Controlling laser-dressed resonance line shape using attosecond extreme-ultraviolet pulse with a spectral minimum.

High-harmonic generation from a gas target exhibits sharp spectral features and rapid phase variation near the Cooper minimum. By applying spectral filtering, shaped isolated attosecond pulses can be generated where the pulse is split into two in the time domain. Using such shaped extreme-ultraviolet (XUV) pulses, we theoretically study attosecond transient absorption (ATA) spectra of helium [Formula: see text] autoionizing state which is resonantly coupled to the [Formula: see text] dark state by a time-delayed infrared laser. Our simulations show that the asymmetric [Formula: see text] Fano line shape can be readily tuned into symmetric Lorentzian within the time delay of a few tens of attoseconds. Such efficient control is due to the destructive interference in the generation of the [Formula: see text] state when it is excited by a strongly shaped XUV pulse. This is to be compared to prior experiments where tuning the line shape of a Fano resonance would take tens of femtoseconds. We also show that the predicted ATA spectral line shape can be observed experimentally after propagation in a gas medium. Our results suggest that strongly shaped attosecond XUV pulses offer the opportunity for controlling and probing fine features of narrow resonances on the few-ten attoseconds timescale.

Hierarchical joint analysis of marginal summary statistics-Part I: Multipopulation fine mapping and credible set construction.

Recent advancement in genome-wide association studies (GWAS) comes from not only increasingly larger sample sizes but also the shift in focus towards underrepresented populations. Multipopulation GWAS increase power to detect novel risk variants and improve fine-mapping resolution by leveraging evidence and differences in linkage disequilibrium (LD) from diverse populations. Here, we expand upon our previous approach for single-population fine-mapping through Joint Analysis of Marginal SNP Effects (JAM) to a multipopulation analysis (mJAM). Under the assumption that true causal variants are common across studies, we implement a hierarchical model framework that conditions on multiple SNPs while explicitly incorporating the different LD structures across populations. The mJAM framework can be used to first select index variants using the mJAM likelihood with different feature selection approaches. In addition, we present a novel approach leveraging the ideas of mediation to construct credible sets for these index variants. Construction of such credible sets can be performed given any existing index variants. We illustrate the implementation of the mJAM likelihood through two implementations: mJAM-SuSiE (a Bayesian approach) and mJAM-Forward selection. Through simulation studies based on realistic effect sizes and levels of LD, we demonstrated that mJAM performs well for constructing concise credible sets that include the underlying causal variants. In real data examples taken from the most recent multipopulation prostate cancer GWAS, we showed several practical advantages of mJAM over other existing multipopulation methods.

Modulation of anti-cardiac fibrosis immune responses by changing M2 macrophages into M1 macrophages.

BACKGROUND: Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported. METHODS: Here, we took glycogen synthetase kinase 3ß (GSK3ß) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment. RESULTS: NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF. CONCLUSION: Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF.

Immune cell infiltration and drug response in glioblastoma multiforme: insights from oxidative stress-related genes.

BACKGROUND: GBM, also known as glioblastoma multiforme, is the most prevalent and lethal type of brain cancer. The cell proliferation, invasion, angiogenesis, and treatment of gliomas are significantly influenced by oxidative stress. Nevertheless, the connection between ORGs and GBM remains poorly comprehended. The objective of this research is to investigate the predictive significance of ORGs in GBM and their potential as targets for therapy. METHODS: We identified differentially expressed genes in glioma and ORGs from public databases. A risk model was established using LASSO regression and Cox analysis, and its performance was evaluated with ROC curves. We then performed consistent cluster analysis on the model, examining its correlation with immunity and drug response. Additionally, PCR, WB and IHC were employed to validate key genes within the prognostic model. RESULTS: 9 ORGs (H6PD, BMP2, SPP1, HADHA, SLC25A20, TXNIP, ACTA1, CCND1, EEF1A1) were selected via differential expression analysis, LASSO and Cox analysis, and incorporated into the risk model with high predictive accuracy. Enrichment analyses using GSVA and GSEA focused predominantly on malignancy-associated pathways. Subtype C of GBM had the best prognosis with the lowest risk score. Furthermore, the model exhibited a strong correlation with the infiltration of immune cells and had the capability to pinpoint potential targeted therapeutic medications for GBM. Ultimately, we selected HADHA for in vitro validation. The findings indicated that GBM exhibits a significant upregulation of HADHA. Knockdown of HADHA inhibited glioma cell proliferation and diminished their migration and invasion capacities and influenced the tumor growth in vivo. CONCLUSION: The risk model, built upon 9 ORGs and the identification of GBM subtypes, suggests that ORGs have a broad application prospect in the clinical immunotherapy and targeted drug treatment of GBM. HADHA significantly influences the development of gliomas, both in vivo and in vitro.

