Deciphering the dual role of N-methyl-D-Aspartate receptor in postoperative cognitive dysfunction: A comprehensive review.

Postoperative cognitive dysfunction (POCD) is a common complication following surgery, adversely impacting patients' recovery, increasing the risk of negative outcomes, prolonged hospitalization, and higher mortality rates. The N-methyl-D-aspartate (NMDA) receptor, crucial for learning, memory, and synaptic plasticity, plays a significant role in the development of POCD. Various perioperative factors, including age and anesthetic use, can reduce NMDA receptor function, while surgical stress, inflammation, and pain may lead to its excessive activation. This review consolidates preclinical and clinical research to explore the intricate relationship between perioperative factors affecting NMDA receptor functionality and the onset of POCD. It discusses the influence of aging, anesthetic administration, perioperative injury, pain, and inflammation on the NMDA receptor-related pathophysiology of POCD. The comprehensive analysis presented aims to identify effective treatment targets for POCD, contributing to the improvement of patient outcomes post-surgery.

Heritable microbiome variation is correlated with source environment in locally adapted maize varieties.

Beneficial interactions with microorganisms are pivotal for crop performance and resilience. However, it remains unclear how heritable the microbiome is with respect to the host plant genotype and to what extent host genetic mechanisms can modulate plant-microbiota interactions in the face of environmental stresses. Here we surveyed 3,168 root and rhizosphere microbiome samples from 129 accessions of locally adapted Zea, sourced from diverse habitats and grown under control and different stress conditions. We quantified stress treatment and host genotype effects on the microbiome. Plant genotype and source environment were predictive of microbiome abundance. Genome-wide association analysis identified host genetic variants linked to both rhizosphere microbiome abundance and source environment. We identified transposon insertions in a candidate gene linked to both the abundance of a keystone bacterium Massilia in our controlled experiments and total soil nitrogen in the source environment. Isolation and controlled inoculation of Massilia alone can contribute to root development, whole-plant biomass production and adaptation to low nitrogen availability. We conclude that locally adapted maize varieties exert patterns of genetic control on their root and rhizosphere microbiomes that follow variation in their home environments, consistent with a role in tolerance to prevailing stress.

Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression.

BACKGROUND: Nexrutine is an herbal extract derived from Phellodendron amurense, known for its anti-inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear. METHODS: A mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM-460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM-460 cells was determined using the CCK-8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin-1, and tight junction protein (ZO-1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto-oncogene (RELA) was analyzed using qPCR and western blot assays. RESULTS: The Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro-inflammatory cytokines, enhanced the barrier integrity-related proteins, and increased NCM-460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus-mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC-related symptoms. CONCLUSION: This study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.

Relationship Between Fasting Blood Glucose and Readmission Within 1 Year in Elderly Patients with Heart Failure.

INTRODUCTION: Elevated blood glucose has been linked to unfavorable outcomes among individuals with heart failure (HF). Nevertheless, evidence is scarce regarding the association between fasting blood glucose (FBG) levels and the likelihood of readmission within one year for elderly patients. To address this gap, a retrospective cohort study was conducted, integrating electronic health records of restricted health data from PhysioNet. METHODS: The study focused on HF patients aged 60 years and older, utilizing baseline data, comorbidities, and laboratory test results as covariates. A total of 374 patients were included in the study. The relationship between 1-year readmission rates and various glucose levels was assessed using Kaplan-Meier plots. The analysis employed three multivariate Cox regression models to examine patients with varying glucose levels. RESULTS: Following adjustments for relevant factors, an association was observed between FBG levels and the rate of readmission in elderly patients with HF (HR=1.0264 [95% CI 0.9994-1.0541]). The diabetes group faced a higher risk of readmission compared to the normal group. However, this difference in outcome events was not statistically significant, with hazard ratios and their corresponding 95% confidence intervals of 1.2134 (0.9811~1.5007), 1.2393 (0.9993~1.5371), and 1.1905 (0.9570~1.4809), respectively. The robustness of the model was further demonstrated through risk models with subgroup analysis, revealing that FBG levels consistently exerted a stable effect on outcome events, unaffected by covariates such as age, gender, body mass index, glomerular filtration rate, and brain natriuretic peptide. CONCLUSION: These findings suggest a notable association between elevated FBG at the time of initial hospitalization and the likelihood of readmission within one year among elderly patients with HF.

