No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches.

Fostemsavir is an approved gp120-directed attachment inhibitor and prodrug for the treatment of human immunodeficiency virus type 1 infection in combination with other antiretrovirals (ARVs) in heavily treatment-experienced adults with multi-drug resistance, intolerance, or safety concerns with their current ARV regimen. Initial in vitro studies indicated that temsavir, the active moiety of fostemsavir, and its metabolites, inhibited organic cation transporter (OCT)1, OCT2, and multidrug and toxin extrusion transporters (MATEs) at tested concentration of 100 uM, although risk assessment based on the current Food and Drug Administration in vitro drug-drug interaction (DDI) guidance using the mechanistic static model did not reveal any clinically relevant inhibition on OCTs and MATEs. However, a DDI risk was flagged with EMA static model predictions. Hence, a physiologically based pharmacokinetic (PBPK) model of fostemsavir/temsavir was developed to further assess the DDI risk potential of OCT and MATEs inhibition by temsavir and predict changes in metformin (a sensitive OCT and MATEs substrate) exposure. No clinically relevant impact on metformin concentrations across a wide range of temsavir concentrations was predicted; therefore, no dose adjustment is recommended for metformin when co-administered with fostemsavir.

Associations of COVID-19-related fear with kidney disease quality of life and its subscales among hemodialysis patients as modified by health literacy: a multi-hospital survey.

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06-0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31-0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = -6.12 (95% CI = -7.66 to - 4.58, p = 0.001) and FCoV-19 B = -0.91 (95% CI = -1.03 to - 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic.

Live birth after vitrification of oocytes from capacitation in vitro maturation.

Female fertility preservation is a rapidly growing field in medicine. Oocyte cryopreservation and assisted reproductive technique with vitrified-warmed oocytes have been successful with in vivo matured oocytes after conventional ovarian stimulation protocols. The use of in vitro matured oocytes after vitrification and warming has been limited. Capacitation in vitro maturation (CAPA-IVM) represents the latest refinement of IVM protocols and provides in vitro matured oocytes with improved competence. This case report describes the first successful live birth following oocyte vitrification from a CAPA-IVM cycle. This milestone achievement holds a significant promise to expand fertility preservation options and improve accessibility for women wishing to cryopreserve their eggs for future use.

Arthroscopic debridement and antibiotic-loaded cement for treatment of chronic infected tibial tunnel post-ACL reconstruction: A case report.

INTRODUCTION AND IMPORTANCE: Chronic extra-articular infections of the tibial tunnel are rare, and there are only a few cases reported in the literature, so the diagnosis and management of these infections are still unclear. CASE PRESENTATION: We report a 36-year-old patient with chronic infection of the tibial tunnel after ACL reconstruction surgery. The patient was treated with arthroscopic debridement of the tibial tunnel and antibiotic cement filling. Seven months postoperative, there were no signs of infection at the surgical site and the knee joint. The patient has no pain, no joint instability, no limitation of range of motion, and no limitation in daily activities. CLINICAL DISCUSSION: The definitive diagnosis of chronic infection of the tibial tunnel should be carefully based on clinical signs, blood tests, and imaging to rule out combined intra-articular infections. The arthroscopic technique can be a favorable method to control and debride the inflammatory tissue of the tibial tunnel, limiting the recurrence rate postoperatively. CONCLUSION: Arthroscopic debridement and antibiotic-loaded cement can be considered an alternative to traditional surgical methods in the treatment of chronic infection of the tibial bone tunnel after ACL reconstruction. LEVEL OF EVIDENCE: A case report.

Impact of inadequate bowel cleansing in sigmoidoscopy screening.

BACKGROUND AND STUDY AIMS: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening. PATIENTS AND METHODS: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models. RESULTS: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists. CONCLUSIONS: Inadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method.Trial registration Clinicaltrials.gov (NCT01538550).

Air-water interfacial collapse and rate-limited solid desorption control Perfluoroalkyl acid leaching from the vadose zone.

