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1.
Lancet Planet Health ; 8(7): e463-e475, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38969474

RÉSUMÉ

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.


Sujet(s)
Infections à hénipavirus , Virus Nipah , Virus Nipah/physiologie , Infections à hénipavirus/épidémiologie , Infections à hénipavirus/transmission , Humains , Animaux , Chiroptera/virologie , Asie du Sud-Est/épidémiologie , Phylogenèse , Zoonoses/épidémiologie , Zoonoses/virologie
2.
iScience ; 27(7): 110025, 2024 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-38974972

RÉSUMÉ

Drug repurposing is a promising approach to find new therapeutic indications for approved drugs. Many computational approaches have been proposed to prioritize candidate anticancer drugs by gene or pathway level. However, these methods neglect the changes in gene interactions at the edge level. To address the limitation, we develop a computational drug repurposing method (iEdgePathDDA) based on edge information and pathway topology. First, we identify drug-induced and disease-related edges (the changes in gene interactions) within pathways by using the Pearson correlation coefficient. Next, we calculate the inhibition score between drug-induced edges and disease-related edges. Finally, we prioritize drug candidates according to the inhibition score on all disease-related edges. Case studies show that our approach successfully identifies new drug-disease pairs based on CTD database. Compared to the state-of-the-art approaches, the results demonstrate our method has the superior performance in terms of five metrics across colorectal, breast, and lung cancer datasets.

3.
Front Immunol ; 15: 1406409, 2024.
Article de Anglais | MEDLINE | ID: mdl-38994358

RÉSUMÉ

Objective: There have been reports of neuromyelitis optica spectrum disorder (NMOSD) coexisting with connective tissue disorders. The objective of this study was to describe the characteristics of NMOSD coexisting with autoimmune diseases (AID). Methods: This retrospective study evaluated NMOSD patients with and without AID. The enrolled patients had at least one attack, with duration of more than 1 year. Data on the demographics, clinical features, and laboratory findings were assessed. The Poisson model was used to investigate the risk factors associated with the annualized relapse rate (ARR), whereas the Cox model was used to evaluate the risk factors for the first relapse. Results: A total of 180 patients (154 women and 26 men) with NMOSD were identified: 45 had AID and 135 did not. Female patients had a higher prevalence of concomitant AID (p = 0.006) and a greater relapse rate within the first year. There were no statistically significant differences in the characteristics of patients. Kaplan-Meier analysis revealed that NMOSD patients with seropositive aquaporin 4 antibodies (AQP4-Ab; log-rank: p = 0.044), had a shorter time to relapse. Patients seropositive for AQP4-Ab (HR = 2.402, 95%CI = 1.092-5.283, p = 0.029) had a higher risk of suffering a first relapse, according to the Cox model. Patients with and without AID showed a similar declining tendency in terms of change in ARR throughout the first 5 years of the disease. The ARR was greater in the first year [incidence rate ratio (IRR) = 1.534, 95%CI = 1.111-2.118] and the first 2 years (IRR = 1.474, 95%CI = 1.056-2.058) in patients with coexisting AID diagnosis prior to the NMOSD onset. Conclusions: Patients with NMOSD with coexisting AID had similar characteristics when compared with those without AID. NMOSD patients with AID diagnosed before onset had a higher risk of relapse in the early stage of the disease.


Sujet(s)
Aquaporine-4 , Maladies auto-immunes , Neuromyélite optique , Récidive , Humains , Neuromyélite optique/épidémiologie , Neuromyélite optique/immunologie , Neuromyélite optique/diagnostic , Femelle , Mâle , Adulte , Études rétrospectives , Adulte d'âge moyen , Maladies auto-immunes/épidémiologie , Maladies auto-immunes/immunologie , Maladies auto-immunes/complications , Aquaporine-4/immunologie , Autoanticorps/sang , Autoanticorps/immunologie , Facteurs de risque , Sujet âgé , Jeune adulte
4.
PeerJ ; 12: e17706, 2024.
Article de Anglais | MEDLINE | ID: mdl-39006021

RÉSUMÉ

Objectives: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure. Materials and Methods: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation. Results: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group. Conclusions: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.


Sujet(s)
Transfert d'embryon , Oestradiol , Fécondation in vitro , Hormone folliculostimulante , Hormone lutéinisante , Réserve ovarienne , Induction d'ovulation , Progestérone , Humains , Femelle , Adulte , Études rétrospectives , Fécondation in vitro/méthodes , Réserve ovarienne/effets des médicaments et des substances chimiques , Réserve ovarienne/physiologie , Oestradiol/sang , Hormone folliculostimulante/sang , Hormone lutéinisante/sang , Transfert d'embryon/méthodes , Progestérone/sang , Induction d'ovulation/méthodes , Ovocytes/effets des médicaments et des substances chimiques , Ovocytes/croissance et développement , Grossesse , Ovogenèse/effets des médicaments et des substances chimiques , Ovogenèse/physiologie , Prélèvement d'ovocytes/méthodes
5.
Article de Anglais | MEDLINE | ID: mdl-39011845

RÉSUMÉ

OBJECTIVES: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China. METHODS: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. RESULTS: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. CONCLUSIONS: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124686, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38950479

RÉSUMÉ

Neomycin sulfate (NEO) is a kind of aminoglycoside antibiotics. Because of its strong ototoxicity, nephrotoxicity and other side effects, its content in the body should be strictly monitored during use. In this paper, a rapid colorimetric detection method for NEO based on ultrasmall polyvinylpyrrolidone modified gold nanoparticles (PVP/Au NPs) with peroxidase-like activity was developed. Firstly, ultra small PVP/Au NPs with weak peroxidase-like activity were synthetized. When they were mixed with NEO, strong hydrogen bonds were formed between NEO and PVP, resulting in the aggregation of PVP/Au NPs, and the aggregated PVP/Au NPs showed stronger peroxidase-like activity. Therefore, rapid colorimetric detection of NEO was achieved by utilizing the enhanced peroxidase-like activity mechanism caused by the aggregation of ultra small PVP/Au NPs. The naked eye detection limit of this method is 50 nM. Within the range of 1 nM-300 nM, there was a good linear relationship between NEO concentration and the change in absorbance intensity of PVP/Au NPs-H2O2-TMB solution at 652 nm, with the regression curve of y = 0.0045x + 0.0525 (R2 = 0.998), and the detection limit is 1 nM. In addition, this method was successfully applied to the detection of NEO in mouse serum. The recoveries were 104.4 % -107.6 % compared with HPLC assay results, indicating that this method for NEO detection based on PVP/Au NPs has great potential in actual detection of NEO in serum.

7.
Inorg Chem ; 63(28): 13117-13126, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-38946108

RÉSUMÉ

Constructing the plasmonic metal/semiconductor heterostructure with a suitable Schottky barrier height (SBH) and the sufficiently reliable active sites is of importance to achieve highly efficient and selective photocatalytic CO2 reduction into hydrocarbon fuels. Herein, we report Au/sulfur vacancy-rich ZnIn2S4 (Au/VSR-ZIS) hierarchical photocatalysts, fabricated via in situ photodepositing Au nanoparticles (NPs) onto the nanosheet self-assembled ZnIn2S4 (ZIS) micrometer flowers (MFs) with rich sulfur vacancies (VS). Density functional theory (DFT) calculations confirm that for the Au/VSR-ZIS system, the Au NPs serve as the reaction sites for H2O oxidation, and the VSR-ZIS MFs serve as those for CO2 reduction. The rich VS in the Au/VSR-ZIS hybrid can reduce its SBH so as to boost more hot electrons in the Au NPs across its Schottky barrier and then inject into the conduction band (CB) of the VSR-ZIS MFs. In addition, VS can also act as the electron sink to trap the photogenerated electrons, retarding the recombination of photogenerated carriers. The two merits effectively enhance the photogenerated electron density in the surface of VSR-ZIS MFs, availing CO2 photoreduction. In addition, the introduction of rich VS in the Au/VSR-ZIS hybrid can offer more active sites, benefiting the CO2 adsorption and accelerating the desorption of CO* from the surface of the photocatalyst. Therefore, under visible light illumination with no sacrificial reagent, the optimum photocatalyst (Au/VSR-ZIS-0.4) presents the enhanced and selective CO2 photoreduction into CO (8.15 µmol g-1h-1 and near 100%), which are superior to those of most of ZIS-based and plasmon-based photocatalysts. The photocatalytic activity is about 40.0-fold as high as that of the Vs-poor-ZIS (VSP-ZIS) MFs. This work contributes a viable strategy for designing highly efficient plasmonic photocatalysts by using the synergism of the anion vacancies and the optimized SBH induced by them.

10.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3441-3451, 2024 Jul.
Article de Chinois | MEDLINE | ID: mdl-39041116

RÉSUMÉ

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.


Sujet(s)
Diabète de type 2 , Médicaments issus de plantes chinoises , Macrophages , Obésité , Diabète de type 2/traitement médicamenteux , Diabète de type 2/immunologie , Diabète de type 2/complications , Obésité/traitement médicamenteux , Obésité/immunologie , Obésité/métabolisme , Obésité/complications , Humains , Macrophages/effets des médicaments et des substances chimiques , Macrophages/immunologie , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/administration et posologie , Animaux , Médecine traditionnelle chinoise
11.
Nanoscale ; 2024 Jul 22.
Article de Anglais | MEDLINE | ID: mdl-39037336

RÉSUMÉ

Solid-state lithium batteries have advantages of high energy density and usage safety and are considered as promising next-generation power sources. Among them, the garnet-type oxide electrolyte has become a widely studied inorganic electrolyte due to its high ionic conductivity and chemical stability. In this paper, nanoscale Y2O3 (NYO) particles are introduced as sintering aids for fabricating Ta-doped Li7La3Zr2O12 (LLZTO) ceramics, and the sintering effects of various NYO ratios on the properties of LLZTO are investigated. Among the samples, the LLZTO-5%NYO sample exhibits the highest ionic conductivity (7.39 × 10-4 S cm-1) and the lowest activation energy (0.17 eV). At various current densities, the polarization voltage of LLZTO-5%NYO is also the lowest without a short circuit. The full cells of LFP|LLZTO-5%NYO|Li exhibit a high capacity of 163.9 mA h g-1 with a high initial coulombic efficiency of 97.4%, and the capacity retention rate is up to 98.1% after 50 cycles. This work may inspire the development of analogous solid-state electrolytes and lithium batteries.

12.
Article de Anglais | MEDLINE | ID: mdl-39034205

RÉSUMÉ

BACKGROUND: Access to health care is an important factor affecting survival of patients with multiple myeloma (MM) in the U.S. general population. The U.S. Military Health System (MHS) provides universal health care to beneficiaries and has been associated with improved survival across multiple malignancies. In this study, we compared survival of MHS beneficiaries with MM with MM patients from the U.S. general population. MATERIALS AND METHODS: The Department of Defense's Automated Central Tumor Registry (ACTUR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to extract data for MM patients from MHS and the U.S. general population, respectively. Patients had histologically confirmed MM between 1987 and 2013 and were followed through 2015 for overall survival. Two SEER patients were matched to each ACTUR patient by age group, sex, race, and diagnosis year group. Five and 10-year survival was compared between ACTUR and SEER patients to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) with adjustment for potential confounders. RESULTS: Median survival of the ACTUR patients was 47.1 months (95% CI: 43.9-50.4) compared to 33.0 months (95% CI, 32.0-35.0) of the SEER patients. Five and 10-year death rates were significantly lower for ACTUR patients than the SEER patients with an adjusted HR of 0.74 (95% CI, 0.68-0.81) and 0.79 (95% CI, 0.74-0.85), respectively. The survival advantage of ACTUR patients was preserved when stratified by age, sex, race, and diagnosis year. CONCLUSION: MHS beneficiaries with MM had improved overall survival compared to MM patients from the U.S. general population.

13.
Diabetes Obes Metab ; 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38962934

RÉSUMÉ

AIM: To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight-adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people. METHODS: A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross-sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non-linear correlations were investigated using restricted cubic spline curves. RESULTS: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non-linearly associated with ADL impairment. CONCLUSIONS: There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.

