Mediator subunit MED8 interacts with heat shock transcription factor HSF3 to promote fucoxanthin synthesis in the diatom Phaeodactylum tricornutum.

Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.

High cardiovascular mortality risk among older merkel cell carcinoma patients.

OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM. RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect. CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

Microphase behaviors and shear moduli of double-network gels: The effect of crosslinking constraints and chain uncrossability.

By performing coarse-grained molecular dynamics simulations, we study the effect of crosslinking and chain uncrossability on the microphase behaviors and mechanical properties of the double-network gels. The double-network systems can be viewed as two separate networks interpenetrating each other uniformly, and the crosslinks in each network are generated, forming a regular cubic lattice. The chain uncrossability is confirmed by appropriately choosing the bonded and nonbonded interaction potentials. Our simulations reveal a close relation between the phase and mechanical properties of the double-network systems and their network topological structures. Depending on the lattice size and the solvent affinity, we have observed two different microphases: one is the aggregation of solvophobic beads around the crosslinking points, which leads to locally polymer-rich domains, and the other is the bunching of polymer strands, which thickens the network edges and thus changes the network periodicity. The former is a representation of the interfacial effect, while the latter is determined by the chain uncrossability. The coalescence of network edges is demonstrated to be responsible for the large relative increase in the shear modulus. Compressing and stretching induced phase transitions are observed in the current double-network systems, and the sharp discontinuous change in the stress that appears at the transition point is found to be related to the bunching or debunching of the network edges. The results suggest that the regulation of network edges has a strong influence on the network mechanical properties.

Roles of sirtuin family members in chronic obstructive pulmonary disease.

The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1-7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment.

Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets.

Fucoxanthin, one of the most abundant carotenoids from edible brown seaweeds, for years has been used as a bioactive dietary supplement and functional food ingredient. Recently, fucoxanthin was reported to penetrate the blood-brain barrier, and was superior to other carotenoids to exert anti-neurodegenerative disorder effects via acting on multiple targets, including amyloid protein aggregation, oxidative stress, neuroinflammation, neuronal loss, neurotransmission dysregulation and gut microbiota disorder. However, the concentration of fucoxanthin required for in vivo neuroprotective effects is somewhat high, and the poor bioavailability of this molecule might prevent its clinical use. As such, new strategies have been introduced to overcome these obstacles, and may help to develop fucoxanthin as a novel lead for neurodegenerative disorders. Moreover, it has been shown that some metabolites of fucoxanthin may produce potent in vivo neuroprotective effects. Altogether, these studies suggest the possibility for future development of fucoxanthin as a one-compound-multiple-target or pro-drug type pharmaceutical or nutraceutical treatment for neurodegenerative disorders.Trial registration: ClinicalTrials.gov identifier: NCT03625284.Trial registration: ClinicalTrials.gov identifier: NCT02875392.Trial registration: ClinicalTrials.gov identifier: NCT03613740.Trial registration: ClinicalTrials.gov identifier: NCT04761406.

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway.

BACKGROUND: Although long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) has been reported to be involved in atherosclerosis (AS) development, its specific mechanism remains unclear. METHODS: DANCR expression levels in blood samples of AS patients and oxidized low-density lipoprotein (ox-LDL) treated vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The small interfering RNA targeting DANCR (si-DANCR) was used to silence DANCR expression. Cell viability was assessed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Levels of inflammatory cytokines, anti-oxidative enzyme superoxide dismutase (SOD) activity, and malonaldehyde (MDA) were detected by specific commercial kits. An animal AS model was established to confirm the role of DANCR/microR-214-5p/COX20 (the chaperone of cytochrome c oxidase subunit II COX2) in AS development. RESULTS: DANCR was significantly increased in the blood samples of AS patients and ox-LDL treated VSMCs and HUVECs. DANCR downregulation obviously increased viability and reduced apoptosis of ox-LDL-treated VSMCs and HUVECs. Meanwhile, DANCR downregulation reduced the levels of inflammatory cytokines, including interleukin (IL)-6 (IL-6), IL-1beta (IL-1ß), IL-6 and tumor necrosis factor (TNF)-alpha (TNF-α) and MDA while increasing the SOD level in ox-LDL-treated VSMCs and HUVECs. DANCR regulated COX20 expression by acting as a competing endogenous RNA (ceRNA) of miR-214-5p. Rescue experiments demonstrated that miR-214-5p downregulation obviously attenuated si-DANCR-induced protective effects on ox-LDL-caused endothelial injury. CONCLUSIONS: Our results revealed that DANCR promoted AS progression by targeting the miR-214-5p/COX20 axis, suggesting that DANCR might be a potential therapeutic target for AS.

