Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 409
Filtrar
Mais filtros

País/Região como assunto
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 119(48): e2212436119, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409903

RESUMO

Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic Escherichia coli (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system rbfSR, which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. rbfSR is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and Citrobacter rodentium, a surrogate for EHEC in mice. Introducing rbfSR into C. rodentium enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained rbfSR which has been kept in O157:H7 since then. Thus, acquiring rbfSR represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when rbfSR was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.


Assuntos
Escherichia coli Êntero-Hemorrágica , Escherichia coli O157 , Microbiota , Animais , Humanos , Camundongos , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli O157/genética , Riboflavina , Virulência/genética , Intestinos
2.
J Cogn Neurosci ; 36(8): 1695-1714, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579269

RESUMO

The brain is a hierarchical modular organization that varies across functional states. Network configuration can better reveal network organization patterns. However, the multi-hierarchy network configuration remains unknown. Here, we propose an eigenmodal decomposition approach to detect modules at multi-hierarchy, which can identify higher-layer potential submodules and is consistent with the brain hierarchical structure. We defined three metrics: node configuration matrix, combinability, and separability. Node configuration matrix represents network configuration changes between layers. Separability reflects network configuration from global to local, whereas combinability shows network configuration from local to global. First, we created a random network to verify the feasibility of the method. Results show that separability of real networks is larger than that of random networks, whereas combinability is smaller than random networks. Then, we analyzed a large data set incorporating fMRI data from resting and seven distinct tasking conditions. Experiment results demonstrates the high similarity in node configuration matrices for different task conditions, whereas the tasking states have less separability and greater combinability between modules compared with the resting state. Furthermore, the ability of brain network configuration can predict brain states and cognition performance. Crucially, derived from tasks are highlighted with greater power than resting, showing that task-induced attributes have a greater ability to reveal individual differences. Together, our study provides novel perspectives for analyzing the organization structure of complex brain networks at multi-hierarchy, gives new insights to further unravel the working mechanisms of the brain, and adds new evidence for tasking states to better characterize and predict behavioral traits.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Adulto , Masculino , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Feminino , Adulto Jovem , Mapeamento Encefálico , Conectoma , Desempenho Psicomotor/fisiologia
3.
Anal Chem ; 96(28): 11581-11587, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38951996

RESUMO

Ferroptosis is an iron-dependent programmed cell death that is characterized by the dysregulation of lipid reactive oxygen species (ROS) production, causing abnormal changes in hypochlorous acid (HClO) levels in lysosomes. Super-resolution imaging can observe the fine structure of the lysosome at the nanometer level; therefore, it can be used to detect lysosome HClO levels during ferroptosis at the suborganelle level. Herein, we utilize a ratiometric fluorescent probe, SRF-HClO, for super-resolution imaging of lysosome HClO. Structured-illumination microscopy (SIM) improves the accuracy of lysosome targeting and enables the probe SRF-HClO to be successfully applied to rapidly monitor the up-regulated lysosome HClO at the nanoscale during inflammation and ferroptosis. Importantly, the probe SRF-HClO can also detect HClO changes in inflammatory and ferroptosis mice and evaluate the inhibitory effect of ferroptosis on mice tumors.


Assuntos
Ferroptose , Corantes Fluorescentes , Ácido Hipocloroso , Lisossomos , Ferroptose/efeitos dos fármacos , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Lisossomos/química , Lisossomos/metabolismo , Animais , Camundongos , Humanos , Imagem Óptica , Células RAW 264.7
4.
Development ; 148(6)2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33658224

RESUMO

Starch accumulation is key for the maturity of rice pollen grains; however, the regulatory mechanism underlying this process remains unknown. Here, we have isolated a male-sterile rice mutant, abnormal pollen 1 (ap1), which produces nonviable pollen grains with defective starch accumulation. Functional analysis revealed that AP1 encodes an active L-type lectin receptor-like kinase (L-LecRLK). AP1 is localized to the plasma membrane and its transcript is highly accumulated in pollen during the starch synthesis phase. RNA-seq and phosphoproteomic analysis revealed that the expression/phosphorylation levels of numerous genes/proteins involved in starch and sucrose metabolism pathway were significantly altered in the mutant pollen, including a known rice UDP-glucose pyrophosphorylase (OsUGP2). We further found that AP1 physically interacts with OsUGP2 to elevate its enzymatic activity, likely through targeted phosphorylation. These findings revealed a novel role of L-LecRLK in controlling pollen maturity via modulating sucrose and starch metabolism.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Pólen/genética , Amido/genética , Regulação da Expressão Gênica de Plantas/genética , Lectinas/genética , Proteínas Mutantes/genética , Oryza/crescimento & desenvolvimento , Fosfotransferases/genética , Proteínas de Plantas/isolamento & purificação , Pólen/crescimento & desenvolvimento , Receptores Mitogênicos/genética , Amido/metabolismo
5.
Small ; 20(28): e2309620, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38294996

