Lipid metabolism-related miRNAs with potential diagnostic roles in prostate cancer.

BACKGROUND: Prostate cancer (PCa), the second most prevalent solid tumor among men worldwide, has caused greatly increasing mortality in PCa patients. The effects of lipid metabolism on tumor growth have been explored, but the mechanistic details of the association of lipid metabolism disorders with PCa remain largely elusive. METHODS: The RNA sequencing data of the GSE45604 and The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) datasets were extracted from the Gene Expression Omnibus (GEO) and UCSC Xena databases, respectively. The Molecular Signatures Database (MSigDB) was utilized to identify lipid metabolism-related genes. The limma R package was used to identify differentially expressed lipid metabolism-related genes (DE-LMRGs) and differentially expressed microRNAs (DEMs). Moreover, least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (XGBoost), and support vector machine-recursive feature elimination (SVM-RFE) were applied to select signature miRNAs and construct a lipid metabolism-related diagnostic model. The expression levels of selected differentially expressed lipid metabolism-related miRNAs (DE-LMRMs) in PCa and benign prostate hyperplasia (BPH) specimens were verified using quantitative real-time polymerase chain reaction (qRT‒PCR). Furthermore, a transcription factor (TF)-miRNA‒mRNA network was constructed. Eventually, Kaplan‒Meier (KM) curves were plotted to illustrate the associations between signature miRNA-related mRNAs and TFs and overall survival (OS) along with biochemical recurrence-free survival (BCR). RESULTS: Forty-seven LMRMs were screened based on the correlation analysis of 29 DE-LMRGs and 56 DEMs, in which 27 LMRMs were stably expressed in the GSE45604 dataset. Subsequently, receiver operating characteristic (ROC) curves and machine learning methods were employed to develop a lipid metabolism-related diagnostic signature, which may be of diagnostic value for PCa patients. qRT‒PCR results showed that all seven key DE-LMRMs were differentially expressed between PCa and BPH tissues. Eventually, a TF-miRNA‒mRNA network was constructed. CONCLUSIONS: These results suggested that 7 key diagnostic miRNAs were closely related to PCa pathological processes and provided new targets for the diagnosis and treatment of PCa. Moreover, CLIC6 and SCNN1A linked to miR-200c-3p had good prognostic potential and provided valuable insights into the pathogenesis of PCa.

Long-Term Survival and Prognostic Factors After Laparoscopic Radical Nephrectomy.

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

Phytoavailability and transfer of mercury in soil-pepper system: Influencing factors, fate, and predictive approach for effective management of metal-impacted spiked soils.

Mercury (Hg) contamination and accumulation in food crops is a global threat posing potential health risk to humans. However, Hg phytoavailability in soil-pepper system and its influencing factors largely remain unknown. In this study, a greenhouse pot experiment was conducted to grow peppers using 21 Chinese agricultural soils with varied soil properties and aged Hg levels. Mercury concentration in pepper leaves and fruits ranged from 0.021 to 0.057 mg kg-1 and 0.005-0.022 mg kg-1 respectively, while fruit Hg content in three soils (Anhui, Hubei, Beijing) exceeded the safety limit. Fruit Hg concentration was better positively correlated with soil Mg(NO3)2-extractable Hg content (r = 0.7, P < 0.0001) than soil total Hg content (r = 0.45, P < 0.0001). Highest bioconcentration factor (BCF, ratio of Hg plant to Hg soil) yielded in acidic soils, while the lowest BCF occurred in alkaline soils. Path analysis indicated available-Hg (R2 = 0.40) and total-Hg (R2 = 0.40) had direct positive effects on the pepper fruit Hg concentration, while direct negative effects including pH (R2 = -0.86), organic matter (R2 = -0.7), crystalline-Fe (R2 = -0.68). Those agreed with the stepwise multiple linear regression analysis which yielded a regression predictive model (R2 = 0.73, P < 0.0001). Soil available-Hg, total-Hg, pH, organic matter and crystalline-Fe & Mn were the most influencing factors of Hg phytoavailability. These results provide new insights into the phytoavailability of Hg in soil-pepper system, thus facilitating the management of pepper cultivation in Hg-enriched soils.