OII-DS: A benchmark Oral Implant Image Dataset for object detection and image classification evaluation.

In recent years, there is been a growing reliance on image analysis methods to bolster dentistry practices, such as image classification, segmentation and object detection. However, the availability of related benchmark datasets remains limited. Hence, we spent six years to prepare and test a bench Oral Implant Image Dataset (OII-DS) to support the work in this research domain. OII-DS is a benchmark oral image dataset consisting of 3834 oral CT imaging images and 15240 oral implant images. It serves the purpose of object detection and image classification. To demonstrate the validity of the OII-DS, for each function, the most representative algorithms and metrics are selected for testing and evaluation. For object detection, five object detection algorithms are adopted to test and four evaluation criteria are used to assess the detection of each of the five objects. Additionally, mean average precision serves as the evaluation metric for multi-objective detection. For image classification, 13 classifiers are used for testing and evaluating each of the five categories by meeting four evaluation criteria. Experimental results affirm the high quality of our data in OII-DS, rendering it suitable for evaluating object detection and image classification methods. Furthermore, OII-DS is openly available at the URL for non-commercial purpose: https://doi.org/10.6084/m9.figshare.22608790.

Wake-Riding Effect-Inspired Opto-Hydrodynamic Diatombot for Non-Invasive Trapping and Removal of Nano-Biothreats.

Contamination of nano-biothreats, such as viruses, mycoplasmas, and pathogenic bacteria, is widespread in cell cultures and greatly threatens many cell-based bio-analysis and biomanufacturing. However, non-invasive trapping and removal of such biothreats during cell culturing, particularly many precious cells, is of great challenge. Here, inspired by the wake-riding effect, a biocompatible opto-hydrodynamic diatombot (OHD) based on optical trapping navigated rotational diatom (Phaeodactylum tricornutum Bohlin) for non-invasive trapping and removal of nano-biothreats is reported. Combining the opto-hydrodynamic effect and optical trapping, this rotational OHD enables the trapping of bio-targets down to sub-100 nm. Different nano-biothreats, such as adenoviruses, pathogenic bacteria, and mycoplasmas, are first demonstrated to be effectively trapped and removed by the OHD, without affecting culturing cells including precious cells such as hippocampal neurons. The removal efficiency is greatly enhanced via reconfigurable OHD array construction. Importantly, these OHDs show remarkable antibacterial capability, and further facilitate targeted gene delivery. This OHD serves as a smart micro-robotic platform for effective trapping and active removal of nano-biothreats in bio-microenvironments, and especially for cell culturing of many precious cells, with great promises for benefiting cell-based bio-analysis and biomanufacturing.

Effects of high-frequency repetitive transcranial magnetic stimulation on the nutritional status of patients in a persistent vegetative state: A pilot study.

Purpose: This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated. Methods: Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects' stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects' serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up. Results: (1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05). Conclusion: The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota-gut-brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.

Extracellular vesicles: Critical bilateral communicators in periphery-brain crosstalk in central nervous system disorders.

Growing evidence shows that there is a comorbid mechanism between the central nervous system (CNS) and the peripheral organs. The bilateral transmission of signal molecules in periphery-brain crosstalk plays an important role in the underlying mechanism, which result from complex networks of neurohumoral circuits. Secreted by almost all cells and considered innovative information transport systems, extracellular vesicles (EVs) encapsulate and deliver nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood-brain barrier (BBB), they are also identified primarily as essential communicators between the periphery and the CNS. In addition to transporting molecules under physiological or pathological conditions, EVs also show novel potential in targeted drug delivery. In this review, we discuss the mechanisms implicated in the transport of EVs in crosstalk between the peripheral and the central immune systems as well as in crosstalk between the peripheral organs and the brain in CNS disorders, especially in neurodegenerative diseases, stroke, and trauma. This work will help in elucidating the contributions of EVs to brain health and disorders, and promote the development of new strategies for minimally invasive treatment.