RESUMO

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2/Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2Te3 nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2/Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1 s-1, and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

6.
Small ; : e2402613, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850186

RESUMO

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

7.
Chembiochem ; 25(5): e202300790, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38242853

RESUMO

Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, nonselective cation channel with a widespread distribution throughout the body. It is involved in many pathological and physiological processes, making it a potential therapeutic target for various diseases, including Alzheimer's disease, Parkinson's disease, and cancers. New analytical techniques are beneficial for gaining a deeper understanding of its involvement in disease pathogenesis and for advancing the drug discovery for TRPM2-related diseases. In this work, we present the application of collision-induced affinity selection mass spectrometry (CIAS-MS) for the direct identification of ligands binding to TRPM2. CIAS-MS circumvents the need for high mass detection typically associated with mass spectrometry of large membrane proteins. Instead, it focuses on the detection of small molecules dissociated from the ligand-protein-detergent complexes. This affinity selection approach consolidates all affinity selection steps within the mass spectrometer, resulting in a streamlined process. We showed the direct identification of a known TRPM2 ligand dissociated from the protein-ligand complex. We demonstrated that CIAS-MS can identify binding ligands from complex mixtures of compounds and screened a compound library against TRPM2. We investigated the impact of voltage increments and ligand concentrations on the dissociation behavior of the binding ligand, revealing a dose-dependent relationship.


Assuntos
Doença de Alzheimer , Canais de Cátion TRPM , Humanos , Ligantes , Descoberta de Drogas , Biblioteca Gênica
8.
J Med Virol ; 96(3): e29517, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476091

RESUMO

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Plantas Medicinais , Humanos , Ultrafiltração , Extratos Vegetais/farmacologia , Antivirais/farmacologia , Proteínas de Membrana
9.
BMC Cancer ; 24(1): 98, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233760

RESUMO

Acute myeloid leukemia (AML), characterized by the abnormal accumulation of immature marrow cells in the bone marrow, is a malignant tumor of the blood system. Currently, the pathogenesis of AML is not yet clear. Therefore, this study aims to explore the mechanisms underlying the development of AML. Firstly, we identified a competing endogenous RNA (ceRNA) SUCLG2-AS1-miR-17-5p-JAK1 axis through bioinformatics analysis. Overexpression of SUCLG2-AS1 inhibits proliferation, migration and invasion and promotes apoptosis of AML cells. Secondly, luciferase reporter assay and RIP assay validated that SUCLG2-AS1 functioned as ceRNA for sponging miR-17-5p, further leading to JAK1 underexpression. Additionally, the results of MeRIP-qPCR and m6A RNA methylation quantification indicted that SUCLG2-AS1(lncRNA) had higher levels of m6A RNA methylation compared with controls, and SUCLG2-AS1 is regulated by m6A modification of WTAP in AML cells. WTAP, one of the main regulatory components of m6A methyltransferase complexes, proved to be highly expressed in AML and elevated WTAP is associated with poor prognosis of AML patients. Taken together, the WTAP-SUCLG2-AS1-miR-17-5p-JAK1 axis played essential roles in the process of AML development, which provided a novel therapeutic target for AML.


Assuntos
Adenina/análogos & derivados , Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , Leucemia Mieloide Aguda/genética , RNA Longo não Codificante/genética , Proliferação de Células/genética , Fatores de Processamento de RNA , Proteínas de Ciclo Celular , Janus Quinase 1/genética
10.
J Magn Reson Imaging ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970314

RESUMO

BACKGROUND: Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research. PURPOSE: To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional, prospective. SUBJECTS: A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years). FIELD STRENGTH/SEQUENCE: 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences. ASSESSMENT: The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer. STATISTICAL TESTS: This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87). DATA CONCLUSION: GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

