Inhibitory neuron map of sevoflurane induced neurotoxicity model in young primates.

Introduction: Sevoflurane, one of the most commonly used anesthetic agents in children, may induce neuronal dysfunction and cognitive impairment. Exposure to sevoflurane might induce an imbalance between neural excitation and inhibition which could be a mechanism behind anesthesia-induced cognitive and affective dysfunctions. However, the underlying mechanisms remain unclear. Methods: In this study, we used two rhesus macaques in the control group, and one rhesus macaques in the anesthesia group. We employed single-nucleus RNA sequencing (snRNA-seq) technology to explore alterations in distinct types of inhibitory neurons involved in the long-term cognitive impairment caused by sevoflurane in young macaques. Results: Following sevoflurane treatment, an upregulation was observed in the SST+ inhibitory neuron in the LHX6+ neighborhood in the hippocampus of rhesus macaques. This alteration might impact brain development by influencing interneuron migration and maturation. Additionally, we proposed a novel classification of inhibitory neurons, defined by CNR1 and LHX6 applicable to both humans and macaques. Discussion: Our study proposed a novel classification of inhibitory neurons defined by LHX6 and CNR1, relevant in macaques and humans. We also provide evidence that sevoflurane upregulated the SST+ inhibitory neuron in the LHX6+ neighborhood in the hippocampus of rhesus macaques, which may underlie the potential neurotoxic effects induced by general anesthetics. Our results also offer a more reliable approach for studying the structure and function of the human brain.

Effects of Sevoflurane Anesthesia on Cerebral Lipid Metabolism in the Aged Brain of Marmosets and Mice.

Objective: In the lipid-rich brain, lipids performed signaling processes associated with the control system of the cell cycle, stress, and inflammatory reactions, as well as maintained brain and cellular homeostasis. The effects of general anesthesia on brain impairment in the elderly were controversial and complex. The study sought to evaluate the effect of lipid metabolism in the brain of aged marmosets and mice under long-term exposure to sevoflurane. Methods: A total of 6 marmosets over 8-year-old and 10 mice aged 18 months were divided into the sevoflurane anesthesia and control groups, respectively. Marmosets in the sevoflurane anesthesia group were exposed to 1.5-2.5% sevoflurane and 100% O2 for 6 h. Mice anesthetized with sevoflurane were exposed to 3% sevoflurane and 60% O2 for 6 h. All prefrontal cortex tissues of marmosets and mice were harvested for the analysis of lipidomics. Results: Compared to the control group, we found that phosphatidylethanolamine (PE) (18:0/22:5), PE (16:0/22:5), PE (18:2/22:5), PE (14:0/22:5), and PE (18:1/22:5) increased in the prefrontal cortex of marmosets in the sevoflurane group, while triglyceride (TAG)56:5-fatty acid (FA) 20:4, TAG58:10-FA22:6, and TAG60:10-FA22:6 decreased. For aged mice, we indicated that lipid components phosphatidic acid (PA) (18:1/20:2) and TAG52:5-FA20:4 in the sevoflurane group increased, but PE (14:0/22:4), diglyceride (DAG) (16:1/18:2), and lysophosphatidylcholine (LPC) (16:1) + AcO decreased. More deeply, sevoflurane anesthesia resulted in the presence of 70 specific lipids in mice and marmosets. The enriched lipid subclasses were mainly monoacylglycerophosphoethanolamines and five other subclasses. Conclusion: Sevoflurane caused slight changes in lipid metabolism both in the aged brain of marmosets and mice. However, the pathways of lipid metabolism were not affected. The effects of sevoflurane on lipid metabolism in aged brains may differ among species.

The Effect of Sevoflurane Anesthesia on the Biomarkers of Neural Injury in the Prefrontal Cortex of Aged Marmosets.