Bone marrow mesenchymal stem cells alleviate stress-induced hyperalgesia via restoring gut microbiota and inhibiting neuroinflammation in the spinal cord by targeting the AMPK/NF-κB signaling pathway.

Aim Spinal neuroinflammation contributes to the mechanism of stress-induced hyperalgesia (SIH). Recent research has demonstrated that bone marrow mesenchymal stem cells (BMSCs) alleviate chronic pain. However, what remains unidentified is whether BMSCs could improve hyperalgesia induced by chronic restraint stress (CRS). In another dimension, our previous study proved that gut microbiota played an important role in CRS-induced hyperalgesia in mice. Yet, whether BMSCs treatments change gut microbiota composition in CRS mice remains unexplored. MAIN METHODS: Mechanical allodynia and thermal hyperalgesia were used to assess pain behavior. Composition of fecal samples were verified by 16S rRNA analysis. Western blot was used to investigate the expression of adenosine monophosphate-activated protein kinase (AMPK)/ nuclear factor kappa B (NF-κB) signaling pathway, pro-inflammatory cytokines [interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), IL-6], and the markers of microglia and astrocytes. The morphology of glia cells was evaluated by immunofluorescence staining. KEY FINDINGS: CRS down-regulated phosphorylated AMPK (p-AMPK), up-regulated phosphorylated NF-κB p65 (p-NF-κB p65), activated microglia and astrocytes and promoted the secretion of IL-1ß, TNF-α and IL-6 in the spinal cord. BMSCs alleviated CRS-induced hyperalgesia by inhibiting the activation of microglia and astrocytes and by reducing neuroinflammation via improving the disrupted AMPK/NF-κB pathway. Furthermore, BMSCs also raised the relative abundance of Muribaculaceae and Lachnospiraceae in CRS mice feces, which was significantly related to its effect of relieving hyperalgesia. SIGNIFICANCE: Our results support that BMSCs could alleviate CRS-induced hyperalgesia by reducing AMPK/NF-κB-dependent neuroinflammation in the spinal cord and restoring the homeostasis of gut microbiota.

Secondary preventing effect of lung cancer in non-high-risk population: A retrospective investigation of opportunistic screening with low-dose computed tomography in Wuhan.

Background: Given the mortality benefit of low-dose computed tomography (LDCT) screening on high-risk populations, the retrospective investigation intended to identify the benefits of LDCT on lung cancer screening among the general demographic cohorts. Methods: We used an opportunistic screening with LDCT implemented during the pandemic in Wuhan to study the impact on subsequent thoracic surgeries, especially surgeries for lung cancer. Patients who received LDCT from October 1, 2019, to July 31, 2020, in three Triple-A accredited hospitals in Wuhan were included in the study. Relative week volumes of both surgeries before and after the chest LDCT screening were compared pairwise. The counts of surgeries for pulmonary nodules or masses, and corresponding pathological results among different gender and age groups were also compared. Result: The relative weekly volumes of thoracic surgery were significantly greater than those of stomach surgery after the opportunistic screening with LDCT. They were 33% (95% CI, 0.20-0.46; p<0. 001) higher than those of stomach surgery. For every 1,000 chest LDCT scans conducted in a given week, on average, 3.52(95% CI,0.56-6.49, p =0.03) thoracic surgeries were performed in the following week. After the implementation of opportunistic screening with LDCT, there was a higher percentage of young females with pulmonary nodule or mass (64.4% vs. 45.8%, p = 0.032). The fraction of lung cancer surgery in the treatment period was significantly greater than that in the control period (74.09% vs. 68.79%, p=0.007). There was a higher percentage of stage I lung cancer surgery in young and mid-age females than in the senior age group (64% vs. 53%, p= 0.05). Interpretation: Opportunistic screening with LDCT can advance the early diagnosis window of lung cancer in non-high-risk populations, especially young women who are easy to be ignored.

Detection of Green Asparagus Using Improved Mask R-CNN for Automatic Harvesting.