Advancing autologous CAR T-cell therapy through real-time patient health data integration: a simulation-based approach.

Autologous chimeric antigen receptor T-cell therapy presents promising treatment outcomes for various cancers. However, its potential is restrained by unique supply chain challenges, including dynamic patient health conditions and extended turnaround time. These challenges often lead to missed optimal treatment windows, impeding the effective delivery of life-saving treatments. This article presents SimPAC (simulation-based decision support for Patient-centric manufacturing of autologous cell therapies). SimPAC is designed to model and incorporate real-time patient health conditions into the supply chain decisions of autologous chimeric antigen receptor T-cell therapy. SimPAC integrates system dynamics and agent-based simulation techniques, facilitating the adaptation of manufacturing processes and production schedules based on real-time patient health conditions. SimPAC can model various patient disease progressions using parametric functions, nonparametric functions, or tabular data. Additionally, SimPAC offers easy configuration options to model various cell therapy supply chains. We provide two case studies to demonstrate the capabilities of SimPAC and highlight the benefits of patient-centric manufacturing, including improved survival rates and potential economic advantages. However, while the benefits are significant, our study also emphasizes the importance of balancing improved patient outcomes, economic viability and ethical considerations in the context of personalized medicine. SimPAC can be used to explore applications of this approach to diverse therapeutic contexts and supply chain configurations.

Ambient energy harvesters in wearable electronics: fundamentals, methodologies, and applications.

In recent years, wearable sensor devices with exceptional portability and the ability to continuously monitor physiological signals in real time have played increasingly prominent roles in the fields of disease diagnosis and health management. This transformation has been largely facilitated by materials science and micro/nano-processing technologies. However, as this technology continues to evolve, the demand for multifunctionality and flexibility in wearable devices has become increasingly urgent, thereby highlighting the problem of stable and sustainable miniaturized power supplies. Here, we comprehensively review the current mainstream energy technologies for powering wearable sensors, including batteries, supercapacitors, solar cells, biofuel cells, thermoelectric generators, radio frequency energy harvesters, and kinetic energy harvesters, as well as hybrid power systems that integrate multiple energy conversion modes. In addition, we consider the energy conversion mechanisms, fundamental characteristics, and typical application cases of these energy sources across various fields. In particular, we focus on the crucial roles of different materials, such as nanomaterials and nano-processing techniques, for enhancing the performance of devices. Finally, the challenges that affect power supplies for wearable electronic products and their future developmental trends are discussed in order to provide valuable references and insights for researchers in related fields.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

Insecticidal activity of the spider neurotoxin PPTX-04 through modulating insect voltage-gated sodium channel.

Ion channels on cell membrane are molecular targets of more than half peptide neurotoxins from spiders. From Pardosa pseudoannulata, a predatory spider on a range of insect pests, we characterized a peptide neurotoxin PPTX-04 with an insecticidal activity. PPTX-04 showed high toxicity to Nilaparvata lugens, a main prey of P. pseudoannulata, and the toxicity was not affected by the resistance to etofenprox (IUPAC chemical name:1-ethoxy-4-[2-methyl-1-[(3-phenoxyphenyl)methoxy]propan-2-yl]benzene, purity: 99%). On N. lugens voltage-gated sodium channel NlNav1 expressed in Xenopus oocytes, PPTX-04 prolonged the channel opening and induced tail currents, which is similar to pyrethroid insecticides. However, PPTX-04 potency on NlNav1 was not affected by mutations conferring pyrethroid resistance in insects, which revealed that PPTX-04 and pyrethroids should act on different receptors in NlNav1. In contrast, two mutations at the extracellular site 4 significantly reduced PPTX-04 potency, which indicated that PPTX-04 would act on a potential receptor containing the site 4 in NlNav1. The result from the molecular docking supported the conclusion that the binding pocket of PPTX-04 in NlNav1 should contain the site 4. In summary, PPTX-04 had high insecticidal activity through acting on a distinct receptor site in insect Nav, and was a potential resource to control insect pests and manage resistance to pyrethroids.

