Functional and structural MRI based obsessive-compulsive disorder diagnosis using machine learning methods.

BACKGROUND: The success of neuroimaging in revealing neural correlates of obsessive-compulsive disorder (OCD) has raised hopes of using magnetic resonance imaging (MRI) indices to discriminate patients with OCD and the healthy. The aim of this study was to explore MRI based OCD diagnosis using machine learning methods. METHODS: Fifty patients with OCD and fifty healthy subjects were allocated into training and testing set by eight to two. Functional MRI (fMRI) indices, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DC), and structural MRI (sMRI) indices, including volume of gray matter, cortical thickness and sulcal depth, were extracted in each brain region as features. The features were reduced using least absolute shrinkage and selection operator regression on training set. Diagnosis models based on single MRI index / combined MRI indices were established on training set using support vector machine (SVM), logistic regression and random forest, and validated on testing set. RESULTS: SVM model based on combined fMRI indices, including ALFF, fALFF, ReHo and DC, achieved the optimal performance, with a cross-validation accuracy of 94%; on testing set, the area under the receiver operating characteristic curve was 0.90 and the validation accuracy was 85%. The selected features were located both within and outside the cortico-striato-thalamo-cortical (CSTC) circuit of OCD. Models based on single MRI index / combined fMRI and sMRI indices underperformed on the classification, with a largest validation accuracy of 75% from SVM model of ALFF on testing set. CONCLUSION: SVM model of combined fMRI indices has the greatest potential to discriminate patients with OCD and the healthy, suggesting a complementary effect of fMRI indices on the classification; the features were located within and outside the CSTC circuit, indicating an importance of including various brain regions in the model.

Excellent Dark/Light Dual-Mode Photoresponsive Activities Based on g-C3N4/CMCh/PVA Nanocomposite Hydrogel Using Electron Beam Radiation Method.

Photocatalytic technology for inactivating bacteria in water has received much attention. In this study, we reported a dark-light dual-mode sterilized g-C3N4/chitosan/poly (vinyl alcohol) hydrogel (g-CP) prepared through freeze-thaw cycling and an in situ electron-beam radiation method. The structures and morphologies of g-CP were confirmed using Fourier infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), solid ultraviolet diffuse reflectance spectroscopy (UV-vis DRS), and Brunauer-Emmett-Teller (BET). Photocatalytic degradation experiments demonstrated that 1 wt% g-CP degraded rhodamine B (RhB) up to 65.92% in 60 min. At the same time, g-CP had good antimicrobial abilities for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) within 4 h. The shapes of g-CP were adjustable (such as bar, cylinder, and cube) and had good mechanical properties and biocompatibility. The tensile and compressive modulus of 2 wt% g-CP were 0.093 MPa and 1.61 MPa, respectively. The Cell Counting Kit-8 (CCK-8) test and Hoechst33342/PI double staining were used to prove that g-CP had good biocompatibility. It is expected to be applied to environmental sewage treatment and wound dressing in the future.

Down-Regulation of Circular RNA_000926 Attenuates Renal Cell Carcinoma Progression through miRNA-411-Dependent CDH2 Inhibition.

Many studies have recognized that circular RNAs (circRNAs) can be promising targets for renal cell carcinoma (RCC) by acting as competing endogenous RNAs for miRNAs. This study intends to uncover the implication of a novel circRNA, circ_000926 in RCC, and how it affects tumorigenesis. Microarray-based circRNA/gene expression profiling of RCC was used to identify differentially expressed circRNAs/genes in RCC and normal tissues. miRNAs targeting the screened circRNAs/genes were predicted online, followed by analyzing circ_000926 expression in RCC. The crosstalk among circ_000926, miRNA-411 (miR-411), and CDH2 was then validated. The expression of circ_000926, miR-411, and cadherin 2 (CDH2) was up-regulated or down-regulated in RCC cells to unearth their effects on the biological behaviors of RCC cells. circ_000926 was highly expressed in RCC tissues and cell lines, whereas CDH2 was verified to be a target of miR-411. As a competing endogenous RNA, circ_000926 could directly bind to miR-411 to up-regulate CDH2. Down-regulation of circ_000926 resulted in inhibited growth, migration, and invasion abilities of RCC cells, as well as suppressed epithelial-mesenchymal transition and tumor growth. However, the inhibition of miR-411 or elevation of CDH2 reversed the antitumor effects induced by silencing circ_000926. Down-regulation of circ_000926 exerts an inhibitory effect on RCC progression through miR-411-dependent CDH2 inhibition, highlighting a potential target for RCC treatment.

