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The actual role of coronavirus disease 2019 (COVID-19) in brain damage has been increasingly reported, necessitating a meta-analysis to collate and summarize the inconsistent findings from functional imaging and voxel-based morphometry (VBM) studies. A comprehensive voxel-wise meta-analysis of the whole brain was conducted to identify alterations in functional activity and gray matter volume (GMV) between COVID-19 patients and healthy controls (HCs) by using Seed-based d Mapping software. We included 15 functional imaging studies (484 patients with COVID-19, 534 HCs) and 9 VBM studies (449 patients with COVID-19, 388 HCs) in the analysis. Overall, patients with COVID-19 exhibited decreased functional activity in the right superior temporal gyrus (STG) (extending to the right middle and inferior temporal gyrus, insula, and temporal pole [TP]), left insula, right orbitofrontal cortex (OFC) (extending to the right olfactory cortex), and left cerebellum compared to HCs. For VBM, patients with COVID-19, relative to HCs, showed decreased GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (extending to the bilateral OFC), and left cerebellum, and increased GMV in the bilateral amygdala (extending to the bilateral hippocampus, STG, TP, MTG, and right striatum). Moreover, overlapping analysis revealed that patients with COVID-19 exhibited both decreased functional activity and increased GMV in the right TP (extending to the right STG). The multimodal meta-analysis suggests that brain changes of function and structure in the temporal lobe, OFC and cerebellum, and functional or structural alterations in the insula and the limbic system in COVID-19. These findings contribute to a better understanding of the pathophysiology of brain alterations in COVID-19. SIGNIFICANCE STATEMENT: This first large-scale multimodal meta-analysis collates existing neuroimaging studies and provides voxel-wise functional and structural whole-brain abnormalities in COVID-19. Findings of this meta-analysis provide valuable insights into the dynamic brain changes (from infection to recovery) and offer further explanations for the pathophysiological basis of brain alterations in COVID-19.
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Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.
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Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Hipocampo , Imagen por Resonancia Magnética , Humanos , Trastorno Depresivo Mayor/microbiología , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Masculino , Hipocampo/fisiopatología , Hipocampo/diagnóstico por imagen , Hipocampo/microbiología , Adulto , Femenino , Disbiosis/microbiología , Disbiosis/fisiopatología , Adulto Joven , Estudios de Casos y Controles , Persona de Mediana Edad , Heces/microbiologíaRESUMEN
RIPK1/TAK1 are important for programmed cell death, including liver death, necroptosis and apoptosis. However, there have been few published reports on the functions of RIPK1/TAK1 in invertebrates. In this study, full-length ChRIPK1 and ChTAK1 were cloned from C. hongkongensis through the rapid amplification of cDNA ends (RACE) technology. ChRIPK1 has almost no homology with human RIPK1 and lacks a kinase domain at the N-terminus but has a DD and RHIM domain. ChTAK1 is conserved throughout evolution. qRTâPCR was used to analyze the mRNA expression patterns of ChRIPK1 in different tissues, developmental stages, and V. coralliilyticus-infected individuals, and both were highly expressed in the mantle and gills, while ChRIPK1 was upregulated in hemocytes and gills after V. coralliilyticus or S. aureus infection, which indicates that ChRIPK1 is involved in immune regulation. Fluorescence assays revealed that ChRIPK1 localized to the cytoplasm of HEK293T cells in a punctiform manner, but the colocalization of ChRIPK1 with ChTAK1 abolished the punctiform morphology. In the dual-luciferase reporter assay, both ChRIPK1 and ChRIPK1-RIHM activated the NF-κB signaling pathway in HEK293T cells, and ChTAK1 activated ChRIPK1 in the NF-κB signaling pathway. The apoptosis rate of the hemocytes was not affected by the necroptosis inhibitor Nec-1 but was significantly decreased, and ChRIPK1 expression was knocked down in the hemocytes of C. hongkongensis. These findings indicated that ChRIPK1 induces apoptosis but not necroptosis in oysters. This study provides a theoretical basis for further research on the molecular mechanism by which invertebrates regulate the programmed cell death of hemocytes in oysters.
