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1.
Medicine (Baltimore) ; 103(19): e38076, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728481

RESUMO

BACKGROUND: nonalcoholic fatty liver disease (NAFLD) is a common liver disease affecting the global population and its impact on human health will continue to increase. Genetic susceptibility is an important factor influencing its onset and progression, and there is a lack of reliable methods to predict the susceptibility of normal populations to NAFLD using appropriate genes. METHODS: RNA sequencing data relating to nonalcoholic fatty liver disease was analyzed using the "limma" package within the R software. Differentially expressed genes were obtained through preliminary intersection screening. Core genes were analyzed and obtained by establishing and comparing 4 machine learning models, then a prediction model for NAFLD was constructed. The effectiveness of the model was then evaluated, and its applicability and reliability verified. Finally, we conducted further gene correlation analysis, analysis of biological function and analysis of immune infiltration. RESULTS: By comparing 4 machine learning algorithms, we identified SVM as the optimal model, with the first 6 genes (CD247, S100A9, CSF3R, DIP2C, OXCT 2 and PRAMEF16) as predictive genes. The nomogram was found to have good reliability and effectiveness. Six genes' receiver operating characteristic curves (ROC) suggest an essential role in NAFLD pathogenesis, and they exhibit a high predictive value. Further analysis of immunology demonstrated that these 6 genes were closely connected to various immune cells and pathways. CONCLUSION: This study has successfully constructed an advanced and reliable prediction model based on 6 diagnostic gene markers to predict the susceptibility of normal populations to NAFLD, while also providing insights for potential targeted therapies.


Assuntos
Predisposição Genética para Doença , Aprendizado de Máquina , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Calgranulina B/genética , Nomogramas , Feminino , Masculino
2.
Heliyon ; 10(9): e30050, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707463

RESUMO

In recent years, Chinese short video platforms have experienced vigorous development, accompanied by increasing expectations and demands from users. This study aims to explore the factors influencing user satisfaction on mainstream Chinese short video platforms and provide a scientific and objective evaluation framework to support the enhancement of user satisfaction and the development of short video platforms. Through a combination of qualitative and quantitative research methods, multiple mainstream Chinese short video platforms were evaluated and analyzed. Firstly, semi-structured interviews with users were conducted using Grounded Theory to delve into the key factors shaping users' expectations, needs, and satisfaction towards short video platforms. Secondly, the CRITIC-VIKOR method was employed to assign comprehensive weights to various factors and to evaluate the satisfaction levels of the mainstream platforms. The study revealed that the core categories affecting user satisfaction include content quality and interaction, trust and values, and user experience. The weighted values of the main categories are as follows: interface and interaction design 0.124, personalized experience 0.115, platform stability and performance 0.075, privacy and security 0.133, user service and communication 0.060, social impact and values 0.124, content quality and diversity 0.088, social interaction 0.094, and advertising experience 0.186. Furthermore, the satisfaction evaluation of mainstream short video platforms indicated that bilibili platform garnered the highest user satisfaction among surveyed users. This study provides specific directions for improving user experience and enhancing user satisfaction for short video platforms, while also offering a evaluation framework based on Grounded Theory and CRITIC-VIKOR method for similar studies, thus expanding the theoretical and practical fields of user satisfaction research.

3.
Schizophr Res ; 269: 48-55, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729085

RESUMO

BACKGROUND: The effect of cognitive function on suicidal tendency in patients with schizophrenia is still inconclusive. This study aimed to explore the effect of cognitive impairment on suicidal tendency in schizophrenia patients and the risk factors of suicidal tendency in schizophrenia patients with cognitive impairment. METHODS: A total of 988 subjects were recruited for this study and finally 517 patients were included in the statistical analysis. Sociodemographic information was collected for each subject. Mini-Mental State Examination (MMSE) was used to assess patients' cognitive functioning. In addition, the Positive and Negative Syndrome Scale (PANSS) positive subscale, Insomnia Severity Index (ISI), and Beck Scale for Suicide Ideation (BSI) were used to assess psychotic symptoms, severity of insomnia, and intensity of suicidal ideation, respectively. RESULTS: Schizophrenia patients with cognitive dysfunction were significantly less likely to develop suicidal tendencies than those without cognitive dysfunction (P < 0.05, OR = 0.58, 95%CI: 0.39-0.81). In patients with cognitive impairment, those with suicidal tendency had substantially higher scores on BSI, ISI, EC, PD, IRI, F1, and PANSS positive subscale, and took more types of antipsychotic drugs than those without suicidal tendency (all P < 0.05), and the results of binary logistic regression analysis showed that, PANSS positive subscale score (B = 0.06, p = 0.04, OR = 1.07, 95%CI: 1.00-1.13) was a risk factor for suicidal tendencies. CONCLUSIONS: Our findings suggest that schizophrenia patients with cognitive dysfunction are significantly less likely to develop suicidal tendencies. Moreover, positive symptom is a risk factor for suicidal tendencies in schizophrenia patients with cognitive dysfunction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38743092

RESUMO

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

5.
Gut ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38744443

RESUMO

OBJECTIVE: Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear. DESIGN: We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry. RESULTS: Hepatocyte-specific Sqle tg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-γ+ and Granzyme B+ CD8+ T cells while enriching Arg-1+ myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqle knockout suppressed tumour growth with increased cytotoxic CD8+ T cells and reduced Arg-1+ MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+ T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+ T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+ T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+ T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models. CONCLUSION: SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+ T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

6.
Langmuir ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719232

RESUMO

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

7.
bioRxiv ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38712292

RESUMO

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC. Summary: In neutrophil-enriched triple-negative breast cancer (TNBC) models, CREB binding protein (CBP)/P300 bromodomain (BRD) inhibition reduces tumor growth and systemic neutrophil accumulation while stimulating an antitumor immune response. This improves standard-of-care therapies, suggesting a potential therapeutic benefit of CBP/P300 BRD inhibitors for neutrophil-enriched TNBC.

8.
Dalton Trans ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712507

RESUMO

Interfacial engineering emerges as a potent strategy for regulating the catalytic reactivity of metal phosphides. Developing a facile and cost-effective method to construct bifunctional metal phosphides for highly efficient electrochemical overall water splitting remains an essential and challenging issue. Here, a multiphase transition metal phosphide is constructed through the direct phosphorization of a Ni-Co metal-organic framework grown on nickel foam (Ni-Co-MOF/NF), which is prepared by utilizing nickel foam as conductive substrate and nickel source. The resulting transition metal phosphide manifests a pillar-layered morphology, wherein CoP, Ni2P, and Ni5P4 nanoparticles are embedded within each carbon sheet and these carbon sheets assemble into a pillar-shaped structure on the nickel foam (Ni2P-Ni5P4-CoP-C/NF). The heterogeneous Ni2P-Ni5P4-CoP-C/NF with multiple interfaces serves as a highly efficient bifunctional electrocatalyst with overpotentials of -100 mV and 293 mV in the hydrogen evolution reaction and oxygen evolution reaction, respectively, at 50 mA cm-2 in alkaline media. This superior catalytic performance should mainly be ascribed to its enriched active centers and multiphase synergy. When directly applied for alkaline overall water splitting, the Ni2P-Ni5P4-CoP-C/NF couple demonstrates satisfactory activity (1.55 V @10 mA cm-2) along with sustained durability over 18 hours. This method brings fresh enlightenment to the economical and controllable preparation of multi-metal phosphides for energy conversion.

9.
Sci Rep ; 14(1): 10013, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693245

RESUMO

The reduction of interfacial interaction and the deterioration of processing properties of aluminum hydrides (AlH3) is the main challenges preventing its practical application. Here, a simple and effective core-shell structure aluminum hydrides@polydopamine (AlH3@PDA) complex was constructed through in-situ polymerization. The evolution of element states on the surface of AlH3 conducted by X-ray photoelectron spectroscopy indicated the successful introduction of PDA to form the core@shell structure, the thickness of the PDA coated layer increased with the increasing PDA dosage from 0.1 to 1.6% in mass fraction, and the maximum of thickness is 50 nm in TEM testing. Py GC/MS results proved that the increase of dopamine concentration leads to higher proportions of self-assemble units, whereas lower dopamine concentrations favor higher levels of chemical bonded components. Regarding whether PDA is a covalent polymer or a noncovalent aggregate of some species, the formation of intermediates, such as dopaminechrome and 5,6-dihydroxyindole played an important role to coordination interaction with AlH3 in FTIR, Raman, and UV-Vis spectra testing. Compared with pure AlH3, the formation of organic PDA coating improved AlH3 heat resistance. The adhesion work with GAP adhesive was also improved from 107.02 J/m2 of pure AlH3 to 111.13 mJ/m2 of AlH3@PDA-5 complex. This paper provides well support for further practical application of AlH3 in solid propellants.