Comparative transcriptomic analysis of fireflies (Coleoptera: Lampyridae) to explore the molecular adaptations to fresh water.

Aquatic insects are well adapted to freshwater environments, but the molecular basis of these adaptations remains largely unknown. Most firefly species (Coleoptera: Lampyridae) are terrestrial, but the larvae of several species are aquatic. Here, larval and adult transcriptomes from Aquatica leii (freshwater) and Lychnuris praetexta (terrestrial) were generated to test whether the genes associated with metabolic efficiency and morphology have undergone adaptive evolution to fresh water. The aquatic fireflies had a significantly lower ratio of nonsynonymous to synonymous substitutions than the terrestrial insects, indicating a genomewide evolutionary constraint in the aquatic fireflies. We identified 341 fast-evolving genes and 116 positively selected genes in the aquatic fireflies. Of these, 76 genes exhibiting both fast evolution and positive selection were primarily involved in ATP production, energy metabolism and the hypoxia response. We identified 7,271 differentially expressed genes (DEGs) in A. leii (adults versus larvae) and 8,309 DEGs in L. praetexta (adults versus larvae). DEGs specific to the aquatic firefly (n = 1,445) were screened via interspecific comparisons (A. leii versus L. praetexta) and were significantly enriched for genes involved in metabolic efficiency (e.g., ATP production, hypoxia, and immune responses) and certain aspects of morphology (e.g., cuticle chitin, tracheal and compound eye morphology). These results indicate that sequence and expression-level changes in genes associated with both metabolic efficiency and morphological attributes related to the freshwater lifestyle contributed to freshwater adaptation in fireflies. This study provides new insights into the molecular mechanisms of aquatic adaptation in insects.

[Pancreatic ß-cell Functions Measured by Continuous Glucose Monitoring in Han Chinese with Varied Degree of Glucose Tolerance].

OBJECTIVES: To compare the pancreatic ß-cell functions of Han people between those with normal glucose tolerance (NGT),prediabetes (PD),and newly-diagnosed type 2 diabetes mellitus (NDDM), and to evaluate the value of the continuous glucose monitoring system (CGMS) in determining ß-cell functions. METHODS: A total of 169 volunteers of Han people (20-75 years old, 72 male and 97 female) without diagnosed diabetes were given 75-g oral glucose tolerance test (OGTT) and insulin release tests. The body mass index (BMI) of the participants ranged from 18.5 to 28.0 kg/m².They were categorized into NGT (n=87), PD (n=52) and NDDM (n=30) groupsaccording to the World Health Organization (WHO) 1999 criteria.Blood samples were taken to test triglyceride(TG),total cholesterol (TC),and glycosylated hemoglobin A1c (HbA1c). The participants were also given a 72 h continuous glucose monitoring. The ß-cell functions were calculated using the OGTT and insulin release test results, which included homeostasis model assessment insulin resistance (HOMA-IR),homeostasis model assessment ß-cell function (HOMA-B),basic secretion, early phase secretion, and second phase secretion. The area under the curve of glucose (AUC-G) was estimated through the CGMS.A multivariate stepwise regression model was developed to identify predictors of ß-cell functions. RESULTS: Significant differences in age,BMI,HOMA-IR,HOMA-B,AUC-G, basic secretion, early phase secretion and second phase secretion were found between the NGT and PD groups (P<0.05) and between the NGT and NDDM groups (P<0.05). Differences in AUC-G and basic secretion and early phase secretion were found between the PD and NDDM groups (P<0.05),but not in age, BMI, HOMA-IR, HOMA-B, and second phase secretion.The multivariate stepwise regression analysis showed that HOMA-B (standardized partical regression coefficient ß=-0.244,P=0.001), basic secretion (ß=-0.355,P<0.001), and HbA1c (ß=0.638,P<0.001) contributed significantly to the AUC-G. CONCLUSIONS: ß-cell functions decline in those with prediabetes, which appears first at the second phase secretion. Changes in ß-cell secretion functions are more obvious than in insulin resistance during the progression from PD to NDDM.AUC-G can be a better indicator of impaired ß-cellfunctions.

[Characteristics of 72 h glucose profiles detected by continuous glucose monitoring system in patients with insulinoma].