Background: Surgery under general anesthesia leads to neural injury, especially in older patients. Sevoflurane anesthesia without surgery for 2 h does not induce neural injury, however, whether prolonger sevoflurane anesthesia without surgery has the same consequence is still unknown. Methods: In the present study, aged marmosets were exposed to a clinical concentration of sevoflurane (1.5-2%) for 6 h to access the effects of prolonged sevoflurane anesthesia on the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), Caspase3 activity and myelin formation in the brain. Results: Sevoflurane anesthesia did not alter the expression of IL-6 (120.1 ± 2.21 vs. 120.8 ± 2.25, p = 0.74), TNF-α (189.3 ± 31.35 vs. 218.7 ± 21.47, p = 0.25) and Caspase3 (57.35 ± 1.54 vs. 58.67 ± 1.19, p = 0.53) in the prefrontal cortex (PFC) of aged marmosets. The amount of MBP expression (60.99 ± 6.21 vs. 58.91 ± 2.71, p = 0.77) did not change following sevoflurane exposure. Conclusion: Sevoflurane anesthesia did not increase the levels of IL-6 and TNF-α, activated the the expression of Caspase3, and induced myelination deficits in the PFC of aged marmosets.

Identification of Prefrontal Cortex and Amygdala Expressed Genes Associated With Sevoflurane Anesthesia on Non-human Primate.

Clinical trials and animal studies have indicated that long-term use or multiple administrations of anesthesia may lead to fine motor impairment in the developing brain. Most studies on anesthesia-induced neurotoxicity have focused on the hippocampus and prefrontal cortex (PFC); however, the role of other vital encephalic regions, such as the amygdala, is still unclear. Herein, we focused on sevoflurane, the most commonly used volatile anesthetic in infants, and performed a transcriptional analysis of the PFC and amygdala of macaques after multiple exposures to the anesthetic by RNA sequencing. The overall, overlapping, and encephalic region-specific transcriptional patterns were separately analyzed to reveal their functions and differentially expressed gene sets that were influenced by sevoflurane. Specifically, functional, protein-protein interaction, neighbor gene network, and gene set enrichment analyses were performed. Further, we built the basic molecular feature of the amygdala by comparing it to the PFC. In comparison with the amygdala's changing pattern following sevoflurane exposure, functional annotations of the PFC were more enriched in glial cell-related biological functions than in neuron and synapsis development. Taken together, transcriptional studies and bioinformatics analyses allow for an improved understanding of the primate PFC and amygdala.

Epitranscriptomic Analysis of N6-methyladenosine in Infant Rhesus Macaques after Multiple Sevoflurane Anesthesia.

Clinical investigations to date have proposed the possibility that exposure to anesthetics is associated with neurodevelopmental deficits. Sevoflurane is the most commonly used general anesthetic in pediatric patients. Animal studies have demonstrated that multiple exposures to sevoflurane during the postnatal period resulted in neuropathological brain changes and long-term cognitive deficits. However, the underlying mechanisms remain to be clarified. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was performed to acquire genome-wide profiling of RNA N6-methyladenosine (m6A) in the prefrontal cortex of infant rhesus macaques. The macaques in the sevoflurane group had more m6A peaks than the macaques in the control group (p ≤ 0.05). After sevoflurane treatment, the mRNA levels of YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 3 (YTHDF3) were decreased, and sevoflurane anesthesia dynamically regulated RNA m6A methylation. Gene ontology (GO) analysis revealed that after sevoflurane exposure, genes with increased methylation of m6A sites were enriched in some physiological processes relevant to neurodevelopment, mainly focused on synaptic plasticity. The female macaques had 18 hypermethylated genes. The males had 35 hypermethylated genes, and some physiological processes related to the regulation of synaptic structure were enriched. Rhesus macaques are genetically closer to human beings. Our findings can help in the study of the mechanism of sevoflurane-relevant neurodevelopmental deficits at the posttranscriptional level and can provide new insights into potential clinical preventions and interventions for the neurotoxicity of neonatal anesthesia exposure.

Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor and cognitive deficits.