Immature rat testis sustained long-term development using an integrative model.

BACKGROUND: Xenotransplantation has been primarily performed using fresh donor tissue to study testicular development for about 20 years, and whether the cultured tissue would be a suitable donor is unclear. In this study, we combined testicular culture and xenotransplantation into an integrative model and explored whether immature testicular tissue would survive and continue to develop in this model. METHODS: In the new integrative model group, the testes of neonatal rats on postnatal day 8 (PND 8) were cultured for 4 days ex vivo and then were transplanted under the dorsal skin of castrated nude mice. The xenografted testes were resected on the 57th day after xenotransplantation and the testes of rats in the control group were harvested on PND 69. The survival state of testicular tissue was evaluated from morphological and functional perspectives including H&E staining, immunohistochemical staining of 8-OH-dG, immunofluorescence staining, TUNEL assay, ultrastructural study, gene expression and protein analysis. RESULTS: (a) We found that complete spermatogenesis was established in the testes in the new integrative model group. Compared with the control in the same stage, the seminiferous epithelium in some tubules was a bit thinner and there were vacuoles in part of the tubules. Immunofluorescence staining revealed some ACROSIN-positive spermatids were present in seminiferous tubule of xenografted testes. TUNEL detection showed apoptotic cells and most of them were germ cells in the new integrative model group. 8-OH-dG immunohistochemistry showed strongly positive-stained in the seminiferous epithelium after xenotransplantation in comparison with the control group; (b) Compared with the control group, the expressions of FOXA3, DAZL, GFRα1, BOLL, SYCP3, CDC25A, LDHC, CREM and MKI67 in the new integrative model group were significantly elevated (P < 0.05), indicating that the testicular tissue was in an active differentiated and proliferative state; (c) Antioxidant gene detection showed that the expression of Nrf2, Keap1, NQO1 and SOD1 in the new integrative model group was significantly higher than those in the control group (P < 0.05), and DNA methyltransferase gene detection showed that the expression of DNMT3B was significantly elevated as well (P < 0.05). CONCLUSION: The new integrative model could maintain the viability of immature testicular tissue and sustain the long-term survival in vivo with complete spermatogenesis. However, testicular genes expression was altered, vacuolation and thin seminiferous epithelium were still apparent in this model, manifesting that oxidative damage may contribute to the testicular development lesion and it needs further study in order to optimize this model.

Early Diagnostic Value of Urinary NGAL in Acute Kidney Injury in Septic Patients.

Background: The aim of this study was to evaluate the predictive value of urinary neutrophil gelatinase-associated lipid (uNGAL) for the prediction of sepsis-associated acute kidney injury (SA-AKI). Methods: From September to December 2012, 110 patients were prospectively enrolled from the intensive care units (ICUs) of 3 general hospitals. After being admitted to the ICU, the patients were continuously observed for 72 hours. According to the Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis of acute kidney injury (AKI), the patients were divided into the AKI group (33 patients) and non-AKI group (77 patients). Per the sepsis diagnostic criteria, the patients were classified as septic (79 patients) and non-septic (31 patients). Serum creatinine and uNGAL of the patients were analyzed daily. The difference in uNGAL in septic and non-septic patients, patients with and without AKI, and septic patients with with and without AKI were compared. In addition, the difference in serum creatinine and uNGAL in patients with and without AKI were recorded and compared, and the sensitivity and specificity of uNGAL and sCr for the diagnosis of AKI in the ICU patients were evaluated using the receiver operating characteristic (ROC) curve. Results: uNGAL levels were all significantly different in septic and non-septic patients (P = .001, P = .028, P = .010, respectively), patients with and without AKI (P = .001, P = .042, P = .001, respectively), septic patients with AKI and septic patients without AKI (P = .003, P = .012, P = .001, respectively) at 24, 48 and 72 hours after being admitted to the ICU, while the difference in sCr was not significant (P = .169) after 24 hours. The area under the ROC curve of uNGAL and sCr in patients admitted to the ICU at 24 hours were 0.828 (95% CI, 0.742 to 0.914) and 0.583 (95% CI, 0.471 to 0.695), respectively. The cutoff value of uNGAL was 170 ng/mL in patients admitted to the ICU at 24 hours, and the sensitivity and specificity were 0.778 and 0.784, respectively. The sensitivity of uNGAL was superior sCr. Conclusion: uNGAL has relatively high sensitivity and specificity in predicting the occurrence of AKI in septic patients, which is superior to sCr and has certain clinical early diagnostic value. uNGAL could be used as an indicator for early diagnosis of AKI in septic patients in the ICU.

