Spermidine suppresses the activation of hepatic stellate cells to cure liver fibrosis through autophagy activator MAP1S.

BACKGROUND AND AIMS: Liver diseases present a wide range of fibrosis, from fatty liver with no inflammation to steatohepatitis with varying degrees of fibrosis, to established cirrhosis leading to HCC. In a multivariate analysis, serum levels of spermidine were chosen as the top metabolite from 237 metabolites and its levels were drastically reduced along with progression to advanced steatohepatitis. Our previous studies that showed spermidine supplementation helps mice prevent liver fibrosis through MAP1S have prompted us to explore the possibility that spermidine can alleviate or cure already developed liver fibrosis. METHODS: We collected tissue samples from patients with liver fibrosis to measure the levels of MAP1S. We treated wild-type and MAP1S knockout mice with CCl4 -induced liver fibrosis with spermidine and isolated HSCs in culture to test the effects of spermidine on HSC activation and liver fibrosis. RESULTS: Patients with increasing degrees of liver fibrosis had reduced levels of MAP1S. Supplementing spermidine in mice that had already developed liver fibrosis after 1 month of CCl4 induction for an additional 3 months resulted in significant reductions in levels of ECM proteins and a remarkable improvement in liver fibrosis through MAP1S. Spermidine also suppressed HSC activation by reducing ECM proteins at both the mRNA and protein levels, and increasing the number of lipid droplets in stellate cells. CONCLUSIONS: Spermidine supplementation is a potentially clinically meaningful approach to treating and curing liver fibrosis, preventing cirrhosis and HCC in patients.

Childhood trauma and psychological sub-health among Chinese adolescents: the mediating effect of Internet addiction.

BACKGROUND: The factors related to psychological sub-health (PSH) have been widely described, but the research on the mechanism behind the complex relationship between childhood trauma and PSH is limited. This study investigated the current situation and risk factors of PSH among Chinese adolescents. And further, explore whether Internet addiction (IA) plays a potential mediating effect in childhood trauma and PSH. METHODS: The study was conducted in October 2020 in Anhui Province, China. The PSH state of 866 adolescents was investigated, including demographic information such as gender, age, and grade. Childhood trauma, IA, and PSH were measured by the Childhood Trauma Questionnaire Short Form (CTQ-SF), Young's Internet Addiction Test (IAT), and the Multidimensional Sub-health Questionnaire of Adolescents (MSQA). The mediating effect is further verified by the structural equation model (SEM). RESULTS: In this study, 866 adolescents were selected as subjects, and the proportion of male and female is roughly equal. The prevalence of PSH in adolescents was 25.8%, and left-behind children, boarding, or adolescents who have had non-suicidal self-injury (NSSI) are more likely to have PSH. Through the mediation test, the direct effect of childhood trauma on PSH was 0.23 (95% CI [4.91,9.00],p <0.001), and the mediating effect of IA on childhood trauma and PSH was 0.07 (95% CI [1.42, 3.32],p <0.001). and the proportion of them is 75.14% and 24.86% respectively. CONCLUSIONS: Childhood trauma has direct and indirect effects on PSH, and IA plays a mediating effect in the indirect effect. Therefore, clarifying these relationships helps formulate and implement effective interventions to improve psychological health (PH) in Chinese adolescents.

Consistency of functional connectivity across different movies.

Movie fMRI has emerged as a powerful tool for investigating human brain function, and functional connectivity (FC) plays a predominant role in fMRI-based studies. Accordingly, movie-watching FC may have great potential for future studies on human brain function. Before wide application of movie-watching FC, however, it is essential to evaluate how much it is influenced by differences in movies. The main aim of this study was to investigate the consistency of movie-watching FC across different movies. For this purpose, we performed three sets of analyses on the four movie fMRI runs (with different movie stimuli) included in the HCP dataset. The first set was performed to evaluate the agreement of movie-watching FC in exact values using intra-class correlation (ICC), and the ICC of movie-watching FC across different movies (0.37 on average) was found to be comparable to that of resting-state FC across repeated scans. The second set was performed to evaluate the agreement of movie-watching FC in connectivity patterns, and the results indicate that individuals could be identified with relatively high accuracies (94%-99%) across different movies based on their FC matrices. The final set was performed to test the generalizability of predictive models based on movie-watching FC, as this generalizability is highly dependent on the consistency of the FC. The results indicate that predictive models trained based on FC extracted from one movie fMRI run can make good predictions on FC extracted from runs with different movie stimuli. Taken together, our findings indicate that movie-watching FC is highly consistent across different movies, and conclusions drawn based on movie-watching FC are generalizable.