Clinical surgical practices have found that children who undergo multiple anesthesia may have an increased risk of deficiencies in cognition and fine motor control. Here, we report that YT521-B homology domain family 1 (YTHDF1), a critical reader protein for N6-methyladenosine-modified mRNA, was significantly downregulated in the prefrontal cortex of young mice after multiple sevoflurane anesthesia exposures. Importantly, sevoflurane led to a decrease in protein synthesis in mouse cortical neurons that was fully rescued by YTHDF1, suggesting that anesthesia may affect early brain development by affecting m6A-dependent mRNA translation. Transcriptome-wide experiments showed that numerous mRNA targets related to synaptic functions in the prefrontal mouse cortex were associated with m6A methylation and YTHDF1. In particular, we found that synaptophysin, a critical presynaptic protein, was specifically modified by m6A methylation and associated with YTHDF1, and m6A methylation of synaptophysin decreased with multiple sevoflurane exposures. Importantly, we showed that fine motor control skills and cognitive functions were impaired in mice with multiple anesthesia exposures, and these effects were fully reversed by reintroducing YTHDF1 through a blood-brain barrier (BBB)-crossing viral delivery system. Finally, we found that the fine motor skills in children who underwent prolonged anesthesia were compromised 6 months after surgery. Our findings indicated that impairment in the translational regulation of mRNA via N6-methyladenosine methylation is a potential mechanism underlying the effects of anesthesia on neural development in the young brain. 1. N6-methyladenosine (m6A) modifications were involved in anesthesia-induced neurotoxicity. 2. Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor deficits in young mice. 3. YTHDF1, a m6A reader protein, rescued sevoflurane-induced protein synthesis inhibition and fine motor deficits in young mice.

Fine particles in surgical smoke affect embryonic cardiomyocyte differentiation through oxidative stress and mitophagy.

Surgical smoke is widespread in operating rooms, and fine particles are the main toxic components. However, the effect of fine particles in surgical smoke on embryonic development has not yet been studied. This study evaluated the effect of fine particles in surgical smoke on embryonic development and compared it with that of atmospheric fine particles. Afterwards, differentiated cardiomyocytes were purified, and the effect of exposure to fine particles in surgical smoke on cardiomyocyte differentiation was evaluated. Fine particles in surgical smoke exhibited weak embryotoxicity toward an embryonic stem cell test model, and their inhibitory effect on cardiomyocyte differentiation was slightly stronger than that of atmospheric fine particles. Fine particles in surgical smoke specifically inhibited the differentiation of the mesoderm lineage and promoted the differentiation of the ectoderm lineage. Furthermore, fine particles in surgical smoke reduced the beating rate of purified cardiomyocytes, promoted mitophagy, reduced ATP production and increased the reactive oxygen species (ROS) content. Antioxidants attenuated the inhibition of cardiomyocyte differentiation and the reduction in the cardiomyocyte beating rate caused by fine particles in surgical smoke and simultaneously restored mitophagy and other processes to the control levels. However, mitophagy inhibitors treatment blocked only the inhibition of cardiomyocyte differentiation caused by fine particles in surgical smoke; it had little effect on other changes caused by fine particles. Based on the results described above, we propose that fine particles in surgical smoke and atmospheric fine particles exhibit similar levels of toxicity toward embryonic development. Fine particles in surgical smoke potentially affect the beating of cardiomyocytes by damaging mitochondria and increasing oxidative stress.

Dusp4 Contributes to Anesthesia Neurotoxicity via Mediated Neural Differentiation in Primates.

BACKGROUND: Children who are exposed to anesthesia multiple times may undergo cognitive impairment during development. The underlying mechanism has been revealed as anesthesia-induced cognitive deficiency in young rodents and monkeys. However, the molecular mechanism of sevoflurane-induced neural development toxicity is unclear. METHODS: By combining RNA sequencing analysis of macaques' prefrontal cortex and human neural differentiation, this study investigates the mechanism of sevoflurane-induced neurotoxicity in primates. RESULTS: The level of dual specificity protein phosphatase 4 (Dusp4) was significantly downregulated in non-human primates after sevoflurane treatment. We further uncovered the dynamical expression of Dusp4 during the human neural differentiation of human embryonic stem cells and found that knockdown of Dusp4 could significantly inhibit human neural differentiation. CONCLUSION: This study indicated that Dusp4 is critically involved in the sevoflurane-induced inhibition of neural differentiation in non-human primate and the regulation of human neural differentiation. It also suggested that Dusp4 is a potential therapeutic target for preventing the sevoflurane-induced neurotoxicity in primates.

Role of Parkin-mediated mitophagy in glucocorticoid-induced cardiomyocyte maturation.

