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1.
Plant J ; 118(5): 1500-1515, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516730

RESUMO

Meloidogyne incognita is one of the most widely distributed plant-parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion. Virus-induced gene silencing of MiCE108 impaired the parasitism of M. incognita in Nicotiana benthamiana. The ectopic expression of MiCE108 in Arabidopsis suppressed the deposition of callose, the generation of reactive oxygen species, and the expression of marker genes for bacterial flagellin epitope flg22-triggered immunity, resulting in increased susceptibility to M. incognita, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst) DC3000. The MiCE108 protein physically associates with the plant defense protease RD21A and promotes its degradation via the endosomal-dependent pathway, or 26S proteasome. Consistent with this, knockout of RD21A compromises the innate immunity of Arabidopsis and increases its susceptibility to a broad range of pathogens, including M. incognita, strongly indicating a role in defense against this nematode. Together, our data suggest that M. incognita deploys the effector MiCE108 to target Arabidopsis cysteine protease RD21A and affect its stability, thereby suppressing plant innate immunity and facilitating parasitism.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Nicotiana , Doenças das Plantas , Tylenchoidea , Animais , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/parasitologia , Tylenchoidea/fisiologia , Tylenchoidea/patogenicidade , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Doenças das Plantas/parasitologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Nicotiana/genética , Nicotiana/parasitologia , Nicotiana/imunologia , Nicotiana/metabolismo , Pseudomonas syringae/fisiologia , Pseudomonas syringae/patogenicidade , Botrytis/fisiologia , Botrytis/patogenicidade , Cisteína Proteases/metabolismo , Cisteína Proteases/genética , Imunidade Vegetal , Interações Hospedeiro-Parasita , Raízes de Plantas/parasitologia , Raízes de Plantas/genética , Raízes de Plantas/imunologia , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética
2.
PLoS Comput Biol ; 20(8): e1012297, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39093861

RESUMO

Understanding the computational mechanisms that underlie the encoding and decoding of environmental stimuli is a crucial investigation in neuroscience. Central to this pursuit is the exploration of how the brain represents visual information across its hierarchical architecture. A prominent challenge resides in discerning the neural underpinnings of the processing of dynamic natural visual scenes. Although considerable research efforts have been made to characterize individual components of the visual pathway, a systematic understanding of the distinctive neural coding associated with visual stimuli, as they traverse this hierarchical landscape, remains elusive. In this study, we leverage the comprehensive Allen Visual Coding-Neuropixels dataset and utilize the capabilities of deep learning neural network models to study neural coding in response to dynamic natural visual scenes across an expansive array of brain regions. Our study reveals that our decoding model adeptly deciphers visual scenes from neural spiking patterns exhibited within each distinct brain area. A compelling observation arises from the comparative analysis of decoding performances, which manifests as a notable encoding proficiency within the visual cortex and subcortical nuclei, in contrast to a relatively reduced encoding activity within hippocampal neurons. Strikingly, our results unveil a robust correlation between our decoding metrics and well-established anatomical and functional hierarchy indexes. These findings corroborate existing knowledge in visual coding related to artificial visual stimuli and illuminate the functional role of these deeper brain regions using dynamic stimuli. Consequently, our results suggest a novel perspective on the utility of decoding neural network models as a metric for quantifying the encoding quality of dynamic natural visual scenes represented by neural responses, thereby advancing our comprehension of visual coding within the complex hierarchy of the brain.