OBJECTIVE: To identify the characteristics of glucose profiles in patients with insulinoma using continuous glucose monitoring system (CGMS). METHODS: Six patients with insulinoma (All of the patients were diagnosed after operations with pathological tests) admitted to the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University from October 2009 to November 2011 were recruited for this study (group A). They were compared with 71 patients with normal glucose tolerance (NGT) (group B) and 3 patients with responsive hypoglycemia (group C). All of the participants received 75 g oral glucose tolerance tests (OGTT), insulin release tests, and 72 h CGM. Glucose fluctuations and hypoglycemia risks were assessed by the following parameters obtained from CGMS: mean blood glucose (MBG) and standard deviation (SD), mean amplitude of glycemic excursion (MAGE), mean daily differences (MODD), low glucose index (LBGI), glycaemic Risk Assessment Diabetes Equation (GRADE) and M-value. RESULTS: Group A had significantly lower levels of HbA1c, fasting blood glucose, and 2 h-BG than group B (P < 0.05). Compared with Group B, Group A had lower levels of 72 h-MBG (P < 0.001) and higher levels of LBGI, M-value, GRADE, SD and MODD (P < 0.05). The insulinoma patients had 27 occasions of hypoglycemia (glucose < 2.8 mmol/L), more likely in early morning, at a fasting state or preprandial periods. Such events were rare in the control groups (2 occasions in Group B and one occasion in Group C). CONCLUSION: Insulinoma patients present a greater level of glucose fluctuations and frequent hypoglycemia. Hypoglycemia risk detected by CGM is helpful for differentiating diagnosis of insulinoma.

Artificial nonenzymatic antioxidant Prussian blue/KGM-BSA nanocomposite hydrogel dressing as ROS scavenging for diabetic wound healing.

The process of diabetic wound healing was influenced by the excessive proliferation of reactive oxygen species (ROS). Therefore, in the process of healing diabetic wounds, it was crucial to removing ROS. This study designed composited nanoparticles: KBP, consisted by Konjac glucomannan, bovine serum albumin, and Prussian blue. Then they were embedded in Konjac glucomannan and hydroxypropyl trimethylammonium chloride chitosan composite hydrogel (KH), The KBP@KH hydrogel finally achieved excellent efficacy in diabetic wound healing. The in vitro and in vivo experiments demonstrated that KPB nanoparticles exhibited favorable ROS scavenging capability and biosafety. The KBP@KH hydrogel not only effectively eliminated ROS from diabetic wounds, but also exhibited excellent wound adaptability. The KBP@KH hydrogel facilitated angiogenesis and suppressed the production of inflammatory factors. Overall, the KBP@KH hydrogel dressing was characterized by its user-friendly nature, safety, and high efficiency.

A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase beta.

DNA repair is required to maintain genome stability in stem cells and early embryos. At critical junctures, oxidative damage to DNA requires the base excision repair (BER) pathway. Since early zebrafish embryos lack the major polymerase in BER, DNA polymerase ß, repair proceeds via replicative polymerases, even though there is ample polb mRNA. Here, we report that Polb protein fails to appear at the appropriate time in development when AP endonuclease 1 (Apex), the upstream protein in BER, is knocked down. Because polb contains a Creb1 binding site, we examined whether knockdown of Apex affects creb1. Apex knockdown results in loss of Creb1 and Creb complex members but not Creb1 phosphorylation. This effect is independent of p53. Although both apex and creb1 mRNA rescue Creb1 and Polb after Apex knockdown, Apex is not a co-activator of creb1 transcription. This observation has broad significance, as similar results occur when Apex is inhibited in B cells from apex(+/-) mice. These results describe a novel regulatory circuit involving Apex, Creb1 and Polb and provide a mechanism for lethality of Apex loss in higher eukaryotes.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

[Relationship between body fat distribution and insulin resistance, islet ß cell function and metabolic disorders in adults].

OBJECTIVE: To explore the relationship between body fat distribution, insulin resistance, islet ß cell function and metabolic disorders in adult population. METHODS: From February to November 2012, a total of 174 subjects aged 20-68 years were recruited. Their anthropometric parameters, blood biochemical indices and the results of oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were collected. Body fat distribution was measured with dual energy X-ray absorptiometry (DEXA). RESULTS: The values of trunk/total fat mass (T/B) and android/gynoid fat mass ratio (A/G) were positively correlated with blood pressure, blood lipid, plasma glucose, insulin resistance index (HOMA-IR) and high-sensitivity C-reactive protein. Compared with the group of normal metabolism, the group of metabolic disorders had higher T/B and A/G (P < 0.05). After multiple stepwise regression analysis, the main influencing factors of lnHOMA-IR and lnHOMA-ß were T/B and Grespectively.Logistic regression showed that A (OR = 3.01, 95%CI 1.86-8.17) was a risk factor for diabetes and A/G (OR = 2.71, 95%CI 1.75-6.56) a risk factor for dyslipidemia. CONCLUSIONS: Trunk and android fat deposition aggravates insulin resistance, metabolic disorders. And the main influencing factors of insulin resistance and islet ß cell function are trunk and gynoid fat respectively. Android fat mass is a major risk factor for glycolipid metabolism.