Glucocorticoids can promote cardiomyocyte maturation. However, the mechanism underlying glucocorticoid-mediated cardiomyocyte maturation is still unclear. Mitophagy plays a key role in cardiomyocyte maturation. Based on current knowledge, our study evaluated the effects of the glucocorticoid dexamethasone (100 nM) on the maturation of mouse embryonic stem cell-derived cardiomyocytes and the role of mitophagy in this maturation. The results showed that dexamethasone can promote embryonic stem cell-derived cardiomyocyte maturation, inhibit cardiomyocyte proliferation, and promote myocardial fiber arrangement. However, dexamethasone did not affect mitochondrial morphology in cardiomyocytes. Glucocorticoid receptor inhibitors (RU486, 1 nM) can inhibit dexamethasone-mediated cardiomyocyte maturation. Additionally, dexamethasone can promote mitophagy in embryonic stem cell-derived cardiomyocytes and induce LC3 and lysosomal aggregation in mitochondria. The inhibition of mitophagy can inhibit the cardiomyocyte maturation effect of dexamethasone. Furthermore, our research found that dexamethasone may mediate the occurrence of mitophagy in cardiomyocytes through Parkin. The siRNA-mediated inhibition of Parkin expression can inhibit mitochondrial autophagy caused by dexamethasone, thus inhibiting cardiomyocyte maturation. Overall, our study found that dexamethasone can promote embryonic stem cell-derived cardiomyocyte maturation through Parkin-mediated mitophagy.

Multiple sevoflurane exposures don't disturb the T-cell receptor repertoire in infant rhesus monkeys' thymus.

AIMS: Multiple surgical procedures and anesthesia increase the risk of the development in children. However, the influence of such exposures on the developing childhood immunity organs is rarely reported. MATERIALS AND METHODS: High-throughput sequencing of T-cell receptor (TCR) repertoires (TCRseq) from rhesus monkeys' thymus was performed to investigate whether anesthetics could induce de novo antigen recognition via TCR or TCR development impairments. KEY FINDINGS: No significant difference between sevoflurane and control groups regarding VJ gene combinations and diversity of V and J gene was seen, nor was there an obvious change in similar average number of Complementarity Determining Region 3 (CDR3) aa clonotypes. Our analysis of Rank abundance, Gini coefficient, Simpson index, Normalized Shannon Diversity Entropy (NSDE), Morisita-Horn Similarity Index (MHSI) and Bhattacharyya Distance (BD) indicated there is no difference in TCR diversity and similarity. SIGNIFICANCE: These results suggest early events in thymic T cell development and repertoire generation are not abnormality after multiple sevoflurane exposure during childhood. The stabilization of the immune repertoires suggested the safety of sevoflurane in host immune response in children.

Multiple sevoflurane exposures during pregnancy inhibit neuronal migration by upregulating prostaglandin D2 synthase.

BACKGROUND: The second trimester is a period of neurogenesis and neuronal migration, which may be affected by exposure to anesthetics. Studies have suggested that multiple anesthetic exposures may have a significant impact on neuronal migration. METHODS: Pregnant C57BL/6 mice at embryonic day 14.5 were randomly divided into four groups: Con x 1, Sev x 1, Con x 2, and Sev x 2. Cortical neuronal migration in offspring mice was detected by GFP immunostaining, and the number of cells in the cortex was analyzed. RESULTS: Dual exposure to sevoflurane, not single sevoflurane exposure, caused neuronal migration deficits. Dual exposure to sevoflurane increased the expression of prostaglandin D2 synthase (Ptgds). Furthermore, Ptgds siRNA attenuated neuronal migration deficits induced by dual sevoflurane exposure. CONCLUSION: Our study suggests that multiple sevoflurane exposures in pregnant mice may induce neuronal migration deficits in offspring mice. Additional studies comprising long-term behavioral tests are required to confirm the effects of sevoflurane exposure during pregnancy.

The role of long non-coding RNA SNHG12 in neuroprotection following cerebral ischemic injury.

