Expression and localization of retinoid receptors in the testis of normal and infertile men.

Retinoic acid (RA), the active metabolite of vitamin A, is one of the most important factors regulating spermatogenesis. RA activates downstream pathways through its receptors (retinoic acid receptor alpha [RARA], retinoic acid receptor beta, and retinoic acid receptor gamma [RARG]) and retinoid X receptors (retinoid X receptor alpha [RXRA], retinoid X receptor beta [RXRB], and retinoid X receptor gamma [RXRG]). These receptors may serve as therapeutic targets for infertile men. However, the localization and expression of retinoid receptors in normal and infertile men were unknown. In this study, we found RARA and RARG were mostly localized in spermatocytes and round spermatids, RXRB was mainly expressed in Sertoli cells, and RXRG was expressed in most cell types in the fertile human testis. The localization of RARA, RARG, RXRB, and RXRG in men with hypospermatogenesis (HYPO) was similar to that of men with normal fertility. In addition, the messenger RNA expression levels of RARA, RARG, RXRA, RXRB, and RXRG were significantly decreased in men with Sertoli cell-only syndrome (SCOS) and maturational arrest (MA), but not in men with HYPO. These results suggest that reduced levels of RARA, RARG, RXRB, RXRA, and RXRG are more closely associated with SCOS and MA spermatogenetic failure. These results could contribute to the development of new molecular indicators of spermatogenic dysfunction and might provide novel therapeutic targets for treating male infertility.

The testis-specific gene 1700102P08Rik is essential for male fertility.

Male infertility is a rising problem around the world. Often the cause of male infertility is unclear, and this hampers diagnosis and treatment. Spermatogenesis is a complex process under sophisticated regulation by many testis-specific genes. Here, we report the testis-specific gene 1700102P08Rik is conserved in both the human and mouse and highly expressed in spermatocytes. To investigate the role of 1700102P08Rik in male fertility, knockout mice were generated by CRISPR-Cas9. 1700102P08Rik knockout male mice were infertile with smaller testis and epididymis, but female knockout mice retained normal fertility. Spermatogenesis in the 1700102P08Rik knockout male mouse was arrested at the spermatocyte stage, and no sperm were found in the epididymis. The deletion of 1700102P08Rik causes apoptosis in the testis but did not affect the serum concentration of testosterone, luteinizing hormone, and follicle-stimulating hormone or the synapsis and recombination of homologous chromosomes. We also found that 1700102P08Rik is downregulated in spermatocyte arrest in men. Together, these results indicate that the 1700102P08Rik gene is essential for spermatogenesis and its dysfunction leads to male infertility.

Proteomic analysis of seminal extracellular vesicle proteins involved in asthenozoospermia by iTRAQ.

Asthenozoospermia is a common cause of male infertility, but in most cases its etiology is unknown. The exocytic cell vesicles called seminal extracellular vesicles in the human seminal fluid have been reported to play a pivotal role in promoting the motility of spermatozoa, and functional disorder of seminal extracellular vesicles may cause male infertility. To determine whether abnormal seminal extracellular vesicles are involved in asthenozoospermia, the differential abundance proteins between normozoospermic (NSEV) and asthenozoospermic seminal extracellular vesicles (ASEV) samples were analyzed by iTRAQ coupled with two-dimensional liquid chromatography-tandem mass spectrometry. A total of 3,699 proteins were identified in the seminal extracellular vesicles (false discovery rate <0.01). Overall, 11 proteins were significantly upregulated (>1.2) in ASEV and 80 were significantly downregulated (<0.833). Functional bioinformatic analysis showed that these proteins with differential abundance were mainly associated with transport, metabolism, and signal pathways. The changes of OPTN, SMYD2, EIF2B2, TRPV6, ACE, PRSS8, and PPAP2A in ASEV were verified by western blot analysis, and we found that the abundance of TRPV6 markedly reduced in the seminal extracellular vesicles and ejaculated spermatozoa of asthenozoospermic patients, which indicated trpv6 was important in sperm motility. This study provides deeper insight into the involvement of seminal extracellular vesicles in asthenozoospermia and should aid the search for novel biomarkers of male infertility.

Assessing consistent condom use among migrant men who have sex with men in Shanghai, China: validation of an information-motivation-behavioural skills model.

BACKGROUND: In China, high prevalence of risky sexual behaviours and inequity in health services lead to situations in which migrant men who have sex with men face higher risk of contracting the human immunodeficiency virus. Consistent condom use is a primary means of preventing HIV infection during anal sex among MSM. This study aimed to apply the information-motivation-behavioural skills model to examine the predictors of consistent condom use among migrant MSM in Shanghai, and tested the associations between model constructs. METHODS: A cross-sectional study was conducted among 412 migrant MSM in Shanghai. Data on HIV-related information, motivation, behavioural skills, and behaviours were collected via structured questionnaires. A structural equation model was used to assess the IMB model. RESULTS: Of the 412 participants, 4.4% reported HIV-positive status, and prevalence of consistent condom use in the previous 6 months was 44.9%. A restricted IMB model provided an acceptable fit to the data. Behavioural skills were found to directly predict consistent condom use (ß = 0.629, P < 0.01). Neither information nor motivation could directly predict consistent condom use (P > 0.05), but motivation predicted it indirectly and was mediated by behavioural skills. CONCLUSION: The prevalence of consistent condom use was found to be relatively low among migrant MSM in Shanghai. The restricted IMB model was found to be a good predictor of consistent condom use among them. The results of this study indicate that intervention strategies for safer sexual behaviour should not only include information dissemination, but also emphasize motivation and behavioural skills among this population.

Association between a syndemic of psychosocial problems and unprotected anal intercourse among men who have sex with men in Shanghai, China.

BACKGROUND: Previous studies have discussed the overlapping and reinforcing effects (defined as a syndemic) of psychosocial problems on high-risk sexual behaviors among men who have sex with men (MSM). The present study aimed to apply the syndemic theory to verify the reinforcing effects of psychosocial problems on unprotected anal intercourse (UAI) among MSM in Shanghai, and determine if other important psychosocial factors fit into the syndemic theory. METHODS: Data were collected from 547 MSM in Shanghai, China, through face-to-face interviews. The measures for psychosocial problems included the Rosenberg Self-Esteem Scale; the Generalized Anxiety Disorder-7; the Center for Epidemiological Studies Depression Scale; the University of California, Los Angeles Loneliness Scale; and the Sexual Compulsivity Scale. We used multivariate analysis and binary logistic regression to investigate the associations between psychosocial problems and high-risk sexual behaviors. RESULTS: The prevalence of UAI among MSM in the past 6 months was 54.5%. Education (graduate from college vs. high school) served as a protective factor against UAI (OR 0.59, 95% CI: 0.38-0.94). There was a high prevalence of psychosocial problems, and at least one-third of participants reported experiencing more than two psychosocial symptoms. Of these psychosocial factors that we investigated, lower self-esteem was associated with UAI in both univariate and multivariate regression model (P = 0.009). Result suggests that overlapping and reinforcing effects of psychosocial problems may increase high risk sexual behaviors among MSM in Shanghai, China (OR 1.65, 95% CI: 1.09-2.50; P = 0.018). CONCLUSIONS: We found further evidence for a syndemic of psychosocial problems among MSM in Shanghai, China. This syndemic may also increase high risk sexual behaviors among MSM. Most HIV prevention interventions are focused on behavior change and only have moderate effects; our findings suggest that a shift from behavior-focused interventions to a more comprehensive strategy that addresses psychosocial factors may be necessary.

A one-pot CRISPR-RCA strategy for ultrasensitive and specific detection of circRNA.

Accurate and precise detection of circular RNA (circRNA) is imperative for its clinical use. However, the inherent challenges in circRNA detection, arising from its low abundance and potential interference from linear isomers, necessitate innovative solutions. In this study, we introduce, for the first time, the application of the CRISPR/Cas12a system to establish a one-pot, rapid (30 minutes to 2 hours), specific and ultrasensitive circRNA detection strategy, termed RETA-CRISPR (reverse transcription-rolling circle amplification (RT-RCA) with the CRISPR/Cas12a). This method comprises two steps: (1) the RT-RCA process of circRNA amplification, generating repeat units containing the back-splicing junction (BSJ) sequences; and (2) leveraging the protospacer adjacent motif (PAM)-independent Cas12a/crRNA complex to precisely recognize target sequences with BSJ, thereby initiating the collateral cleavage activity of Cas12a to generate a robust fluorescence signal. Remarkably, this approach exhibits the capability to detect circRNAs at a concentration as low as 300 aM. The sensor has been successfully employed for accurate detection of a potential hepatocellular carcinoma biomarker hsa_circ_0001445 (circRNA1445) in various cell lines. In conclusion, RETA-CRISPR seamlessly integrates the advantages of exponential amplification reaction and the robust collateral cleavage activity of Cas12a, positioning it as a compelling tool for practical CRISPR-based diagnostics.

The regulation network and network motif analysis in ovarian cancer.

OBJECTIVE: Several gene alterations have been identified associated with ovarian cancer (OC) development. However, how these genetic elements are coordinated in transcription network during OC initiation and progression is poorly understood. Thus, the objective of this study was to interpret the transcription regulation network of OC. MATERIALS AND METHODS: The GSE14407 microarray data was used for analysis of the transcription regulation network of OC. RESULTS: The results showed that the TP53 (tumor protein p53) was the most crucial transcription factor in the transcriptome network. P53 could down-regulate CDC14A (CDC14 cell division cycle 14 homolog A [S. cerevisiae]) and FAS (TNF receptor superfamily, member 6) expression, but up-regulate SFN (stratifin) and THBS1 (thrombospondin 1) expression to involve in pathways in cancer, cell cycle, p53 signaling pathway, and apoptosis pathway. CONCLUSION: This transcriptional regulation may provide a better understanding of molecular mechanism and some potential therapeutic targets in the treatment of OC.

CRISPR/Cas12a-Enabled Multiplex Biosensing Strategy Via an Affordable and Visual Nylon Membrane Readout.

Most multiplex nucleic acids detection methods require numerous reagents and high-priced instruments. The emerging clustered regularly interspaced short palindromic repeats (CRISPR)/Cas has been regarded as a promising point-of-care (POC) strategy for nucleic acids detection. However, how to achieve CRISPR/Cas multiplex biosensing remains a challenge. Here, an affordable means termed CRISPR-RDB (CRISPR-based reverse dot blot) for multiplex target detection in parallel, which possesses the advantages of high sensitivity and specificity, cost-effectiveness, instrument-free, ease to use, and visualization is reported. CRISPR-RDB integrates the trans-cleavage activity of CRISPR-Cas12a with a commercial RDB technique. It utilizes different Cas12a-crRNA complexes to separately identify multiple targets in one sample and converts targeted information into colorimetric signals on a piece of accessible nylon membrane that attaches corresponding specific-oligonucleotide probes. It has demonstrated that the versatility of CRISPR-RDB by constructing a four-channel system to simultaneously detect influenza A, influenza B, respiratory syncytial virus, and SARS-CoV-2. With a simple modification of crRNAs, the CRISPR-RDB can be modified to detect human papillomavirus, saving two-thirds of the time compared to a commercial PCR-RDB kit. Further, a user-friendly microchip system for convenient use, as well as a smartphone app for signal interpretation, is engineered. CRISPR-RDB represents a desirable option for multiplexed biosensing and on-site diagnosis.

Psychosocial Problems and Condomless Anal Sex among Transgender Women in Two Cities of China: Study Based on the Syndemic Framework.

Studies examining the association between psychosocial problems and condomless anal sex (CAS) among transgender women (TGW) are rare. In this study, close attention was paid to the effect of co-occurring psychosocial problems on sexual risk behaviors. A cross-sectional study, including 247 TGW, was conducted in Kunming and Shenyang, China. The prevalence of condomless anal sex among TGW in the previous 6 months was 30.8%. Most of the psychosocial factors were associated with one another in bivariate logistic regression models. Low self-esteem (ORm = 2.99, 95% CI = 1.25-7.18), sexual compulsivity (ORm = 2.13, 95% CI = 1.13-4.00), and intimate partner violence (ORm = 2.21, 95% CI = 1.19-4.11) were discovered to be related to condomless anal sex in the multivariate regression model. No significant interactive effects of the syndemic factors on condomless anal sex were detected. More programmatic and effective HIV prevention interventions targeting psychosocial problems are required to reduce HIV infection within the population.

Reassessment of the Proteomic Composition and Function of Extracellular Vesicles in the Seminal Plasma.

Seminal plasma contains a high concentration of extracellular vesicles (EVs). The heterogeneity of small EVs or the presence of nonvesicular extracellular matter (NV) pose major obstacles in understanding the composition and function of seminal EVs. In this study, we employed high-resolution density gradient fractionation to accurately characterize the composition and function of seminal EVs and NV. We found that the seminal EVs could be divided into 3 different subtypes-namely, high-density EV (EV-H), medium-density EV (EV-M), and low-density EV (EV-L)-after purification using iodixanol, while NV was successfully isolated. EVs and NV display different features in size, shape, and expression of some classic exosome markers. Both EV-H and NV could markedly promote sperm motility and capacitation compared with EV-M and EV-L, whereas only the NV fraction induced sperm acrosome reaction. Proteomic analysis results showed that EV-H, EV-M, EV-L, and NV had different protein components and were involved in different physiological functions. Further study showed that EV-M might reduce the production of sperm intrinsic reactive oxygen species through glutathione S-transferase mu 2. This study provides novel insights into important aspects of seminal EVs constituents and sounder footing to explore their functional properties in male fertility.

Predicting the risk of HIV infection among internal migrant MSM in China: An optimal model based on three variable selection methods.

Introduction: Internal migrant Men who have sex with men (IMMSM), which has the dual identity of MSM and floating population, should be more concerned among the vulnerable groups for HIV in society. Establishing appropriate prediction models to assess the risk of HIV infection among IMMSM is of great significance to against HIV infection and transmission. Methods: HIV and syphilis infection were detected using rapid test kits, and other 30 variables were collected among IMMSM through questionnaire. Taking HIV infection status as the dependent variable, three methods were used to screen predictors and three prediction models were developed respectively. The Hosmer-Lemeshow test was performed to verify the fit of the models, and the net classification improvement and integrated discrimination improvement were used to compare these models to determine the optimal model. Based on the optimal model, a prediction nomogram was developed as an instrument to assess the risk of HIV infection among IMMSM. To quantify the predictive ability of the nomogram, the C-index measurement was performed, and internal validation was performed using bootstrap method. The receiver operating characteristic (ROC) curve, calibration plot and dynamic component analysis (DCA) were respectively performed to assess the efficacy, accuracy and clinical utility of the prediction nomogram. Results: In this study, 12.52% IMMSMs were tested HIV-positive and 8.0% IMMSMs were tested syphilis-positive. Model A, model B, and model C fitted well, and model B was the optimal model. A nomogram was developed based on the model B. The C-index of the nomogram was 0.757 (95% CI: 0.701-0.812), and the C-index of internal verification was 0.705. Conclusions: The model established by stepwise selection methods incorporating 11 risk factors (age, education, marriage, monthly income, verbal violence, syphilis, score of CUSS, score of RSES, score of ULS, score of ES and score of DS) was the optimal model that achieved the best predictive power. The risk nomogram based on the optimal model had relatively good efficacy, accuracy and clinical utility in identifying internal migrant MSM at high-risk for HIV infection, which is helpful for developing targeted intervention for them.

Thy1-Positive Spermatogonia Suppress the Proliferation of Spermatogonial Stem Cells by Extracellular Vesicles In Vitro.

The self-renewal of mammalian spermatogonial stem cells (SSCs) supports spermatogenesis to produce spermatozoa, and this is precisely controlled in a stem niche microenvironment in the seminiferous tubules. Although studies have revealed the role of the surrounding factors in SSCs, little is known about whether the division of SSCs is controlled by extracellular vesicles. Here, extracellular vesicles were found in the basal compartment of seminiferous tubules in mouse, rat, rabbit and human testes. In the mice, the testicular extracellular vesicles are secreted by spermatogonia and are taken up by SSCs. Further, the extracellular vesicles from thy1-positive spermatogonia were purified by anti-Thy1-coupled magnetic beads, which suppress their proliferation of SSCs but do not lead to the apoptosis in vitro.

[A multi-center study to evaluate the dynamic changes of uterine artery and umbilical artery flow in a normal pregnancy and hypertensive disorders in pregnancy].

OBJECTIVE: To investigate the dynamic changes of uterine artery and umbilical artery in the first, second, and third trimester of normal pregnancy and hypertensive disorders in pregnancy (HDP). METHODS: A multi-center prospective study was conducted on 1098 women with normal singleton pregnancies at the first prenatal visit in the Second West China Hospital of Sichuan University, First Affiliated Hospital with Nanjing Medical University, Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University, Wuhan Union Hospital Affiliated to Medical School of Huazhong University of Science and Technology and Renji Hospital Affiliated to Medical School of Shanghai Jiao Tong University from April 2005 to July 2006, with the average age of (28.3 ± 3.3). The pulsatility indices (PI), resistance indices (RI) and systolic to diastolic velocity ratios (S/D) of uterine artery and umbilical artery were measured for all subjects in the first (10th-14th gestational weeks), second (20th-26th gestational weeks) and third trimester (30th-36th gestational weeks), respectively. In this longitudinal study, women who developed HDP were classified into HDP group, and the rest into normal pregnancy group. RESULTS: (1) Among the 1098 pregnant women, 44 developed HDP during the index pregnancy, including 20 gestational hypertension, 15 mild pre-eclampsia and 9 severe pre-eclampsia, giving an incidence of 4.17%, and the rest 1054 were normal until delivery. (2) In the normal pregnancy group, the RI, PI and S/D of uterine artery were decreased with the progress of pregnancy (RI: 0.64, 0.57, 0.50; PI: 1.24, 0.98, 0.80; S/D: 3.26, 2.58, 2.20; P < 0.01). However, the above indices showed an increasing trend with the increase of gestations in the HDP group (RI: 0.55, 0.67, 0.64; PI: 1.22, 1.36, 1.20; S/D: 3.18, 3.41, 3.05; P < 0.01). In the second and third trimester, the RI, PI and S/D of uterine artery in the HDP group were higher than those in the normal pregnancy group (P < 0.01). (3) In the normal pregnancy group, the RI, PI and S/D of the umbilical artery decreased from the second to the third trimester (RI: 0.71 and 0.58; PI: 1.16 and 0.87; S/D: 3.58 and 2.48; P < 0.01). However, no significant difference was found in the RI, PI and S/D value of umbilical artery in the second and third trimester between the normal and HDP group (RI: 0.71 and 0.63; PI: 1.20 and 0.95; S/D: 3.71 and 2.69; P > 0.05, respectively), despite the decreasing trend in the HDP group. CONCLUSIONS: In uncomplicated pregnancies, the blood flow resistance of uterine artery decreases and the end-diastolic blood flow of uterine artery increases with the progress of pregnancy. However, in pregnant women with HDP, the blood flow resistance of uterine artery increases significantly with the increase of gestations which shows significant difference to that in normal pregnancies. The blood flow resistance of umbilical artery decreases in both normal and HDP pregnant women with the increasing gestational age.

Tethering of Telomeres to the Nuclear Envelope Is Mediated by SUN1-MAJIN and Possibly Promoted by SPDYA-CDK2 During Meiosis.

During meiosis, telomeres attach to the nuclear envelope (NE) to promote homologous chromosome moving, pairing, synapsis, and recombination. The telomere-NE attachment is mediated by SUN1, TERB1-TERB2-MAJIN (TTM complex), and TRF1. The interaction of the TTM complex with shelterin is mediated by TERB1 and TRF1, but how SUN1 interacts with the TTM complex is not yet fully understood. In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. The binding sites of MAJIN and SPDYA at SUN1 were mapped, and both MAJIN and SPDYA bound to the N-terminal domain of SUN1 and the two binding sites were close to each other. Furthermore, SPDYA bound to SUN1 via the Ringo domain and recruited CDK2 to SUN1. Then, we found that the interaction of SUN1 with MAJIN was decreased by the CDK2 inhibitors. Taken together, our results provide the possible mechanism of SUN1, MAJIN, and SPDYA-CDK2 in promoting the telomere-NE attachment during meiosis.

Specific detection of hypochlorite based on the size-selective effect of luminophore integrated MOF-801 synthesized by a one-pot strategy.

Hypochlorous acid (HClO), as one of the reactive oxygen species, plays a key role in a variety of physiological and pathological processes, while its accurate and specific in vitro monitoring remains a profound challenge. Herein, a novel luminescent metal-organic framework with high chemical stability has been designed for the specific detection of intracellular ClO-. The specificity was realized by the size-selective effect of MOF-801 with an ultra-small aperture, which can inhibit the entry of large-sized interferents into the cages of MOFs. A universal "ship in a bottle" approach has been proposed to construct this novel sensory platform, in which a large class of luminescent molecules containing carboxylic groups serve as modulators and combine with Zr6 clusters, eventually becoming the luminescent genes of these novel designed MOF-801. Luminescent molecules were readily locked in the framework since they were larger than the small pore entrance of MOF-801, skillfully solving the possible issue of dye leakage. By introducing active sites of 5-aminofluorescein (AF) into MOF-801 (AF@MOF-801) as an example, an excellent ClO- sensing probe was fabricated, which showed strong reliability and excellent sensing performance toward intracellular ClO- with an ultrahigh linear correlation of the Stern-Volmer equation, a rapid response time as short as 30 s and a limit of detection (LOD) as low as 0.05172 µM. Compared with the free AF molecular probe, the specificity of AF@MOF-801 NPs toward ClO- was scarcely affected by other possibly coexistent large-sized interferents in biosystems. The in vitro monitoring of ClO- was also tested with these newly developed AF@MOF-801 NPs, prefiguring their great promise as a robust imaging tool to disclose the complexities of ClO- homeostasis and its pathophysiological contributions.

The expression of the new epididymal luminal protein of PDZ domain containing 1 is decreased in asthenozoospermia.

Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na+/H+ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.

[Pregnancy outcome in women with rheumatic heart disease].

OBJECTIVE: To evaluate the pregnancy outcome of women with rheumatic heart disease. METHODS: Clinical data of 65 cases of pregnant women with rheumatic heart disease from Jan 1993 to July 2006 were analyzed. They were divided into four groups according to the degree of mitral stenosis: normal group (> 4.0 cm(2)), slight group (2.5 - 4.0 cm(2)), moderate group (1.5 - 2.5 cm(2)) and severe group (< 1.5 cm(2)); four groups according to the degree of pulmonary hypertension: normal group, slight group (pulmonary hypertension ranging from 31 to 49 mm Hg, 1 mm Hg = 0.133 kPa) moderate group (from 50 to 79 mm Hg) and severe group (equal to and more than 80 mm Hg); two groups according to heart operation: non-operated group and operated group; and four groups according to the degree of New York heart association (NYHA) class. The perinatal mortality and morbidity of mothers and fetus were analysed. RESULTS: (1) The rate of NYHA class IV was 80% (12/15 cases) in moderate-severe group of mitral stenosis and the rate of NYHA class I and II was 80% (16/20 cases) in normal group, with a significant difference between them (P < 0.05). (2) The rate of NYHA class I and II was 73% (24/33 cases) in group of normal pulmonary pressure and the rate of NYHA class IV was 6/7 in severe group of pulmonary hypertension (P < 0.05). (3) The rate of NYHA class I and II was 71% (10/14), and NYHA class III or IV was 14% (2/14) in heart operated women (P < 0.05). (4) The delivery week was 34.6 and the birth weight was 2176 g averagely in NYHA class IV group and had significant differences from NYHA class I group (P < 0.05). There were 9 cases of abortion medically (18.9%, 9/65), 18 of preterm labor medically (28%, 18/65), 4 of fetal growth restriction (FGR) (6%, 4/65) and 3 of perinatal mortality (5%, 3/65), which all happened in groups of NYHA class III and IV. (5) The rate of NYHA class III and IV was 6/7 in atrial fibrillation women. CONCLUSION: Pregnant women with rheumatic heart disease of moderate-severe mitral stenosis, severe pulmonary hypertension and atrial fibrillation are at high risk of heart failure. The fetal outcome is not good in cases of NYHA class III and IV.

Overexpression of Human-Derived DNMT3A Induced Intergenerational Inheritance of Active DNA Methylation Changes in Rat Sperm.

DNA methylation is the major focus of studies on paternal epigenetic inheritance in mammals, but most previous studies about inheritable DNA methylation changes are passively induced by environmental factors. However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable. Here, we established human-derived DNMT3A (hDNMT3A) transgenic rats to study the effect of hDNMT3A overexpression on the DNA methylation pattern of rat sperm and to investigate whether this actively altered DNA methylation status is inheritable. Our results revealed that hDNMT3A was overexpressed in the testis of transgenic rats and induced genome-wide alterations in the DNA methylation pattern of rat sperm. Among 5438 reliable loci identified with 64 primer-pair combinations using a methylation-sensitive amplification polymorphism method, 28.01% showed altered amplified band types. Among these amplicons altered loci, 68.42% showed an altered DNA methylation status in the offspring of transgenic rats compared with wild-type rats. Further analysis based on loci which had identical DNA methylation status in all three biological replicates revealed that overexpression of hDNMT3A in paternal testis induced hypermethylation in sperm of both genotype-negative and genotype-positive offspring. Among the differentially methylated loci, 34.26% occurred in both positive and negative offspring of transgenic rats, indicating intergenerational inheritance of active DNA methylation changes in the absence of hDNM3A transmission. Furthermore, 75.07% of the inheritable loci were hyper-methylated while the remaining were hypomethylated. Distribution analysis revealed that the DNA methylation variations mainly occurred in introns and intergenic regions. Functional analysis revealed that genes related to differentially methylated loci were involved in a wide range of functions. Finally, this study demonstrated that active DNA methylation changes induced by hDNMT3A expression were intergenerationally inherited by offspring without transmission of the transgene, which provided evidence for the transmission of active endogenous-factors-induced epigenetic variations.

C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans.

Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis.

Previous studies have reported aberrant expression of the miR-183-96-182 cluster in a variety of tumors, which indicates its' diagnostic or prognostic value. However, a key characteristic of the miR-183-96-182 cluster is its varied expression levels, and pleomorphic functional roles in different tumors or under different conditions. In most tumor types, the cluster is highly expressed and promotes tumorigenesis, cancer progression and metastasis; yet tumor suppressive effects have also been reported in some tumors. In the present study, we discuss the upstream regulators and the downstream target genes of miR-183-96-182 cluster, and highlight the dysregulation and functional roles of this cluster in various tumor cells. Newer insights summarized in this review will help readers understand the different facets of the miR-183-96-182 cluster in cancer development and progression.