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Mitochondria play a crucial role in spermatogenesis and are regulated by several mitochondrial fusion proteins. However, their functional importance associated with their structure formation and mRNA fate regulation during spermatogenesis remains unclear. Here, we show that mitofusin 2 (MFN2), a mitochondrial fusion protein, interacts with nuage-associated proteins (including MIWI, DDX4, TDRKH and GASZ) in mice. Conditional mutation of Mfn2 in postnatal germ cells results in male sterility due to germ cell developmental defects. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with a high-sequence similarity to MFN2, in testes to facilitate spermatogenesis. Simultaneous mutation of Mfn1 and Mfn2 in testes causes very severe infertile phenotypes. Importantly, we show that MFN2 is enriched in polysome fractions of testes and interacts with MSY2, a germ cell-specific DNA/RNA-binding protein, to control gamete-specific mRNA (such as Spata19) translational activity during spermatogenesis. Collectively, our findings demonstrate that MFN2 interacts with nuage-associated proteins and MSY2 to regulate male germ cell development by controlling several gamete-specific mRNA fates.
Assuntos
Diferenciação Celular/fisiologia , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Células Germinativas/metabolismo , RNA Mensageiro/metabolismo , Espermatogênese/genética , Espermatogênese/fisiologia , Animais , Proteínas Argonautas , RNA Helicases DEAD-box , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fertilidade , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Células Germinativas/patologia , Células HEK293 , Humanos , Infertilidade Masculina/genética , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mutação , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Testículo/metabolismo , Testículo/patologiaRESUMO
In the adolescent group, about half of adolescents with major depressive disorder (MDD) have NSSI. Psychosocial factors are associated with the development of NSSI. Clarifying the relationship between psychosocial factors and NSSI in adolescents with MDD can help us achieve early prevent. Demographic data, Hamilton Depression Scale-24 (HAMA24), childhood trauma questionnaire, emotional intelligence scale and interpersonal reactivity index were collected from 187 adolescents with MDD. Use ANOVA, Chi-square test, Binary Logistic Regression, Pearson correlation analysis, Mediation effect analysis and the Structural Equation Model for data analysis. The results of ANOVA showed that there was significant difference between the two groups in HAMD24 total score, impulsiveness, emotional intelligence, and empathy (p < 0.05). In the regression analysis, women, depression degree, motor impulsiveness (MI), personal distress (PD) and appraisal of other's emotions empathy were the risk factors for MDD adolescents to produce NSSI behavior. Among the indicators that were significantly related to MDD and NSSI, MI and PD mediate the relationship between MDD and NSSI. The structural equation model showed that MDD, PD and MI had a direct impact on NSSI, but PD and MI had multiple intermediary effected in the relationship between MDD and NSSI. Emotional intelligence, emotional neglect and cognitive impulsiveness indirectly affected the occurrence of NSSI behavior. Impulsiveness, personal distress, emotional neglect, and emotional intelligence are important risk factors that affect NSSI behavior in adolescents with MDD, and they affect the occurrence of NSSI in adolescents with MDD through chain mediation.
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Attention deficit is a critical symptom that impairs social functioning in adolescents with major depressive disorder (MDD). In this study, we aimed to explore the dynamic neural network activity associated with attention deficits and its relationship with clinical outcomes in adolescents with MDD. We included 188 adolescents with MDD and 94 healthy controls. By combining psychophysics, resting-state electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) techniques, we aimed to identify dynamic network features through the investigation of EEG microstate characteristics and related temporal network features in adolescents with MDD. At baseline, microstate analysis revealed that the occurrence of Microstate C in the patient group was lower than that in healthy controls, whereas the duration and coverage of Microstate D increased in the MDD group. Mediation analysis revealed that the probability of transition from Microstate C to D mediated anhedonia and attention deficits in the MDD group. fMRI results showed that the temporal variability of the dorsal attention network (DAN) was significantly weaker in patients with MDD than in healthy controls. Importantly, the temporal variability of DAN mediated the relationship between anhedonia and attention deficits in the patient group. After acute-stage treatment, the response prediction group (RP) showed improvement in Microstates C and D compared to the nonresponse prediction group (NRP). For resting-state fMRI data, the temporal variability of DAN was significantly higher in the RP group than in the NRP group. Overall, this study enriches our understanding of the neural mechanisms underlying attention deficits in patients with MDD and provides novel clinical biomarkers.