As one of the major causes of mortality and disability worldwide, ischemic stroke has never been received enough attention. Following ischemia/reperfusion injury, long non-coding RNAs have been extensively found to be involved into inflammatory responses, microvascular endothelial cell death, and angiogenesis in the brain. The small nucleolar RNA host gene 12 was found to be significantly increased following transient middle cerebral artery occlusion. However, the effect and underlying mechanism of small nucleolar RNA host gene 12 in ischemic stroke remain to be explored. We established an oxygen-glucose deprivation/reoxygen in primary neurons model to mimic ischemic stroke. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay and lactate dehydrogenase assay were used to prove that knockdown small nucleolar RNA host gene 12 reduced cell viability after oxygen-glucose deprivation/reoxygen treatment. And the western blot showed that knockdown small nucleolar RNA host gene 12 aggravated the oxygen-glucose deprivation/reoxygen-induced apoptosis. What's more, the pro-inflammatory cytokine level was increased in small nucleolar RNA host gene 12 knockdown primary neurons. Mechanistically, the specific distribution of small nucleolar RNA host gene 12 in primary neurons was detected by fluorescence in situ hybridisation. Additionally, we demonstrate small nucleolar RNA host gene 12 attenuates oxygen-glucose deprivation/reoxygen injury through activating Akt signaling pathway. Therefore, the small nucleolar RNA host gene 12 may be the new potential therapeutic target for the alleviation of cerebral ischemic injury.

Disrupted folate metabolism with anesthesia leads to myelination deficits mediated by epigenetic regulation of ERMN.

BACKGROUND: Exposure to anesthetics during early life may impair cognitive functions. However, the underlying mechanisms remain largely unknown. We set out to determine effects of sevoflurane anesthesia on folate metabolism and myelination in young non-human primates, mice and children. METHODS: Young rhesus macaque and mice received 2.5 to 3% sevoflurane daily for three days. DNA and RNA sequencing and immunohistochemistry among others were used in the studies. We performed unbiased transcriptome profiling in prefrontal cortex of rhesus macaques and mice after the sevoflurane anesthesia. We constructed a brain blood barrier-crossing AAV-PHP.EB vector to harbor ERMN expression in rescue studies. We measured blood folate levels in children after anesthesia and surgery. FINDINGS: We found that thymidylate synthase (TYMS) gene was downregulated after the sevoflurane anesthesia in both rhesus macaque and mice. There was a reduction in blood folate levels in children after the anesthesia and surgery. Combined with transcriptome and genome-wide DNA methylation analysis, we identified that ERMN was the primary target of the disrupted folate metabolism. Myelination was compromised by the anesthesia in the young mice, which was rescued by systematic administration of folic acid or expression of ERMN in the brain through brain-specific delivery of the adeno-associated virus. Moreover, folic acid and expression of ERMN alleviated the cognitive impairment caused by the sevoflurane anesthesia in the mice. INTERPRETATION: General anesthesia leads to disrupted folate metabolism and subsequently defects in myelination in the developmental brain, and ERMN is the important target affected by the anesthesia via epigenetic mechanisms.

Fundamentals of fetal toxicity relevant to sevoflurane exposures during pregnancy.

Over the last three decades, advances in medical and surgical techniques have proven life saving and life-improving for young children. Consequently, early and repeated exposure to general anesthetics in childhood has increased. However, accumulating evidence suggests that general anesthetics may be neurotoxic in children. Of particular concern is the neurotoxicity fetuses may suffer from maternal exposure to sevoflurane during surgeries and fetal intervention procedures performed during the second trimester, as this can cause neurodevelopmental impairment in offspring. In this review we demonstrate that the pathology associated with fetal toxicity resulting from exposure to sevoflurane during pregnancy involves oxidative stress, neuroinflammation, neuroapoptosis, and alteration of synaptic properties. The mechanisms remain to be elucidated, but may include increased tau protein phosphorylation and abnormal methylation. These findings highlight the need for a global and comprehensive understanding of the potential neurotoxicity of anesthetic exposure in fetuses and its long-term effects.

Mesenchymal stromal cells attenuate sevoflurane-induced apoptosis in human neuroglioma H4 cells.