Advancements in deep learning and computer vision have led to the discovery of numerous effective solutions to challenging problems in the field of agricultural automation. With the aim to improve the detection precision in the autonomous harvesting process of green asparagus, in this article, we proposed the DA-Mask RCNN model, which utilizes the depth information in the region proposal network. Firstly, the deep residual network and feature pyramid network were combined to form the backbone network. Secondly, the DA-Mask RCNN model added a depth filter to aid the softmax function in anchor classification. Afterwards, the region proposals were further processed by the detection head unit. The training and test images were mainly acquired from different regions in the basin of the Yangtze River. During the capturing process, various weather and illumination conditions were taken into account, including sunny weather, sunny but overshadowed conditions, cloudy weather, and daytime greenhouse conditions as well as nighttime greenhouse conditions. Performance experiments, comparison experiments, and ablation experiments were carried out using the five constructed datasets to verify the effectiveness of the proposed model. Precision, recall, and F1-score values were applied to evaluate the performances of different approaches. The overall experimental results demonstrate that the balance of the precision and speed of the proposed DA-Mask RCNN model outperform those of existing algorithms.

Research on Government-Enterprise Regulation of Online Car-Hailing Based on Differential Game.

In the Internet era, with the widespread application of digital technology, the way people travel has changed. Compared with traditional taxis, more and more people prefer to choose online car-hailing. The rapid development of the online car-hailing industry has solved the problem of taxi-hailing to a certain extent, but it has also brought some new problems. To change the dilemma of the online car-hailing industry, it is necessary to strengthen the regulation of the online car-hailing industry. In this study, we consider the regulatory system composed of a local government and an enterprise and use the differential game to study the regulation of online car-hailing. In the Nash non-cooperative game, Stackelberg master-slave game, and cooperative game, we, respectively, investigate the indicators, such as the optimal regulatory effort of the government, the optimal regulatory effort of the enterprise, the optimal benefit function of the government, the optimal benefit function of the enterprise, the optimal benefit function of the system, the optimal trajectory of the service quality level for the enterprise, and the optimal trajectory of the goodwill for the enterprise. Moreover, we analyze the corresponding conclusions through examples. We obtained some important results. (i) In the Stackelberg master-slave game, the optimal ratio of the local government subsidy to the enterprise's regulatory cost is only related to the benefit distribution coefficient and has nothing to do with other factors. Moreover, when the benefit distribution coefficient is >1/3, the local government is willing to share the regulatory cost of the enterprise. Otherwise, the local government refuses to share the regulatory cost of the enterprise. (ii) Compared with the Nash non-cooperative game, the optimal regulatory effort of the local government remains unchanged in the Stackelberg master-slave game, but the optimal benefit of the local government increases. Moreover, when the benefit distribution coefficient is >1/3, both the optimal regulatory effort and the optimal benefit of the enterprise increase. (iii) Compared with the Stackelberg master-slave game, in the cooperative game, the optimal regulatory effort of both government and enterprise increases, and the system's optimal benefit also increases. (iv) From the Nash non-cooperative game to the Stackelberg master-slave game and then to the cooperative game when the benefit distribution coefficient is >1/3, the service quality level and goodwill of the enterprise all increase.

Visible-Light-Induced Alkylarylation of Unactivated Alkenes via Radical Addition/Truce-Smiles Rearrangement Cascade.

We disclosed a visible-light-induced alkylarylation reaction of unactivated alkenes via a metal-free radical addition/aryl translocation cascade sequence. Distal olefinic sulfonate was designed as a unique molecular scaffold allowing for a domino process to synthesize valuable alkylarylated alcohols in good yields with excellent diastereoselectivity, featuring mild reaction conditions, broad substrate scope, and excellent functional group tolerance. The mechanism investigation suggests that a visible-light-induced radical chain process dominates the cascade transformation.

Gut microbiota and its role in stress-induced hyperalgesia: Gender-specific responses linked to different changes in serum metabolites.