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Crassostrea , Necroptosis , Filogenia , Transducción de Señal , Animales , Crassostrea/genética , Crassostrea/inmunología , Necroptosis/inmunología , Transducción de Señal/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Regulación de la Expresión Génica/inmunología , Alineación de Secuencia/veterinaria , Perfilación de la Expresión Génica/veterinaria , Secuencia de Aminoácidos , Inmunidad Innata/genética , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/inmunología , Staphylococcus aureus/fisiología , Dinoflagelados/fisiología , Dinoflagelados/genéticaRESUMEN
BACKGROUND: Since 1990 s, China has witnessed a widespread transition to clean cooking fuels, presenting an opportunity to investigate whether household fuel transition could mitigate obesity risk and reconcile inconsistencies in the literature regarding the association between cooking fuels and obesity. METHODS: The China Health and Nutrition Survey (CHNS) is a prospective cohort study covering 12 provinces of China (1989-2015). Participants were classified into persistent cleaner fuel users, fuel transitioners, and persistent polluting fuel users according to self-reported primary cooking fuels. Obesity and central obesity were defined as BMI ≥ 28.0 kg/m2 and waist circumference ≥ 90 cm in men and ≥ 85 cm in women according to Chinese criteria. FINDINGS: Among 13,032 participants, 3657 (28.06 %) were persistent cleaner fuel users; 5264 (40.39 %) transitioned from using polluting fuels to cleaner fuels after the baseline survey; and 4111 (31.55 %) were persistent polluting fuel users. During the period of follow-up of 9.0 ± 6.8 years, 1248 (9.58 %) participants were classified into the obesity category, and 4703 (36.09 %) into the central obesity category. Persistent polluting fuel users had a significantly higher risk of developing obesity (hazard ratio [HR]: 1.45, 95 %CI: 1.22-1.72) and central obesity (HR: 1.32, 95 %CI: 1.21-1.44), compared to persistent cleaner fuel users. Persistent polluting fuel use was positively associated with developing obesity in women (HR: 1.64, 95 %CI: 1.30-2.06), but not in men. Subgroup analyses showed higher HR of persistent polluting fuel use among individuals aged 18-44 years (HR: 2.04, 95 %CI: 1.62-2.56). In contrast, the transitioners did not exhibit a significantly different risk of developing obesity (HR: 0.94, 95 %CI: 0.80-1.10) compared to persistent cleaner fuel users, which was consistent across different sex, age and urbanicity. Similar trends were observed for developing central obesity. INTERPRETATION: Persistent polluting fuel use increased obesity risk while the obesity risk of the transition to cleaner fuels was similar to persistent use of cleaner fuels. The finding underscores the significance of advocating for the adoption of cleaner fuels as a strategy to mitigate the disease burden associated with obesity.
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It is known that selenium (Se) enhances plant growth and arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated mechanisms are unclear. In this study, P. vittata was exposed to 50 µM arsenate (AsV) under hydroponics plus 25 or 50 µM foliar selenate. After 3-weeks of growth, the plant biomass, As and Se contents, As speciation, malondialdehyde (MDA) and glutathione (GSH and GSSG) levels, and important genes related to As-metabolism in P. vittata were determined. Foliar-Se increased plant biomass by 17 - 30 %, possibly due to 9.1 - 19 % reduction in MDA content compared to the As control. Further, foliar-Se enhanced the As contents by 1.9-3.5 folds and increased arsenite (AsIII) contents by 64 - 136 % in the fronds. The increased AsV reduction to AsIII was attributed to 60 - 131 % increase in glutathione peroxidase activity, which mediates GSH oxidation to GSSG (8.8 -29 % increase) in the fronds. Further, foliar-Se increased the expression of AsIII antiporters PvACR3;1-3;3 by 1.6 - 2.1 folds but had no impact on phosphate transporters PvPht1 or arsenate reductases PvHAC1/2. Our results indicate that foliar-Se effectively enhances plant growth and arsenic accumulation by promoting the GSH-GSSG cycle and upregulating gene expression of AsIII antiporters, which are responsible for AsIII translocation from the roots to fronds and AsIII sequestration into the fronds. The data indicate that foliar-Se can effectively improve phytoremediation efficiency of P. vittata in As-contaminated soils.
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Arsénico , Arsenitos , Glutatión , Hojas de la Planta , Pteris , Selenio , Arseniatos/metabolismo , Arsénico/metabolismo , Arsenitos/metabolismo , Biodegradación Ambiental , Glutatión/metabolismo , Malondialdehído/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Pteris/metabolismo , Pteris/crecimiento & desarrollo , Pteris/genética , Pteris/efectos de los fármacos , Selenio/metabolismo , Selenio/farmacología , Contaminantes del Suelo/metabolismoRESUMEN
Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.