High-Purity Fucoxanthin Can Be Efficiently Prepared from Isochrysis zhangjiangensis by Ethanol-Based Green Method Coupled with Octadecylsilyl (ODS) Column Chromatography.

The exploitation of new economically valuable microalgae as a sustainable source of minor high-value products can effectively promote the full utilization of microalgae. The efficient preparation of minor products from microalgae remains the challenge, owing to the coexistence of various components with a similar polarity in the microalgae biomass. In this study, a novel approach based on the sustainable-oriented strategy for fucoxanthin (FX) production was proposed, which consisted of four steps, including the culture of microalga, ethanol extraction, ODS column chromatography, and ethanol precipitation. The high-purity FX (around 95%) was efficiently obtained in a total recovery efficiency of 84.28 ± 2.56%. This study reveals that I. zhangjiangensis is a potentially promising feedstock for FX production and firstly provides a potentially eco-friendly method for the scale-up preparation of FX from the microalga I. zhangjiangensis.

Effects of Comprehensive Swallowing Intervention on Obstructive Sleep Apnea and Dysphagia After Stroke: A Randomized Controlled Trial.

OBJECTIVE: This study aims to explore the effects of comprehensive swallowing intervention on obstructive sleep apnea (OSA) and dysphagia in stroke patients. METHODS: We performed a randomized controlled trial in stroke patients with obstructive sleep apnea (OSA) complicated by dysphagia, divided into treatment group and control group. The treatment group underwent comprehensive swallowing intervention and received swallowing care for 4 weeks, while the control group received only swallowing care. Outcome measurements were obtained at baseline and after the 4-week intervention, evaluated by polysomnography (PSG), videoendoscopic swallowing study (VFSS) synchronized surface electromyography (sEMG), oropharyngeal magnetic resonance imaging (MRI) and swallowing assessment scales. RESULTS: Sixty patients with stroke (30 treatment and 30 control) were eligible to participate in this study. There were no significant differences in any assessment between two groups at baseline. After a 4-week intervention, compared with to control group, there was a significant decrease in the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), and increased mean and minimal oxygen saturation (SaO2), amplitudes of suprahyoid muscle group (ASUPMG) and subhyoid muscle group (ASUBMG). Moreover, the posterior palatal distance (PPD), posterior lingual distance (PLD) and minimal cross-sectional area (MCSA) were obviously elevated in the treatment group. Additionally, the scores of Gugging swallowing screen (GUSS) and VFSS were significantly increased in the treatment group, compared to control group. CONCLUSIONS: The comprehensive swallowing intervention had therapeutic effects on OSA and dysphagia after stroke, and the mechanism was related to enhancing oropharyngeal muscle strength and changing upper airway structure.

Decellularized adipose tissue: A key factor in promoting fat regeneration by recruiting and inducing mesenchymal stem cells.

BACKGROUND: Decellularized adipose tissue (DAT) has attracted much attention due to its wide range of sources and adipose regeneration capacity. However, the lipogenic efficiency of DAT is still controversial due to its unclear mechanism. To this point, it is crucial to clarify the mechanism of DAT in promoting adipose regeneration Objective: This study aims to explore the mechanism of DAT promoting adipose regeneration and survival mechanism of DAT transplantation in vivo. METHODS: DAT preparation by repeated freeze-thaw, enzymatic digestion, and isopropanol degreasing. Histology, DAPI, immunohistochemistry, immunofluorescence and scanning electron microscopy confirmed the efficacy and reproducibility of these approaches. BM-MSCs, ADSCs and UCMSCs were cocultured with DAT for 14 days and then stained with oil red O. Adipogenic genes of three MSCs were detected by RT-PCR. DAT and adipose tissue were transplanted subcutaneously into the back of nude mice to observe medium and long-term morphological changes, vascularization, and lipid-forming efficiency. Mass spectrometry (MS)-based proteomic to analyze the adipogenic protein contents of DAT and adipose tissue. RESULTS: The DAT without any cellular components but with an abundance of collagen; neither DNA nor lipids were detected. Seeding experiments with MSCs indicated that the DAT provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARγ. Within four months after transplantation, HE morphology of DAT was identical to adipose cells. Immunofluorescence markers CD31 and perilipin were increased in DAT, while the retention rate gradually decreased over time, eventually accounting for 33.7% of the original volume. MS-based proteomic analyses identified 1013 types of proteins in adipose tissue and 29 proteins in the DAT. Analyses of GO and KEGG databases suggested that DAT contained a variety of proteins involved in fat metabolism. CONCLUSIONS: DAT can interact with different types of MSCs and ultimately achieve adipose regeneration. The presence of multiple adipogenic proteins in DAT make it play a vital role in adipose regeneration. DAT is expected to be an ideal bio-derived scaffold for adipose tissue engineering.

