Study of the Characteristics of Ba0.6Sr0.4Ti1-xMnxO3-Film Resistance Random Access Memory Devices.

In this study, Ba0.6Sr0.4Ti1-xMnxO3 ceramics were fabricated by a novel ball milling technique followed by spin-coating to produce thin-film resistive memories. Measurements were made using field emission scanning electron microscopes, atomic force microscopes, X-ray diffractometers, and precision power meters to observe, analyze, and calculate surface microstructures, roughness, crystalline phases, half-height widths, and memory characteristics. Firstly, the effect of different sintering methods with different substitution ratios of Mn4+ for Ti4+ was studied. The surface microstructural changes of the films prepared by the one-time sintering method were compared with those of the solid-state reaction method, and the effects of substituting a small amount of Ti4+ with Mn4+ on the physical properties were analyzed. Finally, the optimal parameters obtained in the first part of the experiment were used for the fabrication of the thin-film resistive memory devices. The voltage and current characteristics, continuous operation times, conduction mechanisms, activation energies, and hopping distances of two types of thin-film resistive memory devices, BST and BSTM, were measured and studied under different compliance currents.

Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides.

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of AnVBPO from the brown seaweed Ascophyllum nodosum and CpVBPO from the red seaweed Corallina pilulifera, which produce (R)- and (S)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within AnVBPO and CpVBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO43- on H2O2-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis.

Dynamic changes in the metabolome and microbiome during Citrus depressa Hayata liquid fermentation.

Citri Reticulatae Pericarpium (CRP) is a common traditional Chinese herbal medicine, valued for its multi-bioactivity. However, its processing time, environment, and microorganisms all affect its quality and bioactivity. To address this, the study replaced solid-state fermentation with liquid fermentation using microorganisms and isolated Bacillus amyloliquefaciens, respectively. This aimed to discover a more stable processing method and examine metabolite-micobiota correlations. Non-targeted metabolomics identified 70 differential metabolites, focusing on amino acids, polymethoxyflavones (PMFs), and carbohydrates. Long-read sequencing showed a shift in dominant bacterial genera from Lactobacillus to Pediococcus, then to Clostridium. Spearman analysis revealed a positive correlation between specific Clostridium species and PMFs production. B. amyloliquefaciens fermentation notably increased PMFs content without reducing hesperidin levels, suggesting its potential as an alternative processing method. This study offers valuable insights into metabolome-microbiome interactions for future biotransformation research.

Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice.

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

Real-Time Indoor Visible Light Positioning (VLP) Using Long Short Term Memory Neural Network (LSTM-NN) with Principal Component Analysis (PCA).

New applications such as augmented reality/virtual reality (AR/VR), Internet-of-Things (IOT), autonomous mobile robot (AMR) services, etc., require high reliability and high accuracy real-time positioning and tracking of persons and devices in indoor areas. Among the different visible-light-positioning (VLP) schemes, such as proximity, time-of-arrival (TOA), time-difference-of-arrival (TDOA), angle-of-arrival (AOA), and received-signal-strength (RSS), the RSS scheme is relatively easy to implement. Among these VLP methods, the RSS method is simple and efficient. As the received optical power has an inverse relationship with the distance between the LED transmitter (Tx) and the photodiode (PD) receiver (Rx), position information can be estimated by studying the received optical power from different Txs. In this work, we propose and experimentally demonstrate a real-time VLP system utilizing long short-term memory neural network (LSTM-NN) with principal component analysis (PCA) to mitigate high positioning error, particularly at the positioning unit cell boundaries. Experimental results show that in a positioning unit cell of 100 × 100 × 250 cm3, the average positioning error is 5.912 cm when using LSTM-NN only. By utilizing the PCA, we can observe that the positioning accuracy can be significantly enhanced to 1.806 cm, particularly at the unit cell boundaries and cell corners, showing a positioning error reduction of 69.45%. In the cumulative distribution function (CDF) measurements, when using only the LSTM-NN model, the positioning error of 95% of the experimental data is >15 cm; while using the LSTM-NN with PCA model, the error is reduced to <5 cm. In addition, we also experimentally demonstrate that the proposed real-time VLP system can also be used to predict the direction and the trajectory of the moving Rx.

Ribosomal Protein L9 Maintains Stemness of Colorectal Cancer via an ID-1 Dependent Mechanism.

The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133+ cancer stem cells (CSCs) were then separated from CD133- cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133+ colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133+ HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.

Comparison of networks of loneliness, depressive symptoms, and anxiety symptoms in at-risk community-dwelling older adults before and during COVID-19.

Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.

Deficiency of ADAR2 ameliorates metabolic-associated fatty liver disease via AMPK signaling pathways in obese mice.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2-/-/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD-induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3ß pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.

HIF-1α Pathway Orchestration by LCN2: A Key Player in Hypoxia-Mediated Colitis Exacerbation.

In this study, we investigated the role of hypoxia in the development of chronic inflammatory bowel disease (IBD), focusing on its impact on the HIF-1α signaling pathway through the upregulation of lipocalin 2 (LCN2). Using a murine model of colitis induced by sodium dextran sulfate (DSS) under hypoxic conditions, transcriptome sequencing revealed LCN2 as a key gene involved in hypoxia-mediated exacerbation of colitis. Bioinformatics analysis highlighted the involvement of crucial pathways, including HIF-1α and glycolysis, in the inflammatory process. Immune infiltration analysis demonstrated the polarization of M1 macrophages in response to hypoxic stimulation. In vitro studies using RAW264.7 cells further elucidated the exacerbation of inflammation and its impact on M1 macrophage polarization under hypoxic conditions. LCN2 knockout cells reversed hypoxia-induced inflammatory responses, and the HIF-1α pathway activator dimethyloxaloylglycine (DMOG) confirmed LCN2's role in mediating inflammation via the HIF-1α-induced glycolysis pathway. In a DSS-induced colitis mouse model, oral administration of LCN2-silencing lentivirus and DMOG under hypoxic conditions validated the exacerbation of colitis. Evaluation of colonic tissues revealed altered macrophage polarization, increased levels of inflammatory factors, and activation of the HIF-1α and glycolysis pathways. In conclusion, our findings suggest that hypoxia exacerbates colitis by modulating the HIF-1α pathway through LCN2, influencing M1 macrophage polarization in glycolysis. This study contributes to a better understanding of the mechanisms underlying IBD, providing potential therapeutic targets for intervention.

Deflection of sliding droplets by dielectrophoresis force on a superhydrophobic surface.

In this study, we experimentally identify the effect of liquid dielectrophoresis (LDEP) force on a superhydrophobic surface in directing the trajectory of moving water droplets across designed interdigitated electrodes and show that this method is capable of rapidly selecting droplets at a high speed (200 mm/s). As the droplets traverse down the surface by the electric field, their deflection on the edge of these electrodes is achieved successively, allowing for the selective manipulation of discrete droplets. A series of experiments were conducted to validate the relationships among droplet deflections, applied electric fields, and dynamic contact angles. Our findings reveal that the principal driving force behind the droplet deflections is the LDEP force, which can provide instant manipulation of moving droplets rather than a variation in contact angles brought about by electrowetting. This study presents a proof-of-concept experiment utilizing LDEP for high-throughput droplet selection and also highlights the potential applications of this mechanism in high-speed digital microfluidics (DMF) and biological separation methodologies.

Water-Regulated Evolution of Inversion, Reinversion, and Amplification of Circularly Polarized Luminescence of Supramolecular Organogels Based on Glutamide-Cyanostilbene Amphiphile.

Water incorporated with supramolecular building blocks in organic solvents can play a key role in the circularly polarized luminescence (CPL) inversion and amplification of supramolecular assemblies. Herein, we demonstrate that fine-tuning the water content regulated the assembly structure evolution and made the circular dichroism and CPL sign of the system undergo intriguing inversion, reinversion, and amplification processes based on a unique and interesting glutamide-cyanostilbene system, as supported by morphology, spectroscopic observations, and time-dependent density functional theory calculation.

Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.

Novel 5-HT7 receptor antagonists modulate intestinal immune responses and reduce severity of colitis.

Inflammatory bowel disease (IBD) encompasses several debilitating chronic gastrointestinal (GI) inflammatory disorders, including Crohn's disease and ulcerative colitis. In both conditions, mucosal inflammation is a key clinical presentation associated with altered serotonin (5-hydroxytryptamine or 5-HT) signaling. This altered 5-HT signaling is also found across various animal models of colitis. Of the 14 known receptor subtypes, 5-HT receptor type 7 (5-HT7) is one of the most recently discovered. We previously reported that blocking 5-HT signaling with either a selective 5-HT7 receptor antagonist (SB-269970) or genetic ablation alleviated intestinal inflammation in murine experimental models of colitis. Here, we developed novel antagonists, namely, MC-170073 and MC-230078, which target 5-HT7 receptors with high selectivity. We also investigated the in vivo efficacy of these antagonists in experimental colitis by using dextran sulfate sodium (DSS) and the transfer of CD4+CD45RBhigh T cells to induce intestinal inflammation. Inhibition of 5-HT7 receptor signaling with the antagonists, MC-170073 and MC-230078, ameliorated intestinal inflammation in both acute and chronic colitis models, which was accompanied by lower histopathological damage and diminished levels of proinflammatory cytokines compared with vehicle-treated controls. Together, the data reveal that the pharmacological inhibition of 5-HT7 receptors by these selective antagonists ameliorates the severity of colitis across various experimental models and may, in the future, serve as a potential treatment option for patients with IBD. In addition, these findings support that 5-HT7 is a viable therapeutic target for IBD.NEW & NOTEWORTHY This study demonstrates that the novel highly selective 5-HT7 receptor antagonists, MC-170073 and MC-230078, significantly alleviated the severity of colitis across models of experimental colitis. These findings suggest that inhibition of 5-HT7 receptor signaling by these new antagonists may serve as an alternative mode of treatment to diminish symptomology in those with inflammatory bowel disease.