Assuntos
Encéfalo , Biologia Computacional , Modelos Neurológicos , Animais , Encéfalo/fisiologia , Aprendizado Profundo , Estimulação Luminosa , Córtex Visual/fisiologia , Neurônios/fisiologia , Percepção Visual/fisiologia , Redes Neurais de Computação , Vias Visuais/fisiologia , Humanos
3.
BMC Genomics ; 25(1): 554, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831306

RESUMO

BACKGROUND: Sperm storage capacity (SSC) determines the duration of fertility in hens and is an important reproduction trait that cannot be ignored in production. Currently, the genetic mechanism of SSC is still unclear in hens. Therefore, to explore the genetic basis of SSC, we analyzed the uterus-vagina junction (UVJ) of hens with different SSC at different times after insemination by RNA-seq and Ribo-seq. RESULTS: Our results showed that 589, 596, and 527 differentially expressed genes (DEGs), 730, 783, and 324 differentially translated genes (DTGs), and 804, 625, and 467 differential translation efficiency genes (DTEGs) were detected on the 5th, 10th, and 15th days after insemination, respectively. In transcription levels, we found that the differences of SSC at different times after insemination were mainly reflected in the transmission of information between cells, the composition of intercellular adhesion complexes, the regulation of ion channels, the regulation of cellular physiological activities, the composition of cells, and the composition of cell membranes. In translation efficiency (TE) levels, the differences of SSC were mainly related to the physiological and metabolic activities in the cell, the composition of the organelle membrane, the physiological activities of oxidation, cell components, and cell growth processes. According to pathway analysis, SSC was related to neuroactive ligand-receptor interaction, histidine metabolism, and PPAR signaling pathway at the transcriptional level and glutathione metabolism, oxidative phosphorylation, calcium signaling pathway, cell adhesion molecules, galactose metabolism, and Wnt signaling pathway at the TE level. We screened candidate genes affecting SSC at transcriptional levels (COL4A4, MUC6, MCHR2, TACR1, AVPR1A, COL1A1, HK2, RB1, VIPR2, HMGCS2) and TE levels(COL4A4, MUC6, CYCS, NDUFA13, CYTB, RRM2, CAMK4, HRH2, LCT, GCK, GALT). Among them, COL4A4 and MUC6 were the key candidate genes differing in transcription, translation, and translation efficiency. CONCLUSIONS: Our study used the combined analysis of RNA-seq and Ribo-seq for the first time to investigate the SSC and reveal the physiological processes associated with SSC. The key candidate genes affecting SSC were screened, and the theoretical basis was provided for the analysis of the molecular regulation mechanism of SSC.


Assuntos
Galinhas , RNA-Seq , Espermatozoides , Animais , Galinhas/genética , Feminino , Masculino , Espermatozoides/metabolismo , Perfilação da Expressão Gênica , Inseminação , Transcriptoma , Análise de Sequência de RNA , Perfil de Ribossomos
4.
J Am Chem Soc ; 146(39): 26884-26896, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39164893

RESUMO

Monosubstituted tetrazines are important bioorthogonal reactive tools due to their rapid ligation with trans-cyclooctene. However, their application is limited by the reactivity-stability paradox in biological environments. In this study, we demonstrated that steric effects are crucial in resolving this paradox through theoretical methods and developed a simple synthetic route to validate our computational findings, leading to the discovery of 1,3-azole-4-yl and 1,2-azole-3-yl monosubstituted tetrazines as superior bioorthogonal tools. These new tetrazines surpass previous tetrazines in terms of high reactivities and elevated stabilities. The most stable tetrazine exhibits a reasonable stability (71% remaining after 24 h incubation in cell culture medium) and an exceptionally high reactivity (k2 > 104 M-1 s-1 toward trans-cyclooctene). Due to its good stability in biological systems, a noncanonical amino acid containing such a tetrazine side chain was genetically encoded into proteins site-specifically via an expanded genetic code. The encoded protein can be efficiently labeled using cyclopropane-fused trans-cyclooctene dyes in living mammalian cells with an ultrafast reaction rate exceeding 107 M-1 s-1, making it one of the fastest protein labeling reactions reported to date. Additionally, we showed its superiority through in vivo reactions in living mice, achieving an efficient local anchoring of proteins. These tetrazines are expected to be optimal bioorthogonal reactive tools within living systems.