Some Per- and polyfluoroalkyl substances (PFAS) are strongly retained in the vadose zone due to their sorption to both soils and air-water interfaces. While significant research has been dedicated to understanding equilibrium behavior for these multi-phase retention processes, leaching and desorption from aqueous film-forming foam (AFFF) impacted soils under field relevant conditions can exhibit significant deviations from equilibrium. Herein, laboratory column studies using field collected AFFF-impacted soils were employed to examine the leaching of perfluoroalkyl acids (PFAAs) under simulated rainfall conditions. The HYDRUS 1-D model was calibrated to estimate the unsaturated hydraulic properties of the soil in a layered system using multiple boundary condtions. Forward simulations of equilibrium PFAS partitioning using the HYDRUS model and simplified mass balance calculations showed good agreement with the net PFAS mass flux out of the column. However, neither were able to predict the PFAS concentrations in the leached porewater. To better understand the mechanisms controlling the leaching behavior, the HYDRUS 1-D two-site leaching model incorporating solid phase rate limitation and equilibrium air-water interfacial partitioning was employed. Three variations of the novel model incorporating different forms of equilibrium air-water interfacial partitioning were considered using built-in numerical inversion. Results of numerical inversion show that a combination of air-water interfacial collapse and rate-limited desorption from soils can better predict the unique leaching behavior exhibited by PFAAs in AFFF-impacted soils. A sensitivity analysis of the initial conditions and rate-limited desorption terms was conducted to assess the agreement of the model with measured data. The models demonstrated herein show that, under some circumstances, laboratory equilibrium partitioning data can provide a reasonable estimation of total mass leaching, but fail to account for the significant rate-limited, non-Fickian transport which affect PFAA leaching to groundwater in unsaturated soils.

Breast cancer epigenetics: current and evolving treatment.

BACKGROUND: Breast cancer (BC) presents persistent challenges due to subtype-specific limited efficacy and potential resistance to standard therapy, influenced by the dynamic reversible nature of epigenetic plasticity. This study aims to comprehensively explore the evolving BC epigenetic landscape, analyzing trends and evaluating the therapeutic potential of epigenetic drugs (epi-drugs) for BC treatment. METHODS: We conducted a cross-sectional study of BC epigenetic trials using ClinicalTrials.gov until July 18, 2023. Additionally, results from randomized controlled trials were retrieved from the registry or PubMed using trial registration numbers. RESULTS: In total, 22 epi-drugs were investigated in 100 trials, with 11 currently being studied in 38 ongoing trials for BC. Over the years, epigenetic clinical trials for BC have notably increased, with histone deacetylase inhibitors constituting 45.45% of the candidate agents in the development pipeline. All ongoing trials are enrolling human epidermal growth factor receptor2 (HER2)-negative BC patients. Epi-drugs are commonly explored in combination with multiple anti-cancer therapies, such as aromatase or microtubule inhibitors, using an intermittent sequential administration approach. Emerging strategies include new-generation epi-drugs and combination involving immunotherapy or targeted therapy. Among candidate drugs, tucidinostat and entinostat, in combination with exemestane, demonstrated significant improvements in progression-free survival in phase III trials for hormone receptor-positive, HER2-negative BC patients. CONCLUSION: This study highlights the growing interest in BC epigenetics, suggesting a potential shift from a one-size-fits-all approach to precision medicine, and emphasizes the necessity for robust evidence on their efficacy and safety to support continuous development and approval, addressing the unmet needs in BC treatment.

Genome-wide identification, characterization, and expression analysis of the small auxin-up RNA gene family during zygotic and somatic embryo maturation of the cacao tree (Theobroma cacao).

Small auxin-up RNA (SAUR) proteins were known as a large family that supposedly participated in various biological processes in higher plant species. However, the SAUR family has been still not explored in cacao (Theobroma cacao L.), one of the most important industrial trees. The present work, as an in silico study, revealed comprehensive aspects of the structure, phylogeny, and expression of TcSAUR gene family in cacao. A total of 90 members of the TcSAUR gene family have been identified and annotated in the cacao genome. According to the physic-chemical features analysis, all TcSAUR proteins exhibited slightly similar characteristics. Phylogenetic analysis showed that these TcSAUR proteins could be categorized into seven distinct groups, with 10 sub-groups. Our results suggested that tandemly duplication events, segmental duplication events, and whole genome duplication events might be important in the growth of the TcSAUR gene family in cacao. By re-analyzing the available transcriptome databases, we found that a number of TcSAUR genes were exclusively expressed during the zygotic embryogenesis and somatic embryogenesis. Taken together, our study will be valuable to further functional characterizations of candidate TcSAUR genes for the genetic engineering of cacao.