The diagnostic accuracy of procalcitonin and C-reactive protein for sepsis: A systematic review and meta-analysis.

BACKGROUND: The objective of this study was to systematically evaluate the clinical value of procalcitonin and C-reactive protein in the diagnosis of adult patients with sepsis. METHOD: PubMed, Cochrane, Embase, Wanfang, China National Knowledge Infrastructure, and VIP database were searched by the index words to identify the qualified prospective studies, and relevant literature sources were also searched. The most recent research was done in the April 2017. The only languages included were English or Chinese. In the experiment group, patients were diagnosed with sepsis, severe sepsis, or septic shock; in the control group, the patients were of noninfectious origin or a systemic inflammatory response syndrome. The diagnostic accuracy was analyzed by heterogeneity, diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and the summary receiver-operating characteristic curve. RESULTS: At least nine studies were involved in the meta-analysis with 495 patients in the sepsis group and 873 patients in the nonsepsis group. In terms of the diagnostic accuracy of C-reactive protein (CRP) for sepsis, the overall area under the summary receiver operator characteristic (SROC) curve was 0.73 (95% confidence interval [CI], 0.69-0.77), with a sensitivity and specificity of 0.80 (95% CI, 0.63-0.90) and 0.61 (95% CI, 0.50-0.72) respectively, and the DOR was 6.89 (95% CI, 3.86-12.31). In terms of the diagnostic accuracy of procalcitonin (PCT) for sepsis, the overall area under the SROC curve was 0.85 (95% CI, 0.82-0.88), with a sensitivity and specificity of 0.80 (95% CI, 0.69-0.87) and 0.77 (95% CI, 0.60-0.88) respectively, and the DOR was 12.50 (95% CI, 3.65-42.80). CONCLUSION: In this meta-analysis, our results together indicate a moderate degree of value of PCT and CRP for the diagnosis of sepsis in adult patients. The diagnosis accuracy and specificity of PCT are higher than those of CRP.

[Establishment of a method for in vitro culture of fetal rat testis tissue].

OBJECTIVE: To establish a method for in vitro culture of the fetal rat testis tissue. METHODS: Nine sexually mature specific-pathogen-free rats, 3 males and 6 females, weighing 200－250 g, were used for this study. The estrus of the female rats was determined according to the results of the vaginal smear test. The female rats were mated with the male ones in proestrus and estrus at night in the ratio of 2∶1 and observed the following day for conception (0.5 day post-conception ［dpc］) based on the presence of sperm in the vaginal smear. At 15.5 dpc, the fetal testes were isolated under the anatomical microscope, some for HE staining and the rest divided into a control and an hCG group to be cultured in a soft agar culture system at 37 ℃ in a humidified atmosphere containing 5% CO2. From the first day of culture (d 0), the development of the testes was observed under the inverted microscope, the culture medium collected and replaced on d 1, d 2, d 3 and d 4, and the testis tissue obtained on d 4. The concentration of testosterone in the culture medium was determined and the testis tissues were fixed, dehydrated and embedded for histological examination. RESULTS: Fetal rats were successfully obtained with the vaginal smear at 15.5 dpc, and the fetal testes effectively isolated, which were well developed, with gradual increase of their volume and enlargement of convoluted seminiferous tubules under the inverted microscope. Testosterone was observed in the culture medium, its concentration gradually increasing and reaching the peak on d 3, and its secretion stimulated by hCG. At 15.5 dpc. The fetal testes showed a histomorphological integrity, with typical seminiferous tubules, gonocytes, Sertoli cells and Leydig cells, but no central necrosis. Transmission electron microscopy revealed gonocytes and Sertoli cells within and Leydig cells between the seminiferous tubules, without obvious swelling of the mitochondria and endoplasmic reticula in the cells. CONCLUSIONS: The fetal rat testis tissue cultured in the soft agar culture system can develop well, retain its normal activity, and excrete testosterone into the culture medium.