Predictors of non-suicidal self-injury in adolescents with depressive disorder: the role of alexithymia, childhood trauma, and body investment.

Purpose: This study analyzes the relationship of alexithymia, childhood trauma, and body investment to non-suicidal self-injury (NSSI) behaviors in adolescents with depressive disorder and whether they have predictive and diagnostic value for non-suicidal self-injury (NSSI) behaviors in adolescents with depressive disorder. Patients and methods: A total of 225 patients with a diagnosis of adolescent depressive disorder were included in the study and were divided into two groups according to the DSM-5 criteria: 98 cases without NSSI and 127 cases with NSSI. Compare the demographic data, 24-item Hamilton Depression Scale (HAMD-24), 20-item Toronto Alexithymia Scale (TAS-20), Childhood Trauma Questionnaire-Short Form (CTQ-SF), and Body Investment Scale (BIS) scores between two groups. Binary logistic regression was used to analyze the independent risk factors contributing to NSSI behaviors in adolescents with depression, and establish four predictive models. Based on the models' predictive probability, the ROC curves were plotted to calculate the value of the predictive diagnostic effect. Results: The group without NSSI had lower scores than the group with NSSI on HAMD-24 total score, TAS-20 total score, difficulty identifying feelings, difficulty describing feelings, and externally focused thinking, as well as lower scores on CTQ-SF total score, physical neglect, emotional neglect, physical abuse, and emotional abuse. In contrast, the BIS total score, body image feelings and attitudes, body care, and body protection factor scores were higher for the group without NSSI. The BIS body care factor score and the CTQ-SF emotional abuse factor score were significantly linked with adolescents diagnosed with depressive disorder who exhibited NSSI behaviors. These results provide a good diagnostic model for adolescents with depressive disorder. Conclusion: Low levels of body care and childhood emotional abuse may independently contribute to the implementation of NSSI in adolescents with depressive disorder. Body investment and childhood trauma are valuable in diagnosing and predicting NSSI behaviors and should be considered as potentially important factors in clinical treatment.

Insomnia and aggression in stable schizophrenic patients: The mediating role of quality of life.

Aggression in schizophrenia patients is an issue of concern. Previous studies have shown that aggression in schizophrenia patients may be related to insomnia and quality of life to different extents. This study aimed to explore the potential mediating role of quality of life in the relationship between aggression and insomnia among schizophrenia patients. Demographic factors affecting aggression in schizophrenia patients were also explored. PATIENTS AND METHODS: A total of 781 stable patients aged 18-75 who met the ICD10 diagnosis of "schizophrenia" completed the completed questionnaire. Aggression was assessed using the Modified Overt Aggression Scale (MOAS), sleep was assessed using the Insomnia Severity Index Scale (ISI), and quality of life was assessed using the five Likert options. Descriptive statistics and correlation analysis examined the correlation between aggression and other variables. The mediating role of quality of life in the association between insomnia and aggression was examined by pathway analysis. RESULTS: A total of 781 patients participated in this study, and approximately 16 % of the schizophrenia patients were aggressive. According to the mediation analysis, the direct effect of insomnia on aggression was 0.147, and the mediating effect of quality of life on insomnia and aggression was 0.021. Specifically, for the four dimensions of the MOAS, the direct effects of insomnia on verbal aggression, aggression toward property, and aggression toward oneself were 0.028, 0.032, and 0.023, respectively, with mediating effects of 0.003, 0.007, and 0.006, respectively, and no mediating effect on physical aggression was found. CONCLUSION: This study showed that insomnia significantly influenced aggression in schizophrenia patients. Quality of life significantly mediated insomnia and aggression and played a vital role in moderating aggression. Therefore, we suggest that in the future, improving aggression in schizophrenia patients, while paying attention to the importance of sleep, could start with improving quality of life to address this problem from multiple perspectives.

