Altered microRNA expression profiles of human spermatozoa in normal fertile men of different ages.

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.

Extended least squares support vector machine with applications to fault diagnosis of aircraft engine.

Recently, a robust least squares support vector machine (R-LSSVM) was proposed, but its computational complexity is very high compared with the traditional least squares support vector machine (LSSVM). To reduce R-LSSVM's computational complexity, an improved version, i.e., extended LSSVM (E-LSSVM), is developed in this paper. E-LSSVM and R-LSSVM are equivalent in terms of the generalization performance, but the former needs lower computational complexity than the latter. It is proved that the traditional LSSVM is a special case of E-LSSVM, and based on this fact, we know that the bias in the traditional LSSVM owns manifest physical meaning, i.e., the mean of the modeling error. To solve the mathematical model of E-LSSVM, two algorithms, DE-LSSVM (dual E-LSSVM) and PE-LSSVM (primal E-LSSVM), are proposed from dual and primal spaces, respectively. Even competing against the traditional LSSVM, DE-LSSVM takes the edge in term of the training time. In addition, the sparse problem and cross validation of DE-LSSVM are discussed as well. To verify the effectiveness and soundness of the proposed DE-LSSVM and PE-LSSVM, experiments on regression and classification problems are investigated. To be more important, DE-LSSM and PE-LSSVM are successfully applied to the fault diagnosis of aircraft engine, showing that they are eligible for potential techniques of the fault diagnosis of aircraft engine.

Parsimonious kernel extreme learning machine in primal via Cholesky factorization.

Recently, extreme learning machine (ELM) has become a popular topic in machine learning community. By replacing the so-called ELM feature mappings with the nonlinear mappings induced by kernel functions, two kernel ELMs, i.e., P-KELM and D-KELM, are obtained from primal and dual perspectives, respectively. Unfortunately, both P-KELM and D-KELM possess the dense solutions in direct proportion to the number of training data. To this end, a constructive algorithm for P-KELM (CCP-KELM) is first proposed by virtue of Cholesky factorization, in which the training data incurring the largest reductions on the objective function are recruited as significant vectors. To reduce its training cost further, PCCP-KELM is then obtained with the application of a probabilistic speedup scheme into CCP-KELM. Corresponding to CCP-KELM, a destructive P-KELM (CDP-KELM) is presented using a partial Cholesky factorization strategy, where the training data incurring the smallest reductions on the objective function after their removals are pruned from the current set of significant vectors. Finally, to verify the efficacy and feasibility of the proposed algorithms in this paper, experiments on both small and large benchmark data sets are investigated.

BDNF interacts with endocannabinoids to regulate cocaine-induced synaptic plasticity in mouse midbrain dopamine neurons.

Brain-derived neurotrophic factor (BDNF) and endocannabinoids (eCBs) have been individually implicated in behavioral effects of cocaine. The present study examined how BDNF-eCB interaction regulates cocaine-induced synaptic plasticity in the ventral tegmental area and behavioral effects. We report that BDNF and selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF) activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic depression, depolarization-induced suppression of inhibition (DSI), and long-term depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse midbrain slices. The facilitation appears to be mediated by an increase in eCB production via phospholipase Cγ pathway, but not by an increase in CB1 receptor responsiveness or a decrease in eCB hydrolysis. Using Cre-loxP technology to specifically delete BDNF in dopamine neurons, we showed that eCB-mediated I-LTD, cocaine-induced reduction of GABAergic inhibition, and potentiation of glutamatergic excitation remained intact in wild-type control mice, but were impaired in BDNF conditional knock-out mice. We also showed that cocaine-induced conditioned place preference was attenuated in BDNF conditional knock-out mice, in vivo pretreatments with DHF before place conditioning restored cocaine conditioned place preference in these mice, and the behavioral effect of DHF was blocked by a CB1 receptor antagonist. Together, these results suggest that BDNF in dopamine neurons regulates eCB responses, cocaine-induced synaptic plasticity, and associative learning.

[CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity and regulates StAR expression in a transgenic mouse model].

OBJECTIVE: To observe the effects of CMTM2 on cyclophosphamide (CP)-induced reproductive toxicity and the expression of steroidogenic acute regulatory (StAR) protein in the transgenic mouse model. METHODS: Twenty CMTM2 transgenic mice were equally divided into a CMTM2 + CP and a CMTM2 + NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT + CP and a WT + NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and motility by light microscopy and detection of the expression of StAR by Western blot. RESULTS: The levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 + CP group as compared with the CMTM2 + NS group ([42.98 +/- 3.25] nmol/L vs [46.74 +/- 3.38] nmol/L, [16.89 +/- 1.17 ] x 10(6)/ml vs [24.68 +/- 0.95 ] x 10(6)/ml, [72.75 +/- 1.25]% vs [85.14 +/- 1.12]%, P < 0.05), but remarkably less than in the WT + CP group ([37.97 +/- 4.17] nmol/L, [12.75 +/- 1.02] x 10(6)/ml, [50.52 +/- 1.37] %) (P < 0.05). However, the expression of StAR was significantly higher in the CMTM2 + CP than in the WT + CP group (1.16 +/- 0.07 vs 0.69 +/- 0.08, P < 0.05). CONCLUSION: CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of StAR, and hence plays a protective role in the reproductive system.