[Novel methods for studies of testicular development and spermatogenesis: From 2D to 3D culture].

The two-dimensional model of cell culture is an important method in the study of testicular development and spermatogenesis but can not effectively mimic and regulate the testicular microenvironment and the whole process of spermatogenesis due to the lack of relevant cell factors and the disruption of a three-dimensional spatial structure. In the past 20 years, the development and optimization of the in vitro model such as testis organotypic culture and in vivo model such as testis transplantation achieved a transformation from two- to three-dimension. The maintenance and optimization of the testicular niche structure could mimic the testicular microenvironment and cell types including Leydig, Sertoli and germ cells, which showed similar biological behaviors to those in vivo. Besides, the cell suspension or tissue fragment floats in the gas-liquid interface so that the development of somatic and germ cells is well maintained in vitro whilst the feedback linkage between grafted testis tissue and hypothalamus-pituitary of the host rebuilt in the in vitro model provides an endocrinological basis for spermatogenesis, which serves as an effective methodology to better understand the organogenesis and development of the testis as well as testicular function regulation, advancing the concept of treatment of male infertility. Al- though each of the methods may have its limitations, the progress in the processing, freezing, thawing, and transplantation of cells and tissues will surely promote their clinical application and present their value in translational medicine.

In utero exposure to di-(2-ethylhexyl) phthalate induces testicular effects in neonatal rats that are antagonized by genistein cotreatment.

Fetal exposure to endocrine disruptors (EDs) is believed to predispose males to reproductive abnormalities. Although males are exposed to combinations of chemicals, few studies have evaluated the effects of ED mixtures at environmentally relevant doses. Our previous work showed that fetal exposure to a mixture of the phytoestrogen genistein (GEN) and the plasticizer di-(2-ethylhexyl) phthalate (DEHP) induced unique alterations in adult testis. In this follow-up study, we examined Postnatal Day 3 (PND3) and PND6 male offspring exposed from Gestational Day 14 to parturition to corn oil, 10mg/kg GEN, DEHP, or their combination, to gain insight into the early molecular events driving long-term alterations. DEHP stimulated the mRNA and protein expression of the steroidogenic enzyme HSD3B, uniquely at PND3. DEHP also increased the mRNA expression of Nestin, a Leydig progenitor/Sertoli cell marker, and markers of Sertoli cell (Wt1), gonocyte (Plzf, Foxo1), and proliferation (Pcna) at PND3, while these genes were unchanged by the mixture. Redox (Nqo1, Sod2, Sod3, Trx, Gst, Cat) and xenobiotic transporter (Abcb1b, Abcg2) gene expression was also increased by DEHP at PND3, while attenuated when combined with GEN, suggesting the involvement of cellular stress in short-term DEHP effects and a protective effect of GEN. The direct effects of GEN and mono-(2-ethylhexyl) phthalate, the principal bioactive metabolite of DEHP, on testis were investigated in PND3 organ cultures, showing a stimulatory effect of 10 µM mono-(2-ethylhexyl) phthalate on basal testosterone production that was normalized by GEN. These effects contrasted with previous reports of androgen suppression and decreased gene expression in perinatal rat testis by high DEHP doses, implying that neonatal effects are not predictive of adult effects. We propose that GEN, through an antioxidant action, normalizes reactive oxygen species-induced neonatal effects of DEHP. The notion that these EDs do not follow classical dose-response effects and involve different mechanisms of toxicity from perinatal ages to adulthood highlights the importance of assessing impacts across a range of doses and ages.

[Spermatic vein ligation and intra-vaginal ejaculation latency].