Assuntos
Ciclo-Octanos , Estrutura Molecular , Humanos , Ciclo-Octanos/química , Ciclo-Octanos/síntese química , Animais , Azóis/química , Azóis/síntese química
5.
Oncologist ; 29(8): e976-e983, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38943540

RESUMO

BACKGROUND: PREDICT is a web-based tool for forecasting breast cancer outcomes. PREDICT version 3.0 was recently released. This study aimed to validate this tool for a large population in mainland China and compare v3.0 with v2.2. METHODS: Women who underwent surgery for nonmetastatic primary invasive breast cancer between 2010 and 2020 from the First Affiliated Hospital of Wenzhou Medical University were selected. Predicted and observed 5-year overall survival (OS) for both v3.0 and v2.2 were compared. Discrimination was compared using receiver-operator curves and DeLong test. Calibration was evaluated using calibration plots and chi-squared test. A difference greater than 5% was deemed clinically relevant. RESULTS: A total of 5424 patients were included, with median follow-up time of 58 months (IQR 38-89 months). Compared to v2.2, v3.0 did not show improved discriminatory accuracy for 5-year OS (AUC: 0.756 vs 0.771), same as ER-positive and ER-negative patients. However, calibration was significantly improved in v3.0, with predicted 5-year OS deviated from observed by -2.0% for the entire cohort, -2.9% for ER-positive and -0.0% for ER-negative patients, compared to -7.3%, -4.7% and -13.7% in v2.2. In v3.0, 5-year OS was underestimated by 9.0% for patients older than 75 years, and 5.8% for patients with micrometastases. Patients with distant metastases postdiagnosis was overestimated by 10.6%. CONCLUSIONS: PREDICT v3.0 reliably predicts 5-year OS for the majority of Chinese patients with breast cancer. PREDICT v3.0 significantly improved the predictive accuracy for ER-negative groups. Furthermore, caution is advised when interpreting 5-year OS for patients aged over 70, those with micrometastases or metastases postdiagnosis.


Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Prognóstico , Idoso , Estudos de Coortes , População do Leste Asiático
6.
Biochem Biophys Res Commun ; 734: 150662, 2024 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-39245030

RESUMO

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl4)-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration.


Assuntos
Tetracloreto de Carbono , Regeneração Hepática , Fígado , Triglicerídeos , Regeneração Hepática/efeitos dos fármacos , Triglicerídeos/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Fígado/metabolismo , Fígado/patologia , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Ácidos Graxos/metabolismo
7.
Small ; 20(38): e2403342, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38742947

RESUMO

Perovskite solar cell (PSC) is a promising photovoltaic technology that achieves over 26% power conversion efficiency (PCE). However, the high materials costs, complicated fabrication process, as well as poor long-term stability, are stumbling blocks for the commercialization of the PSCs in normal structures. The hole transport layer (HTL)-free carbon-based PSCs (C-PSCs) are expected to overcome these challenges. However, C-PSCs have suffered from relatively low PCE due to severe energy loss at the perovskite/carbon interface. Herein, the study proposes to boost the hole extraction capability of carbon electrode by incorporating functional manganese (II III) oxide (Mn3O4). It is found that the work function (WF) of the carbon electrode can be finely tuned with different amounts of Mn3O4 addition, thus the interfacial charge transfer efficiency can be maximized. Besides, the mechanical properties of carbon electrode can also be strengthened. Finally, a PCE of 19.03% is achieved. Moreover, the device retains 90% of its initial PCE after 2000 h of storage. This study offers a feasible strategy for fabricating efficient paintable HTL-free C-PSCs.

8.
Opt Express ; 32(5): 7044-7052, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439395

RESUMO

The carrier transport performances play key roles in the photoelectric conversion efficiency for photovoltaic effect. Hence, the low carrier mobility and high photogenerated carrier recombination in ferroelectric materials depress the separation of carriers. This work designs a ferroelectric polarization-interface-free PN junction composed with P-type semiconductor BiFeO3 (BFO) derived from the variable valence of Fe and N-type semiconductor BiFe0.98Ti0.02O3 (BFTO) through Ti donor doping. The integration of the ferroelectricity decides the PN junction without polarization coupling like the traditional heterojunctions but only existing carrier distribution differential at the interface. The carrier recombination in PN junction is significantly reduced due to the driving force of the built-in electric field and the existence of depletion layer, thereby enhancing the switching current 3 times higher than that of the single ferroelectric films. Meanwhile, the carrier separation at the interface is significantly engineered by the polarization, with open circuit voltage and short circuit current of photovoltaic effect increased obviously. This work provides an alternative strategy to regulate bulk ferroelectric photovoltaic effects by carrier transport engineering in the polarization-interface-free ferroelectric PN junction.