Are inter-subject functional correlations consistent across different movies?

Movie fMRI has been increasingly used in investigations of human brain function. Inter-subject functional correlation (ISFC), which evaluates stimulus-dependent inter-regional synchrony between brains exposed to the same stimulus, is emerging as an influencing measure for movie fMRI data analyses. Before the wide application of ISFC analyses, it will be useful to investigate the degree to which they are similar and different across different movies. Based on the four movie fMRI runs of 178 subjects included in the "human connectome project (HCP) S1200 Release", we evaluated ISFCs throughout the brain and analyzed their consistency across different movies using intra-class correlation (ICC). We also investigated the generalizability of ISFC-based predictive models, which is closely related to their consistency, with sex classification and grip strength prediction used as test cases. The results showed that the intensity of ISFCs was generally weak (0.047). Except a few within-network ones (e.g., ICC of ISFC in the PON was 0.402), ISFCs throughout the brain exhibited low consistency, as indicated by a mean ICC of 0.130. The accuracies for inter-run predictions (60.7-72.8% for sex classification, and R = 0.122-0.275 for grip strength prediction) were much lower than those for intra-run predictions (73.2-83.0% for sex classification, and R = 0.325-0.403 for grip strength prediction), and this indicates poor generalizability of predictive models based on ISFCs. According to these findings, ISFC analyses capture aspects of brain function that are specific to each individual movie, and this specificity should be taken into account (in some cases might be especially useful) in future naturalistic studies.

External Validation of Ultrasound Radiomics for Small (≤ 4 cm) Renal Mass Differentiation: A Comparison with Radiologists.

BACKGROUND: Renal cell carcinoma, especially in small renal masses (≤ 4 cm) (SRM), has increased. Pathological analysis revealed a high proportion of benign masses, highlighting the urgent need for precise SRM differentiation. OBJECTIVES: This research aimed to independently validate the performance of machine learning-based ultrasound (US) radiomics analysis in differentiating benign from malignant SRM, and to compare its performance with that of radiologists. METHODS: A total of 499 patients from two hospitals were retrospectively included in this study and divided into two cohorts. US images were used to extract radiomics features. To obtain the most robust features, inter-observer correlation coefficient, Spearman correlation coefficient, and least absolute shrinkage and selection operator methods were applied for feature selection. Three models were developed in the training data using the stochastic gradient boosting algorithm, including a clinical model, a radiomics model, and a combined model that integrated clinical factors and radiomics features. The performance of these models was evaluated in the independent external validation data, including discrimination, calibration, and clinical usefulness, and compared with pooled radiologists' assessments. RESULTS: The AUCs of the clinical, radiomics, and combined models were 0.844, 0.942, and 0.954, respectively. The radiomics and combined models significantly outperformed the clinical model (all p < 0.05), while no significant difference was observed between them (p = 0.32). The radiomics and combined models showed good discrimination and calibration. Decision curve analysis exhibited that the combined model had clinical usefulness. Compared with the pooled radiologists' assessment (AUC, 0.799), the combined model showed superior classification results (p < 0.01) and higher specificity (p < 0.01) with similar sensitivity (p = 0.62). CONCLUSION: The combined model incorporating clinical factors and radiomics features accurately distinguished benign from malignant SRM.

Untargeted metabolomics reveal the metabolic profile of normal pulmonary circulation.

BACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation. METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery. RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly. CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.

Effects of length and type of the alkyl chain on the micellization behavior of mixed systems of HS15 with fatty acids.