Development of a physiologically based pharmacokinetic model of fostemsavir and its pivotal application to support dosing in pregnancy.

It is critical to understand the impact of significant physiological changes during pregnancy on the extent of maternal and fetal drug exposure. Fostemsavir (FTR) is a prodrug of temsavir (TMR) and is approved in combination with other antiretrovirals for multi-drug-resistant human immunodeficiency virus (HIV) infections. This physiologically based pharmacokinetic model (PBPK) study was used to estimate TMR PK in pregnant populations during each trimester of pregnancy to inform FTR dosing. A PBPK model was developed and validated for TMR using PK data collected following intravenous TMR and oral FTR dosing (immediate-release and extended-release tablets) in healthy volunteers. Predicted TMR concentration-time profiles accurately predicted the reported clinical data and variability in healthy (dense data) and pregnant (sparse data) populations. Predicted versus observed TMR geometric mean (CV%) clearance following intravenous administration was 18.01 (29) versus 17 (21) (L/h). Predicted versus observed TMR AUC0-inf (ng.h/mL) in healthy volunteers following FTR administration of the extended-release tablet were 9542 (66) versus 7339 (33). The validated TMR PBPK model was then applied to predict TMR PK in a population of pregnant individuals during each trimester. Simulations showed TMR AUC in pregnant individuals receiving FTR 600 mg twice daily was decreased by 25% and 38% in the second and third trimesters, respectively. However, TMR exposure remained within the range observed in nonpregnant adults with no need for dose adjustment. The current PBPK model can also be applied for the prediction of local tissue concentrations and drug-drug interactions in pregnancy.

A Rare Case of Panton-Valentine Leukocidin-Related Cervical Empyema.

Staphylococcus aureus is found in the normal skin and mucosa of approximately 30% of healthy populations and is the most common pathogen in human disease associated with bacteria. They are divided into methicillin-sensitive S . aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The S. aureus strains carrying the Panton-Valentine leukocidin genes (SA-PVL) were initially believed to belong to the MRSA group; however, recent reports showed they also belonged to the MSSA group (MSSA-PVL). SA-PVL is common in skin and soft-tissue infections but rare in musculoskeletal infections, especially in spondylodiscitis. We are reporting a case suffering from cervical spondylodiscitis and epidural abscess associated with MSSA carrying the Panton-Valentine leukocidin genes.

Study protocol: Early neurological deterioration in patients with minor stroke, frequency, predictors, and outcomes in Vietnam single-centre study.

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment.

PFAS Porewater concentrations in unsaturated soil: Field and laboratory comparisons inform on PFAS accumulation at air-water interfaces.

Poly- and perfluoroalkyl substance (PFAS) leaching from unsaturated soils impacted with aqueous film-forming foams (AFFFs) is an environmental challenge that remains difficult to measure and predict. Complicating measurements and predictions of this process is a lack of understanding between the PFAS concentrations measured in a collected environmental unsaturated soil sample, and the PFAS concentrations measured in the corresponding porewater using field-deployed lysimeters. The applicability of bench-scale batch testing to assess this relationship also remains uncertain. In this study, field-deployed porous cup suction lysimeters were used to measure PFAS porewater concentrations in unsaturated soils at 5 AFFF-impacted sites. Field-measured PFAS porewater concentrations were compared to those measured in porewater extracted in the laboratory from collected unsaturated soil cores, and from PFAS concentrations measured in the laboratory using batch soil slurries. Results showed that, despite several years since the last AFFF release at most of the test sites, precursors were abundant in 3 out of the 5 sites. Comparison of field lysimeter results to laboratory testing suggested that the local equilibrium assumption was valid for at least 3 of the sites and conditions of this study. Surprisingly, PFAS accumulation at the air-water interface was orders of magnitude less than expected at two of the test sites, suggesting potential gaps in the understanding of PFAS accumulation at the air-water interface at AFFF-impacted sites. Finally, results herein suggest that bench-scale testing on unsaturated soils can in some cases be used to inform on PFAS in situ porewater concentrations.