[XRD, FTIR and XPS analysis of oxidized particles from Dongshengmiao pyrite-polymetallic sulfide deposit, inner Mongolia].

In the present paper, characteristics of material compositions, phase structures, surface element states, and transformation mechanism of oxidized particles from Dongshengmiao pyrite-polymetallic sulfide deposit were studied using modern analytical testing technology including XRD, FTIR and XPS. The results show that the samples consist of gypsum, calcite, quartz, muscovite, goethite, organic matter, etc. Primary ore in deep oxidation zone mainly under went such processes as oxidization, hydrolysis, dehydration and carbonation. Compared to the surface oxidation zone of arid and extremely arid regions in the northwestern China, the oxidation process and oxidizing condition of the deep oxidation zone were less complex. New mineral type was also not found, and extensively developed sulfate minerals were rare to be seen. The research results can not only be applied to mineral identification of oxidized particles from this type of ore deposit but also play an important role in ore exploration, mining, mineral processing, etc.

Predicting responses to cognitive behavioral therapy in obsessive-compulsive disorder based on multilevel indices of rs-fMRI.

OBJECTIVE: This study aimed to identify neuroimaging predictors to predict the response of cognitive behavioral therapy (CBT) in patients with obsessive-compulsive disorder (OCD) based on indices of resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Fifty patients with OCD were enrolled and allocated to either high or low responder groups after CBT using a 50 % response rate as the delineator. The pre-treatment amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC) in each cerebrum region, defined by automated anatomical labeling atlas, were extracted. Least absolute shrinkage and selection operator and logistic regression were used to select features and establish models. RESULTS: The combination of multilevel rs-fMRI indices achieved the best performance, with a cross-validation area under the receiver operating characteristic curve (AUC) of 0.900. In this combined model, an increase of interquartile range (IQR) in fALFF of right inferior orbital frontal gyrus (IOFG), and ReHo of left hippocampus and superior occipital gyrus (SOG) corresponded to a 26.52 %, 38.67 % and 24.38 % increase in the possibility to be high responders of CBT, respectively. ALFF of left thalamus and ReHo of left putamen were negatively associated with the response to CBT, with a 14.30 % and 19.91 % decrease per IQR increase of the index value. CONCLUSION: The combination of ALFF, fALFF and ReHo achieved a better predictive performance than separate index. Pre-treatment ALFF of the left thalamus, fALFF of the right IOFG, ReHo of the left hippocampus, SOG and putamen can be used as predictors of CBT response.

Effects of dietary iron sources on growth performance, iron status, Fe-containing enzyme activity and gene expression related to iron homeostasis in tissues of weaned pigs.

The aim of this study is to evaluate the effects of dietary iron sources on growth performance, iron status and activities of Fe-containing enzymes and gene expression related to iron homeostasis in tissues of weaned pigs. A total of 480 piglets at d 28 (Duroc X Landrace) were allotted to four groups as a factorial arrangement of treatments with 30 pigs/pen (male: female = 1:1) and 4 replicate pens/treatment. The treatments for iron in the diets were: control basal diet (Con); Con + 150 mg Fe/kg as inorganic Fe (iFe); Con + 75 mg Fe/kg as inorganic Fe + 75 mg Fe/kg as organic Fe-peptide complex (iFe+oFe) and Con + 150 mg of Fe/kg as organic Fe-peptide complex (oFe). The feeding trial lasted for 36 days. There were no significant differences in final body weight, ADG, ADFI, and G/F as well as blood hemoglobin and MCHC contents between piglets fed the control and iron-supplemented groups (P > 0.05). The iron supplemented groups exhibited increased iron content in the liver, kidney and spleen as well as the CAT and SDH activities in liver compared to the control group (P < 0.05), while piglets in oFe group experienced greater Fe accumulation and activities of CAT and SDH in the liver than piglets in the iFe group. Compared with the control group, dietary supplementation of iron increased the NCOA4 mRNA expression and decreased the TfR1 mRNA expression in liver of piglets. The TfR1, NCOA4 and Ferritin mRNA expressions of bone marrow in both iFe and iFe+oFe groups were greater than both in the Con and oFe groups. These results suggest that dietary supplementation of iron does not influence the growth performance and hematological parameters in weaned pigs fed a corn-soybean meal basal diet (75.8 mg/kg) from d 28 to d 70, but increased tissue iron status and activities of Fe-containing enzymes at d 70. The addition of organic Fe-peptide complexes presents greater beneficial effects on enhancing tissue Fe accumulation and Fe-containing enzyme activities, which may be involved in different gene expression patterns related to iron intake and transport in tissues of weaned pigs.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