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Acetilcisteína , Biopelículas , Candida parapsilosis , Candidemia , Infecciones Relacionadas con Catéteres , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Acetilcisteína/farmacología , Humanos , Candida parapsilosis/efectos de los fármacos , Candida parapsilosis/genética , Candida parapsilosis/fisiología , Infecciones Relacionadas con Catéteres/microbiología , Candidemia/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Antifúngicos/farmacologíaRESUMEN
Arsenic-hyperaccumulator Pteris vittata exhibits remarkable absorption ability for chromium (Cr) while beneficial element selenium (Se) helps to reduce Cr-induced stress in plants. However, the effects of Se on the Cr uptake and the associated mechanisms in P. vittata are unclear, which were investigated in this study. P. vittata plants were grown for 14 days in 0.2-strength Hoagland solution containing 10 (Cr10) or 100 µM (Cr100) chromate (CrVI) and 1 µM selenate (Se1). The plant biomass, malondialdehyde contents, total Cr and Se contents, Cr speciation, expression of genes associated with Cr uptake, and Cr subcellular distribution in P. vittata were determined. P. vittata effectively accumulated Cr by concentrating 96-99% in the roots under Cr100 treatment. Further, Se substantially increased its Cr contents by 98% to 11,596 mg kg-1 in the roots, which may result from Se's role in reducing its oxidative stress as supported by 27-62% reduction in the malondialdehyde contents. Though supplied with CrVI, up to 98% of the Cr in the roots was reduced to insoluble chromite (CrIII), with 83-89% being distributed on root cell walls. Neither Cr nor Se upregulated the expression of sulfate transporters PvSultr1;1-1;2 or phosphate transporter PvPht1;4, indicating their limited role in Cr uptake. P. vittata effectively accumulates Cr in the roots mainly as CrIII on cell walls and Se effectively enhances its Cr uptake by reducing its oxidative stress. Our study suggests that Se can be used to enhance P. vittata Cr uptake and reduce its oxidative stress, which may have application in phytostabilization of Cr-contaminated soils.
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Sodium-ion batteries (SIBs) represent a promising energy storage technology with great safety. Because of their high operating potential, superior structural stability, and prominent thermal stability, polyanion-type phosphates have garnered significant interest in superior prospective cathode materials for SIBs. Nevertheless, the disadvantages of poor intrinsic electronic conductivity, sluggish kinetics, and volume variation during sodiation/desodiation remain great challenges for satisfactory rate performance and cycle stability, which severely hinder their further practical applications. In this work, by adjusting the amounts of pretreated multiwalled carbon nanotubes (CNT) added intentionally at the beginning of the preparation, biphasic polyanion-type phosphate materials (marked as NFC) are synthesized through a one-pot solid state reaction methodology, which are composed of CNT-interwoven Na3V2(PO4)2F3 (NVPF) and a small amount of Na3V2(PO4)3 (NVP). Benefiting from the improved electronic conductivity and unique composition and structure, the optimized sample (labeled as NFC-2) illustrates exceptional cycle stability and remarkable rate performance. The discharge capacities of the NFC-2 electrode are 114.8 and 78.6 mAh g-1 tested at 20 and 5000 mA g-1, respectively. Notably, such an electrode still gives out 75.7% capacity retention upon 10â¯000 cycles at 5000 mA g-1. In situ X-ray diffraction analysis demonstrates that the NFC-2 cathode has outstanding structural reversibility during charge/discharge cycles. More importantly, such a biphasic material has achieved impressive electrochemical performance within a wide operating temperature range of -20-50 °C. When temperature is decreased to -20 °C, the NFC-2 electrode still delivers an initial discharge capacity of 102.4 mAh g-1 and exhibits a remarkable capacity retention of 97.8% even after 500 cycles at 50 mA g-1. In addition, the sodium-ion full cell assembled by integrating NFC-2 cathode and hard carbon anode shows a satisfying energy density of 431.3 Wh kg-1 at 20 mA g-1 with a better long-term cycle performance. The synergistic effect among high energy NVPF, conductive CNT, and stable NVP may lead to the great improvement in the electrochemical sodium storage performance of the NFC-2 sample. Such biphasic polyanion-type phosphate materials will inject new ideas into the material design for SIBs with excellent electrochemical performance and further promote practical applications of this advanced energy storage technology.
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Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.
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The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
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Glándulas Suprarrenales , Esteroides , Animales , Glándulas Suprarrenales/metabolismo , Humanos , Esteroides/biosíntesis , Esteroides/metabolismo , Transcriptoma , Ratones , Tupaiidae , Femenino , MultiómicaRESUMEN
BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.
