A molecular mechanism underlies grass carp (Ctenopharyngodon idella) TARBP2 regulating PKR-mediated cell apoptosis.

Interferon-inducible double-stranded RNA-dependent protein kinase (PKR) is one of the key antiviral arms in the innate immune system. The activated PKR performs its antiviral function by inhibiting protein translation and inducing apoptosis. In our previous study, we identified grass carp TARBP2 as an inhibitor of PKR activity, thereby suppressing cell apoptosis. This study aimed to explore the effects of grass carp TARBP2 on PKR activity and cell apoptosis. Grass carp TARBP2 comprises two N-terminal dsRBDs and a C-terminal C4 domain. Subcellular localization analysis conducted in CIK cells revealed that TARBP2-FL (full-length TARBP2), TARBP2-Δ1 (lack of the first dsRBD), and TARBP2-Δ2 (lack of the second dsRBD) are predominantly located in the cytoplasm, while TARBP2-Δ3 (lack of the two dsRBDs) is distributed both in the nucleus and cytoplasm. Colocalization and immunoprecipitation assays confirmed the interaction of TARBP2-FL, TARBP2-Δ1, and TARBP2-Δ2 with PKR, while TARBP2-Δ3 showed no binding. Furthermore, our findings suggested that the inhibitory effect of TARBP2-Δ1 or TARBP2-Δ2 on the PKR-eIF2α pathway is depressed compared to TARBP2-FL. In cell apoptosis assays, it was observed that TARBP2-FL inhibits PKR-mediated cell apoptosis. TARBP2-Δ1 or TARBP2-Δ2 exhibits decreased inhibition to PKR-mediated cell apoptosis, whereas TARBP2-Δ3 nearly completely loses this inhibitory effect. These findings highlight the critical importance of two dsRBDs of TARBP2 in interaction with PKR, as well as in the inhibition of PKR activity, resulting in the suppression of cell apoptosis triggered by prolonged PKR activation.

BNIP3-mediated mitophagy attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62-KEAP1-NRF2 pathway activation to maintain iron and redox homeostasis.

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE.

[Effect of obesity on pulmonary function in asthmatic children of different age groups].

OBJECTIVE: To study the effect of obesity on pulmonary function in newly diagnosed asthmatic children of different age groups. METHODS: Two hundred and ninety-four children with newly diagnosed asthma were classified into preschool-age (<6 years) and school-age (6 to 12.5 years) groups. They were then classified into obese, overweight, and normal-weight subgroups based on their body mass index (BMI). All the children underwent pulmonary function tests, including large airway function tests [forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%)] and small airway function tests [maximal expiratory flow at 25% of vital capacity (MEF25%), maximal expiratory flow at 50% of vital capacity (MEF50%), and maximal expiratory flow at 75% of vital capacity (MEF75%)]. RESULTS: The school-age group showed lower FEV1%, MEF25%, and MEF50% than the preschool-age group (P<0.05) after adjustment for sex and BMI. The normal-weight children in the school-age group had lower FEV1%, MEF25%, and MEF50% compared with their counterparts in the preschool-age group (P<0.05). The overweight children in the school-age group showed lower FVC% and MEF50% than those in the preschool-age group. However, all the pulmonary function parameters showed no significant differences between the obese children in the preschool-age and school-age groups. In the preschool-age group, FVC%, FEV1%, and MEF75% of the obese children were lower than those of the normal-weight children. In the school-age group, only FVC% and FEV1% showed differences between the obese and normal-weight children (P<0.05). CONCLUSIONS: The effect of obesity on the pulmonary function varies with age in children with asthma, and the effect is more obvious in those of preschool age.

MoCps1 is important for conidiation, conidial morphology and virulence in Magnaporthe oryzae.