9.
BMC Cancer ; 24(1): 557, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702629

RESUMO

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.


Assuntos
Movimento Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Regulação para Cima , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Animais , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/metabolismo , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Metástase Neoplásica , Invasividade Neoplásica/genética , Feminino , Masculino
10.
BMC Cancer ; 24(1): 1148, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277718

RESUMO

BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.


Assuntos
Densidade Óssea , Neoplasias da Mama , Feminino , Humanos , Densidade Óssea/genética , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , População do Leste Asiático , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco
11.
Cancer Control ; 31: 10732748241287905, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39313442

RESUMO

Transporters of the solute carrier family 25 (SLC25) regulate the intracellular distribution and concentration of nucleotides, amino acids, dicarboxylates, and vitamins within the mitochondrial and cytoplasmic matrices. This mechanism involves changes in mitochondrial function, regulation of cellular metabolism, and the ability to provide energy. In this review, important members of the SLC25 family and their pathways affecting tumorigenesis and progression are elucidated, highlighting the diversity and complexity of these pathways. Furthermore, the significant potential of the members of SLC25 as both cancer therapeutic targets and biomarkers will be emphasized.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/metabolismo , Prognóstico , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas Mitocondriais , Transportadores de Ânions Orgânicos
12.
Cell Biol Int ; 48(2): 154-161, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37920124

RESUMO

Alopecia areata (AA) is a complex genetic disease that results in hair loss due to an autoimmune-mediated attack on the hair follicle. Mesenchymal stem cells (MSCs) have great potential to induce hair regeneration due to their strong secretion ability and multidirectional differentiation. Recent studies have revealed that the therapeutic potential of MSCs comes from their secretion ability, which can produce large amounts of bioactive substances and regulate the key physiological functions of subjects. The secretion products of MSCs, such as vesicles, exosomes, and conditioned media, have significant advantages in preparing of biological products derived from stem cells. Human umbilical cord mesenchymal stem cells (uMSCs) are the best choice for exosome production. uMSCs are obtained from the human umbilical cord. The umbilical cord is easy to obtain, and the efficiency of uMSCs isolation and culture higher than that of obtaining MSCs from bone marrow or adipose tissue. In this study, we investigated the effects of exosomes released from uMSCs in AA mice. In summary, due to easy isolation and cultivation, simple preparation, and convenient storage, it is possible to obtain uMSCs, or uMSCs exosomes for research and clinical treatment.


Assuntos
Alopecia em Áreas , Exossomos , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Alopecia em Áreas/terapia , Cabelo , Cordão Umbilical , Proliferação de Células , Queratinócitos
13.
Inorg Chem ; 63(38): 17662-17671, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39240171

RESUMO

Electrolysis of infinite seawater is a promising and sustainable approach for clean hydrogen production. However, it remains a big challenge to accomplish corrosion-resistant and chlorine-free seawater electrolysis at low power input. Herein, the bimetallic nickel-iron sulfide-based electrocatalytic nanoarrays are constructed by a facile hydrothermal sulfidation of redox-etched iron foam (IF), which manifests an effective and reliable strategy for the sulfion oxidation reaction (SOR) to assist alkaline seawater electrolysis for the achievement of energy-saving hydrogen production and value-added sulfion upcycling. The resulting NiFeSx/FeNi3/IF required 0.353 and 0.415 V vs RHE for SOR at current densities of 50 and 100 mA cm-2, which are considerably lower than the theoretical potential of the oxygen evolution reaction (OER, 1.23 V vs RHE). In situ spectroscopy analysis demonstrated efficient sulfion oxidation on the surface of NiFeSx/FeNi3/IF. Furthermore, the NiFeSx/FeNi3/IF-assembled electrolyzer delivered a greatly reduced cell voltage of 0.92 V at 50 mA cm-2 and maintains excellent durability for 30 h, achieving high Faradaic efficiency for both hydrogen production and sulfion degradation. In addition, under natural sunlight (660.4 W m-2), only a 0.947 V voltage of the solar panel smoothly powers the SOR-coupled seawater electrolysis for green hydrogen production and economic sulfur recovery.