11.
Reprod Biomed Online ; 48(2): 103370, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38096630

RESUMO

RESEARCH QUESTION: Can rat endometrium be successfully procured and transplanted, and can a similar method be used to procure human endometrium? DESIGN: Rat endometrium was procured using an endometrium stripping method and transplanted into female Sprague-Dawley rats. Macroscopic and histological changes, endometrial receptivity-related protein concentrations and fertility were assessed. Additionally, a preliminary experiment was conducted to procure human endometrium using a similar method. RESULTS: Endometrium was successfully procured from both rats and humans, which contained intact endometrium and parts of the adjacent inner annulus myometrium. Endometrium auto-transplantation was conducted in rats and the procedure lasted a total of 41.3 ± 5.7 min with a mean blood loss of 0.09 ± 0.04 g. The transplanted endometrium survived well, but a fibrotic zone formed between the transplant and recipient tissue. Compared with sham rats, those with endometrium transplantation had similar endometrial thickness and endometrial gland numbers but reduced vascular density at 8 weeks after surgery. Endometrium transplantation also retained expression of the endometrial receptivity-related proteins leukaemia inhibitory factor and vascular endothelial growth factor. In contrast to non-pregnancy in the stripped horn, a mean of 5.0 ± 2.7 fetuses developed in the transplanted horn, and full-term live fetuses were conceived in the horns with transplanted endometrium. CONCLUSIONS: Endometrium procurement by stripping method can obtain an intact and functional endometrium, and endometrium transplantation can reconstruct the uterine cavity and restore fertility in rats.


Assuntos
Endométrio , Fator A de Crescimento do Endotélio Vascular , Humanos , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo , Endométrio/metabolismo , Útero/metabolismo , Fertilidade
12.
Environ Sci Technol ; 58(24): 10536-10547, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38833510

RESUMO

Hydropower plays a pivotal role in low-carbon electricity generation, yet many projects are situated in regions facing heightened water scarcity risks. This research devised a plant-level Hydropower Water Scarcity Index (HWSI), derived from the ratio of water demand for electricity generation to basin-scale available runoff water. We assessed the water scarcity of 1736 hydropower plants in China for the baseline year 2018 and projected into the future from 2025 to 2060. The results indicate a notable increase in hydropower generation facing moderate to severe water scarcity (HWSI >0.05), rising from 10% in 2018 to 24-34% of the national total (430-630 TWh), with a projected peak in the 2030s-2040s under the most pessimistic scenarios. Hotspots of risk are situated in the southwest and northern regions, primarily driven by decreased river basin runoff and intensified sectoral water use, rather than by hydropower demand expansion. Comparative analysis of four adaptation strategies revealed that sectoral water savings and enhancing power generation efficiency are the most effective, potentially mitigating a high of 16% of hydropower risks in China. This study provides insights for formulating region-specific adaptation strategies and assessing energy-water security in the face of evolving environmental and societal challenges.


Assuntos
Mudança Climática , Centrais Elétricas , China , Abastecimento de Água
13.
Environ Sci Technol ; 58(10): 4617-4626, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38419288

RESUMO

Understanding the impact of heavy precipitation on human mobility is critical for finer-scale urban flood risk assessment and achieving sustainable development goals #11 to build resilient and safe cities. Using ∼2.6 million mobile phone signal data collected during the summer of 2018 in Jiangsu, China, this study proposes a novel framework to assess human mobility changes during rainfall events at a high spatial granularity (500 m grid cell). The fine-scale mobility map identifies spatial hotspots with abnormal clustering or reduced human activities. When aggregating to the prefecture-city level, results show that human mobility changes range between -3.6 and 8.9%, revealing varied intracity movement across cities. Piecewise structural equation modeling analysis further suggests that city size, transport system, and crowding level directly affect mobility responses, whereas economic conditions influence mobility through multiple indirect pathways. When overlaying a historical urban flood map, we find such human mobility changes help 23 cities reduce 2.6% flood risks covering 0.45 million people but increase a mean of 1.64% flood risks in 12 cities covering 0.21 million people. The findings help deepen our understanding of the mobility pattern of urban dwellers after heavy precipitation events and foster urban adaptation by supporting more efficient small-scale hazard management.