Conidia play important roles in primary and secondary infections of airborne fungal pathogens. In this study, an insertional mutant with reduced capacity for conidiation was isolated from the rice blast fungus Magnaporthe oryzae. The mutant has a T-DNA insertion that disrupts a gene named MoCPS1. The deduced MoCps1 protein contains three AMP-binding domains. Gene complementation and gene knockout assays confirmed that MoCPS1 is important for conidiation. Conidia produced by the MoCPS1 deletion mutants are much more slender and longer than those produced by the wild-type strain. The Mocps1 mutants are less efficient in both appressorial penetration and invasive growth of infection hyphae, resulting in attenuated virulence toward host plants. MoCPS1 is highly expressed in a mature appressorium. Interestingly, the expression levels of several genes related to conidiation and pathogenicity have been significantly altered in the MoCPS1 deletion mutants. Taken together, our results indicated that MoCPS1 is important for conidiogenesis, conidial morphogenesis, and pathogenesis in the rice blast fungus.

[An analysis of skin prick test reactivity to dust mite in overweight and normal weight children with allergic asthma before and after specific immunotherapy].

OBJECTIVE: To study the skin prick test (SPT) reactivity to house dust mite allergens in overweight and normal weight children with allergic asthma before and after standard subcutaneous specific immunotherapy. METHODS: Two hundred and fifteen children with allergic asthma who had positive SPT responses to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) were enrolled. According to the weight index, they were classified into overweight (n=63) and normal weight groups (n=152). Skin indices (SI) to DP and DF were compared between the two groups at 6 months and 1 year after standard subcutaneous specific immunotherapy. RESULTS: The overweight group had a significantly larger histamine wheal diameter than the normal weight group after controlling the variation in testing time (P<0.05). After controlling the variation in weights, there were significant differences in the SIs to DP and DF before specific immunotherapy and at 6 months and 1 year after specific immunotherapy. At 6 months and 1 year after specific immunotherapy, the SIs to DP and DF were significantly reduced in both groups (P<0.05), and the overweight group had greater decreases in the SIs to DP and DF than the normal weight group. CONCLUSIONS: The overweight children with allergic asthma have stronger responses to histamine than the normal weight patients. Specific immunotherapy can reduce the reactivity to dust mite allergens in children with allergic asthma. Within one year after specific immunotherapy, the overweight children with allergic asthma have a significantly greater decrease in the reactivity to dust mite allergens than the normal weight patients.

Radiomics of Preoperative Multi-Sequence Magnetic Resonance Imaging Can Improve the Predictive Performance of Microvascular Invasion in Hepatocellular Carcinoma.

Background: The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results: The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions: Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.

Human-Guided Functional Connectivity Network Estimation for Chronic Tinnitus Identification: A Modularity View.

The functional connectivity network (FCN) has been used to achieve several remarkable advancements in the diagnosis of neuro-degenerative disorders. Therefore, it is imperative to accurately estimate biologically meaningful FCNs. Several efforts have been dedicated to this purpose by encoding biological priors. However, owing to the high complexity of the human brain, the estimation of an 'ideal' FCN remains an open problem. To the best of our knowledge, almost all existing studies lack the integration of domain expert knowledge, which limits their performance. In this study, we focused on incorporating domain expert knowledge into the FCN estimation from a modularity perspective. To achieve this, we presented a human-guided modular representation (MR) FCN estimation framework. Specifically, we designed an adversarial low-rank constraint to describe the module structure of FCNs under the guidance of domain expert knowledge (i.e., a predefined participant index). The chronic tinnitus (TIN) identification task based on the estimated FCNs was conducted to examine the proposed MR methods. Remarkably, MR significantly outperformed the baseline and state-of-the-art(SOTA) methods, achieving an accuracy of 92.11%. Moreover, post-hoc analysis revealed that the FCNs estimated by the proposed MR could highlight more biologically meaningful connections, which is beneficial for exploring the underlying mechanisms of TIN and diagnosing early TIN.

MoSnf5 Regulates Fungal Virulence, Growth, and Conidiation in Magnaporthe oryzae.

