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Importantly, larger P2 amplitudes were associated with higher activation in cortical regions encompassing the temporo-parietal junction (TPJ). This stresses the importance of this cortical region for the encoding of relevant stimulus information to resolve conflicting contexts in response inhibition. The increased cognitive control in more automatic contexts was also reflected by higher activation of the superior and medial frontal cortices. These findings provide a new perspective on response inhibition, suggesting that early resource allocation is a central modulator of the interaction between automaticity and cognitive control.This paper explores the processes underlying eye movement control in Chinese reading among a population of young 4th and 5th grade readers. Various proposals to explain the underlying mechanisms involved in eye movement control are examined and the paper concludes that the most likely account is of a two-factor process whereby the character is the main driver for longer saccades and that the word plays a role in shorter ones. A computational model is proposed to provide an integrated account of the dynamic interaction of these two factors.

Exposure to air pollution is a known risk factor for asthma exacerbations and hospitalisations. selleck products This study aimed to identify if COVID-19 transport restrictions led to improvements in air quality in Dublin and if this had an impact on asthma-related hospital admissions.

This was a population-based retrospective cohort study.

Daily concentration levels of particulate matter (PM

and PM

) and nitrogen dioxide (NO

) were obtained from the Environmental Protection Agency (EPA). The Hospital In-Patient Enquiry (HIPE) system provided the daily number of asthma-related hospital admissions in Dublin. The figures for 2018-2019 were compared with the period of transport restrictions (from March 2020).

During the period of transport restrictions, there was a significant decrease in mean daily concentrations in both PM

(8.9 vs 7.8μg/m

, P=0.002) and NO

(24.0 vs 16.7μg/m

, P<0.001). There was also a significant reduction in the mean number of daily asthma admissions (4.5 vs 2.8 admissions, P<0.001). is the likely explanation for the lack of correlation between its concentration and asthma admissions, unlike NO2 whose primary source is vehicular emissions. Public Health needs to advocate for transport policies, which can improve air quality and hence improve human health.

It was recognised in the 1978 Alma-Ata Declaration that the integration of traditional medicine into modern health systems is a major lever for achieving universal health coverage. In several African countries, the integration of traditional medicine still faces constraints, despite the development of policies and regulations in favour of this integration. The objective of this study is to conduct a systematic review of the limitations of integrating traditional medicine in Africa.

This is a systematic review protocol for qualitative studies.

The aim will be to conduct a systematic review of qualitative studies according to PRISMA guidelines. Given the qualitative nature of the primary studies, the COREQ guidelines will also be used to complement PRISMA. The search for primary studies will be conducted in Medline, Science Direct, Hinari and Google Scholar databases, using search equations designed based on the keywords constituting the thesauri of the search question. This will be done independently by two authors. The screening steps of the identified articles will be presented in PRISMA 2009 flowchart. The assessment of the risk of bias of the primary studies and the strength of the conclusions or recommendations will be performed by the GRADE tool.

The results of this systematic review will consist of the primary qualitative studies on the limitations of integrating traditional medicine into conventional health systems in African countries. These will be categorised into policy, legal, organisational and sociocultural limitations. They will be reported in accordance with the PRISMA and COREQ guidelines.

A systematic qualitative study of the limitations of effective integration of traditional medicine into conventional health systems in Africa is needed to guide national policies and regulations on traditional medicine. The application of PRISMA and COREQ standards to this review will ensure its quality and reproducibility.

PROSPERO ID CRD42022318699.

