ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer.

Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR (AR-FL) targets. Consequently, AR-V7 not only recapitulates AR-FL's partial functions but also regulates an additional gene expression program uniquely via binding to gene promoters rather than ARE enhancers. AR-V7 binding and AR-V7-mediated activation at these unique targets do not require FOXA1 but rely on ZFX and BRD4. Knockdown of ZFX or select unique targets of AR-V7/ZFX, or BRD4 inhibition, suppresses growth of castration-resistant prostate cancer cells. We also define an AR-V7 direct target gene signature that correlates with AR-V7 expression in primary tumors, differentiates metastatic prostate cancer from normal, and predicts poor prognosis. Thus, AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance, providing information to guide effective therapeutic strategies.

Structural insight into the subclass B1 metallo-ß-lactamase AFM-1.

The emergence of drug-resistant bacteria, facilitated by metallo-beta-lactamases (MBLs), presents a significant obstacle to the effective use of antibiotics in the management of clinical drug-resistant bacterial infections. AFM-1 is a MBL derived from Alcaligenes faecalis and shares 86% homology with the NDM-1 family. Both AFM-1 and NDM-1 demonstrate the ability to hydrolyze ampicillin and other ß-lactam antibiotics, however, their substrate affinities vary, and the specific reason for this variation remains unknown. We present the high-resolution structure of AFM-1. The active center of AFM-1 binds two zinc ions, and the conformation of the key amino acid residues in the active center is in accordance with that of NDM-1. However, the substrate-binding pocket of AFM-1 is considerably smaller than that of NDM-1. Additionally, the mutation of amino acid residues in the Loop3 region, as compared to NDM-1, results in the formation of a dense hydrophobic patch comprised of hydrophobic amino acid residues in this area, which facilitates substrate binding. Our findings lay the foundation for understanding the molecular mechanism of AFM-1 with a high affinity for substrates and provide a novel theoretical foundation for addressing the issue of drug resistance caused by B1 MBLs.

Blocking Metal Nanocluster Growth through Ligand Coordination and Subsequent Polymerization: The Case of Ruthenium Nanoclusters as Robust Hydrogen Evolution Electrocatalysts.

Metal nanoclusters providing maximized atomic surface exposure offer outstanding hydrogen evolution activities but their stability is compromised as they are prone to grow and agglomerate. Herein, a possibility of blocking metal ion diffusion at the core of cluster growth and aggregation to produce highly active Ru nanoclusters supported on an N, S co-doped carbon matrix (Ru/NSC) is demonstrated. To stabilize the nanocluster dispersion, Ru species are initially coordinated through multiple Ru─N bonds with N-rich 4'-(4-aminophenyl)-2,2:6',2''-terpyridine (TPY-NH2) ligands that are subsequently polymerized using a Schiff base. After the pyrolysis of the hybrid composite, highly dispersed ultrafine Ru nanoclusters with an average size of 1.55 nm are obtained. The optimized Ru/NSC displays minimal overpotentials and high turnover frequencies, as well as robust durability both in alkaline and acidic electrolytes. Besides, outstanding mass activities of 3.85 A mg-1 Ru at 50 mV, i.e., 16 fold higher than 20 wt.% Pt/C are reached. Density functional theory calculations rationalize the outstanding performance by revealing that the low d-band center of Ru/NSC allows the desorption of *H intermediates, thereby enhancing the alkaline HER activity. Overall, this work provides a feasible approach to engineering cost-effective and robust electrocatalysts based on carbon-supported transition metal nanoclusters for future energy technologies.

Clade 2.3.4.4 H5 chimeric cold-adapted attenuated influenza vaccines induced cross-reactive protection in mice and ferrets.