[Construction and analysis of gene expression profiles in the testes of patients with unilateral cryptorchidism using cDNA gene chips].

OBJECTIVE: To analyze the differentially expressed genes in the testicular tissues of men with unilateral cryptorchidism using cDNA gene chips. METHODS: Probes were prepared with the mRNA extracted from the testes of 6 patients with unilateral cryptorchidism and 3 normal fertile men. Then the differential gene expression profiles of the two groups were detected with cDNA gene chips containing 45 034 genes. The differentially expressed genes were analyzed with Pathway and GO in the MAS system. RESULTS: Based on the ratio of > 3.0 or < 0.33, 346 differentially expressed genes were detected in the testis tissues of the patients with unilateral cryptorchidism, among which 60 were up-regulated and 286 down-regulated. The up-regulated genes were distributed mainly on chromosomes 1, 15, 5 and 19, associated with cell cycles, sperm motility, flagellar movement, DNA replication, and chromatin modification, while the down-regulated genes, mainly on chromosomes 1, 19, 16 and 11, related with spermatogenesis and anti-apoptosis. CONCLUSION: Unilateral cryptorchidism involves the variation of the expressions of multifunctional genes. The establishment of gene expression profiles of unilateral cryptorchidism in human testes may provide a new theoretical basis for analyzing the genetic factors of unilateral cryptorchidism and investigating the etiology of spermatogenic failure.

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population.

BACKGROUND: Late onset hypogonadism negatively impacts on men's psychological well-being. This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life. METHODS: Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6: aging male's symptoms (AMS) rating scale, hospital anxiety and depression scale (HADS), perceived stress scale (PSS) and the short form health survey-12 (SF-12). In this study, men were treated and monitored for 6 months with oral testosterone undecanoate (TU) capsules or vitamin E/C capsules in a single-blinded fashion. All in the active treatment group were administered a total of 120 - 160 mg TU orally on a daily basis. Total and free T levels between baseline and month 6 were compared. RESULTS: One hundred and sixty eligible subjects were recruited and followed up. In the active treatment group, total serum testosterone concentrations before and after intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L. The mean HADS anxiety subscale scores for the subjects at baseline and at month 6 were 3.47 ± 0.4 and 1.72 ± 0.2, respectively (t = 1.526, P < 0.05). Additionally, the mean HADS depression subscale scores were 4.91 ± 0.6 and 2.39 ± 0.3, respectively (t = 3.466, P < 0.05). The mean scores on PSS for the subjects at baseline and at month 6 were 12.88 ± 2.1 and 9.83 ± 1.7, respectively (t = 4.009, P < 0.05). Significantly improved SF-12 could be observed (t = 1.433 and 1.118, respectively; both P < 0.05). No significant changes were observed in the control group at month 6. CONCLUSION: Androgen replacement not only improves androgen deficiency associated symptoms, but also enhances comprehensive improvement in psychological issues.

A live birth of activated one-day-old unfertilized oocyte for a patient who experienced repeatedly near-total fertilization failure after intracytoplasmic sperm injection.

Total or near-total fertilization failure after intracytoplasmic sperm injection (ICSI) is a rare event, but it occurs repeatedly because of sperm defects in activating oocyte. The case presents a successful pregnancy and live birth after calcium ionophore A23187 (A23187) activation on one-day-old unfertilized oocytes in a patient whose husband suffered oligoasthenoteratozoospermia, and who had experienced repeated near-total fertilization failure after ICSI. In the second ICSI cycle, only one oocyte was fertilized while nine were unfertilized. Oocyte activation with A23187 were performed on the one-day-old unfertilized oocytes after ICSI and resulted in fertilization and embryo transfer. A clinical pregnancy was achieved and a healthy baby was born. To our knowledge, this is the first reported case of a healthy birth after oocyte activation on the one-day-old unfertilized oocyte. This indicates that "rescue oocyte activation" on one-day-old unfertilized oocytes after ICSI may be helpful for preventing total or near-total fertilization failure after ICSI.

Andrology in China: current status and 10 years' progress.