14.
J Am Acad Dermatol ; 90(5): 970-976, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38244613

RESUMO

BACKGROUND: Mast cell degranulation plays a pivotal role in urticaria and is also an early histologic characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of interleukin (IL)-17A blockers remains unclear. OBJECTIVE: To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. METHODS: A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathologic features were assessed. Patterns were compared between patients with ITAUR and nonurticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. RESULTS: Patients with ITAUR experienced early relapse compared with NUR group after treatment withdrawal. Transcriptomic and histopathologic analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A+ mast cells was inversely correlated with the duration of remission. LIMITATIONS: The mechanism of mast cell activation in ITAUR has not been precisely elucidated. CONCLUSION: Ixekizumab treatment increases IL-17A+ mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.


Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Urticária , Humanos , Animais , Camundongos , Interleucina-17 , Mastócitos , Estudos Retrospectivos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Urticária/induzido quimicamente , Índice de Gravidade de Doença , Recidiva , Resultado do Tratamento
15.
Brain Topogr ; 37(6): 1055-1067, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38874853

RESUMO

The ability to comprehend the intention conveyed through human body movements is crucial for effective interpersonal interactions. If people can't understand the intention behind other individuals' isolated or interactive actions, their actions will become meaningless. Psychologists have investigated the cognitive processes and neural representations involved in understanding action intention, yet a cohesive theoretical explanation remains elusive. Hence, we mainly review existing literature related to neural correlates of action intention, and primarily propose a putative Three-stage Dynamic Brain-cognitive Model of understanding action intention, which involves body perception, action identification and intention understanding. Specifically, at the first stage, body parts/shapes are processed by those brain regions such as extrastriate and fusiform body areas; During the second stage, differentiating observed actions relies on configuring relationships between body parts, facilitated by the activation of the Mirror Neuron System; The last stage involves identifying various intention categories, utilizing the Mentalizing System for recruitment, and different activation patterns concerning the nature of the intentions participants dealing with. Finally, we delves into the clinical practice, like intervention training based on a theoretical model for individuals with autism spectrum disorders who encounter difficulties in interpersonal communication.


Assuntos
Encéfalo , Cognição , Intenção , Humanos , Encéfalo/fisiologia , Cognição/fisiologia , Movimento/fisiologia , Compreensão/fisiologia
16.
J Gastroenterol Hepatol ; 39(7): 1299-1309, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38646884

RESUMO

BACKGROUND AND AIM: Circular RNA (circRNA) has been found to mediate ulcerative colitis (UC) progression by regulating intestinal mucosal barrier function. However, the role of circSOD2 in UC process and its underlying molecular mechanism still need to be further elucidated. METHODS: Lipopolysaccharide (LPS)-induced Caco2 cells were used to mimic UC cell models. CircSOD2, miR-378g, and Snail1 levels were determined by quantitative real-time PCR. Cell viability was detected using MTT assay, and inflammatory cytokine levels were measured using ELISA. The intestinal mucosal barrier function was evaluated by testing transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran permeability. Snail1 and tight junction-related markers (Zo-1 and Claudin2) protein levels were examined using western blot. The interaction between miR-378g and circSOD2 or Snail1 was confirmed by dual-luciferase reporter assay. Dextran sulfate sodium (DSS) was used to induce UC rat models in vivo. RESULTS: CircSOD2 was overexpressed in UC patients, and its knockdown significantly increased cell viability, transepithelial electrical resistance, and tight junction-related protein expression, while reduced inflammation cytokine levels and the permeability of FITC-dextran in LPS-induced Caco2 cells. In terms of mechanism, circSOD2 sponged miR-378g to positively regulate Snail1 expression. MiR-378g inhibitor reversed the effect of circSOD2 knockdown on intestinal mucosal barrier injury and Snail1 expression in LPS-induced Caco2 cells. In DSS-induced UC rat models, circSOD2 knockdown also could repair the intestinal mucosal barrier injury through regulating miR-378g/Snail1 axis. CONCLUSION: CircSOD2 could destroy intestinal mucosal barrier function in LPS-induced Caco2 cells and DSS-induced UC rats by miR-378g/Snail1 axis.


