Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective:To investigate the expression of N6-methyladenosine(m6A)reader heterogeneous nuclear ribonucleoprotein A2/B1(hnRNPA2B1)in human gastric cancer(GC)tissue and its effect on the proliferation and invasion of MKN-28 cells.Methods:The Cancer Genome Atlas and Gene Expression Omnibus were used to analyze the expression of hnRNPA2B1 and long noncoding RNA(ln-cRNA)mir-100-let-7a-2-mir-125b-1 cluster host gene(MIR100HG)in GC tissue and their association with the clinical prognosis of patients with GC.Quantitative PCR and Western blotting were used to measure the effect of hnRNPA2B1 on the expression level of MIR100HG and its downstream Wnt/β-catenin signaling pathway;Methylated RNA immunoprecipitation(MeRIP)was used to mea-sure the m6A level of MIR100HG;CCK-8 assay and Transwell assay were used to observe cell proliferation and invasion.Results:Com-pared with paracancerous tissue,human GC tissue showed significant increases in the expression levels of hnRNPA2B1(t=6.101,P<0.001)and MIR100HG(t=2.191,P=0.036 7),and the high expression levels of hnRNPA2B1 and MIR100HG were associated with poor survival in patients with GC.Knockdown of hnRNPA2B1 reduced the mRNA expression level(t=5.156,P=0.007)and m6A level of MIR100HG(t=4.789,P=0.010),inhibited the proliferation and invasion of MKN-28 cells(t=4.915,P=0.008 and t=5.167,P=0.007),and blocked the activity of the Wnt/β-catenin signaling pathway(P<0.05).Overexpression of MIR100HG promoted cell pro-liferation and invasion(t=3.578,P=0.023 and t=8.411,P=0.001),activated the Wnt/β-catenin signaling pathway(P<0.01),and re-versed the antitumor effect induced by hnRNPA2B1 knockdown(t=3.667,P=0.021).Conclusion:This study shows that hnRNPA2B1-mediated m6A modification of MIR100HG promotes the proliferation and invasion of GC MKN-28 cells by activating the Wnt/β-catenin signaling pathway.

Objective To explore the application of serum signal transducer and activator of transcription 3(STAT3),histone deacetylase 2(HDAC2),and developmental endothelial locus-1(Del-1)levels in the evaluation of disease severity and prognosis of children with respiratory syncytial virus pneumonia(RSVP).Methods A total of 109 children with RSVP admitted to Jiamusi Central Hospital from November 2023 to March 2025 were enrolled as the RSVP group.Based on disease severity,RSVP patients were categorized into a low-risk group(n=31),a medium-risk group(n=42),and a high-risk group(n=36).According to the prognosis after 7 days of treatment,they were divided into a favorable prognosis group(n=78)and a poor prognosis group(n=31).Additionally,109 healthy children undergoing physical examination at the same hospital during the same period were selected as the normal control group(NC group).ELISA method was used to detect serum levels of STAT3,HDAC2,and Del-1.Pearson correlation analysis was used to explore the correlations between serum STAT3,HDAC2,Del-1 levels and pulmonary function indices.Multivariate logistic regression analysis was used to explore the factors affecting the prognosis of children with RSVP.Moreover,ROC curve was used to explore the predictive value of serum STAT3,HDAC2,and Del-1 levels for the prognosis of children with RSV.Results Compared with the NC group,the RSVP group had higher serum STAT3 and HDAC2 levels,and lower serum Del-1 levels(P<0.05).Serum STAT3 and HDAC2 levels progressively increased from the low-risk group,medium risk group,to high-risk group,while the time to peak ratio(time to peak tidal expiratory flow to total expiratory time ratio,TPTEF/TE),peak volume ratio(volume to peak expiratory flow to total expired volume ratio,VPEF/VE),and serum Del-1 levels progressively decreased(P<0.05).TPTEF/TE and VPEF/VE were prominently negatively correlated with serum STAT3 and HDAC2 levels,and prominently positively correlated with Del-1 levels(P<0.05).Compared with the favorable prognosis group,the poor prognosis group had significantly lower initial blood oxygen saturation,serum Del-1 levels,and significantly higher serum STAT3 and HDAC2 levels(P<0.05).High expression levels of STAT3 and HDAC2 were independent risk factors affecting the prognosis of children with RSVP,while high expression of Del-1 was an independent protective factor(P<0.05).The AUC values of serum STAT3,HDAC2,and Del-1 levels alone in predicting the prognosis of children with RSV were 0.824,0.818,and 0.842,respectively.The combined prediction AUC was 0.947,which was superior to individual predictions(ZSTAT3-joint=2.436,ZHDAC2-joint=2.570,ZDel-1-joint=2.611,all P<0.05).Conclusion Serum expression of STAT3 and HDAC2 is upregulated,while the expression of Del-1 is down-regulated in children with RSVP.The three markers are closely related to the disease severity and pulmonary function indices,and are important factors affecting the prognosis of children with RSVP.Combined detection of these markers demonstrates high efficacy for prognosis evaluation.

