Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis.

Sulfur-containing functional groups have garnered considerable attention owing to their frequent occurrence in ligands, pharmaceuticals and insecticides. However, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and long-standing goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl electrophiles to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups were crucial for attaining high reactivity and selectivity. This strategy offers a general, modular and divergent platform for rapid synthesis of chiral sulfilimines and sulfoximines that are otherwise difficult to access. Furthermore, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines.

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment in asymmetric transformations. However, methods for their asymmetric catalytic synthesis have rarely been explored. Herein, the catalytic enantioselective addition of aryl boroxines to sulfinylamines via Cu catalyst and the newly developed Xuphos ligand were reported. A series of chiral aryl sulfinamides can be readily accessed in one step. This protocol enables the stereospecific transformation of sulfinamides to sulfonimidoyl fluorides, sulfonimidamides, and sulfonimidate esters. DFT calculations have revealed the reaction pathway, and the migratory insertion is the enantio-determining step. The noncovalent interaction between the oxygen atom of sulfinylamines and the C-H bonds in the ligand is crucial for enantioselectivity control.

Effectiveness of a mHealth platform-based lifestyle integrated multicomponent exercise (PF-Life) program to reverse pre-frailty in community-dwelling older adults: a randomized controlled trial study protocol.

Background: Pre-frailty represents an ideal window of opportunity to potentially prevent frailty and disability. Early and effective interventions to delay or reverse pre-frailty are public health imperative. The present trial aims to evaluate the effectiveness and underlying mechanisms of mobile health (mHealth) platform-supported lifestyle-integrated multicomponent exercise (PF-Life) to reverse pre-frailty in community-dwelling older adults. Methods: This is an open-label, prospective, two-arm parallel randomized controlled trial with allocation concealment and outcome assessment blinding. We aim to recruit 140 pre-frail community-dwelling older adults who will be randomized into two groups. The control group will receive a health education program, while the intervention group will receive PF-Life training as planned for 1 year. The proportion of pre-frailty, functional performance (muscular strength, aerobic capacity, flexibility, and balance), body composition, and physical activity will be measured at pre-intervention, post-intervention, and 12-month follow-up. Inflammatory biomarkers will also be collected to explore the underlying mechanisms. Discussion: This is the first study to evaluate the effects of a novel digital lifestyle-integrated multicomponent exercise for pre-frail older people. The results of this trial will provide much-needed information on the short-and long-term effects of PF-Life based on functional performance and body composition. Meanwhile, inflammatory biomarkers and physical activity levels will be used to elucidate the underlying mechanisms of PF-Life. The findings from this trial will provide evidence for the effectiveness of lifestyle multicomponent exercise intervention supported by the mHealth platform that may reverse or even halt the onset of frailty. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=176477, identifier ChiCTR2200063431.

Implementation of a Multi-Functional-Group Strategy for Enhanced Performance of Perovskite Solar Cells through the Incorporation of 3-Amino-4-Phenylbutyric Acid Hydrochloride.

Reducing the defect density of perovskite films during the crystallization process is critical in preparing high-performance perovskite solar cells (PSCs). Here, a multi-functional molecule, 3-phenyl-4-aminobutyric acid hydrochloride (APH), with three functional groups including a benzene ring, ─NH3 + and ─COOH, is added into the perovskite precursor solution to improve perovskite crystallization and device performance. The benzene ring increases the hydrophobicity of perovskites, while ─NH3 + and ─COOH passivate defects related to I- and Pb2+, respectively. Consequently, the power conversion efficiency (PCE) of the optimal device increased to 24.65%. Additionally, an effective area of 1 cm2 with a PCE of 22.45% is also prepared using APH as an additive. Furthermore, PSCs prepared with APH exhibit excellent stability by 87% initial PCE without encapsulation after exposure at room temperature under 25% humidity for 5000 h and retaining 70% of initial PCE after aging at 85 °C in an N2 environment for 864 h.

Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy.

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI.

Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers.

TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell apoptosis. Despite acting downstream of p53, functional p53 is required for maximal cancer cell killing by BH3-mimetics through an unknown mechanism. Here, we report p53 is activated following BH3-mimetic induced mitochondrial outer membrane permeabilization, leading to BH3-only protein induction and thereby potentiating the pro-apoptotic signal. TP53-deficient lymphomas lack this feedforward loop, providing opportunities for survival and disease relapse after BH3-mimetic treatment. The therapeutic barrier imposed by defects in TP53 can be overcome by direct activation of the cGAS/STING pathway, which promotes apoptosis of blood cancer cells through p53-independent BH3-only protein upregulation. Combining clinically relevant STING agonists with BH3-mimetic drugs efficiently kills TRP53/TP53-mutant mouse B lymphoma, human NK/T lymphoma, and acute myeloid leukemia cells. This represents a promising therapy regime that can be fast-tracked to tackle TP53-mutant blood cancers in the clinic.

Copper-Catalyzed Sulfur Alkylation of Sulfenamides with N-Sulfonylhydrazones.

