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1.
Heliyon ; 10(9): e30061, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38720696

RESUMO

Extensive studies have been conducted on the impact of foreign language reading anxiety on reading, primarily focusing on pedagogy and behavior but lacking electrophysiological evidence. The current study aimed to investigate the influence of foreign language reading anxiety on reading and its underlying mechanisms. The results revealed a negative correlation between foreign language reading anxiety and foreign language reading performance, irrespective of the native language. Adults with low levels of foreign language reading anxiety (LFLRA) demonstrated a significant difference in early lexical component N170 amplitude between foreign and native languages. However, this effect was not observed in adults with high levels of foreign language reading anxiety (HFLRA). In terms of N170 latency, HFLRA showed a longer N170 for the foreign language compared to the native language. Furthermore, the N170 effects were predominantly localized over the left occipitotemporal electrodes. Regarding N400 latency, a significant difference was found in LFLRA individuals between foreign and native language processing, while HFLRA individuals did not exhibit this difference. These findings suggest that HFLRA individuals experience inefficient lexical processing (such as orthography or semantics) during reading in foreign language.

2.
Nutrients ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732518

RESUMO

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.


Assuntos
Colecalciferol , Metabolismo Energético , Jejum , Homeostase , Peixe-Zebra , Animais , Colecalciferol/metabolismo , Colecalciferol/farmacologia , Fígado/metabolismo , Gluconeogênese , Microbioma Gastrointestinal/fisiologia , Glicemia/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue
3.
Sci Rep ; 14(1): 8506, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605164

RESUMO

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Prognóstico , Hepatectomia , Pontuação de Propensão , Recidiva , Resultado do Tratamento
4.
Foods ; 13(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611336

RESUMO

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1ß, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

5.
Mol Psychiatry ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658772

RESUMO

Early onset familial Alzheimer's disease (FAD) with APP, PS1/2 (presenilins) mutation accounts for only a small portion of AD cases, and most are late-onset sporadic. However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1/2, and/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4/C/EBPß double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual Aß aggregation and neurofibrillary tangles formation in the brain validated by Aß PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4/C/EBPß mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.

6.
Cancer Med ; 13(7): e7043, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572921

RESUMO

BACKGROUND: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. METHODS: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. RESULTS: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). CONCLUSIONS: TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos T CD8-Positivos/patologia , Recidiva Local de Neoplasia/genética , Prognóstico , Invasividade Neoplásica/patologia , Estudos Retrospectivos , Microambiente Tumoral/genética
7.
Nat Commun ; 15(1): 2809, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561334

RESUMO

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between the arginine 508 (R508) of the splicing factor 3B subunit 2 (SF3B2), the site that is exclusively methylated by PRMT9, and the pre-mRNA anchoring site, a cis-regulatory element that is critical for RNA splicing. Additionally, using human and mouse cell lines, as well as an SF3B2 arginine methylation-deficient mouse model, we provide strong evidence that SF3B2 is the primary methylation substrate of PRMT9, thus highlighting the conserved function of the PRMT9/SF3B2 axis in regulating pre-mRNA splicing.


Assuntos
Processamento Alternativo , RNA , Animais , Humanos , Camundongos , Arginina/metabolismo , Camundongos Knockout , Mutação , Proteína-Arginina N-Metiltransferases/metabolismo , RNA/metabolismo , Precursores de RNA/metabolismo , Splicing de RNA/genética
8.
Biodegradation ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573500

RESUMO

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL.