Snf5 (sucrose nonfermenting) is a core component of the SWI/SNF complexes and regulates diverse cellular processes in model eukaryotes. In plant pathogenic fungi, its biological function and underlying mechanisms remain unexplored. In this study, we investigated the biological roles of MoSnf5 in plant infection and fungal development in the rice blast pathogen Magnaporthe oryzae. The gene deletion mutants of MoSNF5 exhibited slower vegetative hyphal growth, severe defects in conidiogenesis, and impaired virulence and galactose utilization capacities. Domain dissection assays showed that the Snf5 domain and the N- and C-termini of MoSnf5 were all required for its full functions. Co-immunoprecipitation and yeast two-hybrid assays showed that MoSnf5 physically interacts with four proteins, including a transcription initiation factor MoTaf14. Interestingly, the ∆MoTaf14 mutants showed similar phenotypes as the ∆Mosnf5 mutants on fungal virulence and development. Moreover, assays on GFP-MoAtg8 expression and localization showed that both the ∆Mosnf5 and ∆MoTaf14 mutants were defective in autophagy. Taken together, MoSnf5 regulates fungal virulence, growth, and conidiation, possibly through regulating galactose utilization and autophagy in M. oryzae.

[Levonorgestrel-releasing intrauterine system and combined oral contraceptives as conservative treatments for recurrent ovarian endometriosis: a comparative clinical study].

OBJECTIVE: To evaluate and compare the efficiency and safety of levonorgestrel-releasing intrauterine system (LNG-IUS) and combined oral contraceptives (COC) in the treatment of recurrent ovarian endometriosis after conservative surgery or conservative surgery plus medical therapy. METHODS: A total of 48 patients with recurrent ovarian endometriosis underwent randomization. The regimens of LNG-IUS (n = 24) and COC (n = 24) were offered. The volume of ovarian endometriotic cysts was recorded before treatment and at 6, 12, 18 and 24 months. The volume of ovarian endometriotic cysts, pain score of visual analogue scale (VAS), menstrual pattern, body weight, serum CA125 and serum lipids were compared to the pretreatment level within each treatment group, as well as between two treatment groups during the same period. RESULTS: (1) At 18 months after LNG-IUS, the cysts in 2 subjects entirely disappeared. At 24 months, 18 patients had a disappearance of cysts. The overall size reduction was statistically significant (9.2 ± 3.0) vs (0.9 ± 1.5) cm(3) (P < 0.01). In the COC group, 12 subjects had a complete resolution of cysts at 24 months. The overall size reduction was statistically significant (9.4 ± 2.2) vs (2.9 ± 3.1) cm(3) (P < 0.01). At 18 & 24 months, the cyst size reduction was significantly larger in the LNG-INS group than the COC group (2.4 ± 1.5) vs (4.7 ± 2.6) cm(3) (P < 0.01) and (0.9 ± 1.5) vs (2.9 ± 3.1) cm(3) (P < 0.05); (2) There was a significant improvement of dysmenorrhea, chronic pelvic pain and dyspareunia at 6- & 12-month follow-up in both groups; (3) serum CA125 decreased at 6 & 12 months in both groups with statistical significance. It decreased more sharply in the LNG-IUS group and remained at low levels beyond 12 months; (4) within 6 months of LNS-IUS, irregular bleeding and spotting were the major side effects. Beyond that period the symptoms were significantly relieved. Weight gain and dyslipidemia were the major side effects of COC. CONCLUSION: For patients with recurrent ovarian endometriosis after conservative surgery or conservative surgery plus medical therapy, LNG-IUS and COC may be used to control and reduce endometriotic cysts, relieve pain and reduce the level of CA125. LNG-IUS has the advantages of a greater convenience and minor systemic side effects.

[Evaluation of levonorgestrel-releasing intrauterine system in treatment of recurrent endometriosis after conservative surgery].

