The Association Between Emotion Recognition and Internalizing Problems in Children and Adolescents: A Three-Level Meta-Analysis.

Numerous studies have explored the link between how well youth recognize emotions and their internalizing problems, but a consensus remains elusive. This study used a three-level meta-analysis model to quantitatively synthesize the findings of existing studies to assess the relationship. A moderation analysis was also conducted to explore the sources of research heterogeneity. Through a systematic literature search, a total of 42 studies with 201 effect sizes were retrieved for the current meta-analysis, and 7579 participants were included. Emotion recognition was negatively correlated with internalizing problems. Children and adolescents with weaker emotion recognition skills were more likely to have internalizing problems. In addition, this meta-analysis found that publication year had a significant moderating effect. The correlation between emotion recognition and internalizing problems decreased over time. The degree of internalizing problems was also found to be a significant moderator. The correlation between emotion recognition and internalizing disorders was higher than the correlation between emotion recognition and internalizing symptoms. Deficits in emotion recognition might be relevant for the development and/or maintenance of internalizing problems in children and adolescents. The overall effect was small and future research should explore the clinical relevance of the association.

The impact of heterotopic ovarian tissue transplantation with varied volumes on reproductive endocrine function in oophorectomized rats.

BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. RESULTS: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. CONCLUSION: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.

With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.

Patterns of perceived parenting styles and associations with night eating syndrome symptoms and correlates among Chinese adolescents: a latent profile analysis.

PURPOSE: This paper aimed to explore the association between the patterns of perceived parenting styles and adolescents' night eating syndrome symptoms and correlates, including sleep quality, weight status, loss of control over eating, and psychological distress. METHODS: A sample of 455 Chinese adolescents (54.5% females, aged 12-15 years) were included in the current study. Latent Profile Analysis (LPA) was adopted to examine the patterns of perceived parenting styles. The three-step approach was used to explore the differences in night eating syndrome symptoms and correlates between different profiles. RESULTS: A four-profile solution was found to fit the data best, and the four profiles were labeled as positive parenting, negative parenting, highly engaged parenting, and lowly engaged parenting. Subsequent analyses showed that adolescents across profiles exhibited significant differences in night eating syndrome symptoms and correlates. Specifically, adolescents in the positive parenting profile generally had the lowest scores in night eating and its correlates, while those in the negative parenting group reported the highest scores in night eating and its correlates. CONCLUSION: Using a person-centered approach (i.e., LPA), the present study identified four distinct patterns of perceived parenting styles in a sample of Chinese adolescents, with night eating and related symptomatology differing across each profile. Future interventions targeting night eating among adolescents may consider the potential influence from the patterns of perceived parenting styles to have a better intervention outcome. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

A Comparison of Fixed-Effects and Random-Effects Models for Multivariate Meta-Analysis Using an SEM Approach.

This study compared fixed-effects (FE) and random-effects (RE) models in meta-analysis for synthesizing multivariate effect sizes under the framework of structural equation modeling. Monte Carlo simulations were conducted to examine the performance characteristics of the two models under different data conditions. The results indicated that, for the homogeneous case, there was little difference between the FE model and the RE model applications. But the FE model had better performance in standard error estimation when number of studies is not large and the sample size of primary studies is small. Furthermore, under the heterogeneous case, FE model exhibited biased estimates of population parameters and extreme levels of inflated Type I error in testing the effect size estimates. However, RE model maintained unbiased estimates of the population parameters, and controlled Type I error well under various data conditions investigated. These findings provided empirical evidence that it is likely that RE model application in a meta-analysis would be preferred when the number of primary studies and the sample sizes in the primary studies are reasonably large, and FE model could be favored for situations with smaller numbers of studies and uniformly small sample sizes of primary studies.

Optimizing the Calibration Error of Refraction Angles in Ultrasonic Angle Beam Testing.

Ultrasonic testing is a useful approach for quantifying the flaws in mechanical components. The height of the flaws in ultrasonic angle beam testing is closely related to the calibration value of the probe refraction angle. In order to reduce the calibration error, some ignored data during the traditional calibration process are reanalyzed and fused to determine the refraction angle. Both arithmetical measurement fusion method and weighted measurement fusion method are applied and compared. Monte Carlo simulation is used to estimate the probability distribution of the refraction angle and obtain the optimal refraction angle weights. Experiments were carried out to verify the results of Monte Carlo simulation. The applicability of data fusion on refraction angles is investigated. It was found in the study that the data fused with the refraction angle is helpful for measuring the height of flaws.

Is there a relationship between body mass index and academic achievement? A meta-analysis.

OBJECTIVE: To date, although there have been several systematic reviews about the relationship between overweight/obesity and academic performance, none of the reviews were conducted quantitatively, thus the extent overweight/obesity is related to academic performance still remains unclear. Thus, the aim of this study was to quantitatively review the scientific evidence on the association between body mass index (BMI) and academic performance. STUDY DESIGN: A systematic review of articles examining such relationship was undertaken using four databases, namely, PubMed, Web of Science, EBSCOhost and ProQuest Dissertations & Theses Global. The search period covered the research literature up to July 2017. METHODS: Data from 60 selected studies (involving 164,049 participants) were extracted and analysed following procedures for meta-analysis. RESULTS: Sixty studies met all inclusion criteria and were included. Using a random-effects meta-analysis model, a weak negative correlation between BMI and academic achievement (r = -.111; 95% confidence interval [CI]: -.155 to -.067; P < .01) was revealed. After conducting a series of moderator analyses, such a relationship was found to be significantly moderated by regions and students' study grades. CONCLUSIONS: BMI is weakly and negatively associated with academic achievement. For a better understanding of such a relationship, future studies are needed to explore whether there is a causal relationship and also explore whether there are other factors that potentially moderate such a relationship.

The relationship between neuroticism and night eating: exploring the mediating roles of psychological distress and maladaptive coping.

Night Eating Syndrome has been shown to be associated with various negative physical and psychological consequences. This study explored the relationship between neuroticism and night eating, which had not been studied before. We also examined the possible mediating roles of psychological distress and maladaptive coping for the relationship between neuroticism and night eating. A sample of 578 Chinese college students were assessed on several measures: The Revised Eysenck Personality Questionnaire Short Scale, the Night Eating Questionnaire, the Depression Anxiety Stress Scales, and the Simplified Coping Style Questionnaire. Results indicated that neuroticism was significantly and positively related to night eating (r = .38, p < .01), and the relationship between neuroticism and night eating was partially mediated by psychological distress, but not by maladaptive coping. The results not only revealed a medium-sized relationship between neuroticism and night eating, but also pointed out the importance of psychological distress as related to the relationship between neuroticism and night eating. Unlike neuroticism, which is a personality trait, psychological distress is an emotional state, and it is much more malleable through appropriate intervention. The treatment and intervention for night eating may benefit from our attention to the psychological distress.

Low-Dose Arsenic Trioxide Modulates the Differentiation of Mouse Embryonic Stem Cells.

Arsenic (As) is a well-known environmental pollutant, while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood. Embryonic stem cells (ESCs) exhibit properties of stemness and serve as a popular model to investigate epigenetic modifiers including environmental pollutants. Herein, the effects of low-dose ATO on differentiation were evaluated in vitro using a mouse ESCs (mESCs) cell line, CGR8. Cells treated with 0.2-0.5 µM ATO for 3-4 days had slight inhibition of proliferation with elevation of apoptosis, but obvious alterations of differentiation by morphological checking and alkaline phosphatase (AP) staining. Moreover, ATO exposure significantly decreased the mRNA expression of the stemness maintenance genes including Oct4, Nanog, and Rex-1 ( P < 0.01), whereas obviously increased some tissue-specific differentiation marker genes such as Gata4, Gata-6, AFP, and IHH. These alterations were consistent with the differentiation phenotype induced by retinoic acid (RA) and the expression patterns of distinct pluripotency markers such as SSEA-1 and Oct4. Furthermore, low-dose ATO led to a quantitative increase in Caspase 3 (CASP3) activation and subsequent cleavage of Nanog around 27 kDa, which corresponded with the mouse Nanog cleaved by CASP3 in a tube cleavage assay. Taken together, we suggest that low-dose ATO exposure will induce differentiation, other than apoptosis, of ESCs, such effects might be tuned partially by ATO-induced CASP3 activation and Nanog cleavage coupling with other differentiation related genes involved. The present findings provide a preliminary action mechanism of arsenic on the cell fate determination.