14.
Front Pharmacol ; 15: 1355269, 2024.
Article de Anglais | MEDLINE | ID: mdl-38962317

RÉSUMÉ

Gastric cancer, the fifth most prevalent cancer worldwide, is often diagnosed in advanced stages with limited treatment options. Examining the tumor microenvironment (TME) and its metabolic reprogramming can provide insights for better diagnosis and treatment. This study investigates the link between TME factors and metabolic activity in gastric cancer using bulk and single-cell RNA-sequencing data. We identified two molecular subtypes in gastric cancer by analyzing the distinct expression patterns of 81 prognostic genes related to the TME and metabolism, which exhibited significant protein-level interactions. The high-risk subtype had increased stromal content, fibroblast and M2 macrophage infiltration, elevated glycosaminoglycans/glycosphingolipids biosynthesis, and fat metabolism, along with advanced clinicopathological features. It also exhibited low mutation rates and microsatellite instability, associating it with the mesenchymal phenotype. In contrast, the low-risk group showed higher tumor content and upregulated protein and sugar metabolism. We identified a 15-gene prognostic signature representing these characteristics, including CPVL, KYNU, CD36, and GPX3, strongly correlated with M2 macrophages, validated through single-cell analysis and an internal cohort. Despite resistance to immunotherapy, the high-risk group showed sensitivity to molecular targeted agents directed at IGF-1R (BMS-754807) and the PI3K-mTOR pathways (AZD8186, AZD8055). We experimentally validated these promising drugs for their inhibitory effects on MKN45 and MKN28 gastric cells. This study unveils the intricate interplay between TME and metabolic pathways in gastric cancer, offering potential for enhanced diagnosis, patient stratification, and personalized treatment. Understanding molecular features in each subtype enriches our comprehension of gastric cancer heterogeneity and potential therapeutic targets.

15.
World J Gastrointest Surg ; 16(6): 1691-1699, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38983312

RÉSUMÉ

BACKGROUND: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients. AIM: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT. METHODS: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ²-test. RESULTS: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis (n = 1) and pulmonary infections (n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality (n = 1), postoperative pulmonary infections (n = 8), abdominal infection (n = 1), hepatic artery thromboses (n = 3), portal vein thrombosis (n = 1), and intra-abdominal bleeding (n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups (P > 0.05). CONCLUSION: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers.

16.
Bioorg Chem ; 150: 107584, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38964146

RÉSUMÉ

Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.


Sujet(s)
Maladie d'Alzheimer , Peptides bêta-amyloïdes , Cinnamates , Triazoles , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/métabolisme , Animaux , Triazoles/composition chimique , Triazoles/pharmacologie , Triazoles/synthèse chimique , Cinnamates/composition chimique , Cinnamates/pharmacologie , Cinnamates/synthèse chimique , Humains , Souris , Peptides bêta-amyloïdes/métabolisme , Peptides bêta-amyloïdes/antagonistes et inhibiteurs , Relation structure-activité , Structure moléculaire , Esters/composition chimique , Esters/pharmacologie , Esters/synthèse chimique , Relation dose-effet des médicaments , Acetylcholinesterase/métabolisme , Anticholinestérasiques/composition chimique , Anticholinestérasiques/pharmacologie , Anticholinestérasiques/synthèse chimique , Découverte de médicament , Neuroprotecteurs/composition chimique , Neuroprotecteurs/pharmacologie , Neuroprotecteurs/synthèse chimique , Fragments peptidiques/métabolisme , Fragments peptidiques/antagonistes et inhibiteurs , Mâle
17.
Front Immunol ; 15: 1375013, 2024.
Article de Anglais | MEDLINE | ID: mdl-39040110

RÉSUMÉ

Introduction: Immunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy. Methods: We assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis. Results: We then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group. Discussion: CAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.


Sujet(s)
Fibroblastes associés au cancer , Immunothérapie , Néovascularisation pathologique , Tumeurs de l'estomac , Microenvironnement tumoral , Humains , Tumeurs de l'estomac/thérapie , Tumeurs de l'estomac/immunologie , Tumeurs de l'estomac/mortalité , Fibroblastes associés au cancer/métabolisme , Fibroblastes associés au cancer/immunologie , Microenvironnement tumoral/immunologie , Pronostic , Immunothérapie/méthodes , Néovascularisation pathologique/immunologie , Mâle , Femelle , Régulation de l'expression des gènes tumoraux , Adulte d'âge moyen , Marqueurs biologiques tumoraux
18.
Abdom Radiol (NY) ; 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38890216

RÉSUMÉ

BACKGROUND: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT. METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA. RESULTS: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram. CONCLUSION: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.

19.
J Magn Reson Imaging ; 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38896049

RÉSUMÉ

BACKGROUND: Reduced field of view (rFOV) diffusion-weighted imaging (DWI) in MRI shows potential for enhanced image quality compared with traditional full field of view (fFOV) DWI. Evaluating rFOV DWI's impact on image quality is important for clinical adoption. OBJECTIVE: To assess the efficacy of rFOV DWI in improving image quality, focusing on artifact reduction, signal-to-noise ratio (SNR) improvement, and lesion detectability. STUDY TYPE: Meta-analysis. POPULATION: Systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science ending in January 2024. Thirteen studies with 765 participants focusing on DWI quality using rFOV was analyzed. FIELD STRENGTH/SEQUENCE: SS-EPI, Rtr-SS-EPI, 2D-SS-EPI at 3.0 T. ASSESSMENT: Two investigators performed the data extraction. QUADAS-2 assessed bias. The image quality assessment of rFOV and fFOV DWI were compared. STATISTICAL TESTS: Standardized mean difference (SMD) was utilized to evaluate and standardize MRI image quality. Heterogeneity was assessed using the I2 statistic and publication bias was evaluated with Egger's test. RESULTS: The QUADAS-2 analysis revealed that most studies exhibited a low risk of bias and minimal concerns regarding applicability. Statistical analysis indicated that rFOV DWI yielded higher subjective image quality scores (SMD = 0.535, 95% CI: 0.339, 0.731, I2 = 45.7%) compared with fFOV DWI and was more effective in reducing artifacts (SMD = 0.44, 95% CI: 0.209, 0.672, I2 = 42.3%) than fFOV DWI. However, a decrease in SNR was noted with rFOV DWI (SMD = -0.670, 95% CI: -1.187 to -0.152, I2 = 87.9%). Additionally, rFOV DWI demonstrated enhancements in lesion visibility (SMD = 0.432, 95% CI: -1.187, -0.152, I2 = 53.1%) and anatomical details (SMD = 0.598, 95% CI: 0.121, 1.075, I2 = 90.8%). DATA CONCLUSION: rFOV DWI enhances MRI image quality by reducing artifacts and improving lesion visibility with a SNR trade-off. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

20.
Environ Sci Pollut Res Int ; 31(27): 39748-39759, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38833052

RÉSUMÉ

The objective of this study is to assess the effectiveness of a novel structure comprising a geocomposite drainage layer and a thin sand layer (GDL + sand) in mitigating the rapid dumping of excavated clay and its associated issues, such as landslides. Two sets of direct shear tests were conducted to investigate the influence of sand layer thickness and compaction degree on the interface shear behavior of the GDL + sand structure. As the sand layer thickness increased, both the interface shear strength and friction angle gradually increased, first more sharply and then at a slower rate toward stability, while the interface cohesion decreased gradually. The optimal sand layer thickness for achieving the most effective reinforcement in stabilizing the clay was identified as 10 mm. A higher sand layer compaction degree was found to result in increased interface shear strength, interface friction angle, and interface cohesion. Building on these findings, the reinforcing efficiency of the GDL + sand structure was investigated through mechanism analysis in comparison to that of a geogrid + sand structure and GDL structure as per the interface friction coefficient. The ranking of interface friction coefficients among the three structures emerged as: geogrid + sand > GDL + sand > GDL. These results suggests that the GDL + sand structure exhibits superior reinforcement efficiency compared to the GDL structure and offers better drainage efficiency than the geogrid + sand structure.


Sujet(s)
Argile , Sable , Sable/composition chimique , Argile/composition chimique , Résistance au cisaillement , Silicates d'aluminium/composition chimique , Silice/composition chimique
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