OBJECTIVE: To evaluate the efficiency of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment. METHODS: Twenty-three patients with recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment were treated by LNG-IUS. All patients rejected further operation and had no desire of fertility. The visual analogue scale (VAS) scores of pain, menstrual model, weight and serum CA125 level and the volume of ovarian endometriotic cysts before and after 3, 6, 12, 24 and 36 months of treatment were recorded and compared. RESULTS: (1) VAS score:after 12 months of using LNG-IUS, dysmenorrheal, chronic pelvic pain or dyspareunia were relieved significantly. VAS score were dropped from 5.9±2.3, 4.3±2.0 to 1.0±0.7, 1.4±1.1 (P<0.01). (2) Volum of cysts:after 6 months of using LNG-IUS, the volume of recurrent ovarian endometriotic cysts in 11 patients were reduced from (11.4±6.1) cm3 to (5.5±3.4) cm3 significantly (P<0.01). At 12 months of follow-up, it suggested that 2 patients' ovarian endometriotic cysts disappeared. At 24 months follow-up, 9 patients ovarian endometriotic cysts disappeared (3) CA125: serum CA125 decreased from (65.5±19.6) kU/L to (42.1±13.6) kU/L at 6 months after treatment remarkably (P<0.01). Continued to decrease after 12 months and then become steady. Irregular bleeding and spotting was the main side effects, weight gain was also observed in few patients. CONCLUSIONS: LNG-IUS could be used in treatment of recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment effectively. It could relieve pain, reduce the level of CA125 and decrease the size of ovarian endometriotic cysts. LNG-IUS seems to be an effective, safe, and long term treatment for endometriosis with fewer side effects and better compliance.

[Devine's technique with free skin grafting for concealed penis with prepuce deficit].

OBJECTIVE: To investigate the clinical effect of Devine's technique with free skin grafting in the treatment of concealed penis with prepuce deficit. METHODS: This study included 7 children with concealed penis, aged 6 - 15 (mean 8.6) years, 6 of them treated by circumcision previously. All the patients underwent Devine's operation to resect the inelasticity sarcolemma and lengthen the penis. The length of prepuce deficit ranged from 2 to 4 cm. Intermediate split thickness skin grafts of the corresponding length were taken from the femoribus internus to wrap up the tunica albuginea penis, followed by the procedures of saturation, encapsulation and fixation. RESULTS: Surgery time ranged from 70 to 120 minutes, averaging 90.5 minutes. The penis was prolonged about 2 - 4 cm after surgery. A 6-month follow-up revealed desirable penile appearance and normal penile erection. CONCLUSION: Devine's technique with free skin grafting from the femoribus internus is an ideal treatment for concealed penis with prepuce deficit.

Pathological Analysis and Endoscopic Characteristics of Colorectal Laterally Spreading Tumors.

OBJECTIVE: This study aims to analyze the endoscopic and pathological characteristics of colorectal laterally spreading tumors (LSTs) to assist malignant risk stratification to inform selection of the appropriate treatment strategy. METHODS: Patients with colorectal LST were selected as retrospective study objects. Characteristics, including endoscopic findings and the most common site of LSTs of different diameters and histological types, were analyzed. The risk factors for malignancy in colorectal LST were explored by multivariate logistic regression analysis. RESULTS: LSTs with diameters of ≥20 mm were found mainly in the rectum and mainly with granular-mixed (G-M) morphology (36% and 44.6%, respectively; p < 0.05), while LSTs with diameters of <20 mm were found mainly in the ascending colon and mainly with granular-homogenous (G-H) morphology (40.9% and 46.2%, respectively; p < 0.05). Adenoma was the main histological type in patients with tumors of all diameters. However, the cancerization rate of LSTs was 31% in patients with tumor diameter ≥20 mm, while there was no invasive cancer in patients with tumor diameter < 20 mm. In the low-grade dysphasia (adenoma) group, most of the lesions were located in the ascending colon and most had the morphology LST-G-H (35.8% and 39.2%, respectively; p < 0.05). In the cancerization group, most of the lesions were located in the rectum, with the morphology LST-G-M (51.6% and 67.2%, respectively; p < 0.05), and the diameter was larger than that of the adenoma group (33.84 ± 17.99 mm vs 21.68 ± 8.99 mm). CONCLUSION: The rectum was the most common site for an LST with a diameter ≥20 mm and cancerization, of which the morphology was mainly LST-G-M (endoscopic submucosal dissection is the preferred treatment for this type of LST). LST malignancy was found to be correlated with lesion diameter, location, and morphological appearance.