Assuntos
Colite Ulcerativa , Mucosa Intestinal , MicroRNAs , Fatores de Transcrição da Família Snail , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Células CACO-2 , Animais , RNA Circular/genética , RNA Circular/metabolismo , RNA Circular/fisiologia , Masculino , Modelos Animais de Doenças , Ratos , Ratos Sprague-Dawley , Lipopolissacarídeos , Permeabilidade , Expressão Gênica , Função da Barreira Intestinal
17.
Environ Res ; 250: 118524, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401682

RESUMO

Microplastics (MPs) are emerging pollutants widely distributed in the environment, inducing toxic effects in various organisms. However, the neurotoxicity and underlying mechanisms of simulated sunlight-aged MPs have rarely been investigated. In this study, zebrafish (Danio rerio) were exposed to environmentally relevant concentrations (0, 0.1, 1, 10, and 100 µg/L) of virgin polystyrene (V-PS) and aged polystyrene (A-PS) for 120 hpf to evaluate the neurotoxicity. The results demonstrated that simulated sunlight irradiation altered the physicochemical properties (morphology, functional groups, and chemical composition) of V-PS. Exposure to A-PS causes greater toxicity on locomotor ability in larval zebrafish than V-PS. Motor neuron development was disrupted by transgenic (hb9-GFP) zebrafish larvae exposed to A-PS, with significant alterations in neurotransmitter levels (ACh, DA, 5-HT, and GABA) and enzyme activity (AChE, ChAT, and ChE). Further investigation found that exposure to A-PS had a significantly impact on the expression of neurotransmission and neurodevelopment-related genes in zebrafish. These findings suggest that A-PS induces neurotoxicity by its effects on neurotransmission and neurodevelopment. This study highlights the neurotoxic effects and mechanisms of simulated sunlight irradiation of MPs, providing new insights for assessing the ecological risks of photoaged MPs in the environment.


Assuntos
Larva , Microplásticos , Poliestirenos , Transmissão Sináptica , Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/crescimento & desenvolvimento , Poliestirenos/toxicidade , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Transmissão Sináptica/efeitos dos fármacos
18.
BMC Pregnancy Childbirth ; 24(1): 480, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014317