Radiation Induced Skin Fibrosis (RISF): Opportunity for Angiotensin II-Dependent Intervention.

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.

Computation Offloading and Resource Allocation Based on P-DQN in LEO Satellite Edge Networks.

Traditional low earth orbit (LEO) satellite networks are typically independent of terrestrial networks, which develop relatively slowly due to the on-board capacity limitation. By integrating emerging mobile edge computing (MEC) with LEO satellite networks to form the business-oriented "end-edge-cloud" multi-level computing architecture, some computing-sensitive tasks can be offloaded by ground terminals to satellites, thereby satisfying more tasks in the network. How to make computation offloading and resource allocation decisions in LEO satellite edge networks, nevertheless, indeed poses challenges in tracking network dynamics and handling sophisticated actions. For the discrete-continuous hybrid action space and time-varying networks, this work aims to use the parameterized deep Q-network (P-DQN) for the joint computation offloading and resource allocation. First, the characteristics of time-varying channels are modeled, and then both communication and computation models under three different offloading decisions are constructed. Second, the constraints on task offloading decisions, on remaining available computing resources, and on the power control of LEO satellites as well as the cloud server are formulated, followed by the maximization problem of satisfied task number over the long run. Third, using the parameterized action Markov decision process (PAMDP) and P-DQN, the joint computing offloading, resource allocation, and power control are made in real time, to accommodate dynamics in LEO satellite edge networks and dispose of the discrete-continuous hybrid action space. Simulation results show that the proposed P-DQN method could approach the optimal control, and outperforms other reinforcement learning (RL) methods for merely either discrete or continuous action space, in terms of the long-term rate of satisfied tasks.

Periodontitis and osteoporosis: a two-sample Mendelian randomization analysis.

The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

Hearing disorders, genetic predisposition, and risk of new-onset atrial fibrillation: A prospective cohort study in the UK biobank.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Hearing impairment has been linked to several cardiovascular diseases. However, the association between hearing disorders, genetic predisposition, and new-onset AF remains largely unknown. METHODS: A total of 476,773 participants (mean age 56.5 years) free of AF at baseline (from 2006 to 2010) were included from the UK Biobank study. The presence of hearing disorders including hearing difficulty and tinnitus was self-reported through the touchscreen questionnaire. AF was defined using ICD-10 code: I48 and was followed till February 1st. 2022. The Cox model was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: During a median follow-up of 13.0 years, the AF incidence rate was 2.9 per 1000 person-years. After adjustments for potential confounders, the presence of hearing difficulty (HR, 1.35; 95% CI: 1.32-1.39) and the use of hearing aid (1.45; 1.37-1.53) were significantly associated with risk of new-onset AF. Compared to individuals without tinnitus, the AF risk increased by 17% among those who experienced tinnitus occasionally (1.17; 1.09-1.25), 23% among those who experienced tinnitus frequently (1.23; 1.10-1.39), and 32% among those who experienced tinnitus consistently (1.32; 1.22-1.42). No significant difference was observed across different groups of genetic risk score for AF onset. CONCLUSIONS: Our study provides evidence regarding significant associations of hearing difficulty, use of hearing aid, and tinnitus with risk of incident AF. Findings highlight the potential that screening hearing disorders can benefit AF prevention.

Meet the authors: Xueqin Jin, Jian Huang, Huan Wang, Kan Wang, and Nieng Yan.

In an interview with Dr. Samantha Nelson, a scientific editor of Cell Chemical Biology, the authors of the perspective entitled "A versatile residue numbering scheme for Nav and Cav channels" share their thoughts on life as scientists.

A versatile residue numbering scheme for Nav and Cav channels.