Thickness-induced band-gap engineering in lead-free double perovskite Cs2AgBiBr6 for highly efficient photocatalysis.

In recent years, two-dimensional (2D) lead-free double perovskites have been attracting much attention because of their unique performance in photovoltaic solar cells and photocatalysis. Nonetheless, how thickness affects the photoelectric properties of lead-free double perovskite remains unclear. In this work, by means of density functional theory (DFT) with a spin orbit coupling (SOC) effect, we have investigated the electronic and optical properties systemically, including band structures, carrier mobility, optical absorption spectra, exciton-binding energies, band edges alignment and molecule adsorption performance of Cs2AgBiBr6 with different thicknesses. The calculated results revealed the thickness-induced band gap and optical performance for Cs2AgBiBr6. It shows a low band gap and outstanding optical absorption of visible and ultraviolet light. When the thickness is reduced to a monolayer, Cs2AgBiBr6 moves from an indirect band gap to a direct band gap. Moreover, the carrier mobility of Cs2AgBiBr6 is excellent and the exciton-binding energy increases with the decreased thickness. Importantly, an analysis of molecule adsorption and band edge alignment indicates that Cs2AgBiBr6 is prone to H2O adsorption and H2 desorption theoretically, which is conducive to the photocatalytic water splitting for hydrogen generation and other photovatalytic reactions. Our work suggests that Cs2AgBiBr6 is a potential candidate as a solar cell or a photocatalyst, and we provide theoretical explorations into reducing the layers of lead-free double perovskite materials to 2D atomic thickness for a better photocatalytic application, which can serve as guidelines for the design of excellent photocatalysts.

The Protective Effect of Anthocyanins Extracted from Aronia Melanocarpa Berry in Renal Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Our previous research showed the antioxidant activity of anthocyanins extracted from Aronia melanocarpa of black chokeberry in vitro. Ischemia acute kidney injury is a significant risk in developing progressive and deterioration of renal function leading to clinic chronic kidney disease. There were many attempts to protect the kidney against this progression of renal damage. Current study was designed to examine the effect of pretreatment with three anthocyanins named cyanidin-3-arabinoside, cyanidin-3-glucodise, and cyaniding-3-galactoside against acute ischemia-reperfusion injury in mouse kidney. METHODS: Acute renal injury model was initiated by 30 min clamping bilateral renal pedicle and followed by 24-hour reperfusion in C57Bl/6J mice. Four groups of mice were orally pretreated in 50 mg/g/12 h for two weeks with cyanidin-3-arabinoside, cyanidin-3-glucodise, and cyaniding-3-galactoside and anthocyanins (three-cyanidin mixture), respectively, sham-control group and the renal injury-untreated groups only with saline. RESULTS: The model resulted in renal dysfunction with high serum creatinine, blood urea nitrogen, and changes in proinflammatory cytokines (TNF-ɑ, IL-1ß, IL-6, and MCP-1), renal oxidative stress (SOD, GSH, and CAT), lipid peroxidation (TBARS and MDA), and apoptosis (caspase-9). Pretreatment of two weeks resulted in different extent amelioration of renal dysfunction and tubular damage and suppression of proinflammatory cytokines, oxidative stress, lipid peroxidation, and apoptosis, thus suggesting that cyanidins are potentially effective in acute renal ischemia by the decrease of inflammation, oxidative stress, and lipid peroxidation, as well as apoptosis. CONCLUSION: the current study provided the first attempt to investigate the role of anthocyanins purified from Aronia melanocarpa berry in amelioration of acute renal failure via antioxidant and cytoprotective effects.

Isolation and Purification of Fucoxanthin from Brown Seaweed Sargassum horneri Using Open ODS Column Chromatography and Ethanol Precipitation.