Andrology has a long history in traditional Chinese medicine. There are records of male sexual health, male sexual dysfunction and male infertility from over thousands of years ago. Modern andrology in China had a late start, with the Chinese Andrology Association founded in 1995. Within last decade, andrology in China has grown rapidly. In this review article, we summarized the progress of andrology in last 10 years and outlined the current status of Chinese andrology with a special focus on progress in male erectile dysfunction, prostate diseases, male infertility and male hormonal contraception.

Relationship between fecal lactoferrin and inflammatory bowel disease.

OBJECTIVE: Lactoferrin as a glucoprotein that can reflect the activity of neutrophil leukocytes is a specific and sensitive indicator in the evaluation of intestinal inflammation. The aim of this study was to evaluate the relationship between fecal lactoferrin and intestinal inflammation by quantitative analysis and the effect of fecal lactoferrin in measuring the activity of inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). MATERIAL AND METHODS: A total of 177 fresh stool samples were collected from 42 active UC, 17 inactive UC, 13 active CD, 5 inactive CD, 41 infectious bowel disease, 25 irritable bowel syndrome (IBS) and 34 healthy volunteers. IBD-SCAN was used quantitatively to measure the level of fecal lactoferrin. A modified Harvey-Bradshaw Active Index was used to evaluate the activity of IBD. RESULTS: Fecal lactoferrin was 3.15+/-1.60 microg/g in healthy volunteers, 2.54+/-1.49 microg/g in IBS, 83.3+/-29.9 microg/g in infectious bowel disease, 1126.29+/-431.21 microg/g in active UC, 1035.25+/-456.59 microg/g in active CD, 96.58+/-82.46 microg/g in inactive UC and 133.52+/-88.89 microg/g in inactive CD. Fecal lactoferrin was significantly higher in active IBD than in inactive IBD, IBS and infectious bowel disease. The sensitivity and specificity of fecal lactoferrin were 92% and 88%, respectively, for UC, and 92% and 80%, respectively, for CD. CONCLUSIONS: Fecal lactoferrin is a sensitive and specific marker in measuring the activity of IBD. It provides us with a valid method in discriminating between inflammatory and non-inflammatory bowel disease. In addition, an elevated fecal lactoferrin level can lead us to exclude IBS in clinical practice.

[Construction of an antisense RNA recombinant adenovirus vector of the human PDE5A1 gene promoter].

OBJECTIVE: To construct an antisense RNA recombinant adenovirus vector of the human PDE5A1 promoter gene. METHODS: A cDNA fragment containing the human PDE5A1 promoter and the human PDE5A1-specific exon was determined according to the gene bank. The antisense RNA fragment was synthesized artificially and subcloned into the pENTR. Then, the sequence of pENTR fragment was detected, and the recombinant adenovirus vector pAd/CMV/V5/antisense-PDE5A1 was constructed by LR reaction with the Gateway expression system. The identified recombinant adenovirus plasmid was digested with Pac I and transformed into 293A cells to package recombinant adenovirus particles. The recombinant adenovirus particles were tested with PCR technique and purified after acquisition by CsCl density gradient ultracentrifugation. RESULTS: The sequencing result showed a 145 bp fragment in pENTR, which was proved to be the domain of the antisense RNA fragment. PCR confirmed that the antisense RNA fragment was cloned into the recombinant adenovirus vector pAd/CMV/V5/antisense-PDE5A1 successfully and could infect 293A cells. The titer of virus stocks was up to 10(8) - 10(10)/microl after purification. CONCLUSION: With the Gateway expression system, the culturing and reproduction of 293A cells can reproduce recombinant adenovirus pAd/CMV/V5-DEST successfully, and the recombinant adenovirus vector can meet the need of in vivo gene transfection in laboratory studies.

[Successful treatment of high-flow priapism by selective arteriographic embolization of the pudendal artery].

OBJECTIVE: To evaluate the diagnosis and treatment of high-flow priapism (HFP). METHODS: Four cases of HFP following blunt trauma to the penis or perinea underwent diagnostic examination by colour-flow Doppler ultrasound and/or superselective pudendal arteriography, which revealed bilateral arteriocorporal fistula in 1 case and monolateral in the other 3. Penile detumescence was obtained in 2 cases by superselective bilateral/monolateral arteriographic embolization of the pudendal artery with absorbable gelatin RESULTS: The former 2 cases effected an immediate recovery of the sponge, while the other 2 cases received conservative treatment. Erectile function, able to perform normal sexual intercourse in approximately 2 months. But in the latter 2, follow-up revealed unsatisfactory potency. CONCLUSION: Superselective arteriographic embolization with absorbable gelatin sponge can provide a safe, selective and effective treatment for HFP patients.