Potential biological functions and future perspectives of sialylated milk oligosaccharides.

Sialyllactoses (SLs) primarily include sialylated human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). First, the safety assessment of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) revealed low toxicity in various animal models and human participants. SLs constitute a unique milk component, highlighting the essential nutrients and bioactive components crucial for infant development, along with numerous associated health benefits for various diseases. This review explores the safety, biosynthesis, and potential biological effects of SLs, with a specific focus on their influence across various physiological systems, including the gastrointestinal system, immune disorders, rare genetic disorders (such as GNE myopathy), cancers, neurological disorders, cardiovascular diseases, diverse cancers, and viral infections, thus indicating their therapeutic potential.

Citizen scientists' engagement in flood risk-related data collection: a case study in Bui River Basin, Vietnam.

Time constraints, financial limitations, and inadequate tools restrict the flood data collection in undeveloped countries, especially in the Asian and African regions. Engaging citizens in data collection and contribution has the potential to overcome these challenges. This research demonstrates the applicability of citizen science for gathering flood risk-related data on residential flooding, land use information, and flood damage to paddy fields for the Bui River Basin in Vietnam. Locals living in or around flood-affected areas participated in data collection campaigns as citizen scientists using self-investigation or investigation with a data collection app, a web form, and paper forms. We developed a community-based rainfall monitoring network in the study area using low-cost rain gauges to draw locals' attention to the citizen science program. Fifty-nine participants contributed 594 completed questionnaires and measurements for four investigated subjects in the first year of implementation. Five citizen scientists were active participants and contributed more than 50 completed questionnaires or measurements, while nearly 50% of citizen scientists participated only one time. We compared the flood risk-related data obtained from citizen scientists with other independent data sources and found that the agreement between the two datasets on flooding points, land use classification, and the flood damage rate to paddy fields was acceptable (overall agreement above 73%). Rainfall monitoring activities encouraged the participants to proactively update data on flood events and land use situations during the data collection campaign. The study's outcomes demonstrate that citizen science can help to fill the gap in flood data in data-scarce areas.

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

The Postoperative Breast: Imaging Findings and Diagnostic Pitfalls After Breast-Conserving Surgery and Oncoplastic Breast Surgery.

Breast surgery is the cornerstone of treatment for early breast cancer. Historically, mastectomy and conventional breast-conserving surgery (BCS) were the main surgical techniques for treatment. Now, oncoplastic breast surgery (OBS), introduced in the 1990s, allows for a combination of BCS and reconstructive surgery to excise the cancer while preserving or enhancing the contour of the breast, leading to improved aesthetic results. Although imaging after conventional lumpectomy demonstrates typical postsurgical changes with known evolution patterns over time, OBS procedures show postsurgical changes/fat necrosis in locations other than the lumpectomy site. The purpose of this article is to familiarize radiologists with various types of surgical techniques for removal of breast cancer and to distinguish benign postoperative imaging findings from suspicious findings that warrant further work-up.

Block Copolymers of Polyolefins with Polyacrylates: Analyzing and Improving the Blocking Efficiencies Using MILRad/ATRP Approach.

Despite their industrial ubiquity, polyolefin-polyacrylate block copolymers are challenging to synthesize due to the distinct polymerization pathways necessary for respective blocks. This study utilizes MILRad, metal-organic insertion light-initiated radical polymerization, to synthesize polyolefin-b-poly(methyl acrylate) copolymer by combining palladium-catalyzed insertion-coordination polymerization and atom transfer radical polymerization (ATRP). Brookhart-type Pd complexes used for the living polymerization of olefins are homolytically cleaved by blue-light irradiation, generating polyolefin-based macroradicals, which are trapped with functional nitroxide derivatives forming ATRP macroinitiators. ATRP in the presence of Cu(0), that is, supplemental activators and reducing agents , is used to polymerize methyl acrylate. An increase in the functionalization efficiency of up to 71% is demonstrated in this study by modifying the light source and optimizing the radical trapping condition. Regardless of the radical trapping efficiency, essentially quantitative chain extension of polyolefin-Br macroinitiator with acrylates is consistently demonstrated, indicating successful second block formation.

Dataset of United States Incident Management Situation Reports from 2007 to 2021.