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Trastorno del Espectro Autista , Humanos , Trastorno del Espectro Autista/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Giro del Cíngulo , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Researchers have endeavored to ascertain the network dysfunction associated with behavioral addiction (BA) through the utilization of resting-state functional connectivity (rsFC). Nevertheless, the identification of aberrant patterns within large-scale networks pertaining to BA has proven to be challenging. METHODS: Whole-brain seed-based rsFC studies comparing subjects with BA and healthy controls (HC) were collected from multiple databases. Multilevel kernel density analysis was employed to ascertain brain networks in which BA was linked to hyper-connectivity or hypo-connectivity with each prior network. RESULTS: Fifty-six seed-based rsFC publications (1755 individuals with BA and 1828 HC) were included in the meta-analysis. The present study indicate that individuals with BAs exhibit (1) hypo-connectivity within the fronto-parietal network (FN) and hypo- and hyper-connectivity within the ventral attention network (VAN); (2) hypo-connectivity between the FN and regions of the VAN, hypo-connectivity between the VAN and regions of the FN and default mode network (DMN), hyper-connectivity between the DMN and regions of the FN; (3) hypo-connectivity between the reward system and regions of the sensorimotor network (SS), DMN and VAN; (4) hypo-connectivity between the FN and regions of the SS, hyper-connectivity between the VAN and regions of the SS. CONCLUSIONS: These findings provide impetus for a conceptual framework positing a model of BA characterized by disconnected functional coordination among large-scale networks.
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Conducta Adictiva , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Conducta Adictiva/diagnóstico por imagen , Bases de Datos Factuales , Análisis Multinivel , Mapeo EncefálicoRESUMEN
SCOPE: Premature ovarian insufficiency (POI) is a common female infertility problem, with its pathogenesis remains unknown. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of α-ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms. METHODS AND RESULTS: POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate-limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, Interleukin-18 (IL-18), and Interleukin-1 beta (IL-1ß). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect. CONCLUSION: AKG ameliorates CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.
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Reserva Ovárica , Insuficiencia Ovárica Primaria , Humanos , Ratas , Femenino , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácidos Cetoglutáricos/farmacología , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Piroptosis , Células de la Granulosa/metabolismo , Inflamasomas/metabolismoRESUMEN
OBJECTIVE: This study aims to investigate the perioperative experience and needs of patients with liver cancer for interventional therapy, in order to provide the basis for further improving a patient's medical experience and satisfaction. METHODS: A semi-structured in-depth interview was conducted for 16 patients with liver cancer in interventional therapy using the phenomenological research method of qualitative research. The themes were analyzed, summarized, refined and extracted using the Colaizzi analytical procedure. RESULTS: The study results revealed that the perioperative experience and needs of patients with liver cancer for interventional therapy could mainly be summarized into seven themes: anxiety, fear and helplessness; not understanding the specific procedures of interventional therapy; worrying that the disease would not be treated as expected; lack of understanding of perioperative adverse reactions and the inability to cope with these; concern on the financial burden of health care costs on families; concerned on the physical and mental health of the dependent; the further improvement of diagnosis and treatment procedures. CONCLUSION: Patients with liver cancer undergo a complex psychological experience during interventional therapy. In clinical practice, a patient's psychological needs and changes should be valued, in order to provide a targeted psychological intervention, health guidance and social support, thereby improving the medical experience and satisfaction of patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Salud Mental , Apoyo Social , Investigación CualitativaRESUMEN
BACKGROUND: Numerous neuroimaging studies have reported that Alzheimer's disease (AD) spectrum have been linked to alterations in intrinsic functional activity and cortical thickness (CT) of some brain areas. However, the findings have been inconsistent and the correlation with the transcriptional profile and neurotransmitter systems remain largely unknown. METHODS: We conducted a meta-analysis to identify multimodal differences in the amplitude of low-frequency fluctuation (ALFF)/fractional ALFF (fALFF) and CT in patients with AD and preclinical AD compared to healthy controls (HCs), using the Seed-based d Mapping with Permutation of Subject Images software. Transcriptional data were retrieved from the Allen Human Brain Atlas. The atlas-based nuclear imaging-derived neurotransmitter maps were investigated by JuSpace toolbox. RESULTS: We included 26 ALFF/fALFF studies comprising 884 patients with AD and 1,020 