DIAPH3 promoted the growth, migration and metastasis of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling.

The enhanced ability of cancer cell migration and metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Diaphanous-related formin 3 (DIAPH3) has been reported to regulate the motility of cells by remodeling the cytoskeleton. However, the mechanism through which DIAPH3 regulated the motility of cancer cells remains largely unknown. In this study, we have shown that the expression of DIAPH3 was up-regulated in HCC. DIAPH3 positively regulated the growth, migration, colony formation, epithelia mesenchymal transition, and metastasis of HCC cells. Mechanically, DIAPH3 activated the beta-catenin/TCF signaling by binding HSP90 and disrupting the interaction between GSK3beta and HSP90. Taken together, our study demonstrated the oncogenic activity of DIAPH3 in the progression of HCC and suggested that PDIAPH3 might be a therapeutic target.

How accurate is the prevalence of overweight and obesity in children and adolescents derived from self-reported data? A meta-analysis.

OBJECTIVE: The aim of the current meta-analysis was to evaluate the accuracy of using BMI based on self-reported height and weight (BMIsr) to estimate the prevalence of overweight and obesity among children and adolescents. DESIGN: A systematic literature search was conducted to select studies that compared the prevalence rates of overweight and obesity based on BMIsr and BMIm (BMI based on measured height and weight). A random-effect model was assumed to estimate summary prevalence rates and prevalence ratio (PR). RESULTS: Thirty-seven studies were included. The aggregated prevalence of overweight and obesity based on BMIsr (0·190, 95 % CI 0·163, 0·221) was significantly lower than that based on BMIm (0·233, 95 % CI 0·203, 0·265). The pooled mean PR was 0·823 (95 % CI 0·775, 0·875). Moderator analyses showed that the underestimation was related to gender, age, weight status screened (overweight v. obesity) and weight status screening tool. CONCLUSIONS: BMIsr may produce less biased results under some conditions than others. Future researchers using BMIsr may consider these findings and avoid the conditions that could lead to more severe underestimation of the prevalence of overweight and obesity among children and adolescents.

Prevalence, demographic correlates, and association with psychological distress of night eating syndrome among Chinese college students.

Night eating syndrome (NES) has primarily been studied in Western societies, and the prevalence and associated factors of NES in China still remain unknown. This study examined the prevalence, demographic correlates, and association with psychological distress of NES among Chinese college students. By using the Chinese version of Night Eating Questionnaire (C-NEQ), data were collected from 909 university students sampled from three provinces in China. Results showed that the prevalence of NES was 2.8% (2.4% after excluding students with binge eating); the occurrence of NES was correlated with gender ([Formula: see text]) and the higher night eating scores were significantly correlated with higher psychological distress (rs = .396-.471, ps < .001). Because of the huge population base in China, there could be a large number of Chinese college students with NES. Therefore, more attention is needed for prevention, detection, and treatment of NES for Chinese college students.

Prevalence of binge and loss of control eating among children and adolescents with overweight and obesity: An exploratory meta-analysis.

OBJECTIVE: Due to the inconsistency of the research findings in the current literature, the prevalence of binge and loss of control (LOC) eating among children and adolescents with overweight and obesity remains unclear. By using the meta-analytic approach, this article aimed at exploring the prevalence of binge/LOC eating among children and adolescents with overweight and obesity, and at identifying potential moderators, which may have contributed to the heterogeneity of the existing research findings. METHOD: Four electronic databases (PubMed, Web of Science, EBSCOhost, and ProQuest Dissertations & Theses Global) were searched. The search period covered the research literature up to April 2016. A random-effects meta-analysis model was used to estimate the overall prevalence. Weighted random-effects model ANOVAs and univariate random-effects meta-regression were applied for the analysis of categorical moderators and continuous moderators, respectively. RESULTS: Thirty-six studies were identified. The overall prevalence of binge/LOC eating was estimated to be 26.3% (95% CI: 23.1-29.7%), with 22.2% (95% CI: 18.6-26.3%) and 31.2% (95% CI: 26.1-36.9%) for binge eating and LOC eating, respectively. Treatment status, binge eating vs. LOC eating and assessment methods appeared to be associated with the inconsistencies of the prevalence rates across the studies. DISCUSSION: The findings of this meta-analysis indicated that binge/LOC eating was prevalent among more than one quarter of children and adolescents with overweight and obesity. Considering the close relationship between disordered eating behaviors and obesity, future research concerning overweight and obesity among children and adolescents needs to take binge/LOC eating into consideration. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:91-103).

The association between problematic internet use and burnout: A three-level meta-analysis.

BACKGROUND: Burnout has received considerable attention in recent years because of the adverse consequences for people. Theoretical perspectives propose that problematic internet use is a significant potential risk for burnout. Despite a plethora of studies showing a positive association between problematic internet use and burnout, there remains a contentious debate regarding the extent and direction of this association. METHODS: This study aims to perform a three-level meta-analysis to evaluate the strength of the relationship between problematic internet use and burnout through a quantitative synthesis of eligible studies published until April 2023. RESULTS: A total of 42 studies with 54,121 participants and 103 effect sizes were identified. The results indicated a positive, moderate, and significant association between problematic internet use and burnout. Furthermore, the subgroup analysis found that this association was moderated by population, dimension of burnout, and the measure of burnout, however, some study features (i.e., region, type of problematic internet use, gender, and publication year) could not explain the heterogeneity across individual studies. LIMITATIONS: Studies included in the current meta-analysis mainly used cross-sectional designs, which limited the potential to make inferences on the causal relationship between problematic internet use and burnout. CONCLUSIONS: Individuals with problematic internet use have exhibited higher levels of burnout. Overall, these findings develop a deeper understanding of this association between problematic internet use and burnout and have implications for the direction of future research and interventions.

Research on the Cold Rolling Process, Microstructure and Properties of 305 Austenitic Stainless Steel Thin Strips.

Austenitic stainless steel has high toughness and plasticity; however, it tends to exhibit low yield strength, which severely limits the widespread application of this steel. It can be strengthened by cold working; however, this will cause many defects in the structure. Therefore, annealing treatment must be carried out before use. In this paper, the effects of annealing treatment at different temperatures and times on the microstructure and mechanical properties of cold-rolled 305 stainless steel sheet were studied and the theoretical mechanism was further analyzed to provide better theoretical guidance for production and application. It was found that the microstructure grains obtained by annealing at 850 °C for 30 s were finer and more uniform, and the mechanical properties were also the best, which met the requirements of strong plasticity. Therefore, the rolling and annealing experiments could be carried out again under this annealing condition, and the requirements of the finished product could be finally obtained. At this time, the thickness of the plate was about 0.15 mm, the yield strength was 1238 MPa, and the permeability was below 1.02, which met the production requirements of the metal mask plate.

Associations Between Problematic Internet Use and Mental Health Outcomes of Students: A Meta-analytic Review.

The increasing prevalence of problematic internet use has heightened concerns about its adverse impact on internet users' mental health. Despite reviews investigating the associations between problematic internet use and mental health outcomes, there is a lack of understanding of various aspects of students' mental health. This study aimed to bridge this gap by providing a more comprehensive overall picture of this issue through a quantitative synthesis based on three-level random-effects meta-analytic models. In total, 223 studies with a cumulative total of 498,167 participants and 512 effect sizes were included in this synthesis. The results showed that problematic internet use was moderately and positively associated with depressive symptoms, anxiety, loneliness, and other mental health outcomes, and negatively related to subjective well-being. Moderator analyses revealed that several study features (i.e., school grade, region, measure of problematic internet use, publication year, and gender) could explain the variations in the findings across individual studies. These research results provide solid evidence for the link between problematic internet use and different mental health outcomes and have implications for future research and interventions on students' problematic internet use. Supplementary Information: The online version contains supplementary material available at 10.1007/s40894-022-00201-9.

Systematic investigation of the material basis, multiple mechanisms and quality control of Simiao Yong'an decoction combined with antibiotic in the treatment of sepsis.

BACKGROUND: Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis. Yet, its material basis and relevant mechanisms are still vague. PURPOSE: Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. METHODS: Linear-Trap-LC/MSn was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers' range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC-MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. RESULTS: The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. CONCLUSIONS: Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.