Due to volatility, low solubility and instability, the application of SCFAs and MCFAs is limited, which is expected to be solved by micelles. Taking SCFAs and MCFAs as models, this paper aims to research the influences of alkyl chain length and type on HS15 micelles. The critical micelle concentration (CMC) of various acid-HS15 systems was determined firstly. Then some air-water interface parameters and thermodynamic parameters were analyzed. Subsequently, particle size, cloud points (CP) and fluorophore release curves were measured. With the increase of CMC and Gmin, the decrease of size and CP, and the rapid quenching of fluorophores, it is more difficult for acids with longer-chain to form stable micelles with HS15 because of the strength of iceberg structure. Showing smaller CMC and Gmin, smaller size, higher CP and slower release of fluorescers, branched molecules can bind more closely to the hydrophobic part of HS15 due to their spatial flexibility.

Left-Behind Experience and Behavior Problems Among Adolescents: Multiple Mediating Effects of Social Support and Sleep Quality.

Purpose: Adolescence has always been a period prone to behavior problems. Some studies have shown that left-behind experience, social support, and sleep quality are all crucial factors influencing behavior problems, but the mechanisms of how they are influenced are unclear. This cross-sectional study investigated the prevalence of behavior problems among school-aged adolescents and explored the mediating role of social support and sleep quality in the association between left-behind experience and behavior problems. Patients and Methods: A total of 738 school adolescent students completed this questionnaire. We collected basic information about the participants using a general demographic scale and assessed their sleep quality, social support, and behavioral problems using the Pittsburgh Sleep Quality Index scale, Social Support Rating Scale, and Strengths and Difficulties Questionnaire. The multiple mediating effects of sleep quality and social support were examined by path analysis. Results: Among 738 school-aged adolescent students who completed the survey, a total of 198 students had behavior problems, with an overall prevalence of 26.8%. In the multiple mediation model, the mediation effect of social support and sleep quality on left-behind experience to behavior problems was 56.7% (direct effect: standardized estimate=0.946, indirect effect: standardized estimate=1.239). The model was a saturated model, and fit was no longer considered. Conclusion: We found that social support and sleep quality had a series of multiple mediating effects in the pathway from left-behind experience to behavior problems, and both significantly moderated behavior problems. Therefore, we suggest that we should pay more attention to students' psychological status and improve their use of social support for left-behind adolescents, in addition to giving more external social support. And paying attention to their sleep problems to reduce the occurrence of behavior problems, considering that their psychological development is not mature.

Stand structure adjustment influences the biomass allocation in naturally generated Pinus massoniana seedlings through environmental factors.

The natural regeneration of seedlings is a key factor for forest succession. Nevertheless, studies explaining the mechanism of growth and biomass allocation in regenerated seedlings after disturbance are lacking. Therefore, we measured the growth, biomass accumulation, and biomass allocation in current-age seedlings of Pinus massoniana after selective logging (logging of competitive trees, LCT; logging of inferior trees, LIT; and unlogged control, CK), and established structural equation models (SEMs) among the spatial structure characteristic indexes of the stand, environmental factors, and biomass allocation in different organs. As compared to the CK, the mingling index (M), uniform angle index (W), opening degree (O), soil organic carbon (SOC), available nitrogen (SAN), available phosphorus (SAP), available potassium (SAK), and bulk density (SBD) significantly increased (p < 0.05), while the competition index (CI) and neighborhood comparison (U) significantly decreased after logging (p < 0.05). After the LCT, seedling branch biomass improved, with an increase in the ground-diameter, crown-root ratio, and seedling quality index. More biomass was allocated to foliage and roots by an increase in the height and height-diameter ratio under the LIT. In the CK, increasing stem biomass helped the seedlings absorb and utilize more light. The Pearson correlation coefficient showed that biomass allocation to organs was independent, and seedlings adopted the strategies of heterogeneous adaptation and growth, thereby resulting in the separation of the allocation patterns among the organs. As per the redundancy analysis (RDA), CI was the main factor in biomass allocation. Environmental factors had direct effects on biomass allocation to organs, while the stand spatial structure characteristic indexes had indirect effects on biomass allocation based on SEMs. In summary, the LCT had significant, albeit indirect, effects on SOC, SAN, and SBD by reducing the CI for the regeneration and growth of seedlings in the stand, which was of great significance to the sustainable development of the forest stand of P. massoniana.