Sulfilimines are valuable compounds in both organic synthesis and pharmaceuticals. In this study, we present a copper-catalyzed sulfur alkylation of sulfenamides with N-sulfonylhydrazones. In contrast to prior findings, hydrazones derived from aldehydes act as donor-type carbene precursors, effectively engaging in coupling with sulfenamides via a copper catalyst, demonstrating exclusive S selectivity. The utility of the protocol was highlighted in the rapid access to a wide range of sulfoximine derivatives.

Fospropofol disodium versus propofol for long-term sedation during invasive mechanical ventilation: A pilot randomized clinical trial.

STUDY OBJECTIVE: Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DESIGN: Single-centered, prospective, unblind, randomized, parallel-group clinical trial. SETTING: The general ICU of university-affiliated teaching hospital. PATIENTS: Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. INTERVENTIONS: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of -3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MEASUREMENTS: The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. MAIN RESULTS: The median dose was 4.33 (IQR, 3.08-4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44-2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%-100.00%) in the fospropofol group and 83.33% (IQR, 77.45%-100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. CONCLUSIONS: Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.

Investigation of the Association between Air Pollution and Non-Alcoholic Fatty Liver Disease in the European Population: A Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide. At the same time, the relationship between air pollution and the likelihood of developing NAFLD has been a subject of debate due to conflicting findings in previous observational research. Our objective was to examine the potential correlation between air pollutant levels and the risk of NAFLD in the European population by employing a two-sample Mendelian randomization (MR) analysis. The UK Biobank Consortium provided the summary statistics for various air pollution indicators (PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2, and NOx). Additionally, information on NAFLD was obtained from three studies, including one derivation set and two validation sets. Heterogeneity, pleiotropy, and sensitivity analyses were performed under different MR frameworks, and instrumental variables associated with confounders (such as education, smoking, alcohol, and BMI) were detected by tools. In the derivation set, causal relationships between PM2.5, NO2, and NAFLD were observed in univariable Mendelian randomization (UVMR) (Odds Ratio (OR) = 1.99, 95% confidence interval (95% CI) = [1.22-3.22], p = 0.005; OR = 2.08, 95% CI = [1.27-3.40], p = 0.004, respectively). After adjustment for air pollutants or alcohol intake frequency in multivariable Mendelian randomization (MVMR), the above genetic correlations disappeared. In validation sets, the null associations remained in UVMR. Our findings from MR analysis using genetic data did not provide evidence for a causal association between air pollution and NAFLD in the European population. The associations observed in epidemiological studies could be partly attributed to confounders.

MEA-NAP compares microscale functional connectivity, topology, and network dynamics in organoid or monolayer neuronal cultures.

Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.

Landscape of T cell epitopes displays hot mutations of SARS-CoV-2 variant spikes evading cellular immunity.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS-CoV-2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS-CoV-2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross-T cell responses to the spike protein from these viral strains were quantitated using interferon-γ (IFN-γ) Elispot. Peptides covering the full-length spike protein from different viral strains were used to detect epitope-specific IFN-γ+ CD4+ and CD8+ T cell responses by fluorescence-activated cell sorting. SARS-CoV-2 Delta and Omicron BA.1 strains were found to have broad T cell cross-reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross-T cell immunity between SARS-CoV-2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N-terminal domain (181-246 aa [amino acids], 271-318 aa) and C-terminal domain (1171-1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.

Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.

There are few tumor cell subpopulations with stem cell characteristics in tumor tissue, defined as cancer stem cells (CSCs) or cancer stem-like cells (CSLCs), which can reconstruct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation. The microenvironment that CSCs depend on consists of various cellular components and corresponding medium components. Among these factors existing at a variety of levels and forms, cytokine networks and numerous signal pathways play an important role in signaling transduction. These factors promote or maintain cancer cell stemness, and participate in cancer recurrence, metastasis, and resistance. This review aims to summarize the recent molecular data concerning the multilayered relationship between CSCs and CSC-favorable microenvironments. We also discuss the therapeutic implications of targeting this synergistic interplay, hoping to give an insight into targeting cancer cell stemness for tumor therapy and prognosis.

Severe cytokine release syndrome induced by immune checkpoint inhibitors in cancer patients - A case report and review of the literature.

Cytokine release syndrome (CRS) can be induced by immune checkpoint inhibitors (ICIs). Although the incidence of CRS is low, it is often underreported. Here, we report two severe CRS cases and summarize and review 51 patients with ICI-induced CRS to explore the possible contributing factors to the disease prognosis and provide assistance for therapy. Our analysis found that the population with ICI-induced CRS consists mainly of male patients with an average age of 61.74 years. The primary malignant tumor type was lung cancer, and the clinical stage of most patients was stage IV. Notably, patients who experience a longer time to CRS onset, higher IL-6 levels, and lower platelet counts may be more likely to develop severe CRS. Cardiovascular, respiratory, neurological, and coagulation toxicities are more common in higher-grade CRS and may serve as markers for patient experiencing ICU admission, oxygen supplementation, hypotension, high-dose vasopressors usage, and intubation.

Therapeutic implications of extracorporeal shock waves in burn wound healing.

