ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

BackgroundNegative effects of mobile phone addiction on undergraduate students have led to several health problems including depression， anxiety， attention deficit disorder， cognitive impairment and sleep disturbance. The undergraduate nursing students serve as an important reserve force of the clinical nursing work， and their poor psychological health would have a non-ignorable impact on the quality of the nursing work and the nurse-patient relationship in the future. ObjectiveTo investigate the relation between neuroticism and tendency of mobile phone addiction among undergraduate nursing students， and to examine the pathways through which perceived stress and self-control play a role in the relation by constructing a chain-mediated model. MethodsFrom February to March 2023， a total of 900 undergraduate nursing students across 10 universities in Xi'an， Shaanxi Province were selected through convenient sampling method. Several scales were adopted to assess undergraduate nursing students respectively， including the neuroticism subscale of Eysenck Personality Questionnaire-Revised Short Scale for Chines （EPQ-RSC）， Perceived Stress Scale （PSS）， Self-Control Scale （SCS） and Mobile Phone Addiction Tendency Scale （MPATS）. The assessment were conducted on multiple aspects of these students including neurotic personality， subjective stress， self-control and mobile phone addiction tendency. Model 6 in the SPSS Macro Process 4.1 was used to examine the mediating effect of perceived stress and self-control between neuroticism and mobile phone addiction tendency among undergraduate nursing students. Results① Among the 900 students， 314 cases （34.89%） were found to be addicted to mobile phones. ② The score of neuroticism subscale in EPQ-RSC of nursing undergraduates was positively correlated with the total scores of PSS and MPATS （r=0.400， 0.287， P<0.01）， and negatively correlated with score of SCS （r=-0.364， P<0.01）. The total score of MPATS was positively correlated with the total score of PSS （r=0.362， P<0.01）， and negatively correlated with the total score of SCS （r=-0.468， P<0.01）. The total score of SCS was negatively correlated with the total score of PSS （r=-0.515， P<0.01）. ③ Perceived stress and self-control performed partial mediation between neuroticism personality and mobile phone addiction tendency （with indirect effect values of 0.056 and 0.065， respectively， accounting for 19.72% and 22.89% of the total effect）. Perceived stress and self-control played a chain mediating role between neuroticism personality and mobile phone addiction tendency （with an indirect effect value of 0.064， accounting for 22.54% of the total effect）. ConclusionNeuroticism personality， perceived stress and self-control are confirmed to play important roles in mobile phone addiction tendency among undergraduate nursing students. Neuroticism personality not only directly affects the tendency of mobile phone addiction， but also affects their mobile phone addiction tendency through the chain mediating effect of perceived stress and self-control.［Funded by The 2020 Annual Project of the 13th Five-Year Plan of Education Science in Shaanxi Province （number， SGH20Y1386）］