9.
Materials (Basel) ; 17(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38591630

RESUMO

Investigations regarding the preparation and durability of cement-based materials applied in specific coastal acid rain environments are scarce, particularly those involving the addition of four auxiliary cementitious materials (ACMs) to cement for modification. To improve the durability of concrete structures in coastal acid rain areas, a systematic study was conducted regarding the preparation of high-strength and corrosion-resistant cement-based materials using ACM systems composed of fly ash (FA), granulated blast furnace slag (GBFS), silica fume (SF), and desulfurization gypsum (DG) instead of partial cement. Through an orthogonal experimental design, the effect of the water-binder ratio, cementitious ratio, and replacement cement ratio on the compressive strength, corrosion resistance coefficient, and chloride ion permeability coefficient of the materials were analyzed and the mix proportions of the materials were evaluated and optimized using the comprehensive scoring method. The results show that implementing a FA:GBFS:SF:DG ratio of 2:6:1:1 to replace 60% of cement allows the consumption of calcium hydroxide crystals generated through cement hydration, promotes the formation of ettringite, optimizes the pore structures of cementitious materials, and improves the compressive strength, acid corrosion resistance, and chloride ion permeability of the materials. This study provides a reference for selecting concrete materials for buildings in coastal acid rain environments.

10.
World J Gastroenterol ; 30(9): 1224-1236, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577190

RESUMO

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Telomerase , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Oncogenes , Bibliometria
11.
Plant Physiol Biochem ; 210: 108648, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653094

RESUMO

This study aims to investigate effects of arbuscular mycorrhizal fungi (AMF) inoculation on nitrogen (N) uptake and assimilation in Populus cathayana under drought stress (DS). Herein, we measured photosynthetic performance, antioxidant enzyme system, N level and N assimilation enzymes, proteins content and distribution, transcripts of genes associated with N uptake or transport in P. cathayana with AMF (AM) or without AMF (NM) under soil water limitation and adequate irrigation. Compared with NM-DS P. cathayana, the growth, gas exchange properties, antioxidant enzyme activities, total N content and the proportion of water-soluble and membrane-bound proteins in AM-DS P. cathayana were increased. Meanwhile, nitrate reductase (NR) activity, NO3- and NO2- concentrations in AM-DS P. cathayana were reduced, while NH4+ concentration, glutamine synthetase (GS) and glutamate synthetase (GOGAT) activities were elevated, indicating that AM symbiosis reduces NO3- assimilation while promoting NH4+ assimilation. Furthermore, the transcriptional levels of NH4+ transporter genes (PcAMT1-4 and PcAMT2-1) and NO3- transporter genes (PcNRT2-1 and PcNRT3-1) in AM-DS P. cathayana roots were significantly down-regulated, as well as NH4+ transporter genes (PcAMT1-6 and PcAMT4-3) in leaves. In AM P. cathayana roots, DS significantly up-regulated the transcriptional levels of RiCPSI and RiURE, the key N transport regulatory genes in AMF compared with adequate irrigation. These results indicated that AM N transport pathway play an essential role on N uptake and utilization in AM P. cathayana to cope with DS. Therefore, this research offers a novel perspective on how AM symbiosis enhances plant resilience to drought at aspect of N acquisition and assimilation.


Assuntos
Secas , Micorrizas , Nitrogênio , Populus , Simbiose , Populus/microbiologia , Populus/metabolismo , Populus/genética , Populus/fisiologia , Micorrizas/fisiologia , Micorrizas/metabolismo , Nitrogênio/metabolismo , Simbiose/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Fotossíntese/fisiologia , Resistência à Seca
12.
Front Psychiatry ; 15: 1277415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525255

RESUMO

Background: Postpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated. Methods: Observational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference. Results: A total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 µmol/L, IQR 7.7, 11.0 in PPD; 9.7 µmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 µmol/L, IQR 1.6, 2.6 in PPD; 2.2 µmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90-0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76-0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin. Conclusion: Our results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.