[Association of glycaemic variability and carotid intima-media thickness in patients with type 2 diabetes mellitus].

OBJECTIVE: To investigate the relationship between blood glucose fluctuations and carotid intima-media thickness (CIMT) in type 2 diabetic patients. METHODS: 64 patients with type 2 diabetes mellitus (T2DM) in the Department of Endocrinology and Metabolism, West China Hospital from July 2009 to March 2012 were recruited in this study. The CIMT were measured bilaterally with high-resolution ultrasonography. The glucose excursions were assessed by the following parameters obtained from the continuous glucose monitoring system (CGMS) for 72 h: mean blood glucose (MBG) and its standard deviation (SD), mean amplitude of glycemic excursion (MAGE), mean of daily differences (MODD). Glycosylated hemoglobin (HbAlc), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) of the participants were also determined. According to the levels of CIMT, 64 diabetic patients were classified into two groups: diabetes mellitus without atherosclerosis (A group, n = 37) and diabetes mellitus with atherosclerosis (B group, n = 27). The relationship between the parameters of glycaemic variability and CIMT was examined. RESULTS: (1) There were no differences between A group and B group with regard to gender composition, course of diabetes, body mass index (BMI), diabetic chronic complications, family history of diabetes, smoking, alcohol drinking, diastolic blood pressure (DBP), TG, TC, HDL-c, SD and MAGE (P > 0.05). A group had younger age and lower levels of systolic blood pressure (SBP), LN(LDL-c) and LN (MODD) than B group (P < 0.05). (2) Pearson correlation analyses showed that CIMT was positively correlated with age (r = 0.370, P = 0.005), LN (LDL-c) (r = 0.325, P = 0.009), SD (r = 0.251, P = 0.045) and LN (MODD) (r = 0.346, P = 0.005). (3) Age, smoking, LN (LDL-c) and LN (MODD) were identified as predictors for CIMT in the multiple linear regression analysis. CONCLUSION: Glucose excursions may contribute to the development of atherosclerosis in patients with type 2 diabetes, which is independent from HbA1c levels.

Transcription factor p53-mediated activation of miR-519d-3p and downregulation of E2F1 attenuates prostate cancer growth and metastasis.

Prostate cancer (PCa) is a commonly diagnosed malignancy in men. The transcription factor p53, a well-known cancer suppressor, has been extensively analyzed in the progression of many tumor types, but its involvement in PCa remains not fully understood. Hence, this study aims to explore the possible molecular mechanism underlying p53 in the growth and metastasis of PCa. Based on bioinformatics analysis findings of GEPIA and starBase databases, p53 was demonstrated to be involved in the development of PCa by transcriptionally activating microRNA-519d-3p (miR-519d-3p) expression to suppress the expression of E2F transcription factor 1 (E2F1) and CD147. In order to verify this finding, clinically-obtained PCa tumor tissues were enrolled and commercially-purchased PCa cell lines were used to detect the cell viability, cycle, and apoptosis, as well as invasion and migration by CCK-8, flow cytometry, and Transwell assays respectively. The results of clinical tissue experiments and in vitro cell experiments showed that miR-519d-3p and p53 were poorly-expressed in PCa tissues and cell lines, while E2F1 was highly-expressed. Overexpression of miR-519d-3p led to inhibited PCa cell proliferation, invasion and migration, and p53 overexpression was found to promote miR-519d-3p expression to suppress the malignant characteristics of PCa cells, while the additional E2F1 overexpression restored the malignant traits. Moreover, ChIP analysis and dual-luciferase reporter assay confirmed the interactions among p53, miR-519d-3p, and E2F1. Mechanistically, it was found that p53 transcriptionally activated miR-519d-3p to suppress E2F1 expression. Finally, the in vitro results were further validated by in vivo experiments, which showed that miR-519d-3p prevents tumorigenesis and lymph node metastasis of PCa in nude mice via negatively regulation of E2F1 and CD147. Taken together, the findings uncover that the transcription factor p53 could upregulate miR-519d-3p expression to directly suppress the expression of E2F1, thus inhibiting PCa growth and metastasis. It highlights a novel therapeutic strategy against PCa based on the p53/miR-519d-3p/E2F1 regulatory pathway.