ObjectiveTo investigate the effect of 8-week aerobic exercise on the improvement of core behaviors of male and female autistic mice induced by valproic acid (VPA). MethodsExperimental mice were randomly divided into the control group (CTL), VPA-induced autism group (VPA) and VPA+aerobic exercise group (VEX), with 10 mice in each group. The pregnant mice were injected with VPA intraperitoneally at E12.5, and their offspring were used as autistic mice. Pups were weaned 28 d after birth and began an 8-week aerobic exercise intervention. The day after exercise, mice were tested in behavioral experiments to detect exploratory behavior, social skills, repetitive stereotypic behavior, cognitive ability and mood. The mice were tested for social skills, repetitive stereotyped behaviors, cognitive and learning memory abilities, exploratory behaviors, and emotions by behavioral assays on the following day after the exercise. ResultsBoth male and female mice in the CTL group showed a significant decrease in the total distance and percentage of time spent in the interaction zone in the 4th socialization compared to the 1st socialization (P<0.01); the total distance and percentage of time spent in the interaction zone in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01); in VPA group, both male and female mice showed no significant change in the total distance and percentage of time spent in the interaction zone in the 4th and 5th socialization; in the VEX group, the total distance and percentage of time spent in the interaction zone by male mice in the 4th socialization was significantly decreased compared to the 1st socialization (P<0.01, P<0.05); and in the VEX group the total distance and percentage of time spent in the social interaction zone by both male and female mice in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01, P<0.05). The results of the first phase of three-box socialization experiment showed that male and female mice in the CTL group spent more time socializing with their social partners than in contact with the empty cages (P<0.01); there was no difference in the time spent by male and female mice in the VPA group in socializing with their social partners and the empty cages; and male and female mice in the VEX group spent a longer time socializing with their social partners(P<0.01). The results of the second phase of three-box test showed that male and female mice in the CTL group showed a significant tendency to socialize with new social partners (P<0.01), whereas no significant changes were observed in the mice of VPA group; aerobic exercise significantly ameliorated this deficit in male and female mice with autism. Compared with the CTL group, VPA-induced significant decreases were observed in the total distance freely moved in the central area of the open field, the time and percentage of time spent in the open arm of cross maze, and the distance and time spent in the white box in both male and female autistic mice (P<0.01); a significant increase in the number of bead burials and time spent in self-grooming (P<0.01); a significant decrease in the cognitive index (P<0.01); a significantly longer latency to find the platform, and significantly decreased the percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01). Compared with the VPA group, after 8 weeks of aerobic intervention, male and female mice in the VEX group showed a significant increase in total distance, open-arm dwell time, and percentage of free movement in the central area of the empty field (P<0. 05), and a trend toward a decrease in the dwell time of females in the white box was not significant, the number of beads burying and the time of self-combing were significantly lower(P<0.01, P<0.05); and a significant increase in cognitive index (P<0.05), a significantly shorter time to find the platform, and significantly increased percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01), showing excellent learning memory. ConclusionAutistic mice severely suffer from social and cognitive impairments, repetitive stereotyped behaviors, decreased activity level, and the exhibition of anxiety. 8 weeks of aerobic exercise can improve the social and cognitive abilities, alleviate the stereotyped repetitive behaviors, increase the activity level, and positively regulate the anxiety in autistic mice. It is hypothesized that aerobic exercise has an important role in motor rehabilitation of autism, in order to provide a theoretical basis for clinical research.

ObjectiveTo understand the process and influencing factors affecting the utilization of influenza vaccination services and vaccination decision-making among the elderly in Shanghai, to explore the delivery of influenza vaccination services and the difficulties faced by the health service system, and to provide guidance for optimizing immunization strategies. MethodsBased on the vaccine hesitancy determinants matrix, semi-structured personal interviews were conducted with stakeholders involved in influenza vaccination services in Shanghai from January to February 2024, using a purposive sampling method. Participants were included until thematic saturation was achieved. Interview data were audio-recorded, transcribed, coded, and organized using NVivo 20 software, and analyzed using the thematic framework method. ResultsA total of 25 interviewees were included, including 9 medical staff, 12 elderly people aged 60 and above, and 4 family members. The study found that Shanghai had a well-managed and standardized influenza vaccination service. However, the promotion of vaccine-related information at the grassroots level was passive and limited. Out-of-pocket payment of the vaccine and cultural beliefs of the elderly negatively impacted vaccination rates. Meanwhile, recommendations from family, friends, and medical staff facilitated vaccination, although the impact varied depending on the type of medical staff. Neighborhood committees in townships and streets played a crucial role in delivering vaccination information to the target population. Additionally, the internet, social media, and the COVID-19 vaccine had both positive and negative impacts on influenza vaccination. Strategic optimization of vaccination should prioritize price concessions, enhance publicity strategies, and improve awareness, professionalism, and willingness among medical and healthcare workers to recommend vaccination. ConclusionThe influenza vaccination service in Shanghai is well-managed and standardized. However, it is essential to consider the influence of family and other support systems on the elderly. It is also necessary to enhance the professionalism, service awareness, and willingness to recommend among the medical staff. Furthermore, systematic interventions and publicity efforts should be effectively integrated with social media and the functions of neighborhood committees.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD+)levels and nabothian cysts.This study aimed to assess the association between NAD+levels and nabothian cysts in healthy Chinese women. Methods Multivariate logistic regression analysis was performed to analyze the association between NAD+levels and nabothian cysts. Results The mean age was 43.0±11.5 years,and the mean level of NAD+was 31.3±5.3 μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and 84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from 37.4%to 21.6%from Q1 to Q4 of NAD+and the prevalence of single and multiple nabothian cysts also decreased across the NAD+quartiles.As compared with the highest NAD+quartile(≥34.4 μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD+Q1 was 1.89(1.14-3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD+levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD+levels of 28.0 to 35.0 μmol/L. Conclusion:Low NAD+levels were associated with an increased risk of total and multiple nabothian cysts.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.