10.
Front Neurol ; 15: 1356691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699057

RESUMO

Even though long-term immunosuppressant drugs (ISD) are employed to inhibit immune system activity, enhancing graft functionality and patient survival in solid organ transplantation (SOT), these transplants often lead to immune complications, with post-transplant autoimmune diseases of the central nervous system (CNS) being uncommon. Here, we detail the case of a 66-year-old woman who underwent a renal transplantation 8 months prior, who was admitted with subacute onset of encephalomyelitis, accompanied by headaches, paraplegia, weakness, vomiting, and abdominal pain, with a positive COVID-19 nasopharyngeal swab test 1 month before admission. MRI scans of the brain revealed multiple lesions in the white matter of the bilateral deep frontal lobe, the left temporal lobe and insula lobe. Additionally, there were multiple short segment lesions in the spinal cord and subdural hematoma at T1, T6-T7 posterior. The serum revealed a positive result for GlyR-IgG. Following the administration of corticosteroid and intravenous immunoglobulin, there was a significant improvement in the patient's symptoms within 2 weeks, and her brain MRI showed a reduction in the lesion. Despite its rarity, we believe this to be the inaugural documentation of anti-GlyR encephalomyelitis occurring during renal transplantation. A full panel of antibodies for autoimmune encephalomyelitis is the key leading to the diagnosis.

11.
Nat Commun ; 15(1): 3702, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697969

RESUMO

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.


Assuntos
Região CA1 Hipocampal , Animais , Feminino , Região CA1 Hipocampal/fisiologia , Região CA1 Hipocampal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células de Lugar/fisiologia , Recompensa , Comportamento Animal/fisiologia
12.
Nat Commun ; 15(1): 3766, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704382

RESUMO

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

13.
ISME J ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691444

RESUMO

Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions, and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment and jasmonic acid-mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome, and that depletion of key protective microbial community promotes the fruit disease incidence.

14.
Front Oncol ; 14: 1295575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690170

RESUMO

Objective: To construct and validate radiomics models for hepatocellular carcinoma (HCC) grade predictions based on contrast-enhanced CT (CECT). Methods: Patients with pathologically confirmed HCC after surgery and underwent CECT at our institution between January 2016 and December 2020 were enrolled and randomly divided into training and validation datasets. With tumor segmentation and feature extraction, radiomic models were constructed using univariate analysis, followed by least absolute shrinkage and selection operator (LASSO) regression. In addition, combined models with clinical factors and radiomics scores (Radscore) were constructed using logistic regression. Finally, all models were evaluated using the receiver operating characteristic (ROC) curve with the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: In total 242 patients were enrolled in this study, of whom 170 and 72 formed the training and validation datasets, respectively. The arterial phase and portal venous phase (AP+VP) radiomics model were evaluated as the best for predicting HCC pathological grade among all the models built in our study (AUC = 0.981 in the training dataset; AUC = 0.842 in the validation dataset) and was used to build a nomogram. Furthermore, the calibration curve and DCA indicated that the AP+VP radiomics model had a satisfactory prediction efficiency. Conclusions: Low- and high-grade HCC can be distinguished with good diagnostic performance using a CECT-based radiomics model.

16.
Bone ; : 117123, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735373

RESUMO

BACKGROUND: MicroRNAs (miRNAs) regulate osteogenic differentiation processes and influence the development of osteoporosis (OP). This study aimed to investigate the potential role of miR-466 l-3p in OP. METHODS: The expression levels of miR-466 l-3p and fibroblast growth factor 23 (FGF23) were quantified in the trabeculae of the femoral neck of 40 individuals with or without OP using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of miR-466 l-3p or FGF23 expression on cell proliferation and the expression levels of runt-related transcription factor 2 (RUNX2), type I collagen (Col1), osteocalcin (OCN), osterix (OSX) and dentin matrix protein 1 (DMP1) was quantified in human bone marrow mesenchymal stem cells (hBMSCs) overexpressing miR-466 l-3p. Furthermore, alkaline phosphatase (ALP) staining and alizarin red staining were performed to measure ALP activity and the levels of calcium deposition, respectively. In addition, bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays were conducted to explore the molecular mechanisms underlying the effects of miR-466 l-3p and FGF23 in osteogenic differentiation of hBMSCs. RESULTS: The expression levels of miR-466 l-3p were significantly lower in femoral neck trabeculae of patients with OP than in the control cohort, whereas FGF23 levels exhibited the opposite trend. Furthermore, miR-466 l-3p levels were upregulated and FGF23 levels were downregulated in hBMSCs during osteogenic differentiation. Moreover, the high miR-466 l-3p expression enhanced the mRNA expression of RUNX2, Col1, OCN, OSX and DMP1, as well as cell proliferation, ALP activity, and calcium deposition in hBMSCs. FGF23 was found to be a direct target of miR-466 l-3p. FGF23 overexpression downregulated the expression of osteoblast markers and inhibited the osteogenic differentiation induced by miR-466 l-3p overexpression. qRT-PCR and Western blot assays showed that miR-466 l-3p overexpression decreased the expression levels of mRNAs and proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, whereas FGF23 upregulation exhibited the opposite trend. CONCLUSION: In conclusion, these findings suggest that miR-466 l-3p enhances the osteogenic differentiation of hBMSCs by suppressing FGF23 expression, ultimately preventing OP.

17.
Neuropharmacology ; 254: 109981, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704022

RESUMO

The chemotherapeutic agent Doxorubicin (DOX) is known to cause chemotherapy-induced cognitive impairment (CICI). Maraviroc, a potent C-C chemokine receptor 5 (CCR5) antagonist, shows neuroprotective properties, while its role in CICI remains unclear. This study determined the therapeutic potential of maraviroc on CICI. Adult C57BL/6J mice with implanted breast cancer cells received four weekly intraperitoneal injections of saline (Control group), 5 mg/kg DOX (DOX group), 10 mg/kg maraviroc (MVC group), or 5 mg/kg DOX with 10 mg/kg maraviroc (DOX + MVC group). The Morris Water Maze (MWM) was used for neurobehavioural test. Western blot analysis and immunofluorescence were used to evaluate the expressions of inflammatory markers, apoptosis-related proteins, and synaptic-related proteins. The volume and weight of tumor were also evaluated after treatments. DOX treatment significantly increased chemokines (CCL3, CCL4) and inflammatory cytokines (IL-1ß, TNF-α) in tumor-bearing mice hippocampus. While maraviroc administration reduced hippocampal proinflammatory factors compared to the DOX group. Furthermore, it also lowered apoptosis markers, restored synaptic proteins levels, and inhibited the NF-κB/NLRP3 pathway. Accordingly, maraviroc treatment significantly improved DOX-induced neurobehavioural impairments as evidenced by an increased number of platform crossings and percentage of target quadrant time in the MWM test. Additionally, when combined with DOX, maraviroc had additional inhibitory effects on tumor growth. These findings suggest that maraviroc can mitigate DOX-induced CICI by suppressing elevated proinflammatory chemokines and cytokines through the NF-κB/NLRP3 pathway, potentially offering an anti-tumor benefit. This research presents a promising therapeutic approach for DOX-induced CICI, enhancing the safety and efficacy of cancer treatments.

18.
Biosens Bioelectron ; 258: 116318, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38701538

RESUMO

We report a massive field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13 mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction force into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave.

19.
medRxiv ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38585886

RESUMO

Alzheimer's disease (AD) manifests with varying progression rates across individuals, necessitating the understanding of their intricate patterns of cognition decline that could contribute to effective strategies for risk monitoring. In this study, we propose an innovative interpretable population graph network framework for identifying rapid progressors of AD by utilizing patient information from electronic health-related records in the UK Biobank. To achieve this, we first created a patient similarity graph, in which each AD patient is represented as a node; and an edge is established by patient clinical characteristics distance. We used graph neural networks (GNNs) to predict rapid progressors of AD and created a GNN Explainer with SHAP analysis for interpretability. The proposed model demonstrates superior predictive performance over the existing benchmark approaches. We also revealed several clinical features significantly associated with the prediction, which can be used to aid in effective interventions for the progression of AD patients.

20.
Sci Total Environ ; 927: 172334, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608895

RESUMO

The mercury oxidation performance of Ce/TiO2 catalyst can be further enhanced by transition metal modifications. This study employed density functional theory (DFT) calculations to investigate the adsorption and oxidation mechanisms of Hg0 on Ce/TiO2(001) and its transition metal modified surfaces. According to the calculation results, Ru-, Mo-, Nb-, and Mn-doping increased the affinity of the Ce/TiO2(001) surface towards Hg0 and HCl, thereby facilitating the efficient capture and oxidation of Hg0. The increased adsorption energy (Eads) of the intermediate HgCl on the modified surfaces could promote its conversion to the final product HgCl2. The modification of transition metals impeded the desorption of the final products HgCl2 and HgO, but it did not serve as the rate-determining step. The oxidation of Hg0 by lattice oxygen and HCl followed the Mars-Maessen and Langmuir-Hinshelwood mechanisms, respectively. HCl exhibited higher mercury oxidation ability than lattice oxygen. The reactivity of lattice oxygen could be further improved by doping transition metals, their promotion order was Ru > Nb > Mo > Mn. In a HCl atmosphere, Mn modification could significantly reduce the energy barrier for HCl activation and HgCl2 formation, providing the optimal enhancement for the mercury oxidation ability of Ce/TiO2 catalyst. The screening method of transition metal modified components based on surface adsorption reaction and oxidation energy barrier was proposed in this study, which provided theoretical guidance for the development of CeTi based catalysts with high mercury oxidation activity.

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