Subcellular-Level Mitochondrial Energy Metabolism Response in the Fat Body of the German Cockroach Fed Abamectin.

Mitochondria are the leading organelle for energy metabolism. The toxic effects of environmental toxicants on mitochondrial morphology, energy metabolism, and their determination of cell fate have already been broadly studied. However, minimal research exists on effects of environmental toxicants such as pesticides on mitochondrial energy metabolism at in vitro subcellular level, particularly from an omics perspectives (e.g., metabolomics). Here, German cockroach (Blattella germanica) was fed diets with (0.01 and 0.001 mg/mL) and without abamectin, and highly purified fat body mitochondria were isolated. Swelling measurement confirmed abnormal mitochondrial swelling caused by abamectin stress. The activity of two key mitochondrial energy metabolism-related enzymes, namely succinic dehydrogenase and isocitrate dehydrogenase, was significantly affected. The metabolomic responses of the isolated mitochondria to abamectin were analyzed via untargeted liquid chromatography/mass spectrometry metabolomics technology. Fifty-two differential metabolites (DMs) were identified in the mitochondria between the 0.001 mg/mL abamectin-fed and the control groups. Many of these DMs were significantly enriched in pathways involved in ATP production and energy consumption (e.g., oxidative phosphorylation, TCA cycle, and pentose phosphate pathway). Nineteen of the DMs were typically related to energy metabolism. This study is valuable for further understanding mitochondrial toxicology under environmental toxicants, particularly its subcellular level.

A method for isolating highly purified and active mitochondria from insects.

So far, methods that yield the high purity and activity of the isolated mitochondria from insects have not been reported and determined. Here, we develop methods that combine differential centrifugation and discontinuous Nycodenz density gradient centrifugation to isolate highly purified mitochondria from the thorax muscle of insects, and the methods were widely validated across three orders (Coleoptera, Hymenoptera, and Blattaria) covering four insect species using Western blot and transmission electron microscopy (TEM) analysis. The results showed the removal of the residual contamination with nonmitochondrial components such as nucleus, sarcolemma, cytosol, and endoplasmic reticulum. Furthermore, TEM, mitochondria staining, fluorescence detection, and flow cytometry analyses were employed to assess membrane integrity and activity of the isolated mitochondria. The results showed no loss of mitochondria activity/integrity after isolation. In addition, temporal dynamics in activity of the isolated mitochondria under commonly used laboratory temperature (-20 °C, 4 °C, and 25 °C) were respectively detected using a fluorescence microplate reader. The results showed that it should be avoided to store the isolated mitochondria at room temperature, and the mitochondria can meet the requirements of the most downstream experiments when they were stored at -20 °C. Overall, the study presented a method for isolating highly purified and active mitochondria from insects. This study firstly described a high-speed discontinuous density gradient centrifugation-based method that could be widely applied for mitochondria isolation in insects. The present study also provided an example to assess purity and integrity/activity of the isolated mitochondria.

Comprehensive Cortical Structural Features Predict the Efficacy of Cognitive Behavioral Therapy in Obsessive-Compulsive Disorder.

Although cognitive behavioral therapy (CBT) is effective for patients with obsessive-compulsive disorder (OCD), 40% of OCD patients show a poor response to CBT. This study aimed to identify the cortical structural factors that predict CBT outcomes in OCD patients. A total of 56 patients with OCD received baseline structural MRI (sMRI) scanning and 14 individual CBT sessions. The linear support vector regression (SVR) models were used to identify the predictive performance of sMRI indices, including gray matter volume, cortical thickness, sulcal depth, and gyrification value. The patients' OC symptoms decreased significantly after CBT intervention (p < 0.001). We found the model with the comprehensive variables exhibited better performance than the models with single structural indices (MAE = 0.14, MSE = 0.03, R2 = 0.36), showing a significant correlation between the true value and the predicted value (r = 0.63, p < 0.001). The results indicated that a model integrating four cortical structural features can accurately predict the effectiveness of CBT for OCD. Future models incorporating other brain indicators, including brain functional indicators, EEG indicators, neurotransmitters, etc., which might be more accurate for predicting the effectiveness of CBT for OCD, are needed.