Childhood Trauma and Non-suicidal Self-Injury Among Chinese Adolescents: The Mediating Role of Psychological Sub-health.

The factors associated with non-suicidal self-injury (NSSI) of adolescents have been widely researched. However, the underlying mechanism of the relationship between childhood trauma and NSSI is limited. This study aimed to explore the risk factors for NSSI among Chinese adolescents. Our hypothesis was that psychological sub-health (PSH) played a mediating role between childhood trauma and NSSI. The Childhood Trauma Questionnaire, the Multidimensional Sub-health Questionnaire of Adolescent, and the self-report NSSI were used to measure childhood trauma, PSH, and NSSI. Structural equation model (SEM) was performed to verify our hypothesis. The results showed that 33.9% of the participants in our survey had engaged in NSSI in the past year. Adolescents who were left-behind children or in primary schools were more likely to engage in NSSI. Additionally, 56.2% of the participants had moderate to severe childhood trauma, and 26.1% of the participants had PSH. Furthermore, childhood trauma and PSH would increase the risk of NSSI by 2 times (B = 0.79, p < 0.01) and 5 times (B = 1.64, p < 0.01), respectively. SEM was established (p = 0.512) and the goodness-of-fit indices were examined (CMIN/DF = 0.892; GFI = 0.997; AGFI = 0.992; NFI = 0.991; RFI = 0.980; IFI = 1.00; TLI = 1.00; CFI = 1.00; RMSEA < 0.001). The SEM indicated that childhood trauma positively predicted NSSI both directly and indirectly through PSH. PSH has been confirmed to have partial mediating effects between childhood trauma and NSSI. The assessment of PSH may be an operable and effective method to screen and predict NSSI. Meanwhile, the intervention of childhood trauma and PSH may effectively prevent and reduce the occurrence of NSSI among adolescents.

The relationship between Internet addiction and childhood trauma in adolescents: The mediating role of social support.

Background: Adolescents are at high risk of Internet addiction (IA). Previous studies have shown that the occurrence of IA may be associated with childhood trauma and social support to varying degrees. This study aimed to investigate the pathogenesis of IA in adolescents. Further, to explore the potential mediating role of social support in childhood trauma and IA. This study provides theoretical support for future interventions targeting IA in adolescents. Methods: This study used a descriptive cross-sectional design. The Childhood Trauma Questionnaire (CTQ), Social Support Rating Scale (SSRS), and Young's Internet Addiction Test (IAT) were used to conduct an anonymous questionnaire survey among randomly selected adolescents aged less than 18 years old in two cities in southern Anhui Province. Descriptive statistics and correlation analysis were used to test the correlation between IA and other variables. A binary logistic regression model was used to explore the influencing factors of IA. Multiple regression models were examined with process macro and bootstrapping to confirm significant mediating effects. Results: A total of 844 adolescents, equally divided between males and females, participated in this study, and the prevalence of IA in the region was 23.0%. Through the mediation test, the direct effect of childhood trauma on IA was 0.20 (95% CI [0.12, 0.27], p < 0.001), and the mediating effect of social support on childhood trauma and IA was 0.09 (95% CI [0.06, 0.14]). Conclusion: The study showed that childhood trauma significantly affected the incidence of IA in adolescents. Social support had a significant mediating effect on childhood trauma and IA and attenuated its negative effects.

Anatomical structure interpretation of the effect of soil environment on fine root function.

Fine root anatomy plays an important role in understanding the relationship between fine root function and soil environment. However, in different soil environments, the variation of fine root anatomical structure in different root sequences is not well studied. We measured the soil conditions and anatomical structure characteristics (root diameter, cortical tissue, vascular tissue and xylem) of fine roots of Cupressus funebris in four experimental sites, and analyzed each level of fine roots separately. We link these data to understand the relationship between fine root anatomy and soil conditions. We found that the anatomical structure of fine roots is closely related to soil environmental factors. The fine roots of lower root order are mainly affected by soil nutrients. Among them, the cortical tissue of first-order fine roots was positively correlated with potassium and phosphorus, but negatively correlated with nitrogen, while second- and third-order fine roots was positively correlated with soil total potassium and negatively correlated with nitrogen and phosphorus. For the fine roots of high root order, the cortical tissue disappeared, and the secondary vascular tissue was mainly affected by soil moisture. In addition, we also found that the division of fine root functional groups is not fixed. On the one hand, the function of third-order fine roots will slip. For example, the decrease of soil moisture will promote the transformation of third-order fine roots into transport roots, and the reduction of nitrogen will promote the transformation of third-order fine roots into absorption roots to fix nitrogen. This transformation strategy can effectively prevent the restriction of soil nutrients on plant growth. On the other hand, with the change of habitat, the first- and second-order fine roots are still the absorbing root, and the fourth- and fifth-order fine roots are still the transport root, but the efficiency of absorption and transport will be affected. In conclusion, our findings emphasize the fine roots in different soil environment to show high levels of plasticity, shows that fine root anatomical structure changes may make plants, and reveals that the fine is just order of reaction and its mechanism in the soil environment.

Response strategies of fine root morphology of Cupressus funebris to the different soil environment.

Understanding fine root morphology is crucial to uncover water and nutrient acquisition and transposition of fine roots. However, there is still a lack of knowledge regarding how the soil environment affects the fine root morphology of various root orders in the stable forest ecosystem. Therefore, this experiment assessed the response strategies of fine root morphology (first- to fifth -order fine roots) in four different soil environments. The results showed that fine root morphology was related to soil environment, and there were significant differences in specific root length (SRL), specific surface area (SRA), diameter (D), and root tissue density (RTD) of first- and second -order fine roots. Soil total nitrogen (TN), alkaline nitrogen (AN) and available phosphorus (AP) were positively correlated with SRL and SRA and negatively correlated with D and RTD. Soil moisture (SW) was positively correlated with the D and RTD of first- and second-order fine roots and negatively correlated with the SRL and SRA. Soil temperature (ST), organic carbon (OC), soil bulk density (SBD) and soil porosity (SP) were not significantly correlated with the D, SRL, SRA, and RTD of the first- and second -order fine roots. AN was positively correlated with SRL and SRA and negatively correlated with both D and RTD in the first- and second -order fine roots, and the correlation coefficient was very significant. Therefore, we finally concluded that soil AN was the most critical factor affecting root D, SRL, SRA and RTD of fine roots, and mainly affected the morphology of first- and second -order fine roots. In conclusion, our research provides support for understanding the relationship between fine root morphology and soil environment, and indicates that soil nutrient gradient forms good root morphology at intraspecific scale.

Improvement in storage quality of postharvest tomato fruits by nitroxyl liposomes treatment.

Nitroxyl (HNO) has attracted much attention due to its unique biological activity. To investigate the preservation effect of HNO on fruits, a nitroxyl liposome based on 1-nitrosocyclohexyl acetate was prepared and characterized by infrared spectroscopy and transmission electron microscopy. The optimal preparation conditions were explored, and then HNO liposomes were prepared under the optimal conditions to study the effect of HNO liposomes on postharvest quality of tomatoes. The tomato fruits were treated with different concentrations (0, 5, 10, 15 and 20 µmol L-1) of HNO liposomes and stored at room temperature. The results indicated that treatment with HNO liposomes can more effectively delay the browning and slow down the decrease in lightness of tomatoes. Additionally, HNO liposomes can reduce the activity of PPO and POD, inhibit the increase of MDA and total phenol content. These results suggest that treatment with HNO liposomes can effectively preserve the quality of tomatoes.