Assuntos
Transtorno Depressivo Maior , Humanos , Adolescente , Transtorno Depressivo Maior/diagnóstico por imagem , Anedonia , Eletroencefalografia , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Encéfalo/fisiologiaRESUMO
A quadruple-function dynamically tunable terahertz absorber that uses a hybrid configuration of graphene and vanadium dioxide is proposed in this paper. The absorber achieves dynamic conversion of four functions in one structure: ultra-broadband, broadband, single-frequency narrowband and dual-frequency narrowband, by utilizing the electrical control properties of graphene and the phase-shifting properties of vanadium dioxide. Furthermore, the paper also reveals the physical mechanism of the proposed absorber through the electric field distribution and impedance matching theory. In addition, the influences of the Fermi energy level of graphene and the electrical conductivity of vanadium dioxide on the absorption spectra are investigated, demonstrating the structure's dynamic tunability. Due to the above features, the designed absorber is expected to have potential applications in terahertz imaging, modulation and filtering.
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In this paper, we propose a dual-operating mode metasurface based on graphene and vanadium dioxide (VO2), which can switch operating modes by changing the temperature. At room temperature (25 °C), the metasurface can generates a polarization-insensitive electromagnetically induced transparency (EIT)-like effect that can be modulated by changing the Fermi energy level (EF) of graphene (through adding external voltage). In addition, the theoretical results derived from the two-particle model are in good agreement with the simulation results based on the finite element method. At high temperature (68 °C), the metasurface mode of operation can be changed to a dual-band absorber, providing absorption of 78.6% and 99.9% at 1.13 THz and 2.16 THz, respectively. Both absorption peaks can be dynamically tuned by changing theEFof graphene. The metasurface is also simultaneously polarization insensitive and has a wide incidence angle. The proposed metasurface can be used as a slow light device with a maximum group delay of 0.5 ps at room temperature and as a refractive index sensor with a maximum sensitivity of 0.5 THz/RIU at high temperature. The designed metasurface offers a new way for designing multifunctional terahertz devices, slow light devices, and refractive index sensors.
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Mitochondria tailor their morphology to execute their specialized functions in different cell types and/or different environments. During spermatogenesis, mitochondria undergo continuous morphological and distributional changes with germ cell development. Deficiencies in these processes lead to mitochondrial dysfunction and abnormal spermatogenesis, thereby causing male infertility. In recent years, mitochondria have attracted considerable attention because of their unique role in the regulation of piRNA biogenesis in male germ cells. In this review, we describe the varied characters of mitochondria and focus on key mitochondrial factors that play pivotal roles in the regulation of spermatogenesis, from primordial germ cells to spermatozoa, especially concerning metabolic shift, stemness and reprogramming, mitochondrial transformation and rearrangement, and mitochondrial defects in human sperm. Further, we discuss the molecular mechanisms underlying these processes.
Assuntos
Diferenciação Celular , Células Germinativas/citologia , Infertilidade Masculina/patologia , Mitocôndrias/fisiologia , Doenças Mitocondriais/fisiopatologia , Espermatozoides/citologia , Animais , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , MasculinoRESUMO
Advanced oxidation processes (AOPs), based on sulfate radical (SO4·-) produced by peroxymonosulfate (PMS), can effectively mineralize refractory organic pollutants. However, the coexistence of anions and natural organic matters in actual wastewater prevents the application of AOPs. A simple one-step method was used to prepare FeS/Fe3O4 co-modified biochar materials (FFB) that could activate PMS to degrade quinclorac (QNC) with a removal rate of 100%, even exhibiting optimum degradation of QNC reached 99.31% in irrigation water, demonstrating excellent anti-interference performance for co-existing anions and natural organic matter. Meanwhile, ecotoxicity analysis showed that the toxicity of degradation intermediates was lower than that of QNC. Characterization results demonstrated the even distribution of FeS and Fe3O4 onto biochar, supplying abundant Fe2+ to activate PMS producing reactive oxygen species (ROS), while the generated Fe3+ after reactive continue to be reduced with sulfur species to promote the cycle of Fe2+/Fe3+. The coexistence of ·OH, SO4·-, 1O2, and O2·- in the FFB/PMS-QNC system suggest the possession of two pathway with free radical and non-free radical pathways to degrade QNC. The density functional theory (DFT) was used to analyze the adsorption sites and adsorption energy of PMS, as well as the differential charge density, which further proved the generation of SO4·-, O2·- and 1O2. In addition, the electrochemical test results showed that electron transfer also played an important role in the degradation of QNC. This study provides a feasible approach for the removal of organic pollutants in actual water.
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Poluentes Ambientais , Peróxidos , Peróxidos/química , ÁguaRESUMO
Ovol2, a mouse homolog of Drosophila ovo, was identified as a zinc finger transcription factor predominantly expressed in testis. However, the function of Ovol2 in postnatal male germ cell development remains enigmatic. Here, we firstly examined the mRNA and protein levels of Ovol2 in developing mouse testes by RT-qPCR and western blot and found that both mRNA and protein of Ovol2 are continually expressed in postnatal developing testes from postnatal day 0 (P0) testes to adult testes (P56) and exhibits its higher level at adult testis. Further testicular immuno-staining revealed that OVOL2 is highly expressed in the spermatogonia, spermatocytes and round spermatids. Interestingly, our conditional ovol2 knockout mouse model show that loss of ovol2 in embryonic germ cells does not affect fecundity in mice. Our data also show that Ovol1 may have compensated for the loss of Ovol2 functions in germ cells. Overall, our data indicate that ovol2 is dispensable for germ cell development and spermatogenesis.
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Espermatogênese/genética , Testículo/metabolismo , Fatores de Transcrição/genética , Dedos de Zinco/genética , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fertilidade/genética , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos Knockout , Espermátides/citologia , Espermátides/metabolismo , Espermatócitos/citologia , Espermatócitos/metabolismo , Espermatogônias/citologia , Espermatogônias/metabolismo , Testículo/citologia , Testículo/crescimento & desenvolvimento , Fatores de Transcrição/metabolismoRESUMO
Non-obstructive azoospermia (NOA) is the most severe clinical diagnosis in cases of male infertility. Although in some cases of NOA spermatozoa can be retrieved by microdissection testicular sperm extraction (micro-TESE) to fertilise eggs through intracytoplasmic sperm injection (ICSI), there remains a lack of potential biomarkers for non-invasive diagnosis before micro-TESE surgery. To determine predictive biomarkers for successful sperm retrieval before micro-TESE, the aim of this study was to explore whether microRNAs (miRNAs) were differentially expressed in testicular tissues in NOA patients in whom sperm retrieval had been successful (SSR) versus those in whom it had been unsuccessful (USR) using next-generation small RNA sequencing (RNA-Seq). In all, 180 miRNAs were identified with significantly altered expression levels between SSR and USR testicular tissues. Of these, the expression of 13 miRNAs was upregulated and that of 167 miRNAs was downregulated in the USR compared with SSR group. Unexpectedly, 86 testicular miRNAs were found to be completely absent in the USR group, but showed high expression in the SSR group, suggesting that these miRNAs may serve as biomarkers for micro-TESE and may also play an essential role in spermatogenesis. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the miRNAs that differed significantly between the USR and SSR groups were involved in cell apoptosis, proliferation and differentiation, which are of considerable importance during spermatogenesis. In summary, this study identified a panel of miRNAs highly expressed in testicular tissues of SSR but not USR NOA patients, providing new insights into specific miRNAs that may play important roles in epigenetic regulation during spermatogenesis. The findings provide a basis for further elucidation of the regulatory role of miRNAs in spermatogenesis and clues to identifying useful biomarkers to predict residual spermatogenic loci in NOA patients during treatment with assisted reproductive technologies.
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Azoospermia/metabolismo , MicroRNAs/metabolismo , Recuperação Espermática , Testículo/metabolismo , Adulto , Azoospermia/genética , Humanos , Masculino , MicroRNAs/genética , Microdissecção , Pessoa de Meia-Idade , Injeções de Esperma Intracitoplásmicas , Adulto JovemRESUMO
Mitochondria-associated endoplasmic reticulum membranes (MAMs) regulate important cellular functions including calcium signaling, bioenergetics, and apoptosis during neurodevelopment and carcinogenesis, but its function in male reproduction and spermatogenesis remains enigmatic because the field lacks a complete understanding of the proteome within testis MAMs. To better understand the biological processes and molecular functions of MAM in testes, a global mass spectrometry-based proteomic evaluation of MAM proteins from human and mouse testes are reported here, respectively. The evaluation and analysis showed that the components of MAM were highly conserved not only between different species (human and mouse) but also between different tissues (testes and brains). Bioinformatics interrogation of these MAM protein catalogues uncovered that 815 new potential linkages specifically existed in mouse testes compared with mouse brains. In addition, a comparative analysis showed that 1347 proteins (account for ≈96.56%) were highly conservatively expressed in both human and mouse testis MAMs. Furthermore, functional analysis revealed that testis-specific MAM proteins were related to spermatogenesis, male gamete generation, as well as sexual reproduction. The data identified, for the first time, numerous MAM proteins in mouse and human testes, which provide a possibility to define the relationship between testis MAM proteins and reproductive diseases.
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Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Proteoma/análise , Testículo/metabolismo , Animais , Humanos , Masculino , Espectrometria de Massas/métodos , Camundongos , Camundongos Endogâmicos C57BL , Testículo/citologiaRESUMO
PURPOSE: PIWI-interacting RNA (piRNA) is a sub-group of small RNAs about 30 nucleotides length which specifically expressed in mammalian germ cells. Although piRNAs play pivotal roles in spermatogenesis regulation, little is known in the testicular tissues of infertile men. To explore whether piRNA profile could serve as a biomarker for male infertility diagnosis in a clinic, in this study, we systematically investigated the expression profile of piRNAs in testicular tissues from the patients with non-obstructive azoospermia (NOA) between successful and unsuccessful sperm retrieval before micro-dissection testicular sperm extraction (micro-TESE). METHODS: The differential expression levels of piRNAs were evaluated using small RNA-Seq method. Ontologic analyses were performed to determine the presence of enriched biological processes. RESULTS: A total of 18,324 Homo sapiens piRNAs were identified by small RNA-Seq from NOA patient testicular tissues; among them, 959 piRNAs were significantly altered between successful and unsuccessful sperm retrieval groups, of which 951 testicular piRNAs were significantly downregulated and 8 piRNAs were upregulated in NOA patients with unsuccessful sperm retrieval (USR) groups compared to those with successful sperm retrieval (SSR) groups, respectively. Unexpectedly, 553 testicular piRNAs were found completely absent in USR but showing abundant in SSR, which suggests that those piRNAs might serve as a biomarker for micro-TESE application. A total of 20 significantly differential piRNAs (hsa-piR-20830, hsa-piR-4731, hsa-piR-6254, hsa-piR-419, hsa-piR-7152, hsa-piR-7548, hsa-piR-14195, hsa-piR-5026, hsa-piR-11482, hsa-piR-17765, hsa-piR-17102, hsa-piR-4484, hsa-piR-17260, hsa-piR-17098, hsa-piR-20511, hsa-piR-5802, hsa-piR-19121, hsa-piR-2510, hsa-piR-4745, hsa-piR-11873) were selected to further validate the RNA-Seq data by quantitative real-time polymerase chain reaction. In addition, bioinformatic analyses revealed that those altered piRNAs were involved in many important biological pathways, including apoptosis, cell proliferation, and differentiation. CONCLUSIONS: Our results demonstrate that testicular tissues from NOA patients with successful and unsuccessful spermatozoa retrieval exhibit differential piRNA profiles. This study provides a useful resource to further elucidate the regulatory role of piRNAs in spermatogenesis and provides a profound clue to identify useful biomarkers for predicting residual spermatogenic loci in NOA patients during assisted reproductive treatment.
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Azoospermia/genética , RNA Interferente Pequeno/análise , Recuperação Espermática , Adulto , Ontologia Genética , Humanos , Masculino , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Espermatogênese/genética , Transcriptoma , Resultado do TratamentoRESUMO
Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.
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Arsenitos , Masculino , Animais , Camundongos , Arsenitos/toxicidade , DNA Helicases , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , FertilidadeRESUMO
Genetic and epigenetic changes in sperm caused by male aging may be essential factors affecting semen parameters, but the effects and specific molecular mechanisms of aging on male reproduction have not been fully clarified. In this study, to explore the effect of aging on male fertility and seek the potential molecular etiology, we performed high-throughput RNA-sequencing in isolated spermatogenic cells, including pachytene spermatocytes (marked by the completion of chromosome synapsis) and round spermatids (produced by the separation of sister chromatids) from the elderly and the young men. Functional enrichment analysis of differentially expressed genes (DEGs) in round spermatids between the elderly and young showed that they were significantly enriched in gamete generation, spindle assembly, and cilium movement involved in cell motility. In addition, the expression levels of DEGs in round spermatids (post-meiotic cells) were found to be more susceptible to age. Furthermore, ten genes (AURKA, CCNB1, CDC20, CCNB2, KIF2C, KIAA0101, NR5A1, PLK1, PTTG1, RAD51AP1) were identified to be the hub genes involved in the regulation of sperm quality in the elderly through Protein-Protein Interaction (PPI) network construction and measuring semantic among GO terms and gene products. Our data provide aging-related molecular alterations in meiotic and post-meiotic spermatogenic cells, and the information gained from this study may explain the abnormal aging-related male fertility decline.
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Sêmen , Espermátides , Masculino , Humanos , Idoso , Espermátides/metabolismo , Espermatozoides/metabolismo , Perfilação da Expressão Gênica , Fertilidade/genética , Espermatogênese/genéticaRESUMO
The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.
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Espermatogênese , Espermatogônias , Animais , Masculino , Camundongos , Células-Tronco Germinativas Adultas/metabolismo , Processamento Alternativo/genética , Diferenciação Celular , Espermatogênese/genética , Espermatogônias/metabolismo , Espermatogônias/citologia , Células-Tronco/metabolismo , Células-Tronco/citologia , Testículo/metabolismo , Testículo/citologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/metabolismoRESUMO
The current photocatalytic bactericidal materials in the field of food pathogen control are usually consisted of metals that always suffering from poor stability and possible secondary pollution. Besides, the requirement for high energy excitation also inspires the enthusiasm on exploring non-metallic catalysts. Herein, the non-metallic composite of rice shell biochar loaded with red phosphorus (B@RP) was developed for photocatalysis and photothermal removal of bacteria. The B@RP showed effective photocatalysis performance to stimulate the generation of OH and O2- free radicals for the elimination of Escherichia coli (E. coli). At the same time, the photothermal effect of B@RP can also increase the permeability of cell membrane, which is conducive to free radicals entering the cell interior. Therefore, the non-metallic composite could achieve complete removal of E. coli within 2 h under illumination. Meanwhile, B@RP had excellent stability and the sterilization efficiency maintained 100% after 9 cycles. Hence, B@RP is expected to be a harmless and efficient bactericidal material for food industry.
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Escherichia coli , Oryza , Fósforo , Antibacterianos/farmacologia , CatáliseRESUMO
BACKGROUND: Cognitive dysfunction is common among adolescent patients with major depressive disorder (MDD). However, the pattern and magnitude of cognition impairment in patients during melancholic episodes remains unclear. The purpose of this study was to compare the neurocognitive performance and the underlying cerebral blood flow activation of adolescent patients with melancholic and non-melancholic features. METHODS: Fifty-seven and 44 adolescent patients with MDD with or without melancholic feature (MDD-MEL/nMEL) and 58 healthy controls (HCs) were recruited. We used the repeatable battery for the assessment of neuropsychological status (RBANS) measuring neurocognitive function, and used functional near infrared spectroscopy (fNIRS) monitoring cerebral hemodynamic changes, described by ß value. The non-parametric test and post-hoc analysis were conducted in RBANS scores and ß values among three groups. Spearman correlation and mediating analysis was performed for RBANS scores, ß values, and clinical symptoms in the MDD-MEL group. RESULTS: There were no significant difference in RBANS scores between MDD-MEL and MDD-nMEL group. Compared with patients in MDD-nMEL, patients in MDD-MEL have lower ß values in eight channels (ch10, ch16, ch20, ch25, ch27, ch37, ch41, ch45). The cognitive function is significantly correlated with anhedonia, and the ß values play a partial mediating role between anhedonia and cognitive function. LIMITATION: It's a cross-sectional study and monitoring longitudinal effects are needed to further elucidate the mechanism. CONCLUSION: The cognitive function in adolescents with MDD-MEL may not significantly differ from those with MDD-nMEL. However, the anhedonia may influenced the cognitive function by altering the function of medial frontal cortex.
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Transtorno Depressivo Maior , Humanos , Adolescente , Transtorno Depressivo Maior/psicologia , Anedonia , Estudos Transversais , Depressão , CogniçãoRESUMO
Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.
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RNA de Interação com Piwi , Corpos de Processamento , Masculino , Prófase Meiótica I , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espermatogênese/genéticaRESUMO
INTRODUCTION: Previous studies have shown that abnormal sleep architectures are the important indicator for diagnosing MDD and predicting the efficacy of antidepressants. However, few studies have focused specifically on adolescents. OBJECTIVE: To explore the relationship between abnormal sleep features, including PSG parameters and scale evaluation, and the onset of adolescent MDD, as well as early SSRIs efficacy. METHODS: 102 adolescent MDD patients (age 12 to 19-year-old) and 41 similarly age-marched controls were recruited. Demographic data, the HAMD24 and the PSQI scale assessment scores were collected at baseline, latter two were also collected at follow-up. Part of the participants underwent a minimum 7-d medication-free period, and two consecutive night polysomnography. In the follow-up study, MDD patients were treated with standardized SSRIs. Treatment response was assessed every two weeks. RESULTS: MDD subjects' parental marital status, REM-sleep latency, N2, N2%, N3, REM-sleep duration, REM % showed significant differences at baseline. REM-sleep latency showed significant prediction of the onset of MDD. The HAMD24 and PSQI scale assessment scores decreased over time in the follow-up study. Specifically, the sleep disorder factor score of HAMD24, the scores of PSQI sleep latency, sleep disorder, sleep efficiency and total score showed significantly differences between responder and non-responder groups. PSQI baseline moderate group showed significant prediction of the early efficacy of SSRIs. CONCLUSION: Abnormal sleep PSG parameters and self-evaluation could be predictors for the adolescent MDD onset and early SSRIs efficacy.
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Inibidores Seletivos de Recaptação de Serotonina , Sono , Humanos , Adolescente , Criança , Adulto Jovem , Adulto , Seguimentos , Sono/fisiologia , Antidepressivos , PolissonografiaRESUMO
Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the underlying molecular mechanism that controls alternative mRNA expression during germ cell development remains elusive. Herein, we show that hnRNPH1 is highly expressed in the reproductive system and recruits the PTBP2 and SRSF3 to modulate the alternative splicing in germ cells. Conditional knockout Hnrnph1 in spermatogenic cells causes many abnormal splicing events, thus affecting the genes related to meiosis and communication between germ cells and Sertoli cells. This is characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, which ultimately leads to male sterility. Markedly, Hnrnph1 germline-specific mutant female mice are also infertile, and Hnrnph1-deficient oocytes exhibit a similar defective synapsis and cell-cell junction as seen in Hnrnph1-deficient male germ cells. Collectively, our data support a molecular model wherein hnRNPH1 governs a network of alternative splicing events in germ cells via recruitment of PTBP2 and SRSF3.