PROSPERO ID CRD42022318699.Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although sorafenib is a standard first-line molecule-targeted drug against advanced HCC, the drug resistance development and adverse side effects usually limit its efficacy. This study investigated the effect of fucoidan on the sorafenib sensitivity of sorafenib-resistant human HCC cell line HepG2-SR established by long-time exposure of HepG2 to sorafenib. We demonstrated fucoidan combined with sorafenib synergistically promoted apoptosis and cell cycle arrest whereas inhibited cell migration in HepG2-SR cells. This combination treatment effectively suppressed the cellular epithelial growth factor receptor (EGFR) nuclear distribution and downstream gene transcription. Interestingly, fucoidan bound the cell surface EGFR, dampening EGFR translocation to lipid raft and further nuclear distribution, restoring the sorafenib sensitivity in HepG2-SR cells. Blocking fucoidan-EGFR interaction using EGFR antibody restrained the enhanced anti-tumor effects upon the combined administration. Besides, EGFR knockdown abolished the combination treatment-improved anti-tumor efficacy. This combination also suppressed in vivo xenograft tumor growth in nude mice. Our present study uncovered that fucoidan overcame sorafenib resistance in HCC via its interaction with cell membrane EGFR and further suppression of EGFR redistribution and downstream signaling in sorafenib-resistant cells. Overall, current results suggest that simultaneous treatment of fucoidan and sorafenib might serve as a potential therapeutic strategy against sorafenib-resistant HCC.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation.Small molecules targeting the ubiquitous latent ribonuclease (RNase L), which has limited sequence specificity toward single-stranded RNA substrates, hold great potential to be developed as broad-spectrum antiviral drugs by modulating the RNase L-mediated innate immune responses. The recent development of proximity-inducing bifunctional molecules, as described in the strategy of ribonuclease targeting chimeras, demonstrated that small-molecule RNase L activators can function as the essential RNase L-recruiting component to design bifunctional molecules for targeted RNA degradation. However, only a single screening study on small-molecule RNase L activators with poor potency has been reported to date. Herein, we established a FRET assay and conducted a screening of 240,000 small molecules to identify new RNase L activators with improved potency. The extremely low hit rate of less than 0.03% demonstrated the challenging nature of RNase L activation by small molecules available from current screening collections. A few hit compounds induced enhanced thermal stability of RNase L upon binding, although validation assays did not lead to the identification of compounds with significantly improved RNase L activating potency. The sulfonamide compound 17 induced a thermal shift of ~ 0.9 °C upon binding to RNase L, induced significant apoptosis in cancer cells, and showed single-digit micromolar inhibitory activity against cancer cell proliferation. This study paves the way for future structural optimization for the development of small-molecule RNase L binders.Neuroblastoma (NB) is one of the most common solid pediatric tumors and especially high-risk NBs still account for about 12-15% of cancer related deaths in children. Kigelia africana (KA) is a plant used in traditional African medicine which has already shown its anti-cancer potential in several in vitro and in vivo studies. The aim of this study is to evaluate the effect of KA fruit extract on stage 4 high-risk NB cells. Therefore, NB cell lines with and without MYCN amplification and non-neoplastic cells were treated with KA fruit extract at different concentrations. The effect of KA on cell viability and apoptosis rate were assessed by bioluminescence-/fluorescence-based assays. Several proteins involved in survival, tumor growth, inflammation and metastasis were detected via western blot and immunofluorescence. Secreted cytokines were detected via ELISA. Phytochemical composition of the extract was analyzed by liquid chromatography with tandem mass spectrometry (LC/MS/MS). Our group demonstrates a dose- and time-dependent selective cytotoxic effect of KA fruit extract on NB, especially in MYCN non-amplified tumor cells, by inhibiting cell proliferation and inducing cell death. Western blot and immunofluorescence results demonstrate a regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), disialoganglioside GD2 and epidermal growth factor receptor (EGFR) in KA-treated tumor cells. Our results evidence striking anti-cancer properties of KA fruit and pave the way for further surveys on the therapeutic properties and mechanisms of action in NB.

The limited therapeutic options for ischemic stroke treatment render necessary the identification of new strategies. In recent years, it has been shown that natural compounds may represent a valid therapeutic opportunity. Therefore, the present study aimed to evaluate the protective effect of Ruta graveolens water extract (RGWE) in an in vivo experimental model of brain ischemia.

RGWE effects on ischemic damage and neurological function were evaluated in adult rats subjected to transient occlusion of the Middle Cerebral Artery (tMCAO), receiving two intraperitoneal injections of RGWE, 100 and 300min after the induction of ischemia. In addition, astroglial and microglial activation was measured as GFAP and IBA-1 expression by immunofluorescence and confocal microscopy analysis.

Treatment with RGWE containing 10mg/kg of Rutin, the major component, ameliorates the ischemic damage and improves neurological performances. Interestingly, the pro-inflammatory states of astrocytes and microglia, respectively detected by using C3 and iNOS markers, were significantly reduced in ipsilateral cortical and striatal areas in ischemic RGWE-treated rats.

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