ALKBH5 deficiency attenuates oxygen-glucose deprivation-induced injury in mouse brain microvascular endothelial cells in an m6A dependent manner.

Structural and functional alterations in brain microvascular endothelial cells (BMECs) caused by oxygen-glucose deprivation (OGD) are involved in the pathogenesis of various brain disorders. AlkB homolog 5 (ALKBH5) is a primary m6A demethylase that regulates various cell processes, but its distinct roles in BMEC function remain to be clarified. In the present study, in mouse middle cerebral artery occlusion (MCAO) model, knockout of ALKBH5 reduced neurological deficits, infarct volumes and tissue apoptosis caused by ischemia/reperfusion injury. Evans blue leakage and decreased expression of the tight junction protein ZO-1 and Occludin were also attenuated by ALKBH5 knockout. During the exploration of the underlying mechanisms of the role of ALKBH5 in BMECs, we found that the expression of ALKBH5 was induced at both the mRNA and protein levels by hypoxia; however, its protein stability was impaired by OGD treatment. Knockdown of ALKBH5 expression increased total m6A levels and alleviated OGD-induced BMEC injury. At the same time, the selective ALKBH5 inhibitor Cpd 20m also exhibited a protective effect on cell injury. In contrast, overexpression of ALKBH5 increased the sensitivity of BMECs to OGD. Interestingly, the m6A sequencing data revealed that knockdown of ALKBH5altered the expression of many genes via m6A upregulation. The gene expression alterations were verified by real-time PCR. Taken together, our results suggest that ALKBH5, as well as its target genes, plays important roles in the regulation of brain microvascular endothelial cell function through its RNA demethylase activity.

Enhanced Photocatalytic Degradation of Rhodamine B Dye by Iron-Doped Europium Oxide Nanoparticles.

As a wide-bandgap rare-earth oxide, Eu2O3 was often utilized as an auxiliary material of other photocatalysts because its photocatalytic performance was limited by the luminescence characteristics of Eu3+ and low light utilization. In this study, we improved the photocatalytic degradation performance of the Eu2O3 nanoparticles by doping with Fe cations. The Eu2O3 nanoparticles with different Fe-doping concentrations (1, 3, and 5%, noted as EF1.0, EF3.0, and EF5.0, respectively) were synthesized via chemical precipitation and calcination methods. It was found that doping could reduce Eu2O3's bandgap, which probably originated from the introduction of oxygen vacancies with lower energy levels than the conduction band of Eu2O3. Compared with the undoped Eu2O3 nanoparticles with a removal efficiency of 22% for degrading rhodamine B dye within 60 min, the photocatalytic degradation efficiencies of EF1.0, EF3.0, and EF5.0 were demonstrated to be improved to 42, 48, and 33%, respectively, and EF3.0's performance was the best. The enhanced photocatalytic performance of the doped samples was related to the oxygen vacancies acting as capture centers for electrons, such that the photogenerated electron-hole pairs were efficiently separated and the redox reactions on the surface of the nanoparticles were enhanced accordingly. Additionally, the enhanced light absorption and broadened spectral band further improved EF3.0's degradation efficiency.

Design of a KNN-BZT Ceramic with High Energy Storage Properties and Transmittance under Low Electric Fields.

With the advancement of science and technology, single-function ceramics have been difficult to meet the rapid development of electronic components. It is of great significance to find and develop multifunctional ceramics with excellent performance and environmental friendliness (such as good energy storage and transparency). Especially, the realization of its excellent performance under low electric fields has more reference and practical value. In this study, by Bi(Zn0.5Ti0.5)O3 (BZT) modification in (K0.5Na0.5)NbO3 (KNN), reducing grain size, and increasing band gap energy, the purpose of improving energy storage performance and transparency has been achieved under low electric field. The results show that the submicron average grain size decreased to 0.9 µm and the band gap energy (E g) increased to 2.97 eV for 0.90KNN-0.10BZT ceramics. The transparency is up to 69.27% in the near-infrared region (1344 nm) and the energy storage density is 2.16 J/cm3 under 170 kV/cm. Moreover, the 0.90KNN-0.10BZT ceramic exhibits a power density (P D) of 17.50 MW/cm3 and the stored energy can be discharged in 1.60 µs at 140 kV/cm. This revealed a potential application of KNN-BZT ceramic as an energy storage and transparent capacitor in the electronics industry.

Locus coeruleus input-modulated reactivation of dentate gyrus opioid-withdrawal engrams promotes extinction.

Extinction training during the reconsolidation window following memory recall is an effective behavioral pattern for promoting the extinction of pathological memory. However, promoted extinction by recall-extinction procedure has not been universally replicated in different studies. One potential reason for this may relate to whether initially acquired memory is successfully activated. Thus, the methods for inducing the memory into an active or plastic condition may contribute to promoting its extinction. The aim of this study is to find and demonstrate a manipulatable neural circuit that engages in the memory recall process and where its activation improves the extinction process through recall-extinction procedure. Here, naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice was mainly used as a pathological memory model. We found that the locus coeruleus (LC)-dentate gyrus (DG) circuit was necessary for CPA memory recall and that artificial activation of LC inputs to the DG just prior to initiating a recall-extinction procedure significantly promoted extinction learning. We also found that activating this circuit caused an increase in the ensemble size of DG engram cells activated during the extinction, which was confirmed by a cFos targeted strategy to label cells combined with immunohistochemical and in vivo calcium imaging techniques. Collectively, our data uncover that the recall experience is important for updating the memory during the reconsolidation window; they also suggest a promising neural circuit or target based on the recall-extinction procedure for weakening pathological aversion memory, such as opioid withdrawal memory and fear memory.

Zeolite fly ash-enhanced coagulation treatment of oil recovery wastewater from polymer flooding.

Herein, an enhanced coagulation model is proposed in which zeolite is used as a crystal nucleus to promote flocs. The zeolite is prepared from fly ash by microwave-assisted hydrothermal synthesis. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and specific surface area and pore size analysis (BET) characterization confirmed the successful synthesis of ZFA, and improved the surface properties. Thus, the adsorption capacity of ZFA as crystal nucleus was improved, which enabled it to achieve better results in the process of enhanced coagulation. Compared with those of conventional coagulation, the oil content and SS removal rate of ZFA-enhanced coagulation increased by 85% and 44%, respectively. Compared with that of CFA-enhanced coagulation, the oil removal efficiency increased by 4%, and the SS removal efficiency increased by 9%. The optimal conditions of ZFA-enhanced coagulation were as follows: ZFA dosage of 100 mg/L, pH value of 5-8, ZFA particle size range of 60-75 µm, temperature of 40-50 ℃, and precipitation time of 30 min.

Embryonic opioid exposure impairs inhibitory transmission of striatum in day-old chicks.

Studies of humans, mammalian animals, and chicks reveal that embryonic opioid exposure (EOE) changes the response to pharmacological rewards in postnatal individuals, which may be an outcome of permanent alterations to neural systems. However, the mechanism behind this alteration remains unclear. GABA transmitter has a trophic effect on early GABAergic neuronal development, and EOE decreases GABA concentration in developing brains. Here, we determined whether the development of inhibitory transmission was affected by EOE and whether altered GABA release was the underlying mechanism. We revealed that morphine administration in the early but not the late embryonic period decreased inhibitory transmission in the striatum of chicks. Meanwhile, day-old chicks with early embryonic morphine exposure showed increased psychomotor activity after acute morphine injection compared with saline-exposed chicks. Furthermore, GABA injection in the chick embryo following morphine administration mitigated damage to GABA transmission and recovered the behavioral response to acute morphine injection in chicks. Collectively, our findings suggest that abnormal GABA release in the early embryonic period induced by opioid exposure is attributable to functional and structural developments of the GABA synapse, and that the dysfunction of striatal GABA transmission may be linked to enhanced psychomotor response during initial drug exposure in postnatal life.

The role of hippocampus in memory reactivation: an implication for a therapeutic target against opioid use disorder.

