BCL6B-dependent suppression of ETV2 hampers endothelial cell differentiation.

BACKGROUND: B-cell CLL/lymphoma 6 member B (BCL6B) operates as a sequence-specific transcriptional repressor within the nucleus, playing crucial roles in various biological functions, including tumor suppression, immune response, stem cell self-renew, and vascular angiogenesis. However, whether BCL6B is involved in endothelial cell (EC) development has remained largely unknown. ETS variant transcription factor 2 (ETV2) is well known to facilitate EC differentiation. This study aims to determine the important role of BCL6B in EC differentiation and its potential mechanisms. METHODS: Doxycycline-inducible human induced pluripotent stem cell (hiPSC) lines with BCL6B overexpression or BCL6B knockdown were established and subjected to differentiate into ECs and vessel organoids (VOs). RNA sequencing analysis was performed to identify potential signal pathways regulated by BCL6B during EC differentiation from hiPSCs. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pluripotency and vascular-specific marker genes expression. EC differentiation efficiency was determined by Flow cytometry analysis. The performance of EC was evaluated by in vitro Tube formation assay. The protein expression and the vessel-like structures were assessed using immunofluorescence analysis or western blot. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP)-PCR analysis were used to determine the regulatory relationship between BCL6B and ETV2. RESULTS: Functional ECs and VOs were successfully generated from hiPSCs. Notably, overexpression of BCL6B suppressed while knockdown of BCL6B improved EC differentiation from hiPSCs. Additionally, the overexpression of BCL6B attenuated the capacity of derived hiPSC-ECs to form a tubular structure. Furthermore, compared to the control VOs, BCL6B overexpression repressed the growth of VOs, whereas BCL6B knockdown had little effect on the size of VOs. RNA sequencing analysis confirmed that our differentiation protocol induced landscape changes for cell/tissue/system developmental process, particularly vascular development and tube morphogenesis, which were significantly modulated by BCL6B. Subsequent experiments confirmed the inhibitory effect of BCL6B is facilitated by the binding of BCL6B to the promoter region of ETV2, led to the suppression of ETV2's transcriptional activity. Importantly, the inhibitory effect of BCL6B overexpression on EC differentiation from hiPSCs could be rescued by ETV2 overexpression. CONCLUSIONS: BCL6B inhibits EC differentiation and hinders VO development by repressing the transcriptional activity of ETV2.

Disruption of relapse to cocaine and morphine seeking by LiCl-induced aversive counterconditioning following memory retrieval.

Substance use disorder is conceptualized as a form of maladaptive learning, whereby drug-associated memories, elicited by the presence of stimuli related to drug contexts or cues, contribute to the persistent recurrence of craving and the reinstatement of drug-seeking behavior. Hence, use of pharmacology or non-pharmacology way to disrupt drug-related memory holds promise to prevent relapse. Several studies have shown that memories can be unstable and susceptible to modification during the retrieval reactivation phase, termed the "reconsolidation time window". In this study, we use the classical conditioned place preference (CPP) model to investigate the role of aversive counterconditioning on drug-related memories during reconsolidation. Specifically, we uncovered that reconditioning drug cues through counterconditioning with LiCl-induced aversive outcomes following drug memory retrieval reduces subsequent drug-seeking behavior. Notably, the recall of cocaine- or morphine-CPP was eliminated when LiCl-induced aversive counterconditioning was performed 10 min, but not 6 h (outside the reconsolidation time window) after cocaine or morphine memory retrieval. In addition, the effect of LiCl-induced aversive counterconditioning could last for about 14 days. These results suggest that aversive counterconditioning during the reconsolidation of cocaine or morphine memory can prevent the re-seeking of cocaine or morphine, presumably by updating or replacing cocaine or morphine memories with aversive information.

The first specific probe for pyrrolidine with multifunction by the interaction mechanism of atomic economic reaction.

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

Investigation of zero-phonon line characteristics in ensemble nitrogen-vacancy centers at 1.6†K-300†K.

The ensemble of nitrogen-vacancy (NV) centers is widely used in quantum information transmission, high-precision magnetic field, and temperature sensing due to their advantages of long-lived state and the ability to be pumped by optical cycling. In this study, we investigate the zero-phonon line behavior of the two charge states of NV centers by measuring the photoluminescence of the NV center at 1.6 K-300 K. The results demonstrate a positional redshift, an increase in line width, and a decrease in fluorescence intensity for the ZPL of NV0 and NV- as the temperature increased. In the range of 10 K to 140 K, the peak shift with high concentrations of NV- revealed an anomaly of bandgap reforming. The peak position undergoes a blueshift and then a redshift as temperature increases. Furthermore, the transformation between NV0 and NV- with temperature changes has been obtained in diamonds with different nitrogen concentrations. This study explored the ZPL characteristics of NV centers in various temperatures, and the findings are significant for the development of high-resolution temperature sensing and high-precision magnetic field sensing in ensemble NV centers.

7D High-Dynamic Spin-Multiplexing.

Multiplexing technology creates several orthogonal data channels and dimensions for high-density information encoding and is irreplaceable in large-capacity information storage, and communication, etc. The multiplexing dimensions are constructed by light attributes and spatial dimensions. However, limited by the degree of freedom of interaction between light and material structure parameters, the multiplexing dimension exploitation method is still confused. Herein, a 7D Spin-multiplexing technique is proposed. Spin structures with four independent attributes (color center type, spin axis, spatial distribution, and dipole direction) are constructed as coding basic units. Based on the four independent spin physical effects, the corresponding photoluminescence wavelength, magnetic field, microwave, and polarization are created into four orthogonal multiplexing dimensions. Combined with the 3D of space, a 7D multiplexing method is established, which possesses the highest dimension number compared with 6 dimensions in the previous study. The basic spin unit is prepared by a self-developed laser-induced manufacturing process. The free state information of spin is read out by four physical quantities. Based on the multiple dimensions, the information is highly dynamically multiplexed to enhance information storage efficiency. Moreover, the high-dynamic in situ image encryption/marking is demonstrated. It implies a new paradigm for ultra-high-capacity storage and real-time encryption.

Platelike carbon-encapsulated nickel nanocrystals for efficient electrooxidation of 5-hydroxymethylfurfural.

Platelike carbon-encapsulated nickel nanocrystals (Ni@C) were engineered as a high-performance electrocatalyst for the conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). This electrocatalyst demonstrated remarkable electrocatalytic performance in oxidizing HMF at a low potential, achieving 100% HMF conversion, 97.7% FDCA yield, and 97.4% Faraday efficiency (FE).

Imaging electromagnetic boundary of microdevice using a wide field quantum microscope.

Imaging of electronic device surface or sub-surface electromagnetic fields under operating conditions is important for device design and diagnosis. In this study, we proposed a method to characterize specific magnetic field properties of electromagnetic devices at micron-scale using a solid-state quantum sensor, namely diamond nitrogen-vacancy (NV) centers. By employing a wide-field magnetic field measurement technique based on NV centers, we rapidly obtain the first-order magnetic field distribution of anomalous regions. Furthermore, we approximate the second-order magnetic field (magnetic gradient tensor) using the differential gradient method. To visualize the electromagnetic anomalous regions boundary, we utilize the tensor invariants of the magnetic gradient tensor components, along with their nonlinear combinations. The identification error rate of the anomalous regions is within 12.5%. Additionally, the electromagnetic field of anomalous regions is simulated showing the measurement accuracy. Our study shows that the experimental results are very similar to the theoretical simulation of the electromagnetic field (error: 7%). This work is essential for advancing electromagnetic field characterization of electronic devices and the advancement of quantum magnetic sensor applications.

Measurements of Spatial Angles Using Diamond Nitrogen-Vacancy Center Optical Detection Magnetic Resonance.

This article introduces a spatial angle measuring device based on ensemble diamond nitrogen-vacancy (NV) center optical detection magnetic resonance (ODMR). This device realizes solid-state all-optical wide-field vector magnetic field measurements for solving the angles of magnetic components in space. The system uses diamond NV center magnetic microscope imaging to obtain magnetic vector distribution and calculates the spatial angles of magnetic components based on the magnetic vector distribution. Utilizing magnetism for angle measuring enables non-contact measuring, reduces the impact on the object being measured, and ensures measurement precision and accuracy. Finally, the accuracy of the system is verified by comparing the measurement results with the set values of the angle displacement platform. The results show that the measurement error of the yaw angle of the system is 1°, and the pitch angle and roll angle are 1.5°. The experimental results are in good agreement with the expected results.

Rutin targets AKT to inhibit ferroptosis in ventilator-induced lung injury.