Assuntos
Big Data , Inundações , Humanos , Cidades , China
14.
J Nat Prod ; 87(6): 1532-1539, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38853528

RESUMO

Nematode infections affect a fifth of the human population, livestock, and crops worldwide, imposing a burden to global public health and economies, particularly in developing nations. Resistance to commercial anthelmintics has increased over the years in livestock infections and driven the pursuit for new drugs. We herein present a rapid, cost-effective, and automated assay for nematicide discovery using the free-living nematode Caenorhabditis elegans to screen a highly diverse natural product library enriched in bioactive molecules. Screening of 10,240 fractions obtained from extracts of various biological sources allowed the identification of 7 promising hit fractions, all from marine sponges. These fractions were further assayed for nematicidal activity against the sheep nematode parasite Haemonchus contortus and for innocuity in zebrafish. The most active extracts against parasites and innocuous toward vertebrates belong to two chemotypes. High-performance liquid chromatography (HPLC) coupled with nuclear magnetic resonance (NMR) revealed that the most abundant compound in one chemotype is halaminol A, an aminoalcohol previously identified in a small screen against H. contortus. Terpene-nucleotide hybrids known as agelasines predominate in the other chemotype. This study reinforces the power of C. elegans for nematicide discovery from large collections and the potential of the chemical diversity derived from marine invertebrate biota.


Assuntos
Antinematódeos , Caenorhabditis elegans , Poríferos , Animais , Poríferos/química , Antinematódeos/farmacologia , Antinematódeos/química , Caenorhabditis elegans/efeitos dos fármacos , Estrutura Molecular , Peixe-Zebra , Haemonchus/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos
15.
Cereb Cortex ; 33(9): 5447-5456, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36482789

RESUMO

It has been shown that the functional dependency of the brain exists in both direct and indirect regional relationships. Therefore, it is necessary to map higher-order coupling in brain structure and function to understand brain dynamic. However, how to quantify connections between not directly regions remains unknown to schizophrenia. The word2vec is a common algorithm through create embeddings of words to solve these problems. We apply the node2vec embedding representation to characterize features on each node, their pairwise relationship can give rise to correspondence relationships between brain regions. Then we adopt pearson correlation to quantify the higher-order coupling between structure and function in normal controls and schizophrenia. In addition, we construct direct and indirect connections to quantify the coupling between their respective functional connections. The results showed that higher-order coupling is significantly higher in schizophrenia. Importantly, the anomalous cause of coupling mainly focus on indirect structural connections. The indirect structural connections play an essential role in functional connectivity-structural connectivity (SC-FC) coupling. The similarity between embedded representations capture more subtle network underlying information, our research provides new perspectives for understanding SC-FC coupling. A strong indication that the structural backbone of the brain has an intimate influence on the resting-state functional.


Assuntos
Conectoma , Esquizofrenia , Humanos , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Encéfalo , Algoritmos , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos
16.
Neurol Sci ; 45(4): 1599-1607, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37914867

RESUMO

BACKGROUND: For patients with neuronal surface antibody-associated autoimmune encephalitis (NSAE) whose clinical symptoms gradually improve, the recommended course of immunotherapy in China is about 6 months. We aim to explore the relationship between persistent antibody positivity when immunotherapy is discontinued at 6 months and subsequent relapse. METHODS: Prospective inclusion of NSAE patients with clinical remission after 6-month immunotherapy. Their antibody titers and other clinical data were collected at onset and 6 months later. Based on the antibody test results at 6 months, patients were divided into an antibody-persistent group and an antibody-negative conversion group, and then the rate of relapse between the two groups were compared. RESULTS: The study included 28 NSAE patients who were antibody-positive at diagnosis. After 6-month immunotherapy, there were 16 (57.1%) cases with persistent antibodies and 12 (42.9%) cases with antibody-negative conversion. In the acute phase of onset, seizures were more common in patients with persistent antibodies (87.5% vs. 50.0%, p = 0.044). During a mean follow-up period of 22 months, patients with persistent antibodies were more likely to experience relapse than those with antibody-negative conversion (37.5% vs. 0.0%, p = 0.024). There were no significant differences in antibody types, CSF findings, results of MRI and EEG, tumor combination, immunotherapy, and long-term outcome between the two groups (p > 0.05). CONCLUSIONS: For patients with persistent antibodies when immunotherapy is discontinued at 6 months, persistent antibody positivity was associated with a higher relapse rate.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Doença de Hashimoto , Humanos , Estudos Prospectivos , Encefalite/complicações , Anticorpos , Recidiva , Doenças Autoimunes do Sistema Nervoso/complicações , Autoanticorpos
17.
Neurol Sci ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551680