Purpose of the review: The abuse of opioids induces many terrible problems in human health and social stability. For opioid-dependent individuals, withdrawal memory can be reactivated by context, which is then associated with extremely unpleasant physical and emotional feelings during opioid withdrawal. The reactivation of withdrawal memory is considered one of the most important reasons for opioid relapse, and it also allows for memory modulation based on the reconsolidation phenomenon. However, studies exploring withdrawal memory modulation during the reconsolidation window are lacking. By summarizing the previous findings about the reactivation of negative emotional memories, we are going to suggest potential neural regions and systems for modulating opioid withdrawal memory. Recent findings: Here, we first present the role of memory reactivation in its modification, discuss how the hippocampus participates in memory reactivation, and discuss the importance of noradrenergic signaling in the hippocampus for memory reactivation. Then, we review the engagement of other limbic regions receiving noradrenergic signaling in memory reactivation. We suggest that noradrenergic signaling targeting hippocampus neurons might play a potential role in strengthening the disruptive effect of withdrawal memory extinction by facilitating the degree of memory reactivation. Summary: This review will contribute to a better understanding of the mechanisms underlying reactivation-dependent memory malleability and will provide new therapeutic avenues for treating opioid use disorders.

Corticotropin-releasing factor receptor 1 in infralimbic cortex modulates social stress-altered decision-making.

Chronic stress could lead to a bias in behavioral strategies toward habits. However, it remains unclear which neuronal system modulates stress-induced behavioral abnormality during decision making. The corticotropin-releasing factor (CRF) system in the medial prefrontal cortex (mPFC), which has been implicated in governing strategy choice, is involved in the response to stress. The present study aimed to clarify whether altered function in cortical CRF receptors is linked to abnormal behaviors after chronic stress. In results, mice subjected to a 10-day social defeat preferred to use a habitual strategy. The infralimbic cortex (IL), but not the prelimbic cortex (PL) or anterior cingulate cortex (ACC), showed higher cFos expression in stress-subjected mice than in control mice, which may be associated with habitual behavior choice. Furthermore, CRF receptor 1 (CRFR1) agonist and antagonist infusion in IL during behavioral training mimicked and rescued stress-caused behavioral change in the decision-making assessment, respectively. An electrophysiological approach showed that the frequencies of both spontaneous IPSC and spontaneous EPSC, but not their amplitude, increased after stress and were modulated by CRFR1 agents. Further recordings revealed that an increased ratio of excitation to inhibition (E/I ratio) of IL by stress was rescued under conditions with CRFR1 antagonist. Collectively, these data indicate that CRFR1 plays a critical role in stress-permitted or enhanced glutamatergic and GABAergic presynaptic transmission in direct or indirect ways, as well as the modulation for E/I ratio in the IL. Thus, CRFR1 in the mPFC may be a proper target for treating cases of chronic stress-altered behavior.

Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.

Subcortical white matter (WM) stroke accounts for 25% of all strokes and is the second leading cause of dementia. Despite such clinical importance, we still do not have an effective treatment for ischemic WM stroke, and the mechanisms of WM postischemic neuroprotection remain elusive. 3K3A-activated protein C (APC) is a signaling-selective analogue of endogenous blood protease APC that is currently in development as a neuroprotectant for ischemic stroke patients. Here, we show that 3K3A-APC protects WM tracts and oligodendrocytes from ischemic injury in the corpus callosum in middle-aged mice by activating protease-activated receptor 1 (PAR1) and PAR3. We show that PAR1 and PAR3 were also required for 3K3A-APC's suppression of post-WM stroke microglia and astrocyte responses and overall improvement in neuropathologic and functional outcomes. Our data provide new insights into the neuroprotective APC pathway in the WM and illustrate 3K3A-APC's potential for treating WM stroke in humans, possibly including multiple WM strokes that result in vascular dementia.

Endothelial LRP1 protects against neurodegeneration by blocking cyclophilin A.

The low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic and cell signaling transmembrane protein. Endothelial LRP1 clears proteinaceous toxins at the blood-brain barrier (BBB), regulates angiogenesis, and is increasingly reduced in Alzheimer's disease associated with BBB breakdown and neurodegeneration. Whether loss of endothelial LRP1 plays a direct causative role in BBB breakdown and neurodegenerative changes remains elusive. Here, we show that LRP1 inactivation from the mouse endothelium results in progressive BBB breakdown, followed by neuron loss and cognitive deficits, which is reversible by endothelial-specific LRP1 gene therapy. LRP1 endothelial knockout led to a self-autonomous activation of the cyclophilin A-matrix metalloproteinase-9 pathway in the endothelium, causing loss of tight junctions underlying structural BBB impairment. Cyclophilin A inhibition in mice with endothelial-specific LRP1 knockout restored BBB integrity and reversed and prevented neuronal loss and behavioral deficits. Thus, endothelial LRP1 protects against neurodegeneration by inhibiting cyclophilin A, which has implications for the pathophysiology and treatment of neurodegeneration linked to vascular dysfunction.

Effective Strategy to Achieve Excellent Energy Storage Properties in Lead-Free BaTiO3-Based Bulk Ceramics.

Although extensive studies have been done on lead-free dielectric ceramics to achieve excellent dielectric behaviors and good energy storage performance, the major problem of low energy density has not been solved so far. Here, we report on designing the crossover relaxor ferroelectrics (CRFE), a crossover region between the normal ferroelectrics and relaxor ferroelectrics, as a solution to overcome the low energy density. CRFE exhibits smaller free energy and lower defect density in the modified Landau theory, which helps to obtain ultrahigh energy density and efficiency. The (1-x)Ba0.65Sr0.35TiO3-xBi(Mg2/3Nb1/3)O3 ((1-x)BST-xBMN) (x = 0, 0.08, 0.1, 0.18, 0.2) ceramic was synthesized by a solid-state reaction method. The solid solutions exhibit dielectric frequency dispersion, which suggests typical relaxor characteristics with the increasing BMN content. The crossover ferroelectrics of 0.9BST-0.1BMN ceramic possesses a high energy storage efficiency (η) of 85.71%, a high energy storage density (W) of 3.90 J/cm3, and an ultrahigh recoverable energy storage density (Wrec) of 3.34 J/cm3 under a dielectric breakdown strength of 400 kV/cm and is superior to other lead-free BaTiO3 (BT)-based energy storage ceramics. It also exhibits strong thermal stability in the temperature range from 25 to 150 °C under an electric field of 300 kV/cm, with the fluctuations below 3% and with the energy storage density and energy efficiency at about 2.8 J/cm3 and 82.93%, respectively. The enhanced recoverable energy density and breakdown strength of BT-based materials with significantly high energy efficiency make it a promising candidate to meet the wide requirements for high power applications.

Sensitivity analysis of heat dissipation factors in a hot oil pipeline based on orthogonal experiments.

The study of phase-change heat-transfer characteristics of crude oil has been one of the hot issues in the field of gathering and transportation. The process of phase-change heat transfer of crude oil involves many complicated problems such as natural convection treatment, latent heat treatment, phase-change interface determination and fluid characteristic change. A mathematical model based on the additional capacity heat method is proposed in this article, and the momentum equations of crude oil liquid phase are presented for Newtonian and non-Newtonian fluids. The aim of this study was to investigate the influence of different factors on the heat transfer performance during the shutdown process of an overhead pipe. Experiments were conducted to verify the model and the solution method; the experimental and model results showed good agreement with a maximum relative error of 4.57%. The temperature fields and solidification conditions of crude oil in pipelines under different shutdown conditions were determined, and the sensitivity of the main effect factors was determined through an orthogonal experiment. The results show that the order of influence was oil initial temperature >thickness of insulating layer >air temperature >thickness of wax layer. The results of the study have important guiding significance on the control of shutdown time and the determination of restarting schemes.

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.

Pericytes are positioned between brain capillary endothelial cells, astrocytes and neurons. They degenerate in multiple neurological disorders. However, their role in the pathogenesis of these disorders remains debatable. Here we generate an inducible pericyte-specific Cre line and cross pericyte-specific Cre mice with iDTR mice carrying Cre-dependent human diphtheria toxin receptor. After pericyte ablation with diphtheria toxin, mice showed acute blood-brain barrier breakdown, severe loss of blood flow, and a rapid neuron loss that was associated with loss of pericyte-derived pleiotrophin (PTN), a neurotrophic growth factor. Intracerebroventricular PTN infusions prevented neuron loss in pericyte-ablated mice despite persistent circulatory changes. Silencing of pericyte-derived Ptn rendered neurons vulnerable to ischemic and excitotoxic injury. Our data demonstrate a rapid neurodegeneration cascade that links pericyte loss to acute circulatory collapse and loss of PTN neurotrophic support. These findings may have implications for the pathogenesis and treatment of neurological disorders that are associated with pericyte loss and/or neurovascular dysfunction.

Three-Dimensional Architecture Reduced Graphene Oxide-LiFePO4 Composite: Preparation and Excellent Microwave Absorption Performance.

The present work reports preparation of 3D composites of reduced graphene oxide (RGO) with coral-like LiFePO4 particles in two steps, which involves the fabrication of LiFePO4 particles by the solvothermal method and the subsequent preparation of RGO/coral-like LiFePO4 composites by the etching method. The microwave absorption properties of LiFePO4 particles, coral-like LiFePO4 particles, and the RGO/coral-like LiFePO4 composites were studied. Our results show that the as-prepared RGO/coral-like LiFePO4 composites exhibit significantly improved microwave absorption properties compared with the pure LiFePO4 particles and coral-like LiFePO4 particles. The RGO/coral-like LiFePO4 composite (S-60) possesses optimized reflection loss (RL) performance with an RL value of -61.4 dB and a broad effective absorption bandwidth of 4 GHz (from 11.36 to 14.88 GHz and 16.32 to 16.8 GHz) at the matching thickness of only 2.4 mm. This demonstrates that the RGO/coral-like LiFePO4 composites can be superior candidates for lightweight and high-efficiency microwave absorbers.

Medium spiny neurons of the anterior dorsomedial striatum mediate reversal learning in a cell-type-dependent manner.

The striatum has been implicated in the regulation of cognitive flexibility. Abnormalities in the anterior dorsomedial striatum (aDMS) are revealed in many mental disorders in which cognitive inflexibility is commonly observed. However, it remains poorly understood whether the aDMS plays a special role in flexible cognitive control and what the regulation pattern is in different neuronal populations. Based on the reversal learning task in mice, we showed that optogenetic activation in dopamine receptor 1-expressing medium spiny neurons (D1R-MSNs) of the aDMS impaired flexibility; meanwhile, suppressing these neurons facilitated behavioral performance. Conversely, D2R-MSN activation accelerated reversal learning, but it induced no change through neuronal suppression. The acquisition and retention of discrimination learning were unaffected by the manipulation of any type of MSN. Through bi-direct optogenetic modulation in D1R-MSNs of the same subject in a serial reversal learning task, we further revealed the function of D1R-MSNs during different stages of reversal learning, where inhibiting and exciting the same group of neurons reduced perseverative errors and increased regressive errors. Following D1R- and D2R-MSN activation in the aDMS, neuronal activity of the mediodorsal thalamus decreased and increased, respectively, in parallel with behavioral impairment and facilitation, but not as a direct result of the activation of the striatal MSNs. We propose that D1R- and D2R-MSN sub-populations in the aDMS exert opposing functions in cognitive flexibility regulation, with more important and complex roles of D1R-MSNs involved. Mental disorders with cognitive flexibility problems may feature an underlying functional imbalance in the aDMS' two types of neurons.

Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE.

The endosomal trafficking pathways are essential for many cellular activities. They are also important targets by many intracellular pathogens. Key regulators of the endosomal trafficking include the retromer complex and sorting nexins (SNXs). Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport, but the exact mechanism has remained unclear. We present the crystal structure of the PX domain of SNX5 in complex with IncE, showing that IncE binds to a highly conserved hydrophobic groove of SNX5. The unique helical hairpin of SNX5/6 is essential for binding, explaining the specificity of SNX5/6 for IncE. The SNX5/6-IncE interaction is required for cellular localization of IncE and its inhibitory function. Mechanistically, IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains. Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking.

In Situ Electrochemistry of Rechargeable Battery Materials: Status Report and Perspectives.

The development of rechargeable batteries with high performance is considered to be a feasible way to satisfy the increasing needs of electric vehicles and portable devices. It is of vital importance to design electrodes with high electrochemical performance and to understand the nature of the electrode/electrolyte interfaces during battery operation, which allows a direct observation of the complicated chemical and physical processes within the electrodes and electrolyte, and thus provides real-time information for further design and optimization of the battery performance. Here, the recent progress in in situ techniques employed for the investigations of material structural evolutions is described, including characterization using neutrons, X-ray diffraction, and nuclear magnetic resonance. In situ techniques utilized for in-depth uncovering the electrode/electrolyte phase/interface change mechanisms are then highlighted, including transmission electron microscopy, atomic force microscopy, X-ray spectroscopy, and Raman spectroscopy. The real-time monitoring of lithium dendrite growth and in situ detection of gas evolution during charge/discharge processes are also discussed. Finally, the major challenges and opportunities of in situ characterization techniques are outlined toward new developments of rechargeable batteries, including innovation in the design of compatible in situ cells, applications of dynamic analysis, and in situ electrochemistry under multi-stimuli. A clear and in-depth understanding of in situ technique applications and the mechanisms of structural evolutions, surface/interface changes, and gas generations within rechargeable batteries is given here.

Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory.

SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for the synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines. We show that SNX6 functions independently of retromer to regulate distribution of Homer1b/c in the dendritic shaft. We also find that Homer1b/c translocates from shaft to spines by protein diffusion, which does not require SNX6. Ablation of SNX6 causes reduced distribution of Homer1b/c in distal dendrites, decrease in surface levels of AMPAR and impaired AMPAR-mediated synaptic transmission. These findings reveal a physiological role of SNX6 in CNS excitatory neurons.

Amorphous Phosphorus/Nitrogen-Doped Graphene Paper for Ultrastable Sodium-Ion Batteries.

As the most promising anode material for sodium-ion batteries (SIBs), elemental phosphorus (P) has recently gained a lot of interest due to its extraordinary theoretical capacity of 2596 mAh/g. The main drawback of a P anode is its low conductivity and rapid structural degradation caused by the enormous volume expansion (>490%) during cycling. Here, we redesigned the anode structure by using an innovative methodology to fabricate flexible paper made of nitrogen-doped graphene and amorphous phosphorus that effectively tackles this problem. The restructured anode exhibits an ultrastable cyclic performance and excellent rate capability (809 mAh/g at 1500 mA/g). The excellent structural integrity of the novel anode was further visualized during cycling by using in situ experiments inside a high-resolution transmission electron microscope (HRTEM), and the associated sodiation/desodiation mechanism was also thoroughly investigated. Finally, density functional theory (DFT) calculations confirmed that the N-doped graphene not only contributes to an increase in capacity for sodium storage but also is beneficial in regards to improved rate performance of the anode.

Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability.

Self-renewal and differentiation are the hallmarks of embryonic stem cells (ESCs). However, it is largely unknown about how the pluripotency is regulated. Here we demonstrate that Pcid2 is required for the maintenance of self-renewal both in mouse and human ESCs. Pcid2 plays a critical role in suppression of ESC differentiation. Pcid2 deficiency causes early embryonic lethality before the blastocyst stage. Pcid2 associates with EID1 and is present in the CBP/p300-EID1 complex in the ESCs. We show that MDM2 is an E3 ligase for K48-linked EID1 ubiquitination for its degradation. For the maintenance of self-renewal, Pcid2 binds to EID1 to impede the association with MDM2. Then EID1 is not degraded to sustain its stability to block the HAT activity of CBP/p300, leading to suppression of the developmental gene expression. Collectively, Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human ESCs through modulation of EID1 degradation.