The development of probiotics and prebiotics therapy to ulcerative colitis: a therapy that has gained considerable momentum.

Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.

LINC01605 promotes malignant phenotypes of cervical cancer via miR-149-3p/WNT7B axis.

BACKGROUND: Long non-coding RNAs (LncRNA) play a pivotal role in the progression of various malignancies. Despite recent identification as an oncogene associated with tumorigenesis. The precise role of LINC01605 in cervical cancer (CC) remains unclear. Therefore, the objective of this study was to investigate the influence of LINC01605 on proliferation and invasion of CC cells, while also exploring its potential underlying mechanisms. METHODS: The expression of LINC01605 in CC cell lines was analyzed using the TCGA database and qRT-PCR. Various assays, including CCK-8 and transwell analysis, were conducted on CC cells to assess the influence of LINC01605 on their proliferation, migration, and invasion capabilities. Bioinformatics and dual luciferase reporter gene assays were employed to analyze the target genes of LINC01605 and miR-149-3p. To further investigate the mechanism of action, transfection and investigation were performed using specific siRNA, miRNA mimics, or inhibitors. RESULTS: The expression of LINC01605 exhibited a significant increase in CC cell lines, and this upregulation was associated with an unfavorable prognosis. Modulating the expression of LINC01605, either by down-regulating or up-regulating it, exerted suppressive or stimulatory effects on the growth and invasion of HeLa and Siha cells. LINC01605 functioned as a competitive endogenous RNA (ceRNA) for miR-149-3p, with WNT7B being identified as a target gene of miR-149-3p. The involvement of LINC01605 in CC development is facilitated by its ability to regulate the expression of WNT7B through sequestering miR-149-3p. CONCLUSION: Our study demonstrates that LINC01605 acts as a competitive endogenous RNA in modulating the effects of WNT7B on the proliferation and invasion of CC cells by sequestering miR-149-3p. This research provides novel insights into the involvement of LINC01605 in the advancement of CC.

Research on the trajectory and influential factors of poly-victimization: A longitudinal study of Chinese adolescents.

BACKGROUND: Poly-victimization is more detrimental to adolescents' physical and mental health than is a single type of victimization. However, there has been limited research on the trajectory of poly-victimization among Chinese adolescents. OBJECTIVE: Identify the different developmental trajectories of poly-victimization among Chinese adolescents over time and examine the influencing factors of poly-victimization trajectories. METHODS: Data from four surveys conducted between 2020 and 2022, encompassing a cohort of 319 adolescents who had experienced poly-victimization, were utilized to identify their developmental trajectories via group-based trajectory modeling. Potential influencing factors were screened and compared using ANOVA or chi-square tests, while factors affecting the developmental trajectories of poly-victimization were analyzed through multinomial logistic regression. RESULTS: We identified three poly-victimization trajectories among adolescents: increasing poly-victimization (n = 39, 12.2 %), relieved poly-victimization (n = 228, 71.5 %), and fluctuating poly-victimization (n = 52, 16.3 %). Our findings indicate that boys, and those with poor class grade ranking, a lower level of parental education, lower household economy, smoking, drinking, suicide attempts, and suicide ideation, constitute the primary focus for the prevention and treatment of poly-victimization. CONCLUSION: We identified three poly-victimization trajectories, highlighting a significant heterogeneity in poly-victimization development. Understanding the characteristics of these developmental trajectories is crucial for realizing the dynamics of different poly-victimization subgroups and informing effective interventions.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway.

BACKGROUND: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB). METHODS: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB. RESULTS: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB. CONCLUSION: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Combined effects of copper and cadmium exposure on ovarian function and structure in Nile Tilapia (Oreochromis niloticus).

With the rapid development of industrialization and urbanization, the issue of copper (Cu) and cadmium (Cd) pollution in aquatic ecosystems has become increasingly severe, posing threats to the ovarian tissue and reproductive capacity of aquatic organisms. However, the combined effects of Cu and Cd on the ovarian development of fish and other aquatic species remain unclear. In this study, female Nile tilapia (Oreochromis niloticus) were individually or co-exposed to Cu and/or Cd in water. Ovarian and serum samples were collected at 15, 30, 60, 90, and 120 days, and the bioaccumulation, ovarian development, and hormone secretion were analyzed. Results showed that both single and combined exposure significantly reduced the gonadosomatic index and serum hormone levels, upregulated estrogen receptor (er) and progesterone receptor (pr) gene transcription levels, and markedly affected ovarian metabolite levels. Combined exposure led to more adverse effects than single exposure. The data demonstrate that the Cu and Cd exposure can impair ovarian function and structure, with more pronounced adverse effects under Cu and Cd co-exposure. The Cu and Cd affect the metabolic pathways of nucleotides and amino acids, leading to ovarian damage. This study highlights the importance of considering combined toxicant exposure in aquatic toxicology research and provides insights into the potential mechanisms underlying heavy metal-induced reproductive toxicity in fish.

Iron overload increases the sensitivity of endometriosis stromal cells to ferroptosis via a PRC2-independent function of EZH2.

Given the high concentration of iron in the micro-environment of ovarian endometriosis, it is plausible to hypothesize that ectopic endometrial cells may be more susceptible to undergoing ferroptosis. Manipulation of ferroptosis has been explored as a potential therapeutic strategy to treat related diseases. In this study, we examined the impact on ectopic endometrial stromal cells (EESCs) of iron overload and an inducer of ferroptosis. We found that the iron concentration in the ovarian endometriosis was much higher than control samples. Treatment of cultured EESCs with ferric ammonium citrate (FAC) increase the sensitivity to undergo ferroptosis. By analyzing the RNA-seq results, it was discovered that zeste 2 polycomb repressive complex 2 subunit (EZH2) was significantly downregulated in ferroptosis induced EESCs. Moreover, overexpression of EZH2 effectively prevented the induction of ferroptosis. In addition, the activity or expression of EZH2 is directly and specifically inhibited by the methyltransferase inhibitor GSK343, which raises the sensitivity of stromal cells to ferroptosis. Taken together, our findings revealed that EZH2 act as a suppressor in the induced cell ferroptosis through a PRC2-independent methyltransferase mechanism. Therefore, blocking EZH2 expression and inducing ferroptosis may be effective treatment approaches for ovarian endometriosis.

Spiritual care needs and their attributes among Chinese inpatients with advanced breast cancer based on the Kano model: a descriptive cross-sectional study.

BACKGROUND: Numerous previous research have established the need for spiritual care among patients with cancer globally. Nevertheless, there was limited research, primarily qualitative, on the spiritual care needs of Chinese inpatients with advanced breast cancer. Furthermore, the need for spiritual care was rarely explored using the Kano model. To better understand the spiritual care needs and attributes characteristics of inpatients with advanced breast cancer, this study examined the Kano model. METHODS: A descriptive cross-sectional design study was conducted in the oncology departments of three tertiary grade-A hospitals in China from October 2022 to May 2023. To guarantee high-quality reporting of the study, the Strengthening the Reporting of Observational Studies in Epidemiology Checklist was used. Data on the demographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale (NSTS), and the Kano model-based Nurse Spiritual Therapeutics Attributes Scale (K-NSTAs) were collected through convenience sampling. The Kano model, descriptive statistics, two independent samples t-tests, and one-way analysis of variance were used to analyze the data. RESULTS: The overall score for spiritual care needs was 31.16 ± 7.85. The two dimensions with the highest average scores, "create a good atmosphere" (3.16 ± 0.95), and the lowest average scores, "help religious practice" (1.72 ± 0.73). The 12 items were distributed as follows: three attractive attributes were located in Reserving Area IV; five one-dimensional attributes were distributed as follows: three one-dimensional attributes were located in Predominance Area I, and two were found in Improving Area II; two must-be attributes were located in Improving Area II; and two indifference attributes were located in Secondary Improving Area III. CONCLUSION: The Chinese inpatients with advanced breast cancer had a middle level of spiritual care needs, which need to be further improved. Spiritual care needs attributes were defined, sorted, categorized, and optimized accurately and perfectly by the Kano model. And "create a good atmosphere" and "share self-perception" were primarily one-dimensional and must-be attributes. In contrast, the items in the dimensions of "share self-perception" and "help thinking" were principally attractive attributes. Nursing administrators are advised to optimize attractive attributes and transform indifference attributes by consolidating must-be and one-dimensional attributes, which will enable them to take targeted spiritual care measures based on each patient's characteristics and unique personality traits.

[Comparison of intraoperative effects of computer navigation-assisted and simple arthroscopic reconstruction of posterior cruciate ligament tibial tunnel].

Objective: To compare the intraoperative effects of computer navigation-assisted versus simple arthroscopic reconstruction of posterior cruciate ligament (PCL) tibial tunnel. Methods: The clinical data of 73 patients with PCL tears who were admitted between June 2021 and June 2022 and met the selection criteria were retrospectively analysed, of whom 34 cases underwent PCL tibial tunnel reconstruction with navigation-assisted arthroscopy (navigation group) and 39 cases underwent PCL tibial tunnel reconstruction with arthroscopy alone (control group). There was no significant difference in baseline data between the two groups, including gender, age, body mass index, side of injury, time from injury to surgery, preoperative posterior drawer test, knee range of motion (ROM), Tegner score, Lysholm score, and International Knee Documentation Committee (IKDC) score between the two groups ( P>0.05). The perioperative indicators (operation time and number of guide wire drillings) were recorded and compared between the two groups. The angle between the graft and the tibial tunnel and the exit positions of the tibial tunnel in the coronal, sagittal, and transverse planes respectively were measured on MRI at 1 day after operation. The knee ROM, Tegner score, Lysholm score, and IKDC score were evaluated before operation and at last follow-up. Results: The operation time in the navigation group was shorter than that in the control group, and the number of intraoperative guide wire drillings was less than that in the control group, the differences were significant ( P<0.05). Patients in both groups were followed up 12-17 months, with an average of 12.8 months. There was no perioperative complications such as vascular and nerve damage, deep venous thrombosis and infection of lower extremity. During the follow-up, there was no re-injuries in either group and no revision was required. The results showed that there was no significant difference in the exit positions of the tibial tunnel in the coronal, sagittal, and transverse planes between the two groups ( P>0.05), but the angle between the graft and the tibial tunnel was significantly greater in the navigation group than in the control group ( P<0.05). At last follow-up, 30, 3, 1 and 0 cases were rated as negative, 1+, 2+, and 3+ of posterior drawer test in the navigation group and 33, 5, 1, and 0 cases in the control group, respectively, which significantly improved when compared with the preoperative values ( P<0.05), but there was no significant difference between the two groups ( P>0.05). At last follow-up, ROM, Tegner score, Lysholm score, and IKDC score of the knee joint significantly improved in both groups when compared with preoperative values ( P<0.05), but there was no significant difference in the difference in preoperative and postoperative indicators between the two groups ( P>0.05). Conclusion: Computer-navigated arthroscopic PCL tibial tunnel reconstruction can quickly and accurately prepare tunnels with good location and orientation, with postoperative functional scores comparable to arthroscopic PCL tibial tunnel reconstruction alone.

ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.

The ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with fork head-associated domain)-TRAF6 signaling pathway plays a pivotal role in regulating inflammatory processes, with TIFA and TRAF6 serving as key molecules in this cascade. Despite its significance, the functional mechanism of TIFA-TRAF6 remains incompletely understood. In this study, we unveil that TIFA undergoes liquid-liquid phase separation (LLPS) induced by ALPK1 in response to adenosine diphosphate (ADP)-ß-D-manno-heptose (ADP-Hep) recognition. The phase separation of TIFA is primarily driven by ALPK1, the pT9-FHA domain, and the intrinsically disordered region segment. Simultaneously, TRAF6 exhibits phase separation during ADP-Hep-induced inflammation, a phenomenon observed consistently across various inflammatory signal pathways. Moreover, TRAF6 is recruited within the TIFA condensates, facilitating lysine (K) 63-linked polyubiquitin chain synthesis. The subsequent recruitment, enrichment, and activation of downstream effectors within these condensates contribute to robust inflammatory signal transduction. Utilizing a novel chemical probe (compound 22), our analysis demonstrates that the activation of the ALPK1-TIFA-TRAF6 signaling pathway in response to small molecules necessitates the phase separation of TIFA. In summary, our findings reveal TIFA as a sensor for upstream signals, initiating the LLPS of itself and downstream proteins. This process results in the formation of membraneless condensates within the ALPK1-TIFA-TRAF6 pathway, suggesting potential applications in therapeutic biotechnology development.