Copper pattern on self-assembled monolayer through microcontact printing.

Cu pattern on 3-mercaptopropyltrimethoxysilane self-assembled monolayers (MPTS-SAMs) modified glass substrate was achieved by a combination of hydrophobic treatment through microcontact printing, activation and electroless plating. The MPTS-SAMs modified glass substrate was selectively deactivated by microcontact printing 1-hexadecanethiol ethanol solution. X-ray photoelectron spectroscopy (XPS) and water contact angle measurements confirmed that a selectively deactivated pattern was obtained, which was attributed to the formation of disulfide linkages between MPTS and 1-hexadecanethiol. The substrate was selectively activated by dipping into Ag colloids solution and then applied for electroless Cu plating. XPS spectra suggested an ideal catalytic pattern on the substrate due to the deposition of Ag particles on the MPTS and the formation of S-Ag bonds. SEM showed that the microstructure of Cu pattern on MPTS-SAMs was in good agreement with the corresponding silicon master with a resolution of 10 microm. The average electrical resistivity was about 1.8 x 10(-6) omegacm, measured by four-point probe technique. The results suggested that microcontact printing deactivating reagents on SAMs is a potential technique for Cu patterns preparation.

Prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff.

BACKGROUND: The high prevalence of depression in general population was related to its social-demographics and cognitive performance. However, no studies investigated the prevalence of depression, its social-demographic and cognitive correlates in psychiatric medical staff. Thus, the aims of this study investigated the prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff. METHODS: 186 Chinese psychiatric medical staff were enrolled in Wenzhou Kangning Hospital. Depressive symptom score was assessed by the Self-rating Depression Scale (SDS). Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The prevalence of depression was 17.74% in these medical staff. The RBANS total score in participants with depressive symptom was significantly lower than that in participants with not depressive symptom after controlling for the confounding variables. The Person correlation analysis found that the normal SDS score in these medical staff was significantly related to age, education, occupations, RBANS total score and subscale scores. Stepwise multivariate regression analysis further identified that age and RBANS total score were significantly associated with the normal SDS score in these medical staff. LIMITATIONS: The limitations included cross-sectional study design, the small sample size, and the self-rating scale of depression. CONCLUSIONS: The prevalence of depression in Chinese psychiatric medical staff was higher in comparison with Chinese general population, but lower in comparison with Chinese medical staff. Cognitive deficits might be considered a core feather of depression that should be a valuable target for future interventions. Age influenced depressive symptom in these medical staff .

Effect of olprinone on ischemia-reperfusion induced myocardial injury in rats.