OBJECTIVE: To investigate the intra-vaginal ejaculation latency time (IELT) of varicocele patients, the influence of spermatic vein ligation on IELT, and the relationship of Visual Analogue Score (VAS) with IELT. METHODS: We selected 112 males who had regular sexual life after spermatic vein ligation and conducted follow-up visits for 6 months. According to preoperative IELT, we divided the patients into an IELT < or = 2 min group and an IELT > 2 min group, and compared their IELT, VAS and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores before and 6 months after operation. RESULTS: Follow-up was accomplished in 81 of the patients, 18 in the IELT < or = 2 min group and 63 in the IELT >2 min group. Compared with the baseline, IELT was significantly prolonged postoperatively in both the IELT < or = 2 min group ([1.26 +/- 0.37] vs [4.53 +/- 1.69] min, P < 0.01) and the IELT >2 min group ([5.14 +/- 2.03] vs [7.69 +/- 4.51] min, P < 0.05); the postoperative CIPE-5 scores were remarkably improved in the former (11.27 +/- 3.52 vs 15.64 +/- 2.37, P < 0.05) but insignificantly in the latter group (20.42 +/- 4.65 vs 21.83 +/- 5.49, P > 0.05); the postoperative grades of the CIPE-5 scores showed significant differences in both groups (chi2 = 6.353, P = 0.042 and chi2 = 3.910, P = 0.048); the postoperative VAS was markedly increased (3.18 +/- 0.92 vs 1.56 +/- 0.83 and 3.24 +/- 0.95 vs 1.74 +/- 0.79, P < 0.05), with significant differences in the grades of VAS in both groups (chi2 = 4.433, P = 0.035 and chi2 = 10.088, P = 0.001). The variation of VAS was negatively correlated with that of IELT in both groups (r = -0.572, P < 0.01 and r = -0.465, P < 0.05). CONCLUSION: Varicocele may be one of the causes of premature ejaculation, and some of the varicocele patients with IELT < or = 2 min may benefit from spermatic vein ligation. Improved VAS is negatively correlated with prolonged IELT. The relationship between varicocele and premature ejaculation deserves further studies.

Lower mRNA and protein expression levels of LC3 and Beclin1, markers of autophagy, were correlated with progression of renal clear cell carcinoma.

OBJECTIVE: The aim of this study was to examine the level of autophagy in renal clear cell carcinoma, stratify by clinicopathologic grades and stages and compare it with healthy renal tissue in order to hypothesize on the role of autophagy in the proliferation of renal clear cell carcinoma. METHODS: Renal clear cell carcinoma tissue and matched adjacent tissue were collected from 52 patients who had received surgical resection. Autophagosomes were visualized in both renal clear cell carcinomas and adjacent tissue by transmission electron microscopy. Expression of the markers of autophagy, Beclin1 and LC3, was detected by a reverse transcription-polymerase chain reaction. Beclin1 and LC3 protein levels were examined by immunohistochemistry and western blot, and the correlation between autophagy levels and clinicopathologic data was analyzed. RESULTS: Autophagy was down-regulated in renal clear cell carcinomas compared with matched adjacent tissue as measured by the reverse transcriptase-polymerase chain reaction, immunohistochemistry and western blot analyses. Clinicopathologic analyses indicated that advanced or metastatic renal clear cell carcinomas were associated with a lower expression of autophagy compared with localized renal clear cell carcinomas. Similarly, the Fuhrman nuclear grade of renal clear cell carcinomas was negatively correlated with the level of autophagy. Stage, grade and the level of LC3 II were significant factors for prognosis and the low level of LC3 II was associated with poor prognosis of renal clear cell carcinomas. CONCLUSIONS: The results indicate that autophagy is suppressed in renal clear cell carcinomas. The lower levels of autophagy are correlated with the higher stages and grades of renal clear cell carcinomas. Furthermore, a low level of LC3 II indicates poor prognosis of renal clear cell carcinoma. This is suggestive of association between the low level of autophagy and progression of renal clear cell carcinoma.

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein.

Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP-GEN mixture on adult offspring should be observed further.

[Sexual development characteristics and sex hormone levels in obese male adolescents].