The mechanical effects of chemical stimuli on neurospheres.

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of the CCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

Opioid use disorder in pediatric populations: considerations for perioperative pain management and precision opioid analgesia.

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain. Studies indicate that lower repetitive methadone doses can decrease the incidence of chronic persistent surgical pain (CPSP). Ongoing research explores genetic components influencing severe surgical pain, inadequate opioid analgesia, and opioid use disorder. This new genetic research coupled with better utilization of opioids in the perioperative setting provides hope in personalizing surgical pain management, reducing pain, opioid use, adverse effects, and helping the fight against the opioid pandemic. EXPERT OPINION: The opioid and analgesic pharmacogenomics approach can proactively 'tailor' a perioperative analgesic plan to each patient based on underlying polygenic risks. This transition from population-based knowledge of pain medicine to individual patient knowledge can transform acute pain medicine and greatly reduce the opioid epidemic's socioeconomic, personal, and psychological strains globally.

Metal-ion-triggered symmetry breaking of completely achiral azobenzene amphiphiles in water.

Achieving control over symmetry breaking of completely achiral components in the aqueous phase is a significant challenge in supramolecular chemistry. Herein, we demonstrate that it is possible to construct chiral nanoassemblies by introducing metal ions (Zn2+, Fe3+, Al3+, Cu2+, and Ca2+) into completely achiral azobenzene amphiphiles with key structural factors in the pure aqueous phase. It is found that the coordination interactions, π-π stacking, hydrophilic and hydrophobic interactions, hydrogen bonding, and electrostatic interactions are crucial to the metal-ion-induced symmetry breaking of completely achiral building blocks. This study may provide an intriguing model system for constructing chiral assemblies based on completely achiral molecules.

High-altitude hypoxia promotes BRD4-mediated activation of the Wnt/ß-catenin pathway and disruption of intestinal barrier.

Hypobaric hypoxia, commonly experienced at elevated altitudes, presents significant physiological challenges. Our investigation is centered on the impact of the bromodomain protein 4 (BRD4) under these conditions, especially its interaction with the Wnt/ß-Catenin pathway and resultant effects on glycolytic inflammation and intestinal barrier stability. By combining transcriptome sequencing with bioinformatics, we identified BRD4's key role in hypoxia-related intestinal anomalies. Clinical parameters of altitude sickness patients, including serum BRD4 levels, inflammatory markers, and barrier integrity metrics, were scrutinized. In vitro studies using CCD 841 CoN cells depicted expression changes in BRD4, Interleukin (IL)-1ß, IL-6, and ß-Catenin. Transepithelial electrical resistance (TEER) and FD4 analyses assessed barrier resilience. Hypoxia-induced mouse models, analyzed via H&E staining and Western blot, provided insights into barrier and protein alterations. Under hypoxic conditions, marked BRD4 expression variations emerged. Elevated serum BRD4 in patients coincided with intensified Wnt signaling, inflammation, and barrier deterioration. In vitro, findings showed hypoxia-induced upregulation of BRD4 and inflammatory markers but a decline in Occludin and ZO1, affecting barrier strength-effects mitigated by BRD4 inhibition. Mouse models echoed these patterns, linking BRD4 upregulation in hypoxia to barrier perturbations. Hypobaric hypoxia-induced BRD4 upregulation disrupts the Wnt/ß-Catenin signaling, sparking glycolysis-fueled inflammation and weakening intestinal tight junctions and barrier degradation.

Theoretical efficiency limit of diffractive input couplers in augmented reality waveguides.

Considerable efforts have been devoted to augmented reality (AR) displays to enable the immersive user experience in the wearable glasses form factor. Transparent waveguide combiners offer a compact solution to guide light from the microdisplay to the front of eyes while maintaining the see-through optical path to view the real world simultaneously. To deliver a realistic virtual image with low power consumption, the waveguide combiners need to have high efficiency and good image quality. One important limiting factor for the efficiency of diffractive waveguide combiners is the out-coupling problem in the input couplers, where the guided light interacts with the input gratings again and get partially out-coupled. In this study, we introduce a theoretical model to deterministically find the upper bound of the input efficiency of a uniform input grating, constrained only by Lorentz reciprocity and energy conservation. Our model considers the polarization management at the input coupler and can work for arbitrary input polarization state ensemble. Our model also provides the corresponding characteristics of the input coupler, such as the grating diffraction efficiencies and the Jones matrix of the polarization management components, to achieve the optimal input efficiency. Equipped with this theoretical model, we investigate how the upper bound of input efficiency varies with geometric parameters including the waveguide thickness, the projector pupil size, and the projector pupil relief distance. Our study shines light on the fundamental efficiency limit of input couplers in diffractive waveguide combiners and highlights the benefits of polarization control in improving the input efficiency.