Engineered small extracellular vesicles loaded with miR-654-5p promote ferroptosis by targeting HSPB1 to alleviate sorafenib resistance in hepatocellular carcinoma.

Sorafenib (sora) is the initial therapy for patients with progressive hepatocellular carcinoma (HCC), but the emergence of drug resistance has seriously impacted its therapeutic efficacy. However, the mechanism of sora resistance remains unclear, and effective strategies to overcome drug resistance are still lacking. By establishing a sora-resistant hepatocellular carcinoma cell line, we found that Heat Shock Protein Family B (small) Member 1 (HSPB1) was markedly upregulated in sora-resistant HCC cells. Further research revealed that the ferroptosis resistance induced by HSPB1 upregulation plays a crucial role in sora resistance. In addition, we confirmed that miR-654-5p enhances sora-induced ferroptosis by binding to HSPB1 and reducing its protein levels. To enhance miRNA stability and delivery efficiency in vivo, we used small extracellular vesicles (sEV) derived from human adipose mesenchymal stem cells as miR-654-5p carriers, creating engineered sEV (m654-sEV). The research demonstrated that m654-sEV effectively delivers miR-654-5p to HCC cells, targeting HSPB1 and enhancing sora-induced ferroptosis. This improves therapeutic effects on sora-resistant HCC cells and xenograft tumors, restoring their sensitivity to sora. In summary, m654-sEV, which targets HSPB1 via miR-654-5p delivery, represents a promising strategy for addressing sora-resistant issue. The combined use of m654-sEV and sora has the potential to significantly enhance therapeutic efficacy for patients with sora-resistant HCC.

Exploring the nephrotoxicity of sulfur-containing derivatives in sulfur-fumigated Panacis Quinquefolii Radix based on chemical profiling and untargeted metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Panacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. AIM OF THE STUDY: To investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. MATERIALS AND METHODS: The extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. RESULTS: Thirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO3 sulfonation products and five H2SO3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. CONCLUSION: SF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation.

Pharmacodynamic Material Basis and Potential Mechanism Study of Spatholobi Caulis in Reversing Osteoporosis.

Objective: To elucidate the mechanism of Spatholobi Caulis (SC) in treating osteoporosis (OP) integrated zebrafish model and bioinformatics. Methods: Skeleton staining coupled with image quantification was performed to evaluate the effects of SC on skeleton mineralization area (SSA) and total optical density (TOD). Zebrafish locomotor activity was monitored using the EthoVision XT. Bioactive compounds of SC and their corresponding protein targets were acquired from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Potential therapeutic targets for OP were summarized through retrieving 5 databases, and then, the overlapping genes between SC and OP were acquired. The core genes were selected by CytoHubba. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional analysis of the intersection target genes were carried out by R software. Finally, the molecular docking simulation was manipulated between the ingredients and the hub genes. Results: Compared with the model group, SC significantly increased the SSA and TOD at 10 mg/mL and improved the locomotor activity in a dose-dependent manner (p < 0.001). 33 components of SC were associated with 72 OP-related genes including 10 core genes (MAPK1, VEGFA, MMP9, AKT1, AR, IL6, CALM3, TP53, EGFR, and CAT). Advanced Glycation End Product (AGE) Receptor for AGE (RAGE) signaling pathway was screened out as the principal pathway of SC in anti-OP. The bioactive components (Aloe-emodin, Emodin, Formononetin, Licochalcone A, Luteolin, and Lopac-I-3766) have excellent affinity to core genes (MAPK1, VEGFA, MMP9, AKT1, and IL6). Conclusion: SC had the hierarchical network characteristics of "multicomponents/multitargets/multifunctions/multipathways" in reversing OP, but AGE-RAGE signaling pathway may be the main regulatory mechanism.

Elaborate the Mechanism of Ancient Classic Prescriptions (Erzhi Formula) in Reversing GIOP by Network Pharmacology Coupled with Zebrafish Verification.

Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of "components-targets-signal pathway" was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased (P < 0.05). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF (P < 0.05). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through "multicomponent/multitarget/multipathway" and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model.