Long-term stress causes hyperalgesia; and there are gender differences in the mechanism of pain in male and female individuals. The role of gut microbiota in pain has also been verified. However, whether gut microbiota plays a role in hyperalgesia caused by chronic restraint stress (CRS) with gender differences has not been explored. This study investigated the role of gut microbiota in CRS-induced hyperalgesia gender-specifically through 16 S ribosomal RNA (16 S rRNA) gene sequencing and untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS). The study found that both male and female mice experienced hyperalgesia after CRS and antibiotic treatment. 16 S rRNA gene sequencing reveals gender differences in the fecal microbiota induced by CRS. The pain threshold decreased after transplanting the fecal microbiota from the male and female CRS group to the corresponding pseudo-germ-free mice. In addition, this study detected gender differences in the host gut microbiota and serum metabolism induced by fecal microbiota transplantation (FMT). Specifically, the different serum metabolites between the pseudo-germ-free mice receiving FMT from the CRS group and those from the control group were mainly involved in bile secretion and steroid hormone biosynthesis for male mice, and in taurine and hypotaurine metabolism and tryptophan metabolism for female mice. In summary, the gut microbiota participates in stress-induced hyperalgesia (SIH) with gender differences by influencing the host's gut microbiota composition and serum metabolism. Therefore, our findings provided insights into developing novel gut microbiota-associated drugs for the management of gender-specific SIH.

Influence of early life stress on depression: from the perspective of neuroendocrine to the participation of gut microbiota.

Depression is the most common mental disorder and has become a heavy burden in modern society. Clinical studies have identified early life stress as one of the high-risk factors for increased susceptibility to depression. Alteration of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress is one of the key risk factors for depression susceptibility related to early life stress. Laboratory animal studies have demonstrated that maternal separation (MS) for extended periods elicits HPA axis changes. These changes persist into adulthood and resemble those present in depressed adult individuals, including hyperactivity of the HPA axis. In addition, there is growing evidence that inflammation plays an important role in depression susceptibility concerned with early life stress. Individuals that have experienced MS have higher levels of pro-inflammatory cytokines and are susceptible to depression. Recently, it has been found that the gut microbiota plays an important role in regulating behavior and is also associated with depression. The translocation of gut microbiota and the change of gut microbiota composition caused by early stress may be a reason. In this review, we discussed the mechanisms by which early life stress contributes to the development of depression in terms of these factors. These studies have facilitated a systematic understanding of the pathogenesis of depression related to early life stress and will provide new ideas for the prevention and treatment of depression.

Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?

In recent years, increasing studies have been conducted on the mechanism of gut microbiota in neuropsychiatric diseases and non-neuropsychiatric diseases. The academic community has also recognized the existence of the microbiota-gut-brain axis. Chronic pain has always been an urgent difficulty for human beings, which often causes anxiety, depression, and other mental symptoms, seriously affecting people's quality of life. Hyperalgesia is one of the main adverse reactions of chronic pain. The mechanism of gut microbiota in hyperalgesia has been extensively studied, providing a new target for pain treatment. Enterochromaffin cells, as the chief sentinel for sensing gut microbiota and its metabolites, can play an important role in the interaction between the gut microbiota and hyperalgesia through paracrine or neural pathways. Therefore, this systematic review describes the role of gut microbiota in the pathological mechanism of hyperalgesia, learns about the role of enterochromaffin cell receptors and secretions in hyperalgesia, and provides a new strategy for pain treatment by targeting enterochromaffin cells through restoring disturbed gut microbiota or supplementing probiotics.

Role of competitive endogenous RNA networks in the pathogenesis of coronary artery disease.