BACKGROUND: Inhalation of sevoflurane can induce neuronal apoptosis, cognitive impairment and abnormal behaviors. Bone marrow mesenchymal stem cells (MSCs) can secret neurotrophic factors and cytokines to protect from oxidative stress-related neuronal apoptosis. However, whether MSCs can protect from sevoflurane-induced neuronal apoptosis and the potential mechanisms are unclear. METHODS: A non-contact co-culture of MSCs with human neuroglioma H4 cells (H4 cells) was built. H4 cells were co-cultured with MSCs or without MSCs (control) for 24 h. The co-cultured H4 cells were exposed to 4% sevoflurane for 6 h. The levels of caspase-3, reactive oxygen species (ROS), adenosine triphosphate (ATP), and the release of cytochrome C were determined by Western blot and fluorescence assay. RESULTS: Sevoflurane exposure significantly elevated the levels of cleaved caspase 3 and Bax in H4 cells. However, these phenomena were significantly offset by the co-culture with MSCs in H4 cells. Co-culture with MSCs before, but not after, sevoflurane exposure, significantly attenuated sevoflurane-induced ROS production in H4 cells. MSCs prevented sevoflurane-mediated release of cytochrome C from the mitochondria and production of ATP in H4 cells. CONCLUSIONS: Our study indicated that soluble factors secreted by MSCs attenuated the sevoflurane-induced oxidative stress and apoptosis of neuronal cells by preserving their mitochondrial function.

Nrf2 Activation Induced by Sirt1 Ameliorates Acute Lung Injury After Intestinal Ischemia/Reperfusion Through NOX4-Mediated Gene Regulation.

BACKGROUND/AIMS: Nuclear erythroid 2-related factor-2 (Nrf2) is a major stress-response transcription factor that has been implicated in regulating ischemic angiogenesis. We investigated the effects of Nrf2 in regulating revascularization and modulating acute lung injury. METHODS: The expression of Nrf2 and sirtuin1 (Sirt1) was assessed in lung tissue by western blotting and immunofluorescence staining after intestinal ischemia/reperfusion (IIR) in Nrf2-/- and wild-type (WT) mice. The involvement of Nrf2 in angiogenesis, cell viability, and migration was investigated in human pulmonary microvascular endothelial cells (PMVECs). Additionally, the influence of Nrf2 expression on NOX pathway activation was measured in PMVECs after oxygen-glucose deprivation/reoxygenation. RESULTS: We found activation and nuclear accumulation of Nrf2 in lung tissue after IIR. Compared to IIR in WT mice, IIR in Nrf2-/- mice significantly enhanced leukocyte infiltration and collagen deposit, and inhibited endothelial cell marker CD31 expression. Nrf2 upregulation and translocation into the nucleus stimulated by Sirt1 overexpression exhibited remission of histopathologic changes and enhanced CD31 expression. Nrf2 knockdown repressed non-phagocytic cell oxidase 4 (NOX4), hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) expression after IIR. Nrf2 upregulation by Sirt1 enhances NOX4, HIF-1α and VEGF expression after IIR in WT mice. Furthermore, Nrf2 knockdown suppressed cell viability, capillary tube formation and cell migration in PMVECs after oxygen-glucose deprivation/reoxygenation and also inhibited NOX4, HIF-1 and VEGF expression. Moreover, NOX4 knockdown in PMVECs decreased the levels of VEGF, HIF-1α and angiogenesis. CONCLUSION: Nrf2 stimulation by Sirt1 plays an important role in sustaining angiogenic potential through NOX4-mediated gene regulation.

Surface Modified with a Host Defense Peptide-Mimicking ß-Peptide Polymer Kills Bacteria on Contact with High Efficacy.

Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the major nosocomial pathogens to cause frequent and serious infections that are associated with various biomedical surfaces. This study demonstrated that surface modified with host defense peptide-mimicking ß-peptide polymer, has surprisingly high bactericidal activities against Escherichia coli ( E. coli) and MRSA. As surface-tethered ß-peptide polymers cannot move freely to adopt the collaborative interactions with bacterial membrane and are too short to penetrate the cell envelop, we proposed a mode of action by diffusing away the cell membrane-stabilizing divalent ions, Ca2+ and Mg2+. This hypothesis was supported by our study that Ca2+ and Mg2+ supplementation in the assay medium causes up to 80% loss of bacterial killing efficacy and that the addition of divalent ion chelating ethylenediaminetetraacetic acid into the above assay medium leads to significant recovery of the bacterial killing efficacy. In addition to its potent bacterial killing efficacy, the surface-tethered ß-peptide polymer also demonstrated excellent biocompatibility by displaying no hemolysis and supporting mammalian cell adhesion and growth. In conclusion, this study demonstrated the potential of ß-peptide polymer-modified surface in addressing nosocomial infections that are associated with various surfaces in biomedical applications.