hnRNPU is required for spermatogonial stem cell pool establishment in mice.

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.

hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility.

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.

Transcriptome analysis of meiotic and post-meiotic spermatogenic cells reveals the potential hub genes of aging on the decline of male fertility.

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.

Dynamically tunable terahertz quadruple-function absorber based on a hybrid configuration of graphene and vanadium dioxide.

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.

FeS and Fe3O4 Co-modified biochar to build a highly resistant advanced oxidation process system for quinclorac degradation in irrigation water.

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.

Dual-function tunable metasurface for polarization-insensitive electromagnetic induction transparency and dual-band absorption.

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.

Dynamic network characteristics of adolescents with major depressive disorder: Attention network mediates the association between anhedonia and attentional deficit.

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.

Neural association between cognitive function and anhedonia in adolescents with melancholic major depressive disorder: A fNIRS study.

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.

ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis.

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.

Abnormal sleep features in adolescent MDD and its potential in diagnosis and prediction of early efficacy.

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.

Rice husk biochar mediated red phosphorus for photocatalysis and photothermal removal of E. coli.

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.

Prefrontal cortex neural activity predicts reduction of non-suicidal self-injury in adolescents with major depressive disorder: An event related potential study.

Background: Non-suicidal self-injury (NSSI) is common in adolescent MDD, which is also a risk factor for suicide. However, there is few research on biomarkers and predictors about treatment response of NSSI. The purpose of this study was to find the difference of P300 between adolescent MDD with NSSI and healthy controls, and to explore whether the baseline electrophysiological level can predict the change of NSSI after treatment. Methods: We collected 62 first-episode drug-naïve MDD adolescents with NSSI (MDD with NSSI group) and 44 healthy controls (HC group). The demographic data, HAMD score, self-injury frequency and electrophysiological level of NSSI group and HC group were collected. The HAMD score, frequency of NSSI in was also collected after 8 weeks of antidepressant treatment. Results: Compared to HC, the latency of the N2, P3a, and P3b components were significantly prolonged, whereas the amplitude of P3a and P3b were decreased in the MDD with NSSI group (P < 0.001). The frequency of self-injury decreased significantly after treatment (P < 0.001). Regression analysis showed that the amplitudes of P3b had a significant positive predictive effect on the rate of change of NSSI frequency after 8 weeks. Conclusion: P3b at baseline can be used as potential predictor for the reduction of NSSI in adolescent MDD.

BCOFGs loaded with nano-FexSy for the catalytic degradation of QNC: Contribution and mechanism of OFGs for reductive iron regeneration.

Biochar currently served as the support for dispersed metal nanoparticles and cooperated with pyrite to generate more reactive radicals in organic pollution degradation system. But the mechanism of interaction between biochar and pyrite has not been elucidated. In this paper, biochar with oxygen-containing functional groups (OFGs) served as a stable dispersant to prepare nano-FexSy loaded biochar materials (BCOFGs@nano-FexSy). BCOFGs coordinated with nano-FexSy to overcome its drawbacks, boosting QNC removal efficiency from 28.64% to 100%. The XPS and the linear sweep voltammetry (LSV) results revealed higher Fe(II) content and higher electron transfer rate on used BCOFGs@nano-FexSy, further validating that hydroxyl functional groups on biochar surface provided electrons to Fe(III) to achieve efficient Fe(II)/Fe(III) cycling. Based on comparative experiments and studies on the roles of iron, S(II) species and OFGs, we clearly revealed that OFGs on biochar materials surface coordinated with nano-FexSy to catalyze the degradation of QNC. The degradation efficiency of BCOFGs@nano-FexSy for QNC was still as high as 91.39% after five cycles, providing full demonstrations that OFGs and S(II) as the abundant electron donor coordinated with Fe species for QNC catalytic degradation and further enhanced the catalytic performance and stability of nano-FexSy.

UHRF1 interacts with snRNAs and regulates alternative splicing in mouse spermatogonial stem cells.

Life-long male fertility relies on exquisite homeostasis and the development of spermatogonial stem cells (SSCs); however, the underlying molecular genetic and epigenetic regulation in this equilibrium process remains unclear. Here, we document that UHRF1 interacts with snRNAs to regulate pre-mRNA alternative splicing in SSCs and is required for the homeostasis of SSCs in mice. Genetic deficiency of UHRF1 in mouse prospermatogonia results in gradual loss of spermatogonial stem cells, eventually leading to Sertoli-cell-only syndrome (SCOS) and male infertility. Comparative RNA-seq data provide evidence that Uhrf1 ablation dysregulates previously reported SSC maintenance- and differentiation-related genes. We further found that UHRF1 could act as an alternative RNA splicing regulator and interact with Tle3 transcripts to regulate its splicing event in spermatogonia. Collectively, our data reveal a multifunctional role for UHRF1 in regulating gene expression programs and alternative splicing during SSC homeostasis, which may provide clues for treating human male infertility.

hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells.

