Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 15.208
Filter
1.
Eur J Med Chem ; 278: 116800, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39217860

ABSTRACT

Beta-amyloid (Aß), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by TZ095, a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, TZ095 exhibited remarkable affinity with Aß aggregates (Kd = 81.54 nM for oligomers; Kd = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F0 = 44), enabling real-time monitoring of Aß in live cells and nematodes. Significantly, this work used TZ095 to construct a new protocol that can quickly and conveniently monitor Aß changes at the cellular and nematode levels to evaluate the anti-AD efficacy of candidate compounds, and four reported Aß-lowering drug candidates were administrated for validation. Imaging data demonstrated that TZ095 can visually and quantitatively track the effect of Aß elimination after drug treatment. Furthermore, TZ095 excelled in ex vivo histological staining of 12-month-old APP/PS1 mouse brains, accurately visualizing Aß plaques. Integrating CUBIC technology, TZ095 facilitated whole-brain, 3D imaging of Aß distribution in APP/PS1 mice, enabling high-resolution in situ analysis of Aß plaques. Collectively, these innovative applications of TZ095 offer a promising strategy for rapid, convenient, and real-time monitoring of Aß levels in preclinical therapeutic assessments.

2.
Small ; : e2405436, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221638

ABSTRACT

The overuse of antibiotics poses a serious threat to human health and ecosystems. Therefore, the development of high-performance antibiotic removal materials has attracted increasing attention. However, the adsorption and removal of trace amounts of antibiotics in aqueous systems still face significant challenges. Taking tetracycline (TC) as a representative antibiotic and based on its structural characteristics, a series of TC adsorbents are prepared by grafting alkyl groups to the framework of MIL-101(Cr). The adsorptive capacity of the modified materials for tetracycline markedly surpasses that of MIL-101(Cr), with MIL-101-dod achieving the best adsorption performance. MIL-101-dod demonstrated an outstanding ability to adsorb tetracycline at low concentrations, where a 5.0 mg sample of MIL-101-dod can reduce the concentration of a 90 mL 5 ppm tetracycline solution to below 1 ppb, significantly superior to other sorbents. XPS and IR tests indicate that MIL-101-dod has multiple weak interactions with tetracycline molecules, including C─H…O and C─H…π. This work provides theoretical and experimental support for the development of adsorbents for low-concentration antibiotics.

3.
J Chem Inf Model ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259971

ABSTRACT

Combination therapy is increasingly favored by pharmaceutical companies and researchers as an effective way to quickly discover new drugs with excellent efficacy, especially in the treatment of complex diseases. Previously, we successfully developed a computational screening method to identify such combinations, although it fell short in elucidating their synergistic mechanisms. In this work, we have transitioned to a highest single agent (HSA) synergy model for network screening, which streamlines the discovery of promising combinations and facilitates the investigation of their synergistic effects. Through this refined approach, the trimebutine-methoxsalen combination emerged as a promising candidate for heart failure (HF) treatment, exhibiting significant in vitro cardioprotective effects and effectively mitigating isoproterenol (ISO)-induced structural remodeling in the mouse heart. Further mechanistic studies have demonstrated that trimebutine and methoxsalen could synergistically inhibit intracellular calcium overload in myocardial cells and reduce the production of ROS, thus exerting cardioprotective effects. Overall, this study introduces an advanced computational strategy that not only identifies a novel combination therapy against HF but also sheds light on its underlying synergistic mechanisms.

4.
Ind Health ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39261023

ABSTRACT

Cardiovascular disease (CVD) is becoming prevalent among younger people who have dual roles at both work and home. A possible contributor to CVD is conflict between work and home life. Thus, this study investigated the impact of work-to-family conflict (WFC) and family-to-work conflict (FWC) on metabolic risk factors. We used longitudinal data with a 4-yr interval from the Midlife in Japan study. 152 participants who were employed at baseline without missing variables of interest were included. We assessed the associations of baseline WFC and FWC with changes in metabolic risk factors between baseline and follow-up using Generalized Estimating Equations. After adjusting for baseline sociodemographic, work and family-related, and lifestyle factors, the fully adjusted model showed WFC was significantly associated with changes in low-density lipoprotein cholesterol (LDL-C) and Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. However, FWC was not significantly associated with changes in any metabolic risk factors. Our findings indicated a significant impact of WFC on LDL-C and TC/HDL-C ratio but no significant impact of FWC on metabolic health. Since these metabolic risk factors cause CVD, understanding the physiological responses to occupational psychosocial stress could help create primary prevention interventions and assess their effects on workers' metabolic health.

5.
Sci Rep ; 14(1): 21177, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261556

ABSTRACT

The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid-liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

6.
Transl Pediatr ; 13(8): 1496-1502, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39263302

ABSTRACT

Background: Primary mediastinal choriocarcinoma (PCC) is a rare, highly vascular invasive, and prognostically unfavorable malignant tumor. When occurring outside the gonads, primary choriocarcinoma is commonly found in midline locations such as the mediastinum or retroperitoneum. Currently, there is no standardized treatment strategy for PCC. In the case reported herein, we employed tislelizumab and chemotherapy in the treatment of a patient with PCC, and as in March 2024, the patient remained survive. Case Description: A 15-year-old boy who presented with symptoms of fever and cough for a year. Chest computed tomography (CT) scan showed a relatively large soft tissue shadow in the right upper anterior mediastinum, measuring approximately 5.4 cm × 3.8 cm. The patient's soft tissue exhibited unclear demarcation from surrounding mediastinal structures and was accompanied by lung metastasis. The patient underwent a fine needle aspiration biopsy for a mediastinal mass, and the pathology results indicated a germ cell tumor with solid malignant components in the mediastinum, along with pulmonary metastasis of the solid malignancy. The patient's serum levels of beta-human chorionic gonadotropin (ß-HCG) were elevated at 125,554 mIU/mL (normal range: <5 mIU/mL), and alpha-fetoprotein (AFP) was 75.8 ng/mL (normal range, 0.605-7 ng/mL). The patient's cranial magnetic resonance imaging (MRI) plain scan indicated multiple scattered abnormal signals in both cerebral hemispheres. Subsequently, the patient was transferred to Children's Hospital of Nanjing Medical University for his further treatment. During the treatment period, we employed various therapeutic approaches, including chemotherapy, radiotherapy and tislelizumab therapy. After five cycles of tislelizumab treatment, the patient's symptoms of cerebral edema significantly improved, ß-HCG levels decreased. Brain MRI of the patient revealed multiple abnormal signals within the skull, with some lesions showing reduction in size and significant improvement in the surrounding edema zones. The clinical symptoms of the patient improved and he achieved partial remission (PR). At the moment, the patient is living with the disease. Conclusions: The effectiveness of chemotherapy for PCC is limited. Tislelizumab may potentially serve as salvage treatment options for PCC.

7.
Soft Matter ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263732

ABSTRACT

This study investigates the magneto-optical response of liquid crystals (LCs) with planar anchoring in the presence of γ-Fe2O3 magnetic nanoparticles (MNPs). This research demonstrates the formation of novel magnetic composite chains of LCs wrapped around γ-Fe2O3 MNP chains within the LC matrix under an applied magnetic field. These composite chains exhibit a distinct magneto-optical response, characterized by changes in birefringence and dichroism as the magnetic field direction is altered. Based on experimental findings, a two-subsystem model and an effective volume fraction of composite chains are proposed to describe the magneto-optical behavior of the γ-Fe2O3 MNP-doped LCs. The first subsystem comprises the LC matrix, which retains its inherent anisotropic optical properties and does not respond to the applied magnetic field. The second subsystem consists of the magnetic composite chains, which exhibit a distinct magneto-optical response due to their rotational alignment with the magnetic field. The difference in absorbance, 2αdd, which corresponds to dichroism, decreases with increasing magnetic field angle Θ, indicating a corresponding change in dichroism. This interplay between the two subsystems leads to the macroscopic magneto-optical response observed in the γ-Fe2O3 MNP-doped LCs. Due to the stability of the composite chains, the magneto-optical response is stable and can be reversed.

8.
J Asthma ; : 1-14, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264111

ABSTRACT

OBJECTIVE: This work aims to explore the effectiveness and safety of doxofylline in asthma treatment. DATA SOURCES: Relevant studies published before March 2023 were retrieved from EMBASE, Cochrane Library, PubMed, and Web of Science databases. STUDY SELECTIONS: Risk of Bias tool (RoB 2) was applied to determine the quality of randomized controlled trials (RCTs). Relative risks (RR, 95% confidence intervals [CI]) and weighted mean differences (WMD, 95% CI) were calculated for dichotomous and continuous outcomes, respectively, under fixed or random-effects models. RESULTS: A total of eight clinical trials comprising 1627 patients were analyzed. The meta-analysis revealed no notable change in forced expiratory volume in 1 second (FEV1) (WMD = 0.48; 95% CI: -2.09 to 3.05), the use of albuterol as a rescue medication (WMD = -0.02; 95% CI: -0.57 to 0.52), forced vital capacity (FVC) (WMD = 0.19; 95% CI: -0.28 to 0.67) and FEV1 predicted value (WMD = 1.53; 95%CI:-0.88 to 3.94) between doxofylline and control groups. However, doxofylline treatment significantly reduced adverse reactions (RR = 0.71; 95% CI: 0.60 to 0.84) and decreased the incidence of asthma events (WMD = -0.18; 95% CI: -0.33 to 0.03). Subgroup analysis results indicated that the improvement in FEV1 with doxofylline combined with budesonide was superior to that of budesonide combined with montelukast or tiotropium but inferior to that of budesonide plus formoterol combination. CONCLUSION: Doxofylline treatment significantly reduces the risk of asthma events and adverse events (AEs), demonstrating good safety and longer-term benefits.

9.
Nano Lett ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264273

ABSTRACT

The pseudomagnetic field effect may offer unique opportunities for the emergence of intriguing phenomena. To date, investigations into pseudomagnetic field effects on phonons have been limited to sound waves in metamaterials. The revelation of this exotic effect on the atomic vibration of natural materials remains elusive. Our simulations of twisted graphene nanoribbons reveal well-defined Landau spectra and sublattice polarization of phonon states, mimicking the behavior of Dirac Fermions in magnetic fields. Both valley-specified helical edge currents and snake orbits are obtained. Analysis of dynamics indicates that phonon Landau states have extended lifetimes, which are crucial for the realization of Landau-level lasing. Our findings demonstrate the occurrence of the phonon pseudomagnetic field effect in natural materials, which has important implications for the mechanical tuning of phonon quantum states at the atomic scale.

10.
Medicine (Baltimore) ; 103(36): e39466, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39252232

ABSTRACT

Continuous renal replacement therapy (CRRT) used in cardiac surgery-associated acute kidney injury (CSA-AKI) may have different characteristics from other diseases. We reviewed the medical records of patients with CSA-AKI requiring CRRT who underwent cardiac surgery from January 2020 to September 2021. Patients with AKI caused by other reasons who received CRRT during the same period were also evaluated. A total of 28 patients with CSA-AKI and 12 patients with AKI caused by other reasons were enrolled in this study. Compared with AKI patients caused by other reasons, patients with CSA-AKI were found to have lower mean arterial pressure, higher level of bilirubin, higher vasoactive-inotropic score, and larger daily diuretic dosage. The patients with CSA-AKI were prescribed CRRT earlier than the patients with AKI caused by other reasons. There was a significant difference in the CRRT anticoagulation method between patients with CSA-AKI and patients with AKI caused by other reasons. Six patients with CSA-AKI were treated with regional citrate anticoagulation (RCA), and the other 22 patients were treated with low molecular weight heparin or without anticoagulants. The timing of CRRT initiation in patients with CSA-AKI is earlier than that in patients with AKI caused by other reasons. Although RCA is recommended as the preferred anticoagulant for patients without contraindications, patients with CSA-AKI often have circulatory dysfunction and severe liver damage, so the risk of citrate accumulation is greater, whether to use RCA should be determined according to the individual condition of the patient.


Subject(s)
Acute Kidney Injury , Anticoagulants , Cardiac Surgical Procedures , Continuous Renal Replacement Therapy , Humans , Male , Female , Retrospective Studies , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Continuous Renal Replacement Therapy/methods , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Middle Aged , Aged , Postoperative Complications/etiology , Time Factors
11.
Trends Biotechnol ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39237385

ABSTRACT

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

12.
Leukemia ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237634

ABSTRACT

The phase 3 COMMODORE trial evaluated gilteritinib versus salvage chemotherapy (SC) in a predominantly Asian relapsed/refractory (R/R) FLT3-mutated (FLT3mut+) acute myeloid leukemia (AML) patient population. The primary endpoint was overall survival (OS); secondary endpoints included event-free survival (EFS) and complete remission (CR) rate. As of June 30, 2020 (interim analysis: 32.2 months after study initiation), 234 patients were randomized (gilteritinib, n = 116; SC, n = 118). Median OS was significantly longer with gilteritinib versus SC (9.6 vs. 5.0 months; HR 0.566 [95% CI: 0.392, 0.818]; p = 0.00211) with a median follow-up of 10.3 months. Median EFS was also significantly longer with gilteritinib (2.8 vs. 0.6 months; HR 0.551 [95% CI: 0.395, 0.769]; p = 0.00004). CR rates with gilteritinib and SC were 16.4% and 10.2%, respectively; composite CR rates were 50.0% and 20.3%, respectively. Exposure-adjusted grade ≥3 adverse event (AE) rates were lower with gilteritinib (58.38 events/patient-year [E/PY]) versus SC (168.30 E/PY). Common AEs with gilteritinib were anemia (77.9%) and thrombocytopenia (45.1%). Gilteritinib plasma concentration peaked ~4 h postdose; ~3-fold accumulation occurred with multiple dosing. The COMMODORE trial demonstrated that gilteritinib significantly improved OS and EFS in predominantly Asian patients, validating the outcomes of gilteritinib from the ADMIRAL trial in R/R FLT3mut+ AML.