Objective: To explore mental health status of vocational college students and its association with physical exercise and exercise motivation, so as to provide data support for the promotion of physical exercise, exercise motivation theory and the protection of mental health among vocational college students. Methods: From June 2 to July 2, 2023, a convenience sampling method was used to select 1 763 college students from three vocational colleges in Sichuan, Chongqing, and Guizhou for the survey. Physical Activity Rating Scale (PARS-3), Motives for Physical Activities Measure-Revised (MPAM-R), Patient Health Questionnaire-9 (PHQ-9) and Flourishing Scale (FS) were used to assess physical exercise, exercise motivation, depressive symptoms and flourishing levels of vocational college students. Multiple linear regression analysis was conducted to examine the relationship between physical exercise, exercise motivation, depression as the negative indicator of mental health and flourishing as the positive indicator of mental health. Results: There were negative correlations between physical exercise, exercise motivation and their five factors with depression scores among vocational college students ( r=-0.162--0.133, P <0.01). Physical exercise, health motivation and pleasure motivation were positively correlated with flourishing and its eight factors among vocational college students ( r= 0.054 -0.099, P <0.05). Depression scores and flourishing scores varied significantly across students with different levels of physical exercise and exercise motivation ( F=11.18-15.69, 2.80-16.05, P <0.05). Multiple linear regression analysis indicated that physical exercise, health motivation, and total exercise motivation scores were negatively correlated with depressive symptoms ( β = -0.02 , -0.11, -0.35), and physical exercise, health motivation, pleasure motivation, and total exercise motivation scores were positively correlated with flourishing ( β =0.31, 0.32, 0.50, 0.30) ( P <0.05). Conclusions Physical exercise and exercise motivation are significantly associated with mental health of vocational college students. Enhancing physical exercise and increasing exercise motivation in aspects of health and pleasure can promote mental health of vocational college students.

Objective To investigate the correlation between the methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism and disease in the course of Alzheimer's disease(AD),as well as whether whether it is af-fected by APOE gene.Methods A total of 74 AD patients,85 aMCI patients and 81 healthy controls(HC)were included.The levels of serum homocysteine(Hcy),folate,and vitamin B12,as well as the genotypes of MTHFR C677T and APOE,were determined.Logistic regression analysis was conducted to explore the relationship between MTHFR C677T polymorphism and the risk of AD and aMCI,as well as in different APOE ε4 subgroups.Results Compared with HC group,the serum Hcy levels in AD group and aMCI group were significantly higher(P＜0.001,P＜0.001),while serum folate levels in aMCI group was significantly lower(P=0.017).The serum fo-late level was significantly lower(P=0.038)in individuals with the MTHFR TT genotype compared to those with CC and CT genotypes,while the serum Hcy level was significantly higher(P=0.002).Regression analysis showed that the MTHFR TT genotype might increase the risk of aMCI in the subgroup of APOE e4 non-carriers(OR=3.670,95％CI=1.077-12.509,P=0.038),but not in APOE e4 carriers.Conclusion MTHFR C677T polymorphism plays an important role in Hcy metabolism,which leads to increased serum Hcy levels and decreased folate levels.In APOE ε4 non-carriers,the MTHFR TT genotype may increase the risk of aMCI.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.