BACKGROUND: The present study aimed to construct a network of competitive endogenous RNAs (ceRNAs) related to the pathogenesis of coronary artery disease (CAD), to provide a novel rationale for CAD treatment. METHODS: Bioinformatics methods were applied to screen for differentially expressed long non-coding RNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs) from the GSE68506, GSE59421, and GSE20129 datasets of the Gene Expression Omnibus (GEO) database. The miRcode database was used to predict lncRNA-binding miRNAs. The miRTarBase, miRDB, and TargetScan databases were used to predict the target genes of these miRNAs. An mRNA-miRNA-lncRNA ceRNA network of CAD was established. RESULTS: Between the CAD and normal control groups there were 264 DElncRNAs, 106 DEmiRNAs, and 1,879 DEmRNAs. We screened these differentially expressed gens (DEGs) respectively. There were 21 DElncRNAs, 13 DEmiRNAs, and 143 DEmRNAs in the ceRNA network by using Cytoscape application. The DEmRNAs were involved in the PI3K-Akt signaling pathway and the NF-κB signaling pathway. The key genes in the protein-protein interaction (PPI) network were HSP90AA1, CDKN1A, MCL1, MDM2, MAPK1, ABL1, LYN, CRK, CDK9, and FAS. CONCLUSIONS: The ceRNA network constructed in this study identified new candidate molecules for the treatment of CAD, providing some more comprehensive and higher-quality choices for the target treatment of CAD.

Cyclin G2 promotes the formation of smooth muscle cells derived foam cells in atherosclerosis via PP2A/NF-κB/LOX-1 pathway.

BACKGROUND: To investigate the role and underlying mechanism of cyclin G2 (G2-type cyclin) in the formation of vascular smooth muscle cells (VSMCs) derived foam cells. METHODS: The levels of α-SMA (alpha-SM-actin), p-NF-κB (phosphorylation nuclear transcription factors kappa B), and LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) were measured by immunohistochemistry and western blotting. The mouse aortic root smooth muscle cell line MOVAS was transfected to over-express cyclin G2, which were then stimulated with 80 µg/mL ox-LDL (oxidized low-density lipoprotein) to induce foam cell formation. DT-061 an activator of PP2A (protein phosphatase 2A) agonist was used to verify the role of PP2A in the process. RESULTS: Knocking out the Ccng2 gene in Apoe-/- mice alleviated aortic lipid plaque, foam cell formulation, ameliorative body weight, and LDL-cholesterol. We observed that the number of α-SMA positive cells was significantly decreased in Apoe-/-Ccng2-/- mice compared to Apoe-/- mice. Also, the protein levels of p-NF-κB and LOX-1 were markedly reduced in the aortic root of Apoe-/-Ccng2-/- mice. Upon stimulation with ox-LDL, upregulated cyclin G2 increased the intracellular lipid accumulation in MOVAS cells. Also, it suppressed the activity of PP2A but up-regulated LOX-1. Additionally, the cell nuclear translocation of p-NF-κB was increased. Interestingly, DT-061 intervention, re-activating the activity of PP2A, reduced the levels of nuclear p-NF-κB and LOX-1. This led to decreased lipid endocytosis reducing the formation of VSMCs- derived foam cells. CONCLUSIONS: Cyclin G2 increases the nuclear translocation of p-NF-κB by reducing the enzymatic activity of PP2A and upregulating LOX-1, thereby promotes the formation of VSMCs -derived foam cells in atherosclerosis.

Class-3 semaphorins: Potent multifunctional modulators for angiogenesis-associated diseases.

Semaphorins, the neuronal guidance cues, were shown to have broad influences on pathophysiological processes such as bone remodeling, immune responses, and angiogenesis. In particular, Class-3 Semaphorins (SEMA3) is considered a vital regulator involved in angiogenesis. Scientific evidence has pointed to the role of angiogenesis in many diseases, and numerous efforts have been made to explore the possibilities of curing those diseases by targeting angiogenesis. Nevertheless, the efficacies are limited owing to the complex mechanisms of angiogenesis. Hence, investigating the mechanisms of SEMA3 in angiogenesis may contribute to novel therapeutics for diseases. Previous reviews mainly focused on the various functions of semaphorins in one particular disease, and the specific angiogenesis mechanism of SEMA3 in diverse diseases has not been well elucidated. Additionally, the role of SEMA3 in angiogenesis remains elusive, as contradicting results have been found in different disease types. Some evidence from recent studies implies that, while most SEMA3 molecules inhibit pathological angiogenesis in different diseases, occasionally SEMA3 may also promote angiogenesis. This review summarizes the specific role of SEMA3 in a variety of angiogenesis-associated diseases, and documents SEMA3 may be a promising therapeutic target for treating angiogenesis-associated diseases.