controls, along with 52 studies comprising 2,046 patients with preclinical AD and 2,336 controls. For CT, we included 11 studies comprising 353 patients with AD and 330 controls. Overall, compared to HCs, patients with AD showed decreased ALFF/fALFF in the bilateral posterior cingulate gyrus (PCC)/precuneus and right angular gyrus, as well as increased ALFF/fALFF in the bilateral parahippocampal gyrus (PHG). Patients with peclinical AD showed decreased ALFF/fALFF in the left precuneus. Additionally, patients with AD displayed decreased CT in the bilateral PHG, left PCC, bilateral orbitofrontal cortex, sensorimotor areas and temporal lobe. Furthermore, gene sets related to brain structural and functional changes in AD and preclincal AD were enriched for G protein-coupled receptor signaling pathway, ion gated channel activity, and components of biological membrane. Functional and structural alterations in AD and preclinical AD were spatially associated with dopaminergic, serotonergic, and GABAergic neurotransmitter systems. CONCLUSIONS: The multimodal meta-analysis demonstrated that patients with AD exhibited convergent functional and structural alterations in the PCC/precuneus and PHG, as well as cortical thinning in the primary sensory and motor areas. Furthermore, patients with preclinical AD showed reduced functional activity in the precuneus. AD and preclinical AD showed genetic modulations/neurotransmitter deficits of brain functional and structural impairments. These findings may provide new insights into the pathophysiology of the AD spectrum.
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Enfermedad de Alzheimer , Mapeo Encefálico , Humanos , Mapeo Encefálico/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , NeurotransmisoresRESUMEN
To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Femenino , Humanos , Vacunas contra Papillomavirus/efectos adversos , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/etiología , Vacunación/efectos adversos , Inmunización , China/epidemiologíaRESUMEN
Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8+ T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8+ T cells and contributes to antitumor immunity. CD8+ T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8+ T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.
Asunto(s)
Linfocitos T CD8-positivos , Serotonina , Linfocitos T CD8-positivos/metabolismo , Serotonina/metabolismo , Serotonina/farmacología , Procesamiento Proteico-Postraduccional , Transducción de SeñalRESUMEN
BACKGROUND: Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC. METHODS: RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8). RESULTS: The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups. CONCLUSION: The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer.
Asunto(s)
Adenina/análogos & derivados , Adenocarcinoma , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , PáncreasRESUMEN
Long-term exposure to arsenic can lead to functional damage to many organs and can be life-threatening. It is of great significance to analyze the distribution characteristics of arsenic in water and evaluate its potential risk for preventing and controlling human health hazards caused by water-derived arsenic. Based on the published data from 2000 to 2022, the geographical distribution characteristics of arsenic in drinking water across China were systematically analyzed in detail, and the health risk of arsenic in drinking water was quantitatively assessed using disability-adjusted life years (DALYs), which represent the burden of disease. The results showed that the average concentration of arsenic in drinking water in China was (2.88 ±0.33) µg·L-1, which was lower than the limit of 10 µg·L-1 set by the standard for drinking water quality (GB 5749-2022). Nevertheless, the arsenic in drinking water in some provinces, including Shanxi, Inner Mongolia, and Ningxia, was still higher than the limit. The arsenic concentration in drinking water in northern China was higher than that in southern China, and that in rural areas was higher than that in cities. The estimated health risk of arsenic in drinking water (1.63×10-6 DALYs per person-year) was higher than the acceptable risk level of waterborne exposure of 1.0×10-6 DALYs per person-year set by the World Health Organization. The personal health risks related to arsenic in drinking water in the six geographical regions were ranked as follows:North China > Northeast China > Central South China > Northwest China > Southwest China > East China. Almost all (99.4%) of the health burden associated with water arsenic was attributable to skin and lung cancer, which caused 2 905.25 and 1 513.96 DALYs per year, respectively. Most (78.0%) of the health burden was borne by people aged 45 years or older. In addition, given the proportion of each age group in the total population, older persons over the age of 60 bear a higher drinking-water-associated arsenic burden at the individual level than others, and attention should be consequently paid to them when controlling the risk of arsenic in water.
Asunto(s)
Arsénico , Agua Potable , Contaminantes Químicos del Agua , Humanos , Anciano , Anciano de 80 o más Años , Arsénico/análisis , Agua Potable/efectos adversos , Años de Vida Ajustados por Discapacidad , Medición de Riesgo , Contaminantes Químicos del Agua/efectos adversos , Contaminantes Químicos del Agua/análisis , China/epidemiologíaRESUMEN
Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.