Multimodal non-invasive evaluation in MRI-negative epilepsy patients.

Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children.

BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

MHESMMR: a multilevel model for predicting the regulation of miRNAs expression by small molecules.

According to the expression of miRNA in pathological processes, miRNAs can be divided into oncogenes or tumor suppressors. Prediction of the regulation relations between miRNAs and small molecules (SMs) becomes a vital goal for miRNA-target therapy. But traditional biological approaches are laborious and expensive. Thus, there is an urgent need to develop a computational model. In this study, we proposed a computational model to predict whether the regulatory relationship between miRNAs and SMs is up-regulated or down-regulated. Specifically, we first use the Large-scale Information Network Embedding (LINE) algorithm to construct the node features from the self-similarity networks, then use the General Attributed Multiplex Heterogeneous Network Embedding (GATNE) algorithm to extract the topological information from the attribute network, and finally utilize the Light Gradient Boosting Machine (LightGBM) algorithm to predict the regulatory relationship between miRNAs and SMs. In the fivefold cross-validation experiment, the average accuracies of the proposed model on the SM2miR dataset reached 79.59% and 80.37% for up-regulation pairs and down-regulation pairs, respectively. In addition, we compared our model with another published model. Moreover, in the case study for 5-FU, 7 of 10 candidate miRNAs are confirmed by related literature. Therefore, we believe that our model can promote the research of miRNA-targeted therapy.

Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway.

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFß, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.

Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12.

To investigate the effect of chromium and iron on glucose metabolism via the PI3K/Akt/GLUT4 signaling pathway. Skeletal muscle gene microarray data in T2DM (GSE7014) was selected using Gene Expression Omnibus database. Element-gene interaction datasets of chromium and iron were extracted from comparative toxicogenomics database (CTD). Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID online tool. Cell viability, insulin-stimulated glucose uptake, intracellular reactive oxygen species (ROS) level, and protein expression level were measured in C2C12 cells. The bioinformatics research indicated that PI3K/Akt signaling pathway participated in the effects of chromium and iron associated with T2DM. Insulin-stimulated glucose uptake level was significantly higher in chromium picolinate (Cr group) and lower in ammonium iron citrate (FA group) than that for the control group (P < 0.05); chromium picolinate + ammonium iron citrate (Cr + FA group) glucose uptake level was higher than that for the FA group (P < 0.05). Intracellular ROS level was significantly higher in the FAC group than that for the control group (P < 0.05), and that for the Cr + FA group was lower than that for the FA group (P < 0.05). p-PI3K/PI3K, p-Akt/Akt, and GLUT4 levels were significantly lower in the FA group than that for the control group (P < 0.05), and the Cr + FA group had higher levels than the FA group (P < 0.05). Chromium might have a protective effect on iron-induced glucose metabolism abnormalities through the ROS-mediated PI3K/Akt/GLUT4 signaling pathway.

DEHP and DBP, common phthalates, induce glucose metabolism disorders in rats via oxidative damage of PI3K/Akt/GLUT4 signaling.