13.
Virulence ; 15(1): 2333271, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38515339

RESUMO

Staphylococcus pseudintermedius (S. pseudintermedius) is a common pathogen that causes canine corneal ulcers. However, the pathogenesis remained unclear. In this study, it has been demonstrated that S. pseudintermedius invaded canine corneal epithelial cells (CCECs) intracellularly, mediating oxidative damage and pyroptosis by promoting the accumulation of intracellular reactive oxygen species (ROS) and activating the NLRP3 inflammasome. The canine corneal stroma was infected with S. pseudintermedius to establish the canine corneal ulcer model in vivo. The intracellular infectious model in CCECs was established in vitro to explore the mechanism of the ROS - NLRP3 signalling pathway during the S. pseudintermedius infection by adding NAC or MCC950. Results showed that the expression of NLRP3 and gasdermin D (GSDMD) proteins increased significantly in the infected corneas (p < 0.01). The intracellular infection of S. pseudintermedius was confirmed by transmission electron microscopy and immunofluorescent 3D imaging. Flow cytometry analysis revealed that ROS and pyroptosis rates increased in the experimental group in contrast to the control group (p < 0.01). Furthermore, NAC or MCC950 inhibited activation of the ROS - NLRP3 signalling pathway and pyroptosis rate significantly, by suppressing pro-IL-1ß, cleaved-IL-1ß, pro-caspase-1, cleaved-caspase-1, NLRP3, GSDMD, GSDMD-N, and HMGB1 proteins. Thus, the research confirmed that oxidative damage and pyroptosis were involved in the process of CCECs infected with S. pseudintermedius intracellularly by the ROS - NLRP3 signalling pathway. The results enrich the understanding of the mechanisms of canine corneal ulcers and facilitate the development of new medicines and prevention measures.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Staphylococcus , Animais , Cães , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Úlcera , Linhagem Celular , Inflamassomos/metabolismo , Células Epiteliais/metabolismo , Sulfonamidas
14.
Brain Behav Immun ; 119: 56-83, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38555992

RESUMO

Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.

15.
Opt Express ; 32(4): 4902-4915, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439230

RESUMO

Accurate and rapid autofocus technology plays a crucial role in various fields, including automatic optical inspection technology, bio-chips scanning, and semiconductor manufacturing. The current photoelectric autofocus methods have limitations because of detecting the focal plane solely at the center of the microscope field of view. In the application of Stereo-seq the risk of autofocus errors will be increased, which have reduced the robustness of the system, like when the surface of the tested samples are wrinkling and inconsistent thickness, or the detection spot is at the edge of the sample. To enhance the robustness of the autofocus system and mitigate the constraints of the photoelectric autofocus methods, the laser-based arrayed spots photoelectric autofocus method has been proposed. To achieve the uniform light splitting, a 2D-Dammann grating is incorporated into the optical path of the autofocus system, resulting in the formation of an n × n arrayed spots on the surface of the sample. Through experimental verification, it has been demonstrated that this method can achieve the autofocus range of ±100µm and the autofocus accuracy of ±1/4 DOF when applied to a microscope equipped with a 10× objective lens, thereby satisfying the requirements for microscopic focusing. The arrayed light autofocus method devised in this study presents what we believe is a novel research concept for active autofocus detection and holds significant application value.

16.
Opt Express ; 32(4): 5220-5229, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439254

RESUMO

Laser wireless power transmission (LWPT) systems have significant applications in the field of wireless energy transmission, including spacecraft sensor networks, satellite-to-satellite communication, and remote power supply. However, continuous laser exposure increases the temperature of the photovoltaic (PV) cells in the LWPT system, thus decreasing the electrical output performance. This work, which we believe is a new approach, is on the basis of a notch film designed by a combined merit function proposed to maintain the electrical output performance while under 1064-nm continuous laser irradiation. Moreover, the thermal stability of PV cells under laser irradiation was investigated, which revealed the recoverability of the open-circuit voltage (Voc) of the cells at different temperatures, and the thermal damage to cells was a gradual process. This process began with the vaporization of the encapsulation adhesive, followed by a decline in, but still recoverable and functional, electrical performance, and finally, the cell was completely damaged. The thermal stability of the PV cells coated with the notch film increased ten-fold compared to those without it. Furthermore, the correlation between the minimum Voc and maximum temperature of the cells with notch films of different performances was established. These investigations serve as references for further optimization of LWPT.

17.
Small ; : e2310518, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429235

RESUMO

Due to their significant capacity and reliable reversibility, transition metal sulphides (TMSs) have received attention as potential anode materials for sodium-ion batteries (SIBs). Nonetheless, a prevalent challenge with TMSs lies in their significant volume expansion and sluggish kinetics, impeding their capacity for rapid and enduring Na+ storage. Herein, a Cu1.96 S@NC nanodisc material enriched with copper vacancies is synthesised via a hydrothermal and annealing procedure. Density functional theory (DFT) calculations reveal that the incorporation of copper vacancies significantly boosts electrical conductivity by reducing the energy barrier for ion diffusion, thereby promoting efficient electron/ion transport. Moreover, the presence of copper vacancies creates ample active sites for the integration of sodium ions, streamlines charge transfer, boosts electronic conductivity, and, ultimately, significantly enhances the overall performance of SIBs. This novel anode material, Cu1.96 S@NC, demonstrates a reversible capacity of 339 mAh g-1 after 2000 cycles at a rate of 5 A g-1 . In addition, it maintains a noteworthy reversible capacity of 314 mAh g-1 with an exceptional capacity retention of 96% even after 2000 cycles at 20 A g-1 . The results demonstrate that creating cationic vacancies is a highly effective strategy for engineering anode materials with high capacity and rapid reactivity.

18.
Cancer Immunol Immunother ; 73(4): 71, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430394

RESUMO

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Multiômica , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Análise por Conglomerados , Prognóstico
19.
Chaos ; 34(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447937

RESUMO

Offset boosting plays an important role in chaos application in electronic engineering. A direct variable substitution typically will destroy the dynamics of a discrete map even though the initial condition is well considered. The internal fundamental reason is that the left-hand side of a discrete system does not have the dimension of variable differentiation (DVD) like the one of a continuous system. When the key property of DVD is completely preserved, the offset boosting based on a parameter or the initial condition can be reasonably achieved like in a differential system. Consequently, by the initial condition-oriented offset boosting, flexible multistability like attractor self-reproducing or attractor doubling can be further realized. A circuit experiment is completed for the verification of reliable offset boosting. The systematic exploration of offset boosting in a map will cast a new light on chaos regulation and attractor transportation in a discrete map. As a simple case, a two-dimensional Hénon map is taken as the example demonstrating the achievement of offset boosting via the parameter or initial condition.

20.
Adv Sci (Weinh) ; 11(17): e2305877, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38444306

RESUMO

Precise and efficient regulation of microglia is vital for ischemic stroke therapy and prognosis. The infiltration of neutrophils into the brain provides opportunities for regulatory drugs across the blood-brain barrier, while hindered by neutrophil extracellular traps (NETs) and targeted delivery of intracerebral drugs to microglia. This study reports an efficient neutrophil hijacking nanoplatform (referred to as APTS) for targeted A151 (a telomerase repeat sequence) delivery to microglia without the generation of NETs. In the middle cerebral artery occlusion (MCAO) mouse model, the delivery efficiency to ischemic stroke tissues increases by fourfold. APTS dramatically reduces the formation of NETs by 2.2-fold via reprogramming NETosis to apoptosis in neutrophils via a reactive oxygen species scavenging-mediated citrullinated histone 3 inhibition pathway. Noteworthy, A151 within neutrophils is repackaged into apoptotic bodies following the death pattern reprogramming, which, when engulfed by microglia, polarizes microglia to an anti-inflammatory M2 phenotype. After four times treatment, the cerebral infarction area in the APTS group decreases by 5.1-fold. Thus, APTS provides a feasible, efficient, and practical drug delivery approach for reshaping the immune microenvironment and treating brain disorders in the central nervous system.


Assuntos
Modelos Animais de Doenças , Armadilhas Extracelulares , AVC Isquêmico , Microglia , Neutrófilos , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Camundongos , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , AVC Isquêmico/imunologia , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Masculino , Nanopartículas , Camundongos Endogâmicos C57BL
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