As an abundant marine xanthophyll, fucoxanthin (FX) exhibits a broad range of biological activities. The preparation of high-purity FX is in great demand, however, most of the available methods require organic solvents which cannot meet the green chemistry standard. In the present study, a simple and efficient purification approach for the purification of FX from the brown seaweed Sargassum horneri was carried out. The FX-rich ethanol extract was isolated by octadecylsilyl (ODS) column chromatography using ethanol-water solvent as a gradient eluent. The overwhelming majority of FX was successfully eluted by the ethanol-water mixture (9:1, v/v), with a recovery rate of 95.36%. A parametric study was performed to optimize the aqueous ethanol precipitation process by investigating the effects on the purity and recovery of FX. Under the optimal conditions, the purity of FX was 91.07%, and the recovery rate was 74.98%. Collectively, the eco-friendly method was cost-efficient for the purification of FX. The developed method provides a potential approach for the large-scale production of fucoxanthin from the brown seaweed Sargassum horneri.

Activity and Stability Boosting of an Oxygen-Vacancy-Rich BiVO4 Photoanode by NiFe-MOFs Thin Layer for Water Oxidation.

The introduction of oxygen vacancies (Ov) has been regarded as an effective method to enhance the catalytic performance of photoanodes in oxygen evolution reaction (OER). However, their stability under highly oxidizing environment is questionable but was rarely studied. Herein, NiFe-metal-organic framework (NiFe-MOFs) was conformally coated on oxygen-vacancy-rich BiVO4 (Ov-BiVO4 ) as the protective layer and cocatalyst, forming a core-shell structure with caffeic acid as bridging agent. The as-synthesized Ov-BiVO4 @NiFe-MOFs exhibits enhanced stability and a remarkable photocurrent density of 5.3±0.15 mA cm-2 at 1.23 V (vs. RHE). The reduced coordination number of Ni(Fe)-O and elevated valence state of Ni(Fe) in NiFe-MOFs layer greatly bolster OER, and the shifting of oxygen evolution sites from Ov-BiVO4 to NiFe-MOFs promotes Ov stabilization. Ovs can be effectively preserved by the coating of a thin NiFe-MOFs layer, leading to a photoanode of enhanced photocurrent and stability.

A highly simulated scar model developed by grafting human thin split-thickness skin on back of nude mouse: The remodeling process, histological characteristics of scars.

A predictive scar animal model is needed in order to study the mechanism and assess the therapies before its use in humans. However, due to the differences in wound healing patterns and regeneration ability, none of the existing models can fully simulate the characteristics of human scar. The aim of this study was to build a model that recapitulated the developing process and outcomes of human hypertrophic scar (HS). Nude mice were grafted with thin split-thickness human skins. The dynamic changes and final outcomes of the grafts were investigated. The results showed that human skin grafts survived and underwent progressive scarring remodeling in morphology and histology. Scar related markers (α-SMA, CD34, Collage I, TGF-ß1) were positive in immunohistology. Protein expressions in TGF-ß1/Smad2/3 pathway were increased in accordance with HS during the development process by western blotting. It was finally proved that scar reconstructed by this model matches a real-world human HS. This is a stable, easy to reproduce model for studying the scar formation process and its properties.

HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure.

A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.

Diterpenes from the Marine Algae of the Genus Dictyota.

Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus.

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

New Peptides Isolated from Marine Cyanobacteria, an Overview over the Past Decade.

Marine cyanobacteria are significant sources of structurally diverse marine natural products with broad biological activities. In the past 10 years, excellent progress has been made in the discovery of marine cyanobacteria-derived peptides with diverse chemical structures. Most of these peptides exhibit strong pharmacological activities, such as neurotoxicity and cytotoxicity. In the present review, we summarized peptides isolated from marine cyanobacteria since 2007.

A Review Study on Macrolides Isolated from Cyanobacteria.

Cyanobacteria are rich sources of structurally-diverse molecules with promising pharmacological activities. Marine cyanobacteria have been proven to be true producers of some significant bioactive metabolites from marine invertebrates. Macrolides are a class of bioactive compounds isolated from marine organisms, including marine microorganisms in particular. The structural characteristics of macrolides from cyanobacteria mainly manifest in the diversity of carbon skeletons, complexes of chlorinated thiazole-containing molecules and complex spatial configuration. In the present work, we systematically reviewed the structures and pharmacological activities of macrolides from cyanobacteria. Our data would help establish an effective support system for the discovery and development of cyanobacterium-derived macrolides.

Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection.

Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2(-/-)mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates.