The Demographic Variation in Nutrition Knowledge and Relationship with Eating Attitudes among Chinese University Students.

There is a noticeable absence of health education among college students. This study aimed to evaluate the extent of general nutrition knowledge among Chinese university students and explore its association with eating attitudes. Data were collected from a group of 273 students in Spring of 2023, using a valid and reliable research instrument consisting of three sections: demographic variables, the General Nutrition Knowledge Questionnaire (GNKQ), and the Eating Attitudes Test (EAT-26). The results were analyzed using SPSS, with correlations and t-tests to examine the relationships between nutritional knowledge and dietary attitudes. Furthermore, the present study employed the random forest (RF) algorithm, a machine learning technique, utilizing the Mean Decrease Impurity (MDI) method to investigate the influence of various features on participants' eating attitudes. The findings revealed that Chinese university students had an average accuracy of over 60% in their nutritional knowledge, but their understanding of the relationship between diet and disease still needs improvement. Moreover, male students had significantly lower nutritional knowledge than female students, and there was a positive correlation between nutritional knowledge and parents' income. The study also found a significant correlation between the level of nutritional knowledge and eating attitudes. RF results indicated that the family income level exhibited the most substantial impact on the eating attitudes of the participants. The study highlights the need for nutrition education curriculum developers to focus more on improving students' nutritional knowledge, with particular attention given to male students, low-income individuals, and those with an abnormal BMI.

nSEA: n-Node Subnetwork Enumeration Algorithm Identifies Lower Grade Glioma Subtypes with Altered Subnetworks and Distinct Prognostics.

Advances in molecular characterization have reshaped our understanding of low-grade glioma (LGG) subtypes, emphasizing the need for comprehensive classification beyond histology. Lever-aging this, we present a novel approach, network-based Subnetwork Enumeration, and Analysis (nSEA), to identify distinct LGG patient groups based on dysregulated molecular pathways. Using gene expression profiles from 516 patients and a protein-protein interaction network we generated 25 million sub-networks. Through our unsupervised bottom-up approach, we selected 92 subnetworks that categorized LGG patients into five groups. Notably, a new LGG patient group with a lack of mutations in EGFR, NF1, and PTEN emerged as a previously unidentified patient subgroup with unique clinical features and subnetwork states. Validation of the patient groups on an independent dataset demonstrated the robustness of our approach and revealed consistent survival traits across different patient populations. This study offers a comprehensive molecular classification of LGG, providing insights beyond traditional genetic markers. By integrating network analysis with patient clustering, we unveil a previously overlooked patient subgroup with potential implications for prognosis and treatment strategies. Our approach sheds light on the synergistic nature of driver genes and highlights the biological relevance of the identified subnetworks. With broad implications for glioma research, our findings pave the way for further investigations into the mechanistic underpinnings of LGG subtypes and their clinical relevance.Availability: Source code and supplementary data are available at https://github.com/bebeklab/nSEA.

Monocytes reprogrammed by 4-PBA potently contribute to the resolution of inflammation and atherosclerosis.

Background: Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. Methods: Systems analyses integrating single-cell RNA-sequencing and complementary immunological approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming was assessed by integrated biochemical and genetic approaches. The inter-cellular propagation of homeostasis resolution was evaluated by co-culture assays with donor monocytes trained by 4-PBA and recipient naïve monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high fat diet-fed ApoE -/- mouse model with i.p. 4-PBA administration. Furthermore, the selective efficacy of 4-PBA trained monocytes were examined by i.v. transfusion of ex vivo trained monocytes by 4-PBA into recipient high fat diet-fed ApoE -/- mice. Results: In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 via reducing peroxisome stress and attenuating SYK-mTOR signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ neddylation mediated by TOLLIP. 4-PBA trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo . Conclusion: Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision-therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

Resolving neutrophils due to TRAM deletion renders protection against experimental sepsis.

OBJECTIVE: Proper inflammation resolution is crucial to prevent runaway inflammation during sepsis and reduce sepsis-related mortality/morbidity. Previous studies suggest that deleting TRAM, a key TLR4 signaling adaptor, can reprogram the first inflammatory responder cell-neutrophil from an inflammatory state to a resolving state. In this study, we aim to examine the therapeutic potential of TRAM-deficient neutrophils in vivo with recipient mice undergoing experimental sepsis. MATERIAL AND METHODS: Wild-type or Tram-/- mice were intraperitoneally injected with cecal slurry to induce either severe or mild sepsis. Phenotypic examinations of sepsis and neutrophil characteristics were examined in vivo and ex vivo. The propagations of resolution from donor neutrophils to recipient cells such as monocytes, T cells, and endothelial cells were examined through co-culture assays in vitro. The efficacies of Tram-/- neutrophils in reducing inflammation were studied by transfusing either wild-type or Tram-/- neutrophils into septic recipient mice. RESULTS: Tram-/- septic mice had improved survival and attenuated injuries within the lung and kidney tissues as compared to wild-type septic mice. Wild-type septic mice transfused with Tram-/- resolving neutrophils exhibited reduced multi-organ damages and improved cellular homeostasis. In vitro co-culture studies revealed that donor Tram-/- neutrophils can effectively propagate cellular homeostasis to co-cultured neighboring monocytes, neutrophils, T cells as well as endothelial cells. CONCLUSIONS: Neutrophils with TRAM deletion render effective reprogramming into a resolving state beneficial for ameliorating experimental sepsis, with therapeutic potential in propagating cellular and tissue homeostasis as well as treating sepsis.

Comparative analyses of monocyte memory dynamics from mice to humans.

BACKGROUND: Innate monocytes can adopt dynamic "memory" states ranging from low-grade inflammation to pathogenic exhaustion, dependent upon signal strength and history of challenges. Low-grade inflammatory monocytes facilitate the pathogenesis of chronic inflammatory diseases, while exhausted monocytes drive the pathogenesis of severe sepsis. Although clinical and basic studies suggest the conservation of key features of exhausted monocytes from human and murine sepsis, systems analyses of monocyte exhaustion among human and murine monocytes are lacking. METHODS: We performed cross examination of septic monocytes scRNAseq data recently collected from human sepsis patients as well as experimental septic mice, in reference to monocytes experimentally exhausted in vitro. Furthermore, we performed pseudo-time analyses of in vitro programmed monocytes following prolonged challenges causing either low-grade inflammation or exhaustion. Additional comparative analyses of low-grade inflammatory monocytes were performed with scRNAseq data from selected human patients with chronic low-grade inflammatory diseases. RESULTS: Our systems analyses reveal key features of monocyte exhaustion including reduced differentiation, pathogenic inflammation and immune suppression that are highly conserved in human and murine septic monocytes, and captured by in vitro experimental exhaustion. Pseudo-time analyses reveal that monocytes initially transition into a less-differentiated state with proliferative potential. The expansion of proliferative monocytes can be observed not only in experimentally challenged monocytes, but also in tissues of murine sepsis and human septic blood. We observed that monocytes similarly transition into the less-differentiated state when challenged with a subclinical dose endotoxin under chronic inflammatory conditions. Instead of being exhausted, monocytes with prolonged challenges with super-low dose endotoxin bifurcate into the low-grade inflammatory immune-enhancing or the chemotactic/adhesive state, often see in atherosclerosis or auto-immune diseases. CONCLUSIONS: Key features of monocyte memory dynamics are identified and conserved in human and murine monocytes, which can be captured by prolonged challenges of innate signals with varying signal strength.

Generation of resolving memory neutrophils through pharmacological training with 4-PBA or genetic deletion of TRAM.

Neutrophils are the dominant leukocytes in circulation and the first responders to infection and inflammatory cues. While the roles of neutrophils in driving inflammation have been widely recognized, the contribution of neutrophils in facilitating inflammation resolution is under-studied. Here, through single-cell RNA sequencing analysis, we identified a subpopulation of neutrophils exhibiting pro-resolving characteristics with greater Cd200r and Cd86 expression at the resting state. We further discovered that 4-PBA, a peroxisomal stress-reducing agent, can potently train neutrophils into the resolving state with enhanced expression of CD200R, CD86, as well as soluble pro-resolving mediators Resolvin D1 and SerpinB1. Resolving neutrophils trained by 4-PBA manifest enhanced phagocytosis and bacterial-killing functions. Mechanistically, the generation of resolving neutrophils is mediated by the PPARγ/LMO4/STAT3 signaling circuit modulated by TLR4 adaptor molecule TRAM. We further demonstrated that genetic deletion of TRAM renders the constitutive expansion of resolving neutrophils, with an enhanced signaling circuitry of PPARγ/LMO4/STAT3. These findings may have profound implications for the effective training of resolving neutrophils with therapeutic potential in the treatment of both acute infection as well as chronic inflammatory diseases.

Development of Exhausted Memory Monocytes and Underlying Mechanisms.

Pathogenic inflammation and immuno-suppression are cardinal features of exhausted monocytes increasingly recognized in septic patients and murine models of sepsis. However, underlying mechanisms responsible for the generation of exhausted monocytes have not been addressed. In this report, we examined the generation of exhausted primary murine monocytes through prolonged and repetitive challenges with high dose bacterial endotoxin lipopolysaccharide (LPS). We demonstrated that repetitive LPS challenges skew monocytes into the classically exhausted Ly6Chi population, and deplete the homeostatic non-classical Ly6Clo population, reminiscent of monocyte exhaustion in septic patients. scRNAseq analyses confirmed the expansion of Ly6Chi monocyte cluster, with elevation of pathogenic inflammatory genes previously observed in human septic patients. Furthermore, we identified CD38 as an inflammatory mediator of exhausted monocytes, associated with a drastic depletion of cellular NAD+; elevation of ROS; and compromise of mitochondria respiration, representative of septic monocytes. Mechanistically, we revealed that STAT1 is robustly elevated and sustained in LPS-exhausted monocytes, dependent upon the TRAM adaptor of the TLR4 pathway. TRAM deficient monocytes are largely resistant to LPS-mediated exhaustion, and retain the non-classical homeostatic features. Together, our current study addresses an important yet less-examined area of monocyte exhaustion, by providing phenotypic and mechanistic insights regarding the generation of exhausted monocytes.

Resolving monocytes generated through TRAM deletion attenuate atherosclerosis.

Polarization of low-grade inflammatory monocytes facilitates the pathogenesis of atherosclerosis. However, underlying mechanisms as well as approaches for resolving monocyte polarization conducive to the regression of atherosclerosis are not well established. In this report, we demonstrate that TRIF-related adaptor molecule (TRAM) mediated monocyte polarization in vivo and in vitro. TRAM controlled monocyte polarization through activating Src family kinase c-SRC, which not only induces STAT1/STAT5-regulated inflammatory mediators CCR2 and SIRP-α but also suppresses PPARγ-regulated resolving mediator CD200R. Enhanced PPARγ and Pex5 due to TRAM deficiency facilitated peroxisome homeostasis and reduction of cellular reactive oxygen species, further contributing to the establishment of a resolving monocyte phenotype. TRAM-deficient monocytes propagated the resolving phenotype to neighboring monocytes through CD200R-mediated intercellular communication. At the translational level, we show that TRAM-deficient mice were resistant to high-fat diet-induced pathogenesis of atherosclerosis. We further document that intravenous transfusion of TRAM-deficient resolving monocytes into atherosclerotic mice potently reduced the progression of atherosclerosis. Together, our data reveal that targeting TRAM may facilitate the effective generation of resolving monocytes conducive for the treatment of atherosclerosis.

Mixed halide perovskites for spectrally stable and high-efficiency blue light-emitting diodes.

Bright and efficient blue emission is key to further development of metal halide perovskite light-emitting diodes. Although modifying bromide/chloride composition is straightforward to achieve blue emission, practical implementation of this strategy has been challenging due to poor colour stability and severe photoluminescence quenching. Both detrimental effects become increasingly prominent in perovskites with the high chloride content needed to produce blue emission. Here, we solve these critical challenges in mixed halide perovskites and demonstrate spectrally stable blue perovskite light-emitting diodes over a wide range of emission wavelengths from 490 to 451 nanometres. The emission colour is directly tuned by modifying the halide composition. Particularly, our blue and deep-blue light-emitting diodes based on three-dimensional perovskites show high EQE values of 11.0% and 5.5% with emission peaks at 477 and 467 nm, respectively. These achievements are enabled by a vapour-assisted crystallization technique, which largely mitigates local compositional heterogeneity and ion migration.