the regulation of dynamic gene expression in response to different developmental and environmental cues, but as yet their involvement in fruit ripening is not well understood. Here, we profile seven histone modifications in the woodland strawberry (Fragaria vesca) genome and analyze the histone modification signatures during ripening. Collectively, segments painted by the seven marks cover ~85% of the woodland strawberry genome. We report an eight-state chromatin structure model of the woodland strawberry based on the above histone marks, which reveals a diverse chromatin environment closely associated with transcriptional apparatus. Upon this model we build a chromatin-centric annotation to the strawberry genome. Expression of many genes essential for fruit ripening, such as abscisic acid catabolism, anthocyanin accumulation and fruit softening, are associated with shifts of active genic states and polycomb-associated chromatin states. Particularly, the expression levels of ripening-related genes are well correlated with histone acetylation, indicating a regulatory role of histone acetylation in strawberry ripening. Our identification of the chromatin states underpinning genome expression during fruit ripening not only elucidates the coordination of different pathways of morphological and metabolic development but also provides a framework to understand the signals that regulate fruit ripening.

15.
Neurosci Bull ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956006

RESUMEN

Unlocking task-related EEG spectra is crucial for neuroscience. Traditional convolutional neural networks (CNNs) effectively extract these features but face limitations like overfitting due to small datasets. To address this issue, we propose a lightweight CNN and assess its interpretability through the fully connected layer (FCL). Initially tested with two tasks (Task 1: open vs closed eyes, Task 2: interictal vs ictal stage), the CNN demonstrated enhanced spectral features in the alpha band for Task 1 and the theta band for Task 2, aligning with established neurophysiological characteristics. Subsequent experiments on two brain-computer interface tasks revealed a correlation between delta activity (around 1.55 Hz) and hand movement, with consistent results across pericentral electroencephalogram (EEG) channels. Compared to recent research, our method stands out by delivering task-related spectral features through FCL, resulting in significantly fewer trainable parameters while maintaining comparable interpretability. This indicates its potential suitability for a wider array of EEG decoding scenarios.

16.
Nat Commun ; 15(1): 5866, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997249

RESUMEN

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.


Asunto(s)
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/metabolismo
17.
Cell Discov ; 10(1): 75, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992047

RESUMEN

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

18.
Mol Neurobiol ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976130

RESUMEN

Protein phosphatase 2A (PP2A) is an abundant heterotrimeric holoenzyme in eukaryotic cells coordinating with specific kinases to regulate spatial-temporal protein dephosphorylation in various biological processes. However, the function of PP2A in cortical neurogenesis remains largely unknown. Here, we report that neuronal-specific deletion of Pp2acα in mice displayed microcephaly, with significantly smaller brains and defective learning and memory ability. Mechanistically, neuronal Pp2acα deficiency resulted in elevated endogenous DNA damage and activation of ATR/CHK1 signaling. It was further induced by the loss of direct interaction between PP2AC and ATR as well as the function of PP2AC to dephosphorylate ATR. Importantly, ATR/CHK1 signaling dysregulation altered both the expression and activity of several critical downstream factors including P53, P21, Bcl2, and Bax, which led to decreased proliferation of cortical progenitor cells and increased apoptosis in developing cortical neurons. Taken together, our results indicate an essential function of PP2ACα in endogenous DNA damage response-mediated ATR signaling during neurogenesis, and defective PP2ACα in neurons contributes to microcephaly.

19.
J Environ Manage ; 365: 121633, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38955044

RESUMEN

The development of sustainable advanced energy conversion technologies and efficient pollutant treatment processes is a viable solution to the two global crises of the lack of non-renewable energy resources and environmental harm. In recent years, the interaction of biological and chemical oxidation units to utilize biomass has been extensively studied. Among these systems, bio-electro-Fenton (BEF) and photo-bio-electro-Fenton (PBEF) systems have shown prospects for application due to making rational and practical conversion and use of energy. This review compared and analyzed the electron transfer mechanisms in BEF and PBEF systems, and systematically summarized the techniques for enhancing system performance based on the generation, transfer, and utilization of electrons, including increasing the anode electron recovery efficiency, enhancing the generation of reactive oxygen species, and optimizing operational modes. This review compared the effects of different methods on the electron flow process and fully evaluated the benefits and drawbacks. This review may provide straightforward suggestions and methods to enhance the performance of BEF and PBEF systems and inspire the reader to explore the generation and utilization of sustainable energy more deeply.


Asunto(s)
Oxidación-Reducción , Peróxido de Hidrógeno/química , Hierro/química , Especies Reactivas de Oxígeno , Biomasa
20.
BMC Biol ; 22(1): 158, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075478

RESUMEN

BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.


Asunto(s)
Trampas Extracelulares , Evasión Inmune , Trichinella spiralis , Animales , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Proteínas del Helminto/metabolismo , Larva/inmunología , Larva/parasitología , Trichinella spiralis/fisiología , Trichinella spiralis/inmunología
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