IMPORTANCE: Clade 2.3.4.4 H5Nx avian influenza viruses (AIVs) have circulated globally and caused substantial economic loss. Increasing numbers of humans have been infected with Clade 2.3.4.4 H5N6 AIVs in recent years. Only a few human influenza vaccines have been licensed to date. However, the licensed live attenuated influenza virus vaccine exhibited the potential of being recombinant with the wild-type influenza A virus (IAV). Therefore, we developed a chimeric cold-adapted attenuated influenza vaccine based on the Clade 2.3.4.4 H5 AIVs. These H5 vaccines demonstrate the advantage of being non-recombinant with circulated IAVs in the future influenza vaccine study. The findings of our current study reveal that these H5 vaccines can induce cross-reactive protective efficacy in mice and ferrets. Our H5 vaccines may provide a novel option for developing human-infected Clade 2.3.4.4 H5 AIV vaccines.

N6-methyladenosine methyltransferase METTL3 modulates the cell cycle of granulosa cells via CCND1 and AURKB in Haimen goats.

N6-methyladenosine (m6A) plays a crucial role in many bioprocesses across species, but its function in granulosa cells during oocyte maturation is not well understood in animals, especially domestic animals. We observed an increase in m6A methyltransferase-like 3 (METTL3) in granulosa cells during oocyte maturation in Haimen goats. Our results showed that knockdown of METTL3 disrupted the cell cycle in goat granulosa cells, leading to aggravated cell apoptosis and inhibition of cell proliferation and hormone secretion. Mechanistically, METTL3 may regulate the cell cycle in goat granulosa cells by mediating Aurora kinase B (AURKB) mRNA degradation in an m6A-YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) manner and participating in AURKB transcription via the Cyclin D1 (CCND1)-Retinoblastoma protein (RB)-E2F transcription factor 1 (E2F1) pathway. Overall, our study highlights the essential role of METTL3 in granulosa cells during oocyte maturation in Haimen goats. These findings provide a theoretical basis and technical means for understanding how RNA methylation participates in oocyte maturation through granulosa cells.

chi-miR-130b-3p regulates the ZEA-induced oxidative stress damage through the KEAP1/NRF2 signaling pathway by targeting SESN2 in goat GCs.

As a dominant mycotoxin, zearalenone (ZEA) has attracted extensive attention due to its estrogen-like effect and oxidative stress damage in cells. In order to find a way to relieve cell oxidative stress damage caused by ZEA, we treated goat granulosa cells (GCs) with ZEA and did a whole transcriptome sequencing. The results showed that the expression level of Sesterin2 (SESN2) was promoted extremely significantly in the ZEA group (p < .01). In addition, our research demonstrated that SESN2 could regulate oxidative stress level in GCs through Recombinant Kelch Like ECH Associated Protein 1 (KEAP1)/Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. The overexpression of SESN2 could reduce the oxidative damage, whereas knockdown of SESN2 would aggravate the oxidative damage caused by ZEA. What's more, microRNA (miRNA) chi-miR-130b-3p can bind to SESN2 3'-untranslated region (3'UTR) to regulate the expression of SESN2. The mimics/inhibition of chi-miR-130b-3p would have an effect on oxidative damage triggered by ZEA in GCs as well. In summary, these results elucidate a new pathway by which chi-miR-130b-3p affects the KEAP1/NRF2 pathway in GCs by modulating SESN2 expression in response to ZEA-induced oxidative stress damage.

Exploration of quality variation and stability of hybrid rice under multi-environments.