OBJECTIVE: To investigate the characteristics of sexual development and sex hormone levels in obese male adolescents. METHODS: We included 156 obese male adolescents with micropenis and microorchidia in an observation group and 50 healthy ones in a control group. We measured the body mass index (BMI), penile natural length and testicular volume, investigated the incidence of spermatorrhea and the age of the first spermatorrhea, detected the levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), total testosterone (TT), free testosterone (FT), progesterone (P) and estradiol (E2) using radioimmunoassay, and calculated TT/E2 and testosterone secretion index (TSI). RESULTS: Compared with the healthy controls, the obese adolescents showed significantly higher BMI ([20.4 +/- 1.6] vs [27.1 +/- 2.2] kg/m2, P < 0.05), but shorter penile natural length ([6.7 +/- 2.1] vs [5.6 +/- 1.7] cm, P < 0.05) and lower testis volume ([9.9 +/- 3.1] vs [7.6 +/- 2.3] cm3, P < 0.05). The incidence of spermatorrhea was significantly decreased in the observation group in comparison with that of the control (chi2 = 17.335, P < 0.05), but there was no significant difference in the age of the first spermatorrhea between the two groups (P > 0.05). The levels of LH, E2 and P were remarkably higher in the observation group than in the control ([7.82 +/- 2.14] vs [5.39 +/- 1.76] mIU/ml, P < 0.05; [48.57 +/- 8.34] vs [8.61 +/- 4.08] pg/ml, P < 0.01; and [1.25 +/- 0.58] vs [0.64 +/- 0.19] ng/ml, P < 0.05), while TT and FT were markedly lower in the former than in the latter ([0.73 +/- 0.20] vs [1.47 +/- 0.41] ng/ml, P < 0.01 and [5.09 +/- 2.60] vs [11.28 +/- 4.72] pg/ml, P < 0.01), and so were the TT/E2 ratio and TSI (0.015 +/- 0.004 vs 0.173 +/- 0.037 and 0.098 +/- 0.026 vs 0.272 +/- 0.084, P < 0.01). BMI was correlated positively to PRL and E2, but negatively to TT, FT, TT/E2 and TSI (P < 0.05); the penile natural length positively to TT, FT, TT/E2 and TSI, but negatively to E2 (P < 0.05); and the mean testis volume positively to TT, FT, TT/E2 and TSI, but negatively to LH, PRL and E2 (P < 0.05). CONCLUSION: Testis dysplasia and alteration of sex hormone levels exist in obese male adolescents. Obesity and fat accumulation lead to increased E2 and decreased TT and FT, particularly the reduction of TT/E2 and TSI, which suggest that the body fat content has an important influence on the development of the male reproductive system.

Unveiling the nitrogen removal performance from microbial network establishment in vertical flow constructed wetlands.

The combined effects of substrate types (natural zeolite or shale ceramsite) and hydraulic retention time (HRT, 3-day or 6-day) on nutrient removal and microbial co-occurrence networks in vertical flow constructed wetlands (VFCWs) remains to be elucidated. In this study, zeolite-packed VFCWs demonstrated superior removal rates, achieving 93.65% removal of NH4+-N and 83.84% removal of COD at 6-day HRT. The activity and establishment of microbial community were influenced by combined operating conditions. The abundances of Amx, amoA, nxrA, and nosZ genes increased with longer HRTs in zeolite-packed VFCWs. Additionally, a 6-day HRT significantly increased the relative abundances of Proteobacteria and Nitrospirae. At the species level, zeolite-packed VFCWs exhibited ecological niche sharing as a coping strategy in response to environment changes, while ceramsite-packed VFCWs displayed ecological niche differentiation. Both zeolite-packed and ceramsite-packed VFCWs established functional networks of nitrogen-transforming genera that utilized ecological niche differentiation strategies.

Simultaneous removal of antibiotics and nitrogen by microbial fuel cell-constructed wetlands: Microbial response and carbon-nitrogen metabolism pathways.

Microbial fuel cell-constructed wetlands (MFC-CWs) are attracted extensive attention due to their simultaneous removal performance during the co-occurrence of various pollutants in wastewater. This study explored the performance and mechanisms on the simultaneous removal of antibiotics and nitrogen from MFC-CWs which packed with coke (MFC-CW (C)) and quartz sand (MFC-CW (Q)) substrate. Results showed that removal of sulfamethoxazole (93.60 %), COD (77.94 %), NH4+-N (79.89 %), NO3-- N (82.67 %), and TN (70.29 %) significantly enhanced by MFC-CW (C) due to the enhancement of relative abundance of membrane transport, amino acid metabolism and carbohydrate metabolism pathways. The results indicated that coke substrate can generate more electric energy in MFC-CW. Firmicutes (18.56-30.82 %), Proteobacteria (23.33-45.76 %), and Bacteroidetes (17.1-27.85 %) were dominant phyla in the MFC-CWs. MFC-CW (C) posed significant effects on the microbial diversity and structure, which motivated the functional microbes involved in the transformation of antibiotics and nitrogen and bioelectricity generation. Given the overall performance of MFC-CW, packing with cost-effective substrate to electrode region of MFC-CWs was found to be an effective strategy for simultaneously removing antibiotics and nitrogen in the wastewater treatment.

Intracellular and extracellular untargeted metabolomics reveal the effect of acute uranium exposure in HK-2 cells.

Uranium exposure poses a serious threat to the health of occupational populations and the public. Although metabolomics is a promising research approach to study the toxicological mechanisms of uranium exposure, in vitro studies using human cells are scarce. Applying cultured cell metabolomics, we exhaustively analyzed the intracellular and extracellular differential metabolites upon uranium exposure and characterized the possible biological effects of uranium exposure on human kidney cells. Uranium exposure significantly induced disturbance in the amino acid biosynthesis and linoleic acid metabolism of the cells. Cells exposed to uranium produce excessive amounts of arachidonic acid, which has the potential to cause oxidative stress and damage cells. The results provide new evidence for an oxidative stress mechanism of uranium-induced renal cell injury. Cell metabolomics has proven to be a useful diagnostic tool to study the molecular mechanisms of uranium poisoning.

Health Effects of Particulate Uranium Exposure.

Uranium contamination has become a nonnegligible global health problem. Inhalation of particulate uranium is one of the predominant routes of occupational and environmental exposure. Uranium particle is a complex two-phase flow of matter that is both particulate and flowable. This particular physicochemical property may alter its biological activity. Epidemiological studies from occupationally exposed populations in the uranium industry have concluded that there is a possible association between lung cancer risk and uranium exposure, while the evidence for the risk of other tumors is not sufficient. The toxicological effects of particulate uranium exposure to animals have been shown in laboratory tests to focus on respiratory and central nervous system damage. Fibrosis and tumors can occur in the lung tissue of the respiratory tract. Uranium particles can also induce a concentration-dependent increase in cytotoxicity, targeting mitochondria. The understanding of the health risks and potential toxicological mechanisms of particulate uranium contamination is still at a preliminary stage. The diversity of particle parameters has limited the in-depth exploration. This review summarizes the current evidence on the toxicology of particulate uranium and highlights the knowledge gaps and research prospects.

Artificial Neural Pathway Based on a Memristor Synapse for Optically Mediated Motion Learning.

Animals execute intelligent and efficient interactions with their surroundings through neural pathways, exhibiting learning, memory, and cognition. Artificial autonomous devices that generate self-optimizing feedback mimicking biological systems are essential in pursuing future intelligent robots. Here, we report an artificial neural pathway (ANP) based on a memristor synapse to emulate neuromorphic learning behaviors. In our ANP, optical stimulations are detected and converted into electrical signals through a flexible perovskite photoreceptor. The acquired electrical signals are further processed in a zeolitic imidazolate frameworks-8 (ZIF-8)-based memristor device. By controlling the growth of the ZIF-8 nanoparticles, the conductance of the memristor can be finely modulated with electrical stimulations to mimic the modulation of synaptic plasticity. The device is employed in the ANP to implement synaptic functions of learning and memory. Subsequently, the synaptic feedbacks are used to direct a robotic arm to perform responding motions. Upon repeatedly "reviewing" the optical stimulation, the ANP is able to learn, memorize, and complete the specific motions. This work provides a promising strategy toward the design of intelligent autonomous devices and bioinspired robots through memristor-based systems.