AIMS: This study investigated the effect of olprinone on ischemia-reperfusion (I/R) induced cardiac injury, and the underlying mechanism. MAIN METHODS: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by 24 h reperfusion. After the start of reperfusion, rats were respectively treated with olprinone in three different dosages (0.2, 0.6, 2 mg/kg, intraperitoneal injection, i.p./12 h). Twenty-four hours later, a mean arterial pressure (MAP) heart function analysis system was used to monitor hemodynamic parameters; TTC staining method was used to detect the myocardial infarct size; 24-hour mortality of rats was recorded; western blot was used to detect the protein expressions of Caspase-3, Bax, Bcl-2, Beclin-1 and LC3-II/LC3-I. RESULTS: Cardiac function in I/R group was lower than that in sham group (dp/dt max: 1348.29 ± 266.01 vs. 3333.73 ± 1258.03, -dp/dt max: 1163.23 ± 588.18 vs. 3198.93 ± 1416.00, P < 0.05), which was significantly improved by treatment with high dosage of olprinone (dp/dt max: 1348.29±266.01 vs. 2022.43±493.39, -dp/dt max: 1163.23±588.18 vs. 1784.50±418.92, P < 0.05). The percentage of myocardial infarct size in medium and high dosages of olprinone group was lower than that in I/R group (42.67 ± 2.94, 22.33 ± 3.63 vs. 63.67 ± 5.86, P < 0.05). There was no significant difference in mortality among each group within 24 h. Compared with sham group, the expression of Caspase-3 was significantly up-regulated in I/R group (3.44±0.47-fold of sham, P < 0.05), which was inhibited by medium dosage of olprinone treatment (2.00±0.52-fold of sham, P < 0.05 vs. I/R group); also, expression of Bax was increased compared with sham group (4.06±0.25-fold of sham, P < 0.05), which was markedly inhibited by all dosages of olprinone treatment (low: 2.16±0.61-fold, medium: 2.74±0.66-fold, high 1.65±0.55-fold, P < 0.05 vs. I/R group). Expression of Bcl-2 was increased after I/R (1.17±0.06-fold, P < 0.05), which was further elevated in all dosages of olprinone treatment (low: 1.62 ± 0.13-fold, medium: 1.46 ± 0.13-fold, high: 1.82 ± 0.39-fold, P < 0.05 vs. I/R group). In addition, compared with sham group, the expression of Beclin-1 was up-regulated to 1.44±0.05-fold of sham in I/R group (P < 0.05), which was further increased in low and medium dosages of olprinone group (low: 2.46±0.44-fold, medium: 2.80±0.75-fold, P < 0.05 vs. I/R group). Moreover, expression of LC3-II was elevated in low dosage of olprinone treated group (low: 4.50±0.47-fold, P < 0.05 vs. I/R group). CONCLUSIONS: Olprinone improves the cardiac function in response to myocardial I/R injury by regulation of anti-apoptotic, pro-apoptotic. In addition, autophagic signal pathways may also play a role in olprinone's therapeutic effect.

Association between decreased HDL levels and cognitive deficits in patients with bipolar disorder: a pilot study.

BACKGROUND: Cognitive deficits are common in patients with bipolar disorder (BD). Abnormal high density lipoprotein (HDL) levels have been implicated in cognitive deficits associated with ageing and neurodegenerative disorders. The present study aimed to investigate serum HDL levels, cognitive deficits and their association in patients with BD. METHODS: Thirty-seven patients with BD and 37 gender- and age-matched healthy controls (HCs) were recruited in a case-control study. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum HDL levels were measured using enzymatic colourimetry. RESULTS: There was no difference in serum HDL levels between patients with BD and HCs after adjusting for gender, age, education and body mass index (BMI). Cognitive test scores in patients with BD were significantly lower than those in HCs except for the visuospatial/constructional index after adjusting for confounding variables. Serum HDL levels were positively correlated with RBANS total score and language score in patients with BD. Stepwise multiple regression analysis showed that serum HDL levels were significantly correlated with RBANS total score and subscale scores on immediate memory and language in patients with BD after adjusting for confounding factors. CONCLUSIONS: Our findings suggest that patients with BD had poorer cognitive performance than HCs except for the visuospatial/constructional domain, and decreased serum HDL levels were correlated with cognitive deficits, especially in immediate memory and language domains in patients with BD.

Hypermethylation of CpG islands is associated with increasing chromosomal damage in chinese lead-exposed workers.

Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group. The cytokinesis-blocked micronucleus (CBMN) assay was performed to detect chromosomal damage of PBLs of both lead-exposed and -unexposed workers. The methylation-specific polymerase chain reaction (MSP-PCR) was further used to examine the methylation status of six TSGs (GSTP1, hMLH1, MGMT, p14, p15, and p16). Results showed that MN frequencies of high B-Pb workers 8.1 ± 3.1‰ and low B-Pb workers 5.7 ± 2.3‰ were significantly higher than that of control group 2.8 ± 1.9‰ (P < 0.01), while the MN frequency of high B-Pb workers was also higher than that of the low B-Pb workers (P < 0.01). The MN frequency in PBLs of lead-exposed group with the methylated TSGs was significantly higher than that in PBLs with the unmethylated TSGs (P < 0.05). Notably, the CpG island methylator phenotype (CIMP) correlated with chromosome damage (P < 0.05). Additionally, workers with high B-Pb had higher chromosome damage than those with low B-Pb (P < 0.05). Taken altogether, the results suggest that lead-exposed workers with CIMP positive and high B-Pb have a higher risk of being vulnerable to tumorigenesis. Environ. Mol. Mutagen. 59:549-556, 2018. © 2018 Wiley Periodicals, Inc.

Glutamate synthase MoGlt1-mediated glutamate homeostasis is important for autophagy, virulence and conidiation in the rice blast fungus.

Glutamate homeostasis plays a vital role in central nitrogen metabolism and coordinates several key metabolic functions. However, its function in fungal pathogenesis and development has not been investigated in detail. In this study, we identified and characterized a glutamate synthase gene MoGLT1 in the rice blast fungus Magnaporthe oryzae that was important to glutamate homeostasis. MoGLT1 was constitutively expressed, but showed the highest expression level in appressoria. Deletion of MoGLT1 resulted in a significant reduction in conidiation and virulence. The ΔMoglt1 mutants were defective in appressorial penetration and the differentiation and spread of invasive hyphae in penetrated plant cells. The addition of exogenous glutamic acid partially rescued the defects of the ΔMoglt1 mutants in conidiation and plant infection. Assays for MoAtg8 expression and localization showed that the ΔMoglt1 mutants were defective in autophagy. The ΔMoglt1 mutants were delayed in the mobilization of glycogens and lipid bodies from conidia to developing appressoria. Taken together, our results show that glutamate synthase MoGlt1-mediated glutamate homeostasis is important for pathogenesis and development in the rice blast fungus, possibly via the regulation of autophagy.

[Cystic lymphangioma of the spermatic cord in old man: a case report and review of the literature].

OBJECTIVE: To investigate the clinical and pathological features, diagnosis and treatment of cystic lymphangioma of the spermatic cord. METHODS: One case of cystic lymphangioma of the spermatic cord in a 71-year-old patient was retrospectively analyzed and the relevant literature was reviewed. RESULTS: The patient, presented with spermatic cord hydrocele, was treated by local excision of the tumor, which was pathologically diagnosed as cystic lymphangioma. No relapse was found during a 3-month follow-up after the operation. CONCLUSION: Lymphangioma of the spermatic cord is a benign tumor. Preoperation ultrasonography and CT are important for determining the location and nature of lymphangioma. Surgical excision is an effective option for the treatment of cystic lymphangioma of the spermatic cord.

Analysis of microRNA expression and micronuclei frequency in workers exposed to vinyl chloride monomer in China.

AIM: To identify differently expressed miRNAs associated with vinyl chloride monomer (VCM) and micronuclei (MN) frequency. METHOD: In discovery stage, we used microarray to detect miRNAs expression in peripheral blood lymphocytes between six low and six high VCM-exposed workers grouped by medium cumulative exposure dose. Then we validated four miRNAs using real-time quantitative reverse transcription PCR (qRT-PCR) and detected the micronuclei frequencies using cytokinesis-block micronucleus assay in 94 VCM-exposed workers and 53 healthy control subjects. RESULTS & CONCLUSION: We found eight miRNAs significantly downregulated and seven miRNAs upregulated (|Fold Change| >2; p < 0.05) in the high-exposure group through microarray. We validate that miR-222-3p, miR-146a-5p and miR-151a-5p were downregulated, while miR-22-3p was upregulated in VCM-exposed group (all p < 0.01). Furthermore, we found that expression of miR-22-3p was upregulated in the high micronuclei (MN) frequency subjects. In conclusion, our study suggested that these four miRNAs could be biomarkers of VCM exposure, and moreover miR-22-3p was correlated with MN frequency.