Improving quality is an essential goal of rice breeding and production. However, rice quality is not solely determined by genotype, but is also influenced by the environment. Phenotype plasticity refers to the ability of a given genotype to produce different phenotypes under different environmental conditions, which can be a representation of the stability of traits. Seven quality traits of 141 hybrid combinations, deriving from the test-crossing of 7 thermosensitive genic male sterile (TGMS) and 25 restorer lines, were evaluated at 5 trial sites with intermittent sowing of three to five in Southern China. In the Yangtze River Basin, it was observed that delaying the sowing time of hybrid rice combinations leads to an improvement in their overall quality. Twelve parents were identified to have lower plasticity general combing ability (GCA) values with increased ability to produce hybrids with a more stable quality. The parents with superior quality tend to exhibit lower GCA values for plasticity. The genome-wide association study (GWAS) identified 13 and 15 quantitative trait loci (QTLs) associated with phenotype plasticity and BLUP measurement, respectively. Notably, seven QTLs simultaneously affected both phenotype plasticity and BLUP measurement. Two cloned rice quality genes, ALK and GL7, may be involved in controlling the plasticity of quality traits in hybrid rice. The direction of the genetic effect of the QTL6 (ALK) on alkali spreading value (ASV) plasticity varies in different cropping environments. This study provides novel insights into the dynamic genetic basis of quality traits in response to different cropping regions, cultivation practices, and changing climates. These findings establish a foundation for precise breeding and production of stable and high-quality rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01442-3.

Drug-disease association prediction using semantic graph and function similarity representation learning over heterogeneous information networks.

Discovering new indications for existing drugs is a promising development strategy at various stages of drug research and development. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering available higher-order connectivity patterns in heterogeneous biological information networks, which are believed to be useful for improving the accuracy of new drug discovering. To this end, we propose a computational-based model, called SFRLDDA, for drug-disease association prediction by using semantic graph and function similarity representation learning. Specifically, SFRLDDA first integrates a heterogeneous information network (HIN) by drug-disease, drug-protein, protein-disease associations, and their biological knowledge. Second, different representation learning strategies are applied to obtain the feature representations of drugs and diseases from different perspectives over semantic graph and function similarity graphs constructed, respectively. At last, a Random Forest classifier is incorporated by SFRLDDA to discover potential drug-disease associations (DDAs). Experimental results demonstrate that SFRLDDA yields a best performance when compared with other state-of-the-art models on three benchmark datasets. Moreover, case studies also indicate that the simultaneous consideration of semantic graph and function similarity of drugs and diseases in the HIN allows SFRLDDA to precisely predict DDAs in a more comprehensive manner.

Biocaiv: an integrative webserver for motif-based clustering analysis and interactive visualization of biological networks.

BACKGROUND: As an important task in bioinformatics, clustering analysis plays a critical role in understanding the functional mechanisms of many complex biological systems, which can be modeled as biological networks. The purpose of clustering analysis in biological networks is to identify functional modules of interest, but there is a lack of online clustering tools that visualize biological networks and provide in-depth biological analysis for discovered clusters. RESULTS: Here we present BioCAIV, a novel webserver dedicated to maximize its accessibility and applicability on the clustering analysis of biological networks. This, together with its user-friendly interface, assists biological researchers to perform an accurate clustering analysis for biological networks and identify functionally significant modules for further assessment. CONCLUSIONS: BioCAIV is an efficient clustering analysis webserver designed for a variety of biological networks. BioCAIV is freely available without registration requirements at http://bioinformatics.tianshanzw.cn:8888/BioCAIV/ .

Dynamic changes in intestinal microbiota and metabolite composition of pre-weaned beef calves.

Gut microbes and their metabolites are essential for maintaining host health and production. The intestinal microflora of pre-weaned calves gradually tends to mature with growth and development and has high plasticity, but few studies have explored the dynamic changes of intestinal microbiota and metabolites in pre-weaned beef calves. In this study, we tracked the dynamics of faecal microbiota in 13 new-born calves by 16S rRNA gene sequencing and analysed changes in faecal amino acid levels using metabolomics. Calves were divided into the relatively high average daily gain group (HA) and the relatively low average daily gain group (LA) for comparison. The results demonstrated that the alpha diversity of the faecal microbiota increased with calf growth and development. The abundance of Porphyromonadaceae bacterium DJF B175 increased in the HA group, while that of Lactobacillus reuteri decreased. The results of the LEfSe analysis showed that the microbiota of faeces of HA calves at eight weeks of age was enriched with P. bacterium DJF B175, while Escherichia coli and L. reuteri were enriched in the microbiota of faeces of LA calves. Besides, the total amino acid concentration decreased significantly in the eighth week compared with that in the first week (P < 0.05). Overall, even under the same management conditions, microorganisms and their metabolites interact to play different dynamic regulatory roles. Our results provide new insights into changes in the gut microbiota and metabolites of pre-weaned calves.

PGC-1α Affects Epileptic Seizures by Regulating Mitochondrial Fusion in Epileptic Rats.

BACKGROUND: Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), regulated by AMPK, is an important regulator of mitochondrial fusion. At present, whether the AMPK/PGC-1α signaling pathway regulates mitochondrial dynamics in epileptic rats is still unknown. METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into fourgroups: the control group (0.9% saline, n = 5), the EP groups (lithium-pilocarpine was used to induce epilepsy, and tissues were harvested at 6 and 24 h, every time point, n = 5), the EP + Compound C group (the specific inhibitor of PGC-1α, 15 mg/kg in 2% DMSO, n = 5), and the EP + DMSO group (0.9% saline + 2% DMSO, n = 5). To investigate whether PGC-1α participates in seizures by regulating the expression of mitofusin1/2(MFN1/2)in rats. RESULTS: In this study, the behavioral results indicate that the seizure susceptibility of the rats to epilepsy was increased when the expression of PGC-1α was inhibited. Subsequently, Western blot results suggested that the expression level of both MFN1 and MFN2 in the hippocampus was higher at 6 and 24 h after an epileptic seizure. Besides, the expression of PGC-1α and MFN2 was significantly decreased in the hippocampus when the epileptic rats were treated with Compound C. Furthermore, the immunofluorescence analysis of the localization of MFN1/2 and PGC-1α showed that MFN1/2 was mainly expressed in neurons but not astrocytes in the hippocampus and cerebral cortex of rats. Meanwhile, PGC-1α colocalized with the excitatory post-synaptic marker PSD95, suggesting that PGC-1α may regulate the seizure susceptibility of the rats by mediating excitatory post-synaptic signaling. CONCLUSION: The AMPK/PGC-1α signaling pathway may play an important role in the lithium-pilocarpine-induced epileptic rat model by mediating the expression of fusion proteins.

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages.

ABSTRACT: Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 µg·mL -1 Lipopolysaccharide and 50 ng·mL -1 IFN-γ establish M1 polarization and were also pretreated with 400 µM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis-related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1ß , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1ß and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis-associated proteins.

Cognitive behavior therapy for depression in people with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Cognitive behavioral therapy (CBT) is the recommended treatment for depression in patients with epilepsy (PWE). However, there are no studies that calculate the effect size of CBT on depression and quality of life (QoL) in PWE. METHODS: We searched seven electronic databases (PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, Ovid Medline, and PsycINFO). We included 13 studies examining CBT for depression in PWE and calculated its effect size. RESULTS: A total of 13 studies met the criteria. After treatment, CBT improves depression in PWE (g = 0.36, 95%CI: 0.18 to 0.54, I2 = 50%), and the efficacy maintains during follow-up (g = 0.47, 95%CI: 0.04 to 0.89, I2 = 80%). Subgroup analysis has shown that individual CBT (g = 0.47, 95%CI: 0.20 to 0.73, I2 = 0%) had a greater effect size than group CBT (g = 0.30, 95%CI: 0.07 to 0.53, I2 = 62%) in the treatment of depression. Likewise, CBT has a positive effect on the QoL improvement of PWE (g = 0.34, 95%CI: 0.11 to 0.57, I2 = 64%). In controlling seizures, CBT did not differ from the control group (g = -0.06, 95%CI: -0.32 to 0.19, I2 = 0%). CONCLUSIONS: Cognitive behavioral therapy interventions were effective in improving depression and QoL in PWE, but not effective in controlling seizures. The efficacy of CBT interventions targeting seizure control seems to be uncertain.

Increased EEG gamma power under exposure to drug-related cues: a translational index for cue-elicited craving in METH-dependent individuals.

BACKGROUND: This study explored the feasibility of using EEG gamma-band (30-49 Hz) power as an index of cue-elicited craving in METH-dependent individuals. METHODS: Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment. RESULTS: Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time. CONCLUSIONS: These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence.

The Effect of Behavior Couples Therapy on Alcohol and Drug Use Disorder: a Systematic Review and Meta-Analysis.

AIMS: Behavior couples therapy (BCT) is widely considered to be effective in the treatment of substance use disorders. However, the effect size of BCT in different outcome measures, and at different time points requires further study to prove it. METHODS: Systematic searches were performed in various databases. Ultimately, we identified 12 studies, involving 19 randomized controlled trials. We used Hedges' g as the effect size, and all pooled analyses were performed using random-effects models. RESULTS: After treatment, BCT was superior to control conditions (either an active or inactive control group) in frequency of substance use (g = 0.17), substance use consequences (g = -0.28) and relationship satisfaction (g = 0.45). After a 12-month follow-up, BCT remained superior to control conditions in frequency of substance use (g = 0.32), substance use consequences (g = -0.34) and relationship satisfaction (g = 0.31). In addition, BCT was more effective in reducing the frequency of substance use than individual-based treatment (IBT) (g = 0.23). There was no significant relationship between the effect size of BCT and publication year (t = 0.92, P = 0.372), percentage of females (t = -0.02, P = 0.987) or the number of treatment sessions (t = -0.52, P = 0.609). CONCLUSIONS: BCT was superior to the control conditions in all three outcome measures after treatment and at follow-up, and showed a relatively large effect size for relationship satisfaction. Moreover, BCT was superior to IBT in reducing the frequency of substance use.

Catastrophic health expenditure and its inequality in rural China: based on longitudinal data from 2013 to 2018.

BACKGROUND: Catastrophic health expenditure (CHE) is an important indicator of measuring health inequality. Previous studies mainly focused on specific vulnerable populations rather than a wider range of vulnerable areas through panel data. Rural China is often associated with an underdeveloped economy and insufficient health resources. This study aims to update the information on the extent of and trends in the incidence and inequality of CHE among the households of rural China through longitudinal survey data. METHODS: Data were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS): 2013, 2015, and 2018. In total, 2,575 households were included in the analysis. CHE was defined as household health expenditures exceeding 40% of non-food expenditures. Inequality in CHE was measured using the concentration curve and concentration index. The contribution to CHE inequality was decomposed using the concentration index decomposition method. RESULTS: The incidence of CHE was 0.2341 (95% CI: 0.22, 0.25) in 2013, 0.2136 (95% CI: 0.20, 0.23) in 2015, and 0.2897 (95% CI: 0.27, 0.31) in 2018 in rural China. The concentration curve lay above the equality line, and the concentration index was negative: -0.1528 (95% CI: -0.1941, -0.1115) in 2013, -0.1010 (95% CI: -0.1442, -0. 0577) in 2015, and -0.0819 (95% CI: -0.1170, -0.0467) in 2018. Economic status, age, and chronic diseases were the main contributors to inequality in CHE. CONCLUSIONS: The incidence of CHE in rural China displayed an upward trend from 2013 to 2018, although it was not continuous. Furthermore, a strong pro-low-economic inequality in CHE existed in rural China. Mainly economic status, age, and chronic diseases contributed to this pro-low-economic inequality. Health policies to allocate resources and services are needed to satisfy the needs of rural households and provide more accessible and affordable health services. More concern needs to be directed toward households with chronic diseases and older persons to reduce the incidence of CHE and promote health equality.

Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis.

OBJECTIVE: The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research. METHODS: Gene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes. RESULTS: A total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment. CONCLUSION: The potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research.

Multimodal neuroimaging with optically pumped magnetometers: A simultaneous MEG-EEG-fNIRS acquisition system.

Multimodal neuroimaging plays an important role in neuroscience research. Integrated noninvasive neuroimaging modalities, such as magnetoencephalography (MEG), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), allow neural activity and related physiological processes in the brain to be precisely and comprehensively depicted, providing an effective and advanced platform to study brain function. Noncryogenic optically pumped magnetometer (OPM) MEG has high signal power due to its on-scalp sensor layout and enables more flexible configurations than traditional commercial superconducting MEG. Here, we integrate OPM-MEG with EEG and fNIRS to develop a multimodal neuroimaging system that can simultaneously measure brain electrophysiology and hemodynamics. We conducted a series of experiments to demonstrate the feasibility and robustness of our MEG-EEG-fNIRS acquisition system. The complementary neural and physiological signals simultaneously collected by our multimodal imaging system provide opportunities for a wide range of potential applications in neurovascular coupling, wearable neuroimaging, hyperscanning and brain-computer interfaces.

αSMA-Cre-mediated Ogt deletion leads to heart failure and vascular smooth muscle cell dysfunction in mice.

Dilated cardiomyopathy, a type of heart muscle disease defined by the presence of left ventricular dilatation and contractile dysfunction, is an important cause of sudden cardiac death and heart failure. O-GlcNAcylation is an important post-translational modification of proteins by the addition of O-GlcNAc moieties at serine or threonine residues. Several studies have shown that proper control of O-GlcNAcylation is required for maintaining physiological function of heart by using Ogt (O-GlcNAc transferase) cardiomyocyte-specific knockout mouse models. In this study, we generated a new mouse model (αSMA-Ogt KO) in which Ogt was deleted in both cardiomyocytes and smooth muscle cells by crossing Ogt floxed mice with αSMA-Cre mice. αSMA-Cre-mediated Ogt deletion in mice led to severe postnatal lethality; the survived mice were smaller than control mice, had dilated hearts, and showed observable signs of heart failure. Moreover, the αSMA-Ogt KO heart had more apoptotic cells and fibrosis. The arteries of αSMA-Ogt KO mice exhibited significantly reduced expression of contractile genes and a trend towards arterial stiffness. In conclusion, our data emphasize the importance of OGT in maintaining normal heart function and reveal a novel role of OGT in regulating arterial contractility.

Expression pattern of alkB homolog 5 in goat testis and its role in spermatogonial stem cells.

RNA N6-methyladenosine (m6A) is essential for many bioprocesses in many species, but its role in goat testis development remains elusive, especially alkB homolog 5 (ALKBH5), one of the m6A demethylases. To this end, nine healthy Haimen goats of different ages were chosen randomly to provide testes. The results showed that the expression level of ALKBH5 was increased significantly (P < 0.05) in the 9-month group compared with the 0-day and 3-month groups, and ALKBH5 was located in goat spermatocytes with the highest expression level compared with Leydig cells and Sertoli cells. Thus, pcDNA3.1-ALKBH5 was constructed to explore the influences of the ALKBH5 increase in goat spermatogonial stem cells (SSC) in vitro. The results showed that the expression level of ALKBH5 in SSC transfected with pcDNA3.1-ALKBH5 (OE_ALKBH5) was significantly increased (P < 0.001) compared with that in SSC transfected with pcDNA3.1-EGFP (EGFP). With ALKBH5 overexpression in SSC, flow cytometry analysis showed that cells at G1 phase were significantly reduced (P < 0.01), while cells at S phase significantly increased (P < 0.01), and cell apoptosis was inhibited. Accordingly, the mRNA degradation of CCND1, CCNE1, and BCL2 was suppressed with ALKBH5 overexpression in SSC after treatment with actinomycin D. Furthermore, the mRNA levels of pluripotency maintenance- and cell differentiation-associated genes were changed between the two groups. Overall, the results indicated the crucial role of ALKBH5 during Haimen goat testis development. The results of this study provide a theoretical basis and technical means for RNA methylation participating in goat testis development.