Our previous research confirmed that rutin reduced ventilator-induced lung injury (VILI) in mice. Ferroptosis has been reported to participate in the pathogenic process of VILI. We will explore whether rutin inhibits ferroptosis to alleviate VILI. A mouse model of VILI was constructed with or without rutin pretreatment to perform a multiomics analysis. Hematoxylin-eosin (HE) staining and transmission electron microscopy were used to evaluate lung injury in VILI mice. Dihydroethidium (DHE) staining and the malondialdehyde (MDA) and superoxide dismutase (SOD) levels were detected. Molecular docking was performed to determine the binding affinity between rutin and ferroptosis-related proteins. Western blot analysis, real-time PCR (RT-PCR) and immunohistochemical (IHC) staining were conducted to detect the expression levels of GPX4, XCT, ACSL4, FTH1, AKT and p-AKT in lung tissues. Microscale thermophoresis (MST) was used to evaluate the binding between rutin and AKT1. Transcriptomic and proteomic analyses showed that ferroptosis may play a key role in VILI mice. Metabolomic analysis demonstrated that rutin may affect ferroptosis via the AKT pathway. Molecular docking analysis indicated that rutin may regulate the expression of ferroptosis-related proteins. Moreover, rutin upregulated GPX4 expression and downregulated the expression of XCT, ACSL4 and FTH1 in the lung tissues. Rutin also increased the ratio of p-AKT/AKT and p-AKT expression. MST analysis showed that rutin binds to AKT1. Rutin binds to AKT to activate the AKT signaling pathway, contributing to inhibit ferroptosis, thus preventing VILI in mice. Our study elucidated a possible novel strategy of involving the use of rutin for preventing VILI.

Low-frequency electroacupuncture exerts antinociceptive effects through activation of POMC neural circuit induced endorphinergic input to the periaqueductal gray from the arcuate nucleus.

It has been widely recognized that electroacupuncture (EA) inducing the release of ß-endorphin represents a crucial mechanism of EA analgesia. The arcuate nucleus (ARC) in the hypothalamus is a vital component of the endogenous opioid peptide system. Serving as an integration center, the periaqueductal gray (PAG) receives neural fiber projections from the frontal cortex, insular cortex, and ARC. However, the specific mechanisms how EA facilitates the release of ß-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and in vitro experiments by transcriptomics, microdialysis, photogenetics, chemical genetics, and calcium imaging, combined with transgenic animals. Firstly, we detected 2 Hz EA at the Zusanli (ST36) increased the level of ß-endorphin and transcriptional level of proopiomelanocortin (POMC). Our transcriptomics profiling demonstrated that 2 Hz EA at the ST36 modulates the expression of c-Fos and Jun B in ARC brain nuclear cluster, and the transcriptional regulation of 2 Hz EA mainly occur in POMC neurons by Immunofluorescence staining verification. Meaning while, 2 Hz EA specifically activated the cAMP-PKA-CREB signaling pathway in ARC which mediating the c-Fos and Jun B transcription, and 2 Hz EA analgesia is dependent on the activation of cAMP-PKA-CREB signaling pathway in ARC. In order to investigate how the ß-endorphin produced in ARC transfer to integration center PAG, transneuronal tracing technology was used to observe the 2 Hz EA promoted the neural projection from ARC to PAG compared to 100 Hz EA and sham mice. Inhibited PAGGABA neurons, the transfer of ß-endorphin from the ARC nucleus to the PAG nucleus through the ARCPOMC-PAGGABA neural circuit. Furthermore, by manipulating the excitability of POMC neurons from ARCPOMC to PAGGABA using inhibitory chemogenetics and optogenetics, we found that this inhibition significantly reduced transfer of ß-endorphin from the ARC nucleus to the PAG nucleus and the effectiveness of 2 Hz EA analgesia in neurological POMC cyclization recombination enzyme (Cre) mice and C57BL/6J mice, which indicates that the transfer of ß-endorphin depends on the activation of POMC neurons prefect from ARCPOMC to PAGGABA. These findings contribute to our understanding of the neural circuitry underlying the EA pain-relieving effects and maybe provide valuable insights for optimizing EA stimulation parameters in clinical pain treatment using the in vivo dynamic visual investigating the central analgesic mechanism.

Construction and interpretation of high-order image information based on NV optical magnetic vector detection.

Tensor imaging can provide more comprehensive information about spatial physical properties, but it is a high-dimensional physical quantity that is difficult to observe directly. This paper proposes a fast-transform magnetic tensor imaging method based on the NV magnetic detection technique. The Euler deconvolution interprets the magnetic tensor data to obtain the target three-dimensional (3D) boundary information. Fast magnetic vector imaging was performed using optical detection of magnetic resonance (ODMR) to verify the method's feasibility. The complete tensor data was obtained based on the transformation of the vector magnetic imaging data, which was subsequently solved, and the contour information of the objective was restored. In addition, a fast magnetic moment judgment model and an angular transformation model of the observation space are developed in this paper to reduce the influence of the magnetic moment direction on the results and to help interpret the magnetic tensor data. Finally, the experiment realizes the localization, judgment of magnetic moment direction, and 3D boundary identification of a micron-sized tiny magnet with a spatial resolution of 10 µm, a model accuracy of 90.1%, and a magnetic moment direction error of 4.2°.

High precision microwave measurement based on nitrogen-vacancy color center and application in velocity detection.

Wide-range high-precision velocity detection with nitrogen-vacancy (NV) color center has been realized. By treating the NV color center as a mixer, the high-precision microwave measurement is realized. Through optimization of acquisition time, the microwave frequency resolution is improved to the mHz level. Combined with the frequency-velocity conversion model, velocity detection is realized in the range of 0-100 cm/s, and the velocity resolution is up to 0.012 cm/s. The maximum deviation in repeated measurements does not exceed 1/1000. Finally, combined with the multiplexed microwave reference technique, the range of velocity can be extended to 7.4 × 105 m/s. All of the results provide reference for high-precision velocity detection and play a significant role in various domains of quantum precision measurement. This study provides a crucial technical foundation for the development of high-dynamic-range velocity detectors and novel quantum precision velocity measurement technologies.

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders.

The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.

CuO-Ni(OH)2 heterostructure nanosheets: a high-performance electrocatalyst for 5-hydroxymethylfurfural oxidation.

CuO-Ni(OH)2 heterostructure nanosheets were designed for efficient electrocatalytic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furanedioic acid (FDCA). The CuO-Ni(OH)2 nanosheets exhibited impressive performance, achieving 100% HMF conversion, 99.8% FDCA yield, and 98.4% faradaic efficiency.

Simultaneous detection of multi-channel signals in MHz bandwidth using nitrogen-vacancy centers in a diamond.

In this paper, we propose a method for simultaneously recovering multiple radio wave signals based on nitrogen-vacancy (NV) centers in diamond combining optically detected magnetic resonance (ODMR) spectrum. A controlled magnetic field gradient applied to the laser excitation area on the surface of diamond widens the detectable ODMR bandwidth to 200 MHz. Three different frequency-modulated (FM) signals with distinct carrier frequencies falling within the resonance frequency range are received and demodulated in real-time. Subsequently, the FM signal reception capability of this system is further investigated by measuring baseband signal frequencies ranging from 0.1 Hz to 200 Hz and adjusting the carrier power within a dynamic range from -10 dBm to 30 dBm. This proposal, which accomplishes multi-channel demodulation using a compact and single device, has potential applications in fields such as wireless communication, radar and navigation.

CIAP1/2 can regulate the inflammatory response and lung injury induced by apoptosis in septic rats.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), induced by sepsis, is predominantly caused by inflammation injury. However, there is no clear consensus on how to regulate the inflammatory response. The TNF pathway is one of the primary inflammatory pathways activated in sepsis. cIAP1/2, an essential E3 ubiquitin ligase in the TNF pathway, plays a pivotal role in positively regulating the activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways to promote inflammation while inhibiting apoptosis. We found that Birc2 is the only differential expression gene in TNF pathway, and both cIAP1/2 upregulated in lung lysate with worsen lung injury. However, upon inhibiting cIAP1/2 using AZD5582, lung cell apoptosis was reactivated, and a significant improvement in lung injury was observed. Our study shows that cIAP1/2 expression increased in the lung tissue of a CLP rat ALI model. Inhibiting cIAP1/2 with AZD5582, a second mitochondria-derived activator of caspases (SMAC) mimetic, induced increased apoptosis and reduced lung injury. Therefore, inhibiting cIAP1/2 can alleviate sepsis-induced ALI, providing a new target for regulating organ damage induced by sepsis-induced inflammatory responses.

Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo.

Introduction: The body's ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects. Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated. Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg-1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg-1·d-1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain C max of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism. Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine's bioavailability and its resulting pharmacology.

Noise Suppression of Nitrogen-Vacancy Magnetometer in Lock-In Detection Method by Using Common Mode Rejection.

Nitrogen-vacancy (NV) centers in diamonds are promising solid-state magnetic sensors with potential applications in power systems, geomagnetic navigation, and diamond NV color center current transformers, in which both high bandwidth and high magnetic field resolution are required. The wide bandwidth requirement often necessitates high laser power, but this induces significant laser fluctuation noise that affects the detection magnetic field resolution severely. Therefore, enhancement of the magnetic field resolution of wide-bandwidth NV center magnetic sensors is highly important because of the reciprocal effects of the bandwidth and magnetic field resolution. In this article, we develop a common mode rejection (CMR) model to eliminate the laser noise effectively. The simulation results show that the noise level of the light-detected magnetic resonance signal is significantly reduced by a factor of 6.2 after applying the CMR technique. After optimization of the laser power and modulation frequency parameters, the optimal system bandwidth was found to be 75 Hz. Simultaneously, the system's detection magnetic field resolution was enhanced significantly, increasing from 4.49 nT/Hz1/2 to 790.8 pT/Hz1/2, which represents an improvement of nearly 5.7 times. This wide-bandwidth, high-magnetic field resolution NV color center magnetic sensor will have applications including power systems, geomagnetic navigation, and diamond NV color center current transformers.