Burns are a common type of trauma that seriously affect not only the physical health, but also the mental health and quality of life of the patient. Extracorporeal shock wave therapy (ESWT) is an emerging treatment that has been used in clinical treatment. It has many advantages, including safety, non-invasiveness, efficiency, short treatment duration, fewer complications, and relatively low prices. In clinical settings, ESWT has played an important role in the healing process of burns and the prevention of sequelae. This article reviews the history of ESWT, the mechanism of ESWT to promote burn healing, and the application of ESWT in burns. Current status of ESWT treatment for burns as well as future perspectives for research have been summarized and proposed. However, patients with burns cannot be considered recovered when the wounds have healed, we need some new technology to adjust to the challenges of the future.

Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model.

BACKGROUND: Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study. AIM: To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming. METHODS: Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels. RESULTS: IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway. CONCLUSION: IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

Association of triglyceride-glucose index trajectory and frailty in urban older residents: evidence from the 10-year follow-up in a cohort study.

BACKGROUND: Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. METHODS: This longitudinal study included 1,866 older residents from the "Fujian prospective aging cohort" (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. RESULTS: In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00-2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11-2.88) and 2.17 (95% CI 1.01-3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). CONCLUSIONS: The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Occurrence, spatiotemporal distribution patterns,partitioning and risk assessments of multiple pesticide residues in typical estuarine water environments in eastern China.

The low terrain and the prosperous agriculture in the east of China, have caused the accumulation of pesticide residues in the estuaries. Therefore, this study analyzed the spatiotemporal distribution and partition tendency of 106 pesticides based on their abundance, frequencies, and concentrations in the aquatic environment of 16 river estuaries in 7 major basins in the eastern China by using solid-phase extraction (SPE) with high-performance liquid chromatography tandem mass spectrometry (HPLC‒MS/MS) and gas chromatography tandem mass spectrometry (GC‒MS/MS). In addition, potential risk of multiple pesticides was also evaluated. The results showed that herbicides were the dominant pesticide type, while triazines were the predominate substance group of pesticide. In addition, triadimenol, vinclozolin, diethylatrazine, prometryn, thiamethoxam, atrazine, and metalachlor were the major pesticides in the water, while prometryn, metalachlor, and atrazine were the main pesticides in the sediment. The average total concentration of pesticide was 751.15 ng/L in the dry season, 651.17 ng/L in the wet season, and 617.37 ng/L in the normal season, respectively. The estuaries of the Huai River Basin, the Yangtze River Basin, the Hai River Basin, and the Yellow River Basin have been affected by the low pollution treatment efficiency, weak infrastructure, and agricultural/non-agricultural activities in eastern China, resulting in relatively serious pesticide pollution. The estuaries of Huaihe River, Yangtze River, Xiaoqing River, and Luanhe River had large pesticide abundance and comparatively severe pesticide pollution, while the estuaries of Tuhai River and Haihe River had heavy pesticide contamination in the sediment, which might be induced by historical sedimentary factors. The log KOC values showed that except for thioketone, other pesticides were relatively stable due to the adsorption by sediment. The ecological risk assessment results indicated that insecticides had a high risk. Teenagers were the most severely affected by the noncarcinogenic risk of pesticides, while adults were mostly affected by the carcinogenic risk of pesticides. Therefore, pesticide hazards in the water environment of estuaries in eastern China needs to be further close supervision.

Endothelial exosomes work as a functional mediator to activate macrophages.

Introduction: Intercellular communication is essential for almost all physiological and pathological processes. Endothelial cell (EC)-derived exosomes, working as mediators for intercellular information exchange, are involved in the pathophysiological mechanisms of atherosclerosis. However, the effect of inflamed endothelial exosomes on the function of macrophages (Mϕ) is poorly defined. This study aims to unravel how exosomes derived from tumor necrosis factor-α (TNF-α)-stimulated ECs (exo-T) affect Mϕ in vitro. Methods and results: Exosomes derived from untreated ECs (exo) and exo-T were identified by using TEM, NTA, and western blot, and we observed that PKH67-labeled exo/exo-T were taken up by Mϕ. Exposure to exo-T for 24 h not only skewed Mϕ to the M1 subtype and exacerbated lipid deposition, but also promoted Mϕ apoptosis, while it did not significantly affect Mϕ migration, as detected by RT-qPCR, Dil-ox-LDL uptake assay, flow cytometry, wound healing assay, and transwell assay, respectively. In addition, exo/exo-T-related microRNA-Seq revealed 104 significantly differentially expressed microRNAs (DE-miRNAs). The target genes of DE-miRNAs were mainly enriched functionally in metabolic pathways, MAPK signaling pathway, etc., as determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We further demonstrated by immunoblotting that exo-T intervention improves the phosphorylation of MAPK/NF-κB-related proteins. Discussion and conclusion: Collectively, this study reveals that inflamed endothelial exosomes (TNF-α-stimulated EC-derived exosomes) work as a functional mediator to affect Mϕ function and may activate Mϕ through MAPK/NF-κB signaling pathways.