Mercury fractionation, bioavailability, and the major factors predicting its transfer and accumulation in soil-wheat systems.

Soil mercury (Hg) and its bioaccumulation in food crops have attracted widespread concerns globally due to its harmful effects on biota. However, soil mercury fractionation, bioavailability, and the major factors predicting its transfer and accumulation in soil-wheat-systems have not been thoroughly explored. Twenty-one (21) soil samples collected throughout China with a wide spectrum of physico-chemical characteristics were contaminated with HgCl2 and winter wheat (Triticum aestivum L.) was grown on the soils in a greenhouse pot-culture experiment for 180 days. A four-step sequential extraction was used segregating soil Hg into water-soluble (F1, 0.21 %), exchangeable (F2, 0.07 %), organically bound (F3, 16.40 %), and residual fractions (F4, 83.32 %). Step-wise multiple linear regression (SMLR) and path analysis (PA) were used to develop a prediction model and identify the major controlling factors of soil-wheat Hg transference. The SMLR results revealed that wheat Hg in leaves, husk, and grain was positively correlated with soil total and available Hg, and crystalline manganese (Cryst-Mn), while negatively correlated with soil pH, amorphous manganese (Amor-Mn) and crystalline aluminium (Cryst-Al). Bioconcentration factor (BCF) values were significantly higher in acidic soils (highest 0.05), with phytotoxic effects in some soils, as compared to alkaline soils (lowest 0.006). Furthermore, wheat grain Hg was significantly correlated with total (R2 = 0.25), water-soluble (R2 = 0.54) and NH4Ac-extractable Hg (R2 = 0.43) while also had a good correlation with soil pH (R2 = -0.20). In conclusion, the soil total and available Hg (water-soluble + exchangeable fraction), pH, organic matter, and Amor-Mn are the most important soil variables that support Hg uptake in the wheat plants, which benefit managing Hg-enriched agricultural soils for safe wheat production.

10-7 M genistein partially alleviates 10-7 M MEHP unfavorable effects in a new modified fetal rat testis culture system.

Background: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigation. Moreover, testis organ culture system also needs further modification to provide an effective tool for ex vivo EDCs study. Methods: We firstly modified the agarose organ culture system, in which fetal rat testes were cultured for 4 days (d1 to d4) on agarose gels held by Millicell inserts. Then we used the modified agarose culture system to study the combined effects of multiple EDCs exposure. 15.5 dpc fetal rat testes were isolated and treated with vehicle, MEHP (0.1 µmol/L), GEN (0.1 µmol/L) or MEHP (0.1 µmol/L) + GEN (0.1 µmol/L). Parameters concerning testicular cell development and function were evaluated, trying to gain insight into the early molecular events after multiple EDCs exposure. Results: The development of somatic, germ cells and seminiferous tubule in 15.5 dpc fetal rat testis was better sustained in the modified agarose culture system. Based on the modified system, we found that MEHP at 0.1 µmol/L induced alterations in gonocyte markers, antioxidative enzyme activity as well as transient reduction of testosterone production, accompanied by mitochondria swelling in gonocytes and Sertoli cells. No obvious morphological and histological alterations were observed in all treated groups. However, coadministration of genistein at 0.1 µmol/L partially alleviated MEHP-induced fetal testis damage ex vivo through enhancement of antioxidative action. MEHP at low dose still showed weak endocrine disrupting properties but did not exhibit typical low-dose effects. Conclusion: Our findings indicated that the modified agarose culture system could better mimic testicular microenvironment without obvious hypoxic cell damage. Furthermore, low dose of MEHP induced mild disruption to fetal testis development, cotreatment of genistein at low dose attenuated MEHP induced fetal testis injuries in part by balancing redox state, indicating that low dose of genistein may partially protect fetal testis from phthalates induced injury.