This paper presents a unique 15-year dataset of Incident Management Situation Reports (IMSR), which document daily wildland fire situations across ten geographical regions in the United States. The IMSR dataset includes summaries for each reported day on national and regional wildfire activities, wildfire-specific activities, and committed fire suppression resources (i.e., personnel and equipment). This dataset is distinct from other wildfire data sources as it provides daily information on national fire suppression resource utilization, national and regional preparedness levels, and management priority for each region and fire. We developed an open-source Java program, IMSR-Tool, to process 3,124 IMSR reports available from 2007 to 2021 to generate this structured IMSR dataset, which can be updated when future reports become available. The dataset presented here and its future extension enable researchers and practitioners to study historical wildfire activity and resource use across regions and time, examine fire management perceptions, evaluate strategies for fire prioritization and fire resource allocation, and exploit other broader usage to improve wildfire management and response in the United States.

Removal of per- and polyfluoroalkyl substances from wastewater via aerosol capture.

The widespread use of per- and polyfluoroalkyl substances (PFAS)-containing products in numerous commercial and industrial applications has resulted in their occurrence in wastewater treatment plants (WWTPs). Herein, proof-of-concept bench-scale experiments were performed to measure the extent to which PFAS could be removed from a WWTP if aerosols generated during aeration were captured. Experiments were designed to mimic the aeration rate:water volume ratio, the water volume:surface area ratio, and aeration bubble size applicable to the full-scale aeration vessel. Results showed that substantial (75%) removal of perfluorooctane sulfonate (PFOS) was observed under these operating conditions in the bench-scale system; up to 97% PFOS removal was observed if the aeration rate was increased 3-fold. PFAS removal generally increased with increasing aerosol capture and with increasing PFAS surface activity. Analysis of semi-quantified PFAS showed that the semi-quantified PFAS accounted for approximately 93% of the identified PFAS in the raw wastewater, dominated largely by the presence of 2:2 fluorotelomer carboxylic acid (2:2 FTCA). This preliminary study suggests that aerosol capture in aeration basins has potential for mitigating PFAS in WWTPs. Further testing is needed to assess the feasibility of this approach at the field scale.

3'-Sialyllactose protects against LPS-induced endothelial dysfunction by inhibiting superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis.

AIM: Endothelial hyperpermeability is an early stage of endothelial dysfunction associated with the progression and development of atherosclerosis. 3'-Sialyllactose (3'-SL) is the most abundant compound in human milk oligosaccharides, and it has the potential to regulate endothelial dysfunction. This study investigated the beneficial effects of 3'-SL on lipopolysaccharide (LPS)-induced endothelial dysfunction in vitro and in vivo. MAIN METHODS: We established LPS-induced endothelial dysfunction models in both cultured bovine aortic endothelial cells (BAECs) and mouse models to determine the effects of 3'-SL. Western blotting, qRT-PCR analysis, immunofluorescence staining, and en face staining were employed to clarify underlying mechanisms. Superoxide production was measured by 2',7'-dichlorofluorescin diacetate, and dihydroethidium staining. KEY FINDINGS: LPS significantly decreased cell viability, whereas 3'-SL treatment mitigated these effects via inhibiting ERK1/2 activation. Mechanistically, 3'-SL ameliorated LPS-induced ROS accumulation leading to ERK1/2 activation-mediated STAT1 phosphorylation and subsequent inhibition of downstream transcriptional target genes, including VCAM-1, TNF-α, IL-1ß, and MCP-1. Interestingly, LPS-induced ERK1/2/STAT1 activation leads to the HMGB1 release from the nucleus into the extracellular space, where it binds to RAGE, while 3'-SL suppressed EC hyperpermeability by suppressing the HMGB1/RAGE axis. This interaction also led to VE-cadherin endothelial junction disassembly and endothelial cell monolayer disruption through ERK1/2/STAT1 modulation. In mouse endothelium, en face staining revealed that 3'-SL abolished LPS-stimulated ROS production and VCAM-1 overexpression. SIGNIFICANCE: Our findings suggest that 3'-SL inhibits LPS-induced endothelial hyperpermeability by suppressing superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis. Therefore, 3'-SL may be a potential therapeutic agent for preventing the progression of atherosclerosis.