13.
ACS Synth Biol ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39238421

ABSTRACT

Genome integration enables host organisms to stably carry heterologous DNA messages, introducing new genotypes and phenotypes for expanded applications. While several genome integration approaches have been reported, a scalable tool for DNA message storage within site-specific genome landing pads is still lacking. Here, we introduce an iterative genome integration method utilizing orthogonal serine integrases, enabling the stable storage of multiple heterologous genes in the chromosome of Escherichia coli MG1655. By leveraging serine integrases TP901-1, Bxb1, and PhiC31, along with engineered integration vectors, we demonstrate high-efficiency, marker-free integration of DNA fragments up to 13 kb in length. To further simplify the procedure, we then develop a streamlined integration method and showcase the system's versatility by constructing an engineered E. coli strain capable of storing and expressing multiple genes from diverse species. Additionally, we illustrate the potential utility of these engineered strains for synthetic biology applications, including in vivo and in vitro protein expression. Our work extends the application scope of serine integrases for scalable gene integration cascades, with implications for genome manipulation and gene storage applications in synthetic biology.

14.
J Mol Biol ; : 168784, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245318

ABSTRACT

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (Mpro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 Mpro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the Mpro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the Mpro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 Mpro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.

15.
Mol Med Rep ; 30(4)2024 Oct.
Article in English | MEDLINE | ID: mdl-39219287

ABSTRACT

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the TUNEL assay data shown in Fig. 1C on p. 2853 and Fig. 5H on p. 2857 were strikingly similar to data that had already been published in different form in different articles written by different authors at different research institutes, or were submitted for publication at around the same time (a number of of which have now been retracted). Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 2849­2860, 2019; DOI: 10.3892/mmr.2019.9946].

16.
Front Neurorobot ; 18: 1451924, 2024.
Article in English | MEDLINE | ID: mdl-39224905

ABSTRACT

Real-world robotic operations often face uncertainties that can impede accurate control of manipulators. This study proposes a recurrent neural network (RNN) combining kinematic and dynamic models to address this issue. Assuming an unknown mass matrix, the proposed method enables effective trajectory tracking for manipulators. In detail, a kinematic controller is designed to determine the desired joint acceleration for a given task with error feedback. Subsequently, integrated with the kinematics controller, the RNN is proposed to combine the robot's dynamic model and a mass matrix estimator. This integration allows the manipulator system to handle uncertainties and synchronously achieve trajectory tracking effectively. Theoretical analysis demonstrates the learning and control capabilities of the RNN. Simulative experiments conducted on a Franka Emika Panda manipulator, and comparisons validate the effectiveness and superiority of the proposed method.

17.
Carbohydr Polym ; 345: 122595, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227114

ABSTRACT

Cellulose nanocrystals (CNCs)-based stimuli responsive photonic materials demonstrate great application potential in mechanical and chemical sensors. However, due to the hydrophilic property of cellulose molecular, a significant challenge is to build a water-resistant photonic CNCs material. Here, inspired by butterfly wings with vivid structural color and superhydrophobic property, we have designed a CNCs based superhydrophobic iridescent film with hierarchical structures. The iridescent colored layer is ascribed to the chiral nematic alignment of CNCs, the superhydrophobic layer is ascribed to the micro-nano structures of polymer microspheres. Specially, superhydrophobic iridescent CNCs film could be used as an efficient colorimetric humidity sensor due to the existence of 'stomates' on superhydrophobic layer, which allowed the humid gas to enter into and out from the humidity responsive chiral nematic layers. Meanwhile, superhydrophobic iridescent films show out-standing self-cleaning and anti-fouling performance. Moreover, when the one side of the CNCs film was covered with superhydrophobic layer, the Janus film displays asymmetric expansion and bending behaviors as well as responsive structural colors in hydrous ethanol. This CNCs based hierarchical photonic materials have promising applications including photonic sensors suitable for extreme environment and smart photonic actuators.

18.
Nanoscale ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39248410

ABSTRACT

Two-dimensional (2D) all-carbon van der Waals (vdW) heterostructures consisting of graphene and graphyne component layers are reported to have enormous application prospects. Understanding the thermal transport properties of such graphene/graphyne (G/GY) heterostructures is critical to control their performance and stability in prospective applications. In this study, using molecular dynamics simulations and a machine learning (ML) method, we investigate the thermal conductivity of pristine G/GY heterostructures and their defective counterparts. Our simulation results show a significant reduction in the thermal conductivity of G/GY heterostructures due to the presence of vacancies, which become more aggressive as the defect concentration increases. Besides the concentration, the distribution of defects is another important factor affecting the thermal conductivity of defective G/GY heterostructures. Moreover, the defect effect on the thermal conductivity of G/GY heterostructures is majorly determined by the defect characteristics of their graphene layer. Such an impact is found to originate from the changes in both phonon scattering and heat flux. Based on the ML method together with a transfer learning strategy, we also develop a convolutional neural network that can be used to quickly and effectively predict the thermal conductivities of massive possible structures of defective G/GY heterostructures.

19.
Mol Cancer ; 23(1): 185, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232758

ABSTRACT

The spatial arrangement of immune cells within the tumor microenvironment (TME) and their interactions play critical roles in the initiation and development of cancer. Several advanced technologies such as imaging mass cytometry (IMC) providing the immunological landscape of the TME with single-cell resolution. In this study, we develop a new method to quantify the spatial proximity between different cell types based on single-cell spatial data. Using this method on IMC data from 416 lung adenocarcinoma patients, we show that the proximity between different cell types is more correlated with patient prognosis compared to the traditional features such immune cell density and fractions. Consistent with previous reports, our results validate that proximity of T helper (Th) and B cells to cancer cells is associated with survival benefits. More importantly, we discover that the proximity of M2 macrophages to multiple immune cells is associated with poor prognosis. When Th/B cells are stratified into M2-distal and M2-proximal, the abundance of the former but not the latter category of Th/B cells is correlated with enhanced patient survival. Additionally, the abundance of M2-distal and M2-proximal cytotoxic T cells (Tc) is respectively associated with good and poor prognosis. Our results indicate that the prognostic effect of Th, Tc, and B cells in the tumor microenvironment is modulated by the nearby M2 macrophages. The proposed new method proposed can be readily applied to all single-cell spatial data for revealing functional impact of immune cell interactions.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Lymphocytes, Tumor-Infiltrating , Macrophages , Tumor Microenvironment , Humans , Prognosis , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Tumor Microenvironment/immunology , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Macrophages/immunology , Macrophages/pathology , Macrophages/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/pathology , B-Lymphocytes/metabolism , Single-Cell Analysis/methods
20.
Front Nutr ; 11: 1428852, 2024.
Article in English | MEDLINE | ID: mdl-39234293

ABSTRACT

Objective: This study aimed to initially adopt an International Healthy Eating Report Card for Preschool-Aged Children to assess the prevalence of healthy eating behaviours and favourable family home food environments (FHFEs) among preschool-aged children in Australia, Hong Kong, Singapore, and the US. We also examined which cultural contexts would exhibit significant differences in the report card scores among the four cultural contexts. Methods: In this cross-cultural study, 2059 parent-child dyads, with approximately 500 dyads in each cultural context, were recruited. The parents were asked to complete the validated International Healthy Eating Report Card Scale to assess the dimensions of the Report Card [i.e., Indicator of Children's Eating Behaviours: (1) Children's Dietary Patterns and (2) Children's Mealtime Behaviours, and Indicator of FHFEs: (3) Parental Food Choices and Preparation, (4) Home Healthier Food Availability and Accessibility and (5) Family Mealtime Environments]. Each indicator received a letter grade [i.e., A (≥80%) = excellent, B (60-79%) = good, C (40-59%) = fair, D (20-39%) = poor, F (<20%) = very poor and including the plus (+) and minus (-) signs] to represent the proportion of participants who could meet the predefined benchmarks. We also employed ANCOVA and Bonferroni's post-hoc test to examine the differences in the report card scores between the four cultural contexts. A significance level was set at p < 0.05. Results: The average overall report card grade across the four cultural contexts was "B-" (Good), ranging from "C+" (Singapore and the US) to "B-" (Australia and Hong Kong). The average grade for Children's Eating Behaviours was classified as Fair ("C-"), while the average grade for FHFEs was classified as Good ("B+") for all cultural contexts. A comparison of the overall report card scores revealed that Australia exhibited a significantly higher report card score than Singapore and the US, while Hong Kong achieved a significantly higher score than Singapore. Conclusion: The International Healthy Eating Report Card provided an overview of the prevalence of healthy eating in different cultural contexts. We believe that the International Healthy Eating Report Card may offer new perspectives on interventions for fostering healthy eating in young children.

SELECTION OF CITATIONS
SEARCH DETAIL