RESUMO

BACKGROUND: Antenatal depression is a significant public health issue affecting pregnant women both globally and in China. Using data from a mobile app-based screening programme, this study explored the prevalence and factors associated with antenatal depressive symptoms across different trimesters in Shenzhen. METHODS: A retrospective cross-sectional study was conducted on pregnant women who gave birth in any hospital in Shenzhen between July 2021 and May 2022 and underwent depression screening using an official maternal and infant health mobile app at least once during pregnancy. Depressive symptoms were evaluated using the 9-item Patient Health Questionnaire (PHQ-9), with cut-off scores of 5 and 10 for mild and high level of symptoms, respectively. The prevalence for each trimester was determined by calculating the proportion of women scoring 5 or higher. A variety of sociodemographic, obstetric, psychological, and lifestyle factors were assessed for their association with depressive symptoms. Chi-square test and multivariate logistic regression were performed to identify significant predictors. RESULTS: A total of 110,584 pregnant women were included in the study, with an overall prevalence of depressive symptoms of 18.0% and a prevalence of high-level symptoms of 4.2%. Depressive symptoms were most prevalent in the first trimester (10.9%) and decreased in the second (6.2%) and third trimesters (6.3%). Only a small proportion (0.4%) of women showed persistent depressive symptoms across all trimesters. Anxiety symptoms in early pregnancy emerged as the most significant predictor of depressive symptoms. Other factors linked to an increased risk throughout pregnancy include lower marital satisfaction, living with parents-in-law, experience of negative life events, as well as drinking before and during pregnancy. Factors associated with a reduced risk throughout pregnancy include multiparity and daily physical activity. CONCLUSIONS: This large-scale study provides valuable insights into the prevalence and factors associated with antenatal depressive symptoms in Shenzhen. The findings underscore the need for targeted interventions for high-risk groups and the integration of mental health care into routine antenatal services. Continuous, dynamic monitoring of depressive symptoms for pregnant women and ensuring at-risk women receive comprehensive follow-up and appropriate psychological or psychiatric care are crucial for effectively addressing antenatal depression and improving maternal and infant health outcomes.


Assuntos
Depressão , Aplicativos Móveis , Complicações na Gravidez , Trimestres da Gravidez , Humanos , Feminino , Gravidez , China/epidemiologia , Adulto , Depressão/epidemiologia , Depressão/diagnóstico , Estudos Transversais , Prevalência , Estudos Retrospectivos , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/psicologia , Trimestres da Gravidez/psicologia , Programas de Rastreamento/métodos , Gestantes/psicologia , Fatores de Risco , Adulto Jovem
19.
Lipids Health Dis ; 23(1): 317, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334123

RESUMO

BACKGROUND: This paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD. METHODS: This cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis. RESULTS: In total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P < 0.01). When NHHR was grouped in quartiles, relative to the reference set, the highest NHHR group was also linked to a heightened risk of DKD (OR 1.23, 95% CI 1.01, 1.50, P < 0.05). The outcome of RCS show a "J" shaped correlation between NHHR and DKD risk (P for nonlinear = 0.0136). The risk of developing DKD was the lowest when NHHR equals 2.66. Subgroup analysis revealed that the link of NHHR to DKD persisted in participants aged below 40, females, non-smokers, and those without hyperuricemia. Sensitivity analysis demonstrated a certain robustness in this association. CONCLUSION: A meaningful link is present between NHHR and DKD. An NHHR value of around 2.66 could represent the ideal cutoff for assessing DKD risk.


Assuntos
HDL-Colesterol , Nefropatias Diabéticas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Nefropatias Diabéticas/sangue , HDL-Colesterol/sangue , Estados Unidos/epidemiologia , Adulto , Fatores de Risco , Inquéritos Nutricionais , Idoso , Colesterol/sangue , Modelos Logísticos , LDL-Colesterol/sangue
20.
Nucleic Acids Res ; 50(14): 8392-8398, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35880584

RESUMO

Enzymatic ligation is a popular method in DNA nanotechnology for structural enforcement. When employed as stability switch for chosen components, ligation can be applied to induce DNA nanostructure reconfiguration. In this study, we investigate the reinforcement effect of ligation on addressable DNA nanostructures assembled entirely from short synthetic strands as the basis of structural reconfiguration. A careful calibration of ligation efficiency is performed on structures with programmable nicks. Systematic investigation using comparative agarose gel electrophoresis enables quantitative assessment of enhanced survivability with ligation treatment on a number of unique structures. The solid ligation performance sets up the foundation for the ligation-based structural reconfiguration. With the capability of switching base pairing status between permanent and transient (ON and OFF) by a simple round of enzymatic treatment, ligation induced reconfiguration can be engineered for DNA nanostructures accordingly.


Assuntos
DNA/química , Nanoestruturas , Nanoestruturas/química , Nanotecnologia/métodos , Conformação de Ácido Nucleico
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