Voltage-gated sodium (Nav) and calcium (Cav) channels are responsible for the initiation of electrical signals. They have long been targeted for the treatment of various diseases. The mounting number of cryoelectron microscopy (cryo-EM) structures for diverse subtypes of Nav and Cav channels from multiple organisms necessitates a generic residue numbering system to establish the structure-function relationship and to aid rational drug design or optimization. Here we suggest a structure-based residue numbering scheme, centering around the most conserved residues on each of the functional segments. We elaborate the generic numbers through illustrative examples, focusing on representative drug-binding sites of eukaryotic Nav and Cav channels. We also extend the numbering scheme to compare common disease mutations among different Nav subtypes. Application of the generic residue numbering scheme affords immediate insights into hotspots for pathogenic mutations and critical loci for drug binding and will facilitate drug discovery targeting Nav and Cav channels.

A novel immunogenic cell death-related gene risk signature can identify biomarkers of gliomas and predict the immunotherapeutic response.

Immunogenic cell death (ICD) is a type of cell death that plays a pivotal role in immunity. Recent studies have identified the critical role of ICD in glioma treatment. This study aimed to use ICD-associated differentially expressed genes (ICD-DEGs) to predict survival of glioma patients. We investigated the relationship between clinical prognosis and the date-to-clinical prognosis of 1,721 glioma patients by examining the expression, methylation, and mutation status of ICD-related genes (IRGs) in these patients. Our prediction of survival in glioma patients was based on three risk genes, and we explored the association between these genes and clinical outcomes. Additionally, IRG expression was used to stratify glioma patients. We further examined the relationship among the three subgroups in terms of immune microenvironment heterogeneity and immunotherapy response. In addition, this study also included analyses of histograms and sensitivity to antitumor drugs. The expression of these genes was externally validated by RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) in glioma and normal brain tissue. Our findings reveal that most IRGs are overexpressed in glioma tumor tissues, and this high expression was confirmed through histological validation. We successfully developed predictive models for three prognostic genes associated with ICD. These models not only predict survival in glioma but also correlate with the tumor's immune microenvironment. Finally, using consensus clustering, we identified three ICD-associated subtypes. Notably, patients with the C3 subtype showed high levels of immune cell infiltration, whereas those with the C1 subtype exhibited lower levels of immune cell infiltration. We successfully developed an innovative IRG-based systematic approach for evaluating glioma patients. This stratification in experimental studies opens new avenues for prognosis and assessing immunotherapy responses in glioma patients. Our study demonstrates the effectiveness of this approach in treating glioma, potentially paving the way for more promising and effective therapeutic strategies in the future.

Microvascular decompression for intermediate nerve neuralgia: a case report and literature review.

Intermediate nerve neuralgia (INN) is a rare craniofacial pain syndrome. The diagnosis of INN is challenging because of the complex ear sensory innervation that results in a clinical overlap with both trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN). A 76-year-old woman with a remarkable medical history presented with right otalgia and mandibular pain for 7 years. Neurological examination revealed a diminished sensation in the distribution of the intermediate nerve (IN). Magnetic resonance imaging demonstrated an impression of the anterior inferior cerebellar artery (AICA) on the facial-vestibulocochlear nerve complex (VII/VIII complex). The patient underwent microvascular decompression (MVD) after long-term oral medication. We confirmed that the responsible vessel was close to the VII/VIII complex and isolated the vessel under the microscope via a right-sided suboccipital retrosigmoid approach. The patient's otalgia and mandibular pain disappeared after the operation. There were no additional neurological deficits. In conclusion, MVD is a safe and feasible option for patients with INN who fail to respond to adequate pharmacotherapy.

Enhancing Agrobacterium-mediated plant transformation efficiency through improved ternary vector systems and auxotrophic strains.

Agrobacterium-mediated transformation is an essential tool for functional genomics studies and crop improvements. Recently developed ternary vector systems, which consist of a T-DNA vector and a compatible virulence (vir) gene helper plasmid (ternary helper), demonstrated that including an additional vir gene helper plasmid into disarmed Agrobacterium strains significantly improves T-DNA delivery efficiency, enhancing plant transformation. Here, we report the development of a new ternary helper and thymidine auxotrophic Agrobacterium strains to boost Agrobacterium-mediated plant transformation efficiency. Auxotrophic Agrobacterium strains are useful in reducing Agrobacterium overgrowth after the co-cultivation period because they can be easily removed from the explants due to their dependence on essential nutrient supplementation. We generated thymidine auxotrophic strains from public Agrobacterium strains EHA101, EHA105, EHA105D, and LBA4404. These strains exhibited thymidine-dependent growth in the bacterial medium, and transient GUS expression assay using Arabidopsis seedlings showed that they retain similar T-DNA transfer capability as their original strains. Auxotrophic strains EHA105Thy- and LBA4404T1 were tested for maize B104 immature embryo transformation using our rapid transformation method, and both strains demonstrated comparable transformation frequencies to the control strain LBA4404Thy-. In addition, our new ternary helper pKL2299A, which carries the virA gene from pTiBo542 in addition to other vir gene operons (virG, virB, virC, virD, virE, and virJ), demonstrated consistently improved maize B104 immature embryo transformation frequencies compared to the original version of pKL2299 (33.3% vs 25.6%, respectively). Therefore, our improved Agrobacterium system, including auxotrophic disarmed Agrobacterium strains and a new ternary helper plasmid, can be useful for enhancing plant transformation and genome editing applications.