RESUMO

BACKGROUND: Whether antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) in cerebrospinal fluid (CSF) are partially transferred from serum and the impact of CSF-LGI1-Ab positivity on clinical features and prognosis are unclear. Therefore, we aim to investigate the differences in serum titers, clinical features, and outcomes between LGI1-Ab CSF-positive and LGI1-Ab CSF-negative patients. METHODS: Retrospective analysis of serum titers and clinical features according to CSF LGI1-Ab status. In addition, univariate and multivariate logistic regression were performed to identify predictors of worse outcomes. RESULTS: A total of 60 patients with anti-LGI1 encephalitis and positive serum LGI1-Abs were identified, of whom 8 (13.3%) patients were excluded due to the absence of CSF LGI1-Ab testing. Among the remaining 52 patients, 33 (63.5%) were positive for LGI1-Abs in CSF. CSF-positive patients were more likely to have high serum titers (≥ 1:100) than CSF-negative patients (p = 0.003), and Spearman's correlation analysis showed a positive correlation between CSF and serum titers in CSF-positive patients (r2 = 0.405, p = 0.019). Psychiatric symptoms and hyponatremia were more frequent in CSF-positive patients (p < 0.05). Both univariate and multivariate logistic regression analyses showed that CSF LGI1-Ab positivity and delayed immunotherapy are independent risk factors for incomplete recovery (modified Rankin Scale (mRS) > 0 at last follow-up). CONCLUSIONS: LGI1-Ab CSF-positive patients have higher serum titers, and their CSF titers are positively correlated with serum titers, indicating a possible peripheral origin of CSF LGI1-Abs. CSF-positive patients more often present with psychiatric symptoms, hyponatremia, and worse outcomes, suggesting more severe neuronal damage.

18.
BMC Public Health ; 24(1): 1370, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38773424

RESUMO

BACKGROUND: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. METHODS: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. RESULTS: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. CONCLUSION: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.


Assuntos
Aldosterona , Estilo de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Aldosterona/sangue , Adulto , China/epidemiologia , Fatores Sexuais , Idoso , Obesidade/sangue , Obesidade/epidemiologia , Fatores de Risco
19.
Sensors (Basel) ; 24(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39001053

RESUMO

Appropriate traffic cooperation at intersections plays a crucial part in modern intelligent transportation systems. To enhance traffic efficiency at intersections, this paper establishes a cooperative motion optimization strategy that adjusts the trajectories of autonomous vehicles (AVs) based on risk degree. Initially, AVs are presumed to select any exit lanes, thereby optimizing spatial resources. Trajectories are generated for each possible lane. Subsequently, a motion optimization algorithm predicated on risk degree is introduced, which takes into account the trajectories and motion states of AVs. The risk degree serves to prevent collisions between conflicting AVs. A cooperative motion optimization strategy is then formulated, incorporating car-following behavior, traffic signals, and conflict resolution as constraints. Specifically, the movement of all vehicles at the intersection is modified to achieve safer and more efficient traffic flow. The strategy is validated through a simulation using SUMO. The results indicate a 20.51% and 11.59% improvement in traffic efficiency in two typical scenarios when compared to a First-Come-First-Serve approach. Moreover, numerical experiments reveal significant enhancements in the stability of optimized AV acceleration.

20.
Plant Cell Environ ; 46(4): 1312-1326, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36624579

RESUMO

Ubiquitin-specific proteases (UBPs) process deubiquitination in eukaryotic organisms and are widely involved in plant development and responses to environmental stress. However, their role in cell death and plant immunity remains largely unknown. Here, we identified a rice lesion mimic mutant (LMM) and cloned its causative gene, LMM22. Both dysfunction and overexpression of LMM22 gave rise to the hypersensitive response-like cell death, reactive oxygen species bursts, and activated defence responses. LMM22 encodes an active UBP that is localised to the endoplasmic reticulum (ER) and displays a constitutive expression pattern in rice. LMM22 interacts with SPOTTED LEAF 35 (SPL35), a coupling of ubiquitin conjugation to ER degradation domain-containing protein that is known to participate in ubiquitination and the regulation of cell death and disease response in rice. Additional analyses suggest that LMM22 can positively regulate and stabilise the abundance of SPL35 protein likely through its deubiquitination activity. These data therefore improve our understanding of the function of UBP in rice innate immune responses by demonstrating that LMM22 functions as a critical regulator of SPL35 in cell death and disease resistance.


Assuntos
Oryza , Proteases Específicas de Ubiquitina , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Oryza/genética , Proteínas de Plantas/metabolismo , Morte Celular , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Doenças das Plantas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA