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1.
BMC Infect Dis ; 24(1): 962, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267012

RESUMO

BACKGROUND: Japan implemented strict border control measures and all incoming passengers were subject to entry screening with reverse transcription-polymerase chain reaction or antigen testing. From late 2020, exit screening within 72 h of departure to Japan also became mandatory. In this study, we evaluated the effectiveness of the exit screening policy in Japan by analyzing airport screening data from October 2020 to April 2022. METHODS: In addition to assessing entry screening data over time of passengers from the United Kingdom, we examined the prevalence of coronavirus disease 2019 (COVID-19) in the United Kingdom based on the Office of National Statistics infection survey. We constructed a statistical model that described entry screening positivity over time using Office of National Statistics prevalence data as the explanatory variable. Ideally, the time-dependent patterns of entry screening and Office of National Statistics prevalence data should resemble each other; however, we found that, sometimes, they were different and regarded the difference to statistically partly reflect the effectiveness of exit screening. RESULTS: The average proportion positive in one month before mandatory exit screening was implemented among Japanese passengers was 0.67% (95% confidence interval [CI]: 0.45, 0.98), whereas the proportion positive decreased to 0.49% (95% CI: 0.21, 1.15) in the first month of exit screening. Adjusting for time-dependent prevalence at the origin, we concluded that exit screening contributed to reducing passenger positivity by 59.3% (95% CI: 19.6, 81.3). The overall positivity values among passengers during the Delta and Omicron variant periods were 3.46 times and 1.46 times that during the pre-Delta variant period, respectively. CONCLUSIONS: We used a simplistic statistical model and empirical data from passengers arriving in Japan from the United Kingdom to support that exit screening helped to reduce the proportion positive by 59%. Although the proportion positive later increased considerably and precluded preventing the introduction of imported cases, submitting a certificate for a negative test result contributed to reducing the positivity among travelers.


Assuntos
Aeroportos , COVID-19 , Programas de Rastreamento , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , Japão/epidemiologia , Reino Unido/epidemiologia , SARS-CoV-2/isolamento & purificação , Programas de Rastreamento/métodos , Prevalência , Viagem/estatística & dados numéricos , Teste para COVID-19/métodos , Teste para COVID-19/estatística & dados numéricos
2.
J Environ Manage ; 370: 122422, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243653

RESUMO

Microplastics (MPs) can provide a unique niche for microbiota in waters, thus regulating the nutrients and carbon cycling. Following the vertical transport of MPs in waters, the compositions of attached biofilm may be dramatically changed. However, few studies have focused on the related ecological function response, including the carbon metabolism. In this study, we investigated the microbial carbon metabolism patterns of attached biofilm on different MPs in the vertical profile of urban rivers. The results showed that the carbon metabolism capacity of biofilm on the degradable polylactic acid (PLA) MPs was higher than that in the non-degradable polyethylene terephthalate (PET) MPs. In the vertical profile, the carbon metabolism rates of biofilm on two MPs both decreased with water depth, being 0.74 and 0.91 folds in bottom waters of that in surface waters. Specifically, the utilization of polymers, carbohydrate, and amine of PLA biofilm was significantly inhibited in the bottom waters, which were not altered on the PET. Compared with surface waters, the microbial metabolism function index of PLA biofilm was inhibited in deep waters, but elevated in the PET biofilm. In addition, the water quality parameters (e.g., nutrients) in the vertical profile largely shaped carbon metabolism patterns. These findings highlight the distinct carbon metabolism patterns in aquatic environments in the vertical profile, providing new insights into the effects of MPs on global carbon cycle.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39233456

RESUMO

OBJECTIVE: We conducted a prospective randomized clinical trial to compare the efficacy of low- and high-dose radioiodine for remnant ablation in patients with low-risk differentiated thyroid cancer (DTC) in China. The first-stage results showed equivalence was observed between the two groups. Here, we report recurrence and survival at 3-5 and 6-10 years and biochemical parameters. DESIGN, PATIENTS AND METHODS: Between January 2013 and December 2014, adult patients with DTC were enroled. Patients had undergone total or near-total thyroidectomy, with or without cervical lymph node dissection, with tumour stages T1-T3 with or without lymph node metastasis, but without distant metastasis. Patients were randomly assigned to the low-dose (1850 MBq) or high-dose (3700 MBq) radioiodine group. They were then followed up for 3-5 and 6-10 years. Data on biochemical abnormalities, recurrence and survival were analysed using Kolmogorov-Smirnov and χ2 tests. RESULTS: The data of 228 patients (mean age = 42 years; 70.6% women) were analysed, with 117 patients in the low-dose group and 111 in the high-dose group. There were no significant differences in biochemical abnormalities, recurrence, or survival rates at the 6-10-year follow-up (all p > .05). Nine patients experienced recurrence in the low-dose group (8.7%), while eight patients experienced recurrence in the high-dose group (8.2%). The survival rates were 100% and 98.2% in the low- and high-dose groups, respectively. CONCLUSIONS: The long-term effectiveness and safety of low-dose (1850 MBq) radioiodine are the same as those of high-dose (3700 MBq) radioiodine for thyroid remnant ablation in Chinese patients with low-risk DTC.

4.
ACS Appl Mater Interfaces ; 16(37): 49496-49507, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39231283

RESUMO

The latest synthesized monolayer (ML) MoSi2N4 material exhibits stability in ambient conditions, suitable bandgap, and high mobilities. Its potential as a next-generation transistor channel material has been demonstrated through quantum transport simulations. However, in practical two-dimensional (2D) material transistors, the electrical contacts formed by the channel and the electrode must be optimized, as they are crucial for determining the efficiency of carrier injection. We employed the density functional theory (DFT) combined with the nonequilibrium Green's function (NEGF) method to systematically explore the vertical and horizontal interfaces between the typical metal electrodes and the ML MoSi2N4. The DFT+NEGF method incorporates the coupling between the electrode and the channel, which is crucial for quantum transport. Among these metals, Sc and Ti form n-type Ohmic contacts with zero tunneling barriers at both vertical and horizontal interfaces with ML MoSi2N4, making them optimal for contact metals. In-ML MoSi2N4 contacts display zero Schottky barriers but a 3.11 eV tunneling barrier. Cu and Au establish n-type Schottky contacts, while Pt forms a p-type contact. The Fermi pinning factors of the metal-ML MoSi2N4 contacts for both electrons and holes are above 0.51, much higher than the typical 2D semiconductors. Moreover, there is a strong positive correlation between the Fermi pinning factor and the band gap, with a Spearman rank correlation coefficient of 0.897 and a p-value below 0.001. Our work provides insight into the contact optimization for the ML MoSi2N4 transistors and highlights the promising potential of ML MoSi2N4 as the channel material for the next-generation FETs.

5.
Pharmacol Ther ; 263: 108721, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39284368

RESUMO

Ischaemic stroke (IS) is the second leading cause of death and a major cause of disability worldwide. Currently, the clinical management of IS still depends on restoring blood flow via pharmacological thrombolysis or mechanical thrombectomy, with accompanying disadvantages of narrow therapeutic time window and risk of haemorrhagic transformation. Thus, novel pathophysiological mechanisms and targeted therapeutic candidates are urgently needed. The autophagy-lysosomal pathway (ALP), as a dynamic cellular lysosome-based degradative process, has been comprehensively studied in recent decades, including its upstream regulatory mechanisms and its role in mediating neuronal fate after IS. Importantly, increasing evidence has shown that IS can lead to lysosomal dysfunction, such as lysosomal membrane permeabilization, impaired lysosomal acidity, lysosomal storage disorder, and dysfunctional lysosomal ion homeostasis, which are involved in the IS-mediated defects in ALP function. There is tightly regulated crosstalk between transcription factor EB (TFEB), mammalian target of rapamycin (mTOR) and lysosomal function, but their relationship remains to be systematically summarized. Notably, a growing body of evidence emphasizes the benefits of naturally derived compounds in the treatment of IS via modulation of ALP function. However, little is known about the roles of natural compounds as modulators of lysosomes in the treatment of IS. Therefore, in this context, we provide an overview of the current understanding of the mechanisms underlying IS-mediated ALP dysfunction, from a lysosomal perspective. We also provide an update on the effect of natural compounds on IS, according to their chemical structural types, in different experimental stroke models, cerebral regions and cell types, with a primary focus on lysosomes and autophagy initiation. This review aims to highlight the therapeutic potential of natural compounds that target lysosomal and ALP function for IS treatment.

6.
Front Oncol ; 14: 1421020, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39165687

RESUMO

Background: Due to the low incidence of malignant tracheoesophageal fistula and the paucity of relevant clinical studies, the benefits of stent implantation have not been well documented. It remains unclear which factors may affect fistula closure. Methods: Between January 2015 and January 2021, 344 patients who were diagnosed with malignant tracheoesophageal fistula at Zhongda Hospital, Southeast University, were retrospectively enrolled. Demographic and clinical data were collected. Risk factors for fistula closure identified by univariate analysis were further analyzed using multivariable logistic regression. Results: A total of 288 patients were analyzed in this study, of which 94 were treated conservatively, 170 were treated with an esophageal stent, and 24 were treated with a tracheal stent. Among them, the delta Karnofsky's performance status score values (after 2 weeks/before treatment [p = 0.0028], after 1 month/before treatment [p = 0.0103]) were significantly different between conservative and stent treatment. There was a significant reduction of pneumonia incidence in the stenting group (33.53%) compared to the conservative treatment group (77.05%) after one month (p <0.0001). In addition, the closure of fistulas was influenced by four independent risk factors: 1) treatment methods (p < 0.0001), 2) fistula size (p = 0.0003), 3) preoperative white blood cell count (p = 0.0042), and 4) preoperative Karnofsky's performance status score (p = 0.0001). Conclusions: Stent implantation has become an effective method for treating malignant tracheoesophageal fistula compared to conservative treatment. Additionally, stent implantation, smaller fistula size, lower preoperative white blood cell count, and higher preoperative Karnofsky's performance status score suggest a better outcome.

7.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39201356

RESUMO

Milk thermal treatment, such as pasteurization, high-temperature short-time processing, and the emerging ultra-short-time processing (<0.5 s), are crucial for ensuring milk safety and extending its shelf life. Milk is a nutritive food matrix with various macro/micro-nutrients and other constituents that are possibly affected by thermal treatment for reasons associated with processing strength. Therefore, understanding the relationship between heating strength and milk quality is vital for the dairy industry. This review summarizes the impact of thermal treatment strength on milk's nutritional and sensory properties, the synthesizing of the structural integrity and bioavailability of milk proteins, the profile and stability of fatty acids, the retention of macro/micro-nutrients, as well as the overall flavor profile. Additionally, it examines the formation of heat-induced markers, such as Maillard reaction products, lactulose, furosine, and alkaline phosphatase activity, which serve as indicators of heating intensity. Flavor and heating markers are commonly used to assess the quality of pasteurized milk. By examining former studies, we conclude that ultra-short-time-processing-treated milk is comparable to pasteurized milk in terms of specific parameters (such as whey protein behavior, furosine, and ALP contents). This review aims to better summarize how thermal treatments influence the milk matrix, guiding the dairy industry's development and balancing milk products' safety and nutritional value.


Assuntos
Ácidos Graxos , Leite , Animais , Leite/química , Ácidos Graxos/análise , Temperatura Alta , Proteínas do Leite/análise , Proteínas do Leite/química , Pasteurização/métodos , Manipulação de Alimentos/métodos , Paladar , Humanos , Nutrientes/análise , Biomarcadores
8.
Geriatr Nurs ; 59: 215-222, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39053163

RESUMO

This narrative review follows the JBI approach and comprehensively explores the effects and mechanisms of acute exercise on cognitive function in Alzheimer's disease (AD) and Mild cognitive impairment (MCI) patients. The results showed that the combination of acute exercise and cognitive training improved the cognitive function of AD patients better than aerobic exercise or resistance training alone. For patients with MCI, moderate intensity acute aerobic exercise and resistance exercise were beneficial to enhance Inhibitory control (IC), but high-intensity acute exercise was adverse to improve IC; Brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor 1 (IGF-1) may assume the potential mediating mechanism of acute exercise on cognitive function in AD and MCI patients, but more research is needed to further confirm this mechanism.

9.
Quant Imaging Med Surg ; 14(7): 5176-5204, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022282

RESUMO

Background and Objective: Cervical cancer clinical target volume (CTV) outlining and organs at risk segmentation are crucial steps in the diagnosis and treatment of cervical cancer. Manual segmentation is inefficient and subjective, leading to the development of automated or semi-automated methods. However, limitation of image quality, organ motion, and individual differences still pose significant challenges. Apart from numbers of studies on the medical images' segmentation, a comprehensive review within the field is lacking. The purpose of this paper is to comprehensively review the literatures on different types of medical image segmentation regarding cervical cancer and discuss the current level and challenges in segmentation process. Methods: As of May 31, 2023, we conducted a comprehensive literature search on Google Scholar, PubMed, and Web of Science using the following term combinations: "cervical cancer images", "segmentation", and "outline". The included studies focused on the segmentation of cervical cancer utilizing computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) images, with screening for eligibility by two independent investigators. Key Content and Findings: This paper reviews representative papers on CTV and organs at risk segmentation in cervical cancer and classifies the methods into three categories based on image modalities. The traditional or deep learning methods are comprehensively described. The similarities and differences of related methods are analyzed, and their advantages and limitations are discussed in-depth. We have also included experimental results by using our private datasets to verify the performance of selected methods. The results indicate that the residual module and squeeze-and-excitation blocks module can significantly improve the performance of the model. Additionally, the segmentation method based on improved level set demonstrates better segmentation accuracy than other methods. Conclusions: The paper provides valuable insights into the current state-of-the-art in cervical cancer CTV outlining and organs at risk segmentation, highlighting areas for future research.

10.
Small ; : e2310964, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030863

RESUMO

Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.

11.
Front Sports Act Living ; 6: 1412044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005627

RESUMO

Introduction: Sleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables. Methods: Seventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray. Results: The volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p < 0.0001) in plasma. The plasma anti-inflammatory cytokine IL-10 was downregulated while other ten inflammatory factors were upregulated. Conclusion: This study demonstrates that SD influences biochemical, physiological, cognitive variables, and the significantly changed variables may serve as candidates of SD markers. These findings may further our understanding of the detrimental consequence of sleep disturbance at multiple levels.

12.
ACS Omega ; 9(29): 32066-32079, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072057

RESUMO

Hydraulic fracturing is a widely used technique to enhance the production of coalbed methane reservoirs. However, a common issue is the invasion of coal fines into proppant packs, leading to pore clogging and reduced conductivity. This study investigated the impact of flow velocity on clogging by coal fines in saturated proppant packs to optimize the flow velocity and alleviate clogging during dewatering. Clogging experiments induced by coal fines were conducted on saturated proppant packs with varying superficial velocities. Throughout each experiment, the permeability and effluent concentration were monitored, and the process of clogging was visually observed using an optical microscope. The experimental results showed that both permeability and effluent concentration initially increased and then decreased with an increase in flow velocity, indicating the existence of a critical flow velocity for minimizing clogging in proppant packs. Microscale observations revealed that the dominant regimes of clogging induced by coal fines at low and high flow velocities were surface deposition and hydrodynamic bridging, respectively; a critical flow velocity was required to induce the occurrence of bridging. Removal efficiencies of coal fines in relation to surface deposition and straining against flow velocity were theoretically analyzed, aiming to provide insights into the mechanisms underlying the impact of flow velocity on clogging. The results showed that the overall removal efficiency by surface deposition and straining decreased with an increase in flow velocity. Theoretical data matched well with the experimental results at low flow velocities but failed to explain the outcomes at high flow velocities, primarily due to the onset of bridging at high flow velocities. This study highlights the necessity of developing a removal efficiency model for bridging to accurately describe clogging by coal fines in proppant packs and provides recommendations for clogging control in proppant packs.

13.
Clin Transl Med ; 14(7): e1758, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39073026

RESUMO

 : CRISPR/Cas12a-based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual-CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off-targeting to guarantee fidelity and efficiency. The custom-pooled SOE crRNA array (SOCA) library for double-knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a-mediated high-fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual-crRNA library that covered most of the kinase and metabolism-associated gene targets of FDA-approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross-talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double-knockdown screening based on TCGA databases. Thus, this rapid, efficient and high-fidelity double-knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA- approved drugs for clinical translational medicine in the future.


Assuntos
Sistemas CRISPR-Cas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Humanos , Sistemas CRISPR-Cas/genética , Animais , Testes Genéticos/métodos
14.
Environ Sci Pollut Res Int ; 31(28): 41208-41220, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849616

RESUMO

Reasonable treatment of large amounts of sludge excavated from landfills has gained increasing attention due to the diminishing availability of landfill space in China. In this study, five landfill sludge (LS) treatment technologies using life cycle assessment (LCA) and life cycle cost (LCC) were investigated, i.e., co-incineration in coal-fired power plants (CFPP) and waste incineration power plant (WIPP), co-processing in cement kiln, bricks production, and sintering ceramsite. The LCA results demonstrate that sintering ceramsite outperforms other technologies and LCC results indicate sintering ceramsite also provides the highest economic benefit ($869.94). To further enhance environmental and economic performances of the LS treatment, the substitution of coal with natural gas and biomass can reduce Energy Conservation and Emission Reduction (ECER) index by 74% and 98%, respectively. This substitution can increase economic returns by 24% and 26%, respectively. Furthermore, national-level economic benefit and carbon emission reduction potential of different LS treatment technology alternative scenarios were assessed. Results display that a combination of 50% CFPP, 25% bricks, and 25% ceramsite (biomass) offers the highest economic gain, which is 3.02 times that of 50% CFPP and 50% cement (original case). Conversely, the replacement of 25% brick with 25% cement in the above combination result in the lowest carbon reduction, which is 9.35 times that of the original case.


Assuntos
Esgotos , Instalações de Eliminação de Resíduos , China , Incineração , Carvão Mineral
15.
BMC Cancer ; 24(1): 698, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849760

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.


Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Tetraspanina 30 , Macrófagos Associados a Tumor , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Transição Epitelial-Mesenquimal/genética , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/patologia , Tetraspanina 30/metabolismo , Tetraspanina 30/genética , Metabolismo dos Lipídeos/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Prognóstico , Reprogramação Celular/genética
16.
Adv Sci (Weinh) ; 11(29): e2400560, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38874331

RESUMO

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.


Assuntos
Endocitose , Convulsões , Animais , Camundongos , Convulsões/metabolismo , Convulsões/genética , Endocitose/fisiologia , Endocitose/genética , Camundongos Transgênicos , Modelos Animais de Doenças , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Masculino , Camundongos Knockout
17.
Int Immunopharmacol ; 136: 112367, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823177

RESUMO

SLC25A19 is a mitochondrial thiamine pyrophosphate (TPP) carrier that mediates TPP entry into the mitochondria. SLC25A19 has been recognized to play a crucial role in many metabolic diseases, but its role in cancer has not been clearly reported. Based on clinical data from The Cancer Genome Atlas (TCGA), the following parameters were analyzed among HCC patients: SLC25A19 expression, enrichment analyses, immune infiltration, ferroptosis and prognosis analyses. In vitro, the SLC25A19 high expression was validated by qRT-PCR and Immunohistochemistry. Subsequently, a series of cell function experiments, including CCK8, EdU, clone formation, trans-well and scratch assays, were conducted to illustrate the effect of SLC25A19 on the growth and metastasis of cancer cells. Meanwhile, indicators related to ferroptosis were also detected. SCL25A19 is highly expressed in HCC and predicts a poor prognosis. Elevated SLC25A19 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Our results indicate that SLC25A19 has a generally good prognosis predictive and diagnostic ability. The results of gene enrichment analyses showed that SLC25A19 is significantly correlated with immune infiltration, fatty acid metabolism, and ferroptosis marker genes. In vitro experiments have confirmed that silencing SLC25A19 can significantly inhibit the proliferation and migration ability of cancer cells and induce ferroptosis in HCC. In conclusion, these findings indicate that SLC25A19 is novel prognostic biomarker related to immune invasion and ferroptosis in HCC, and it is an excellent candidate for therapeutic target against HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Ferroptose/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Pessoa de Meia-Idade , Movimento Celular , Proliferação de Células
19.
J Ethnopharmacol ; 333: 118445, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38851472

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qifu Yin (QFY) originates from "Jingyue Quanshu · Volume 51 · New Fang Bazhen · Buzhen" a work by Zhang Jingyue, a distinguished Chinese medical practitioner from the Ming Dynasty. QFY is composed of Ginseng Radix et Rhizoma, Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Ziziphi Spinosae Semen, and Polygalae Radix. QFY is frequently employed to address memory loss and cognitive impairment stemming from vascular dementia, Alzheimer's disease (AD), and related conditions. Our findings indicate that QFY can mitigate nerve cell damage. Moreover, the study explores the impact of QFY on the calcium ion pathway and sphingolipid metabolism in mice with myocardial infarction, presenting a novel perspective on QFY's mechanism in ameliorating myocardial infarction through lipidomics. While this research provides an experimental foundation for the clinical application of QFY, a comprehensive and in-depth analysis of its improvement mechanism remains imperative. AIM OF THE STUDY: To clarify the regulatory mechanism of QFY on intestinal microecology in mice with memory impairment (MI). MATERIAL AND METHODS: The memory impairment mouse model was established by intraperitoneal injection of scopolamine hydrobromide. Kunming (KM) mice were randomly divided into blank group, Ginkgo tablet group (0.276 g/kg), QFY high, medium and low dose groups (17.2 g/kg, 8.6 g/kg, 4.3 g/kg). The effect on memory ability was evaluated by open field and step-down behavioral experiments. The morphological changes of nerve cells in the hippocampus of mice were observed by pathological method. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissue of mice were detected. The expression levels of CREB, Brain-Derived Neurotrophic Factor (BDNF) and Recombinant Amyloid Precursor Protein (APP) in the hippocampus of mice were determined using immunohistochemistry. The expression of N-methyl-D-aspartate receptor (NMDAR) and cAMP response element binding protein (CREB) related factors in the serum of mice was analyzed by ELISA. The levels of apoptosis signal-regulating kinase-1 (ASK1) and c-Jun N-terminal kinase (JNK) mRNA in the hippocampus were detected by quantitative real-time fluorescence polymerase chain reaction (qPCR). The intestinal feces of mice were collected, and the 16 S rDNA technology was used to detect the changes in intestinal microbiota microecological structure of feces in each group. RESULTS: Behavioral experiments showed that the high-dose QFY group exhibited a significant increase in exercise time (P<0.05) and a decrease in diagonal time (P<0.05) compared to the model group. The medium-dose group of QFY showed a reduction in diagonal time (P<0.05). Additionally, the latency time significantly increased in the medium and high-dose groups of QFY (P<0.01). The number of errors in the low, medium and high dose groups was significantly decreased (P<0.05, P<0.01, P<0.01). The nerve cells in the CA1 and CA3 regions of QFY-treated mice demonstrated close arrangement and clear structure. Furthermore, the content of SOD significantly increased (P<0.01) and the content of MDA significantly decreased (P<0.05) in the low and high-dose QFY groups. The content of CAT in the medium-dose group significantly increased (P < 0.05). Immunohistochemical analysis showed a significant reduction in the number of APP expression particles in the CA1 and CA3 regions of all QFY groups. Moreover, BDNF expression significantly increased in the medium and high-dose groups, while CREB expression significantly increased in the low and medium-dose groups of QFY within the CA1 and CA3 regions. Serum analysis revealed significant increases in CREB content in the low, medium, and high dose groups of QFY (P<0.01, P<0.05, P<0.05), and decreases in NMDAR content across all QFY dose groups (P<0.01). PCR analysis showed a significant decrease in the contents of ASK1 and JNK in the medium-dose group (P<0.01). Microecological analysis of intestinal microbiota demonstrated a significant restoration trend in the relative abundance of Fusobacteria, Planctomycetes, and Verrucomicrobia (P<0.01 or P<0.05) at the phylum level in the QFY groups. At the genus level, Akkermansia, Paramuribaculum, Herminiimonas, Erysipelatoclostridium and other genera in the QFY groups showed a significant trend of relative abundance restoration (P<0.01 or P<0.05). CONCLUSION: QFY can improve the memory of MI animals induced by scopolamine hydrobromide by restoring the homeostasis of intestinal microbiota and regulating related indexes in serum and brain tissue.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Transtornos da Memória , Escopolamina , Animais , Transtornos da Memória/tratamento farmacológico , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Animais não Endogâmicos
20.
Adv Mater ; 36(33): e2310659, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38871360

RESUMO

Layered iron/manganese-based oxides are a class of promising cathode materials for sustainable batteries due to their high energy densities and earth abundance. However, the stabilization of cationic and anionic redox reactions in these cathodes during cycling at high voltage remain elusive. Here, an electrochemically/thermally stable P2-Na0.67Fe0.3Mn0.5Mg0.1Ti0.1O2 cathode material with zero critical elements is designed for sodium-ion batteries (NIBs) to realize a highly reversible capacity of ≈210 mAh g-1 at 20 mA g-1 and good cycling stability with a capacity retention of 74% after 300 cycles at 200 mA g-1, even when operated with a high charge cut-off voltage of 4.5 V versus sodium metal. Combining a suite of cutting-edge characterizations and computational modeling, it is shown that Mg/Ti co-doping leads to stabilized surface/bulk structure at high voltage and high temperature, and more importantly, enhances cationic/anionic redox reaction reversibility over extended cycles with the suppression of other undesired oxygen activities. This work fundamentally deepens the failure mechanism of Fe/Mn-based layered cathodes and highlights the importance of dopant engineering to achieve high-energy and earth-abundant cathode material for sustainable and long-lasting NIBs.

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