Deep-learning assisted zwitterionic magnetic immunochromatographic assays for multiplex diagnosis of biomarkers.

Magnetic nanoparticle (MNP)-based immunochromatographic tests (ICTs) display long-term stability and an enhanced capability for multiplex biomarker detection, surpassing conventional gold nanoparticles (AuNPs) and fluorescence-based ICTs. In this study, we innovatively developed zwitterionic silica-coated MNPs (MNP@Si-Zwit/COOH) with outstanding antifouling capabilities and effectively utilised them for the simultaneous identification of the nucleocapsid protein (N protein) of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and influenza A/B. The carboxyl-functionalised MNPs with 10% zwitterionic ligands (MNP@Si-Zwit 10/COOH) exhibited a wide linear dynamic detection range and the most pronounced signal-to-noise ratio when used as probes in the ICT. The relative limit of detection (LOD) values were achieved in 12 min by using a magnetic assay reader (MAR), with values of 0.0062 ng/mL for SARS-CoV-2 and 0.0051 and 0.0147 ng/mL, respectively, for the N protein of influenza A and influenza B. By integrating computer vision and deep learning to enhance the image processing of immunoassay results for multiplex detection, a classification accuracy in the range of 0.9672-0.9936 was achieved for evaluating the three proteins at concentrations of 0, 0.1, 1, and 10 ng/mL. The proposed MNP-based ICT for the multiplex diagnosis of biomarkers holds substantial promise for applications in both medical institutions and self-administered diagnostic settings.

CD22 blockade aggravates EAE and its role in microglia polarization.

AIMS: Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease. Microglia are reportedly involved in the pathogenesis of MS. However, the key molecules that control the inflammatory activity of microglia in MS have not been identified. METHODS: Experimental autoimmune encephalomyelitis (EAE) mice were randomized into CD22 blockade and control groups. The expression levels of microglial CD22 were measured by flow cytometry, qRT-PCR, and immunofluorescence. The effects of CD22 blockade were examined via in vitro and in vivo studies. RESULTS: We detected increased expression of microglial CD22 in EAE mice. In addition, an in vitro study revealed that lipopolysaccharide upregulated the expression of CD22 in microglia and that CD22 blockade modulated microglial polarization. Moreover, an in vivo study demonstrated that CD22 blockade aggravated EAE in mice and promoted microglial M1 polarization. CONCLUSION: Collectively, our study indicates that CD22 may be protective against EAE and may play a critical role in the maintenance of immune homeostasis in EAE mice.

Schisandrol B inhibits calcification of aortic valve by targeting p53 related inflammatory and senescence.

Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. We investigated the effect of SolB on osteogenic differentiation of hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. The study also included an in vivo murine model using aortic valve wire injury surgery to observe SolB's effect on valve calcification. SolB inhibited the osteogenic differentiation of hVICs, reversing the increase in calcified nodule formation and osteogenic proteins. In the murine model, SolB significantly decreased the peak velocity of the aortic valve post-injury and reduced valve fibrosis and calcification. Transcriptome sequencing identified the p53 signaling pathway as a key molecular target of SolB, demonstrating its role as a molecular glue in the mouse double minute 2 (MDM2)-p53 interaction, thereby promoting p53 ubiquitination and degradation, which further inhibited p53-related inflammatory and senescence response. These results highlighted therapeutic potential of SolB for CAVD via inhibiting p53 signaling pathway and revealed a new molecular mechanism of SolB which provided a new insight of theraputic mechanism for CAVD.