Phthalic acid esters (PAEs) are environmental endocrine disruptors thought to interfere with glucose metabolism in humans. Most of the related research has focused on population epidemiological studies, with the underlying mechanisms remaining unresolved. Using an in vivo animal model, we examined the effects of oral administration of two commonly used PAEs [di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP)] on glucose homeostasis and insulin secretion. DEHP (750 mg/kg, 1/40 LD50), DBP (500 mg/kg, 1/40 LD50), and DEHP (750 mg/kg) + DBP (500 mg/kg) exert an influence on glucose metabolism and elicit a reduction in insulin sensitivity in rats. Furthermore, these substances induce detrimental effects on the structure and functionality of pancreatic ß-cells. DEHP and/or DBP triggered an increase in plasma malondialdehyde (MDA) and reduction in superoxide dismutase (SOD) activity; a reduction in the phosphorylation of phosphatidyl inositol 3 kinase (PI3K) and phospho-protein kinase B (p-Akt473) proteins; an increase in the relative expression of Bax, Caspase-8, cleaved-Caspase-9, and cleaved-Caspase-3; and a reduction in the relative expression of Bcl-2-related Bax in pancreatic tissue and of gastrocnemius glucose transporter 4 (GLUT4) in the gastrocnemius muscle. Based on these findings, these PAEs can disrupt glucose metabolism, possibly via oxidative damage of the PI3K/Akt/GLUT4 pathway; this damage induces pancreatic ß-cell apoptosis, affects pancreatic ß-cell function, and affects glucose metabolism and insulin resistance in rats. To the best of our knowledge, this study was the first to show that the combined effect of the two PAEs affects glucose metabolism and insulin resistance in rats that is significantly higher than the effects of each PAE. Thus, safety standards and studies do not consider this effect as a significant oversight when blending PAEs. We assert that this must be addressed and corrected for establishing more impactful and safer standards.

Amorphous MoS2 Decorated Ni3 S2 with a Core-shell Structure of Urchin-Like on Nickel-Foam Efficient Hydrogen Evolution in Acidic and Alkaline Media.

The large-scale commercialization of the hydrogen evolution reaction (HER) necessitates the development of cost-effective and highly efficient electrocatalysts. Although transition metal sulfides, such as MoS2 and Ni3 S2 , hold great potential in the field of HER, their catalytic performance has been unsatisfactory due to incomplete exposure of active sites and poor electrical conductivity. In this work, via a simple hydrothermal strategy, amorphous MoS2 nanoshells in the form of urchin-like MoS2 -Ni3 S2 core-shell heterogeneous structure is realized and in situ loaded on nickel foam (A-MoS2 -Ni3 S2 -NF). In particular, XPS analysis results show that the coupling of amorphous MoS2 and Ni3 S2 makes the electrode surface exhibit electron-abundant property, which will have a positive impact on HER catalytic activity. In addition, the fully exposed active site of amorphous MoS2 is another crucial factor contributing to its high catalytic performance of A-MoS2 -Ni3 S2 -NF electrode. In particular, at a current density of 10 mA cm⁻2 , the overpotential of electrode is 95 mV (1.0 m KOH) and 145 mV (0.5 m H2 SO4 ). This work highlights the importance of amorphous MoS2 and MoS2 -Ni3 S2 of sea-urchin core-shell structure in optimizing HER performance, which provides an important reference for HER research.

SiSGC: A Drug Repositioning Prediction Model Based on Heterogeneous Simplifying Graph Convolution.

Drug repositioning plays a key role in disease treatment. With the large-scale chemical data increasing, many computational methods are utilized for drug-disease association prediction. However, most of the existing models neglect the positive influence of non-Euclidean data and multisource information, and there is still a critical issue for graph neural networks regarding how to set the feature diffuse distance. To solve the problems, we proposed SiSGC, which makes full use of the biological knowledge information as initial features and learns the structure information from the constructed heterogeneous graph with the adaptive selection of the information diffuse distance. Then, the structural features are fused with the denoised similarity information and fed to the advanced classifier of CatBoost to make predictions. Three different data sets are used to confirm the robustness and generalization of SiSGC under two splitting strategies. Experiment results demonstrate that the proposed model achieves superior performance compared with the six leading methods and four variants. Our case study on breast neoplasms further indicates that SiSGC is trustworthy and robust yet simple. We also present four drugs for breast cancer treatment with high confidence and further give an explanation for demonstrating the rationality. There is no doubt that SiSGC can be used as a beneficial supplement for drug repositioning.