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.

Visual P300 as a neurophysiological correlate of symptomatic improvement by a virtual reality-based computer AT system in patients with auditory verbal hallucinations: A Pilot study.

Previous comparative trials showed that virtual reality (VR) therapies achieved larger effects than gold-standard cognitive-behavioral therapy (CBT) on overall auditory verbal hallucinations (AVHs). However, no trial has examined the corresponding underlying electrophysiological mechanisms. We performed a pilot randomized comparative trial evaluating the efficacy of a virtual reality-based computer AT system (CATS) over CBT for schizophrenia (SCZ) patients with treatment-resistant AVHs and explored these potential electrophysiological changes via the visual P300 component. Patients (CATS, n = 32; CBT, n = 33) completed the clinical assessments pre- and post-interventions and at 12-week follow-up. The visual P300 were measured before and after both therapies. The analysis of changes in psychiatric symptoms used linear mixed-effects models, and the P300 response in temporal and time-frequency domains was analyzed with repeated-measures analysis of variance. There was no interaction effect between change in clinical symptoms and treatment group. However, several statistically significant within-group improvements were found for CATS and CBT over time. AVH improved significantly after both treatments, as measured with the Psychotic Symptom Rating Scales-Auditory Hallucinations (PSYRATS-AH) sub-scores. Especially for the CATS group, omnipotence beliefs, anxiety symptoms, self-esteem, and quality of life also remained improved at the 12-week follow-up. Moreover, P300 amplitude had a significant interaction effect and correlation with AVH response. Overall, our analysis did not demonstrate general clinical superiority of CATS over CBT, but CATS improved refractory AVH in SCZ patients, likely by increasing P300 amplitude. These findings support the continued development of CATS for persistent AVH and suggest further trials to clarify the neurological effects of CATS.

UHRF1 establishes crosstalk between somatic and germ cells in male reproduction.

Sertoli cells (SCs) support and nourish germ cells (GCs) through their crosstalk during spermatogenesis. However, the underlying epigenetic mechanism that ensures SCs' functions in this process remains unclear. Here, we report that UHRF1, a critical epigenetic regulator, is mainly expressed in human and mouse pre-mature SCs, and is essential for establishing Sertoli-Germ cell crosstalk. SC-specific UHRF1 knockout mice exhibit complete sterility with Sertoli cell (SC) proliferation and differentiation aberrance, blood-testis barrier (BTB) disruption, and immature germ cell (GC) sloughing. RNA sequencing and Whole Genome Bisulfite Sequencing (WGBS) revealed that many extracellular matrix (ECM)-related genes (e.g., Timp1, Trf, and Spp1) appeared upregulated with the DNA hypomethylation status in UHRF1-deficient SCs. Strikingly, overexpression of Timp1, Trf, and Spp1 in SCs in vitro and in vivo could phenocopy the SC-specific UHRF1-deficient mice. Our data demonstrated that UHRF1 regulates the transcriptional program of ECM-related genes in SCs and establishes SC-GC crosstalk.

Mitochondrial regulation during male germ cell development.

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.

Face Recognition Brain Functional Connectivity in Patients With Major Depression: A Brain Source Localization Study by ERP.

Objective: Patients with major depressive disorder (MDD) presents with face recognition defects. These defects negatively affect their social interactions. However, the cause of these defects is not clear. This study sought to explore whether MDD patients develop facial perceptual processing disorders with characteristics of brain functional connectivity (FC). Methods: Event-related potential (ERP) was used to explore differences between 20 MDD patients and 20 healthy participants with face and non-face recognition tasks based on 64 EEG parameters. After pre-processing of EEG data and source reconstruction using the minimum-norm estimate (MNE), data were converted to AAL90 template to obtain a time series of 90 brain regions. EEG power spectra were determined using Fieldtrip incorporating a Fast Fourier transform. FC was determined for all pairs of brain signals for theta band using debiased estimate of weighted phase-lag index (wPLI) in Fieldtrip. To explore group differences in wPLI, independent t-tests were performed with p < 0.05 to indicate statistical significance. False discovery rate (FDR) correction was used to adjust p-values. Results: The findings showed that amplitude induction by face pictures was higher compared with that of non-face pictures both in MDD and healthy control (HC) groups. Face recognition amplitude in MDD group was lower compared with that in the HC group. Two time periods with significant differences were then selected for further analysis. Analysis showed that FC was stronger in the MDD group compared with that in the HC group in most brain regions in both periods. However, only one FC between two brain regions in HC group was stronger compared with that in the MDD group. Conclusion: Dysfunction in brain FC among MDD patients is a relatively complex phenomenon, exhibiting stronger and multiple connectivity with several brain regions of emotions. The findings of the current study indicate that the brain FC of MDD patients is more complex and less efficient in the initial stage of face recognition.