A Smart DNA Hydrogel Enables Synergistic Immunotherapy and Photodynamic Therapy of Melanoma.

Immunotherapy faces insufficient immune activation and limited immune effectiveness. Herein, we report a smart DNA hydrogel that enables the release of multivalent functional units at the tumor site to enhance the efficacy of immunotherapy. The smart DNA hydrogel was assembled from two types of ultra-long DNA chains synthesized via rolling circle amplification. One DNA chain contained immune adjuvant CpG oligonucleotides and polyaptamers for loading natural killer cell-derived exosomes; the other chain contained multivalent G-quadruplex for loading photodynamic agents. DNA chains formed DNA hydrogel through base-pairing. HhaI restriction endonuclease sites were designed between functional units. Upon stimuli in the tumor sites, the hydrogel was effectively cleaved by the released HhaI and disassembled into functional units. Natural killer cell-derived exosomes played an anti-tumor role, and the CpG oligonucleotide activated antigen-presenting cells to enhance the immunotherapy. Besides the tumor-killing effect of photodynamic therapy, the generated cellular debris acted as an immune antigen to further enhance the immunotherapeutic effect. In a mouse melanoma orthotopic model, the smart DNA hydrogel as a localized therapeutic agent, achieved a remarkable tumor suppression rate of 91.2 %. The smart DNA hydrogel exhibited enhanced efficacy of synergistic immunotherapy and photodynamic therapy, expanding the application of DNA materials in biomedicine.

Overexpression of NtDOGL4 improves cadmium tolerance through abscisic acid signaling pathway in tobacco.

The DELAY OF GERMINATION1-LIKE (DOGL) genes play an essential role in diverse biological processes in plants. However, their exact involvement in the response to cadmium (Cd) stress via the ABA pathway remains unclear. Here, we focused on NtDOGL4, a tobacco DOGL gene whose expression is highly induced upon exposure to Cd. Overexpression of NtDOGL4 in tobacco resulted in elevated endogenous ABA levels, reduced Cd accumulation, and increased tolerance to Cd. Moreover, NtDOGL4 overexpression led to decreased accumulation of reactive oxygen species (ROS) and improved ROS scavenging capacity under Cd stress. Further analyses revealed the direct binding of the transcription factor ABSCISIC ACID-INSENSITIVE 5 (ABI5) to the NtDOGL4 promoter, positively regulating its expression in tobacco. Notably, NtDOGL4 overexpression promoted suberin formation and deposition, while suppressing the expression of Cd transporter genes in tobacco roots, as evidenced by histochemical staining, suberin fraction determination, and qRT-PCR assays. Collectively, our results demonstrate that NtDOGL4 overexpression reduces Cd accumulation, thereby improving Cd stress tolerance through the modulation of antioxidant system, transcription of Cd transporters, and suberin deposition. Notably, the NtABI5-NtDOGL4 module functions as a positive regulator in tobacco's Cd tolerance, underscoring its potential as a molecular target for developing low-Cd crops to ensure environmental safety.

Radiomics analysis based on single phase and different phase combinations of radiomics features from tri-phasic CT to distinguish renal oncocytoma from chromophobe renal cell carcinoma.

OBJECTIVES: To investigate different radiomics models based on single phase and the different phase combinations of radiomics features from 3D tri-phasic CT to distinguish RO from chRCC. METHODS: A total of 96 patients (30 RO and 66 chRCC) were enrolled in this study. Radiomics features were extracted from unenhanced phase (UP), corticomedullary phase (CMP), and nephrographic phase (NP) CT images. Feature selection was based on the least absolute shrinkage and selection operator regression (LASSO) method. The selected features were used to develop different radiomics models using logistic regression (LR) analysis, including model 1 (UP), model 2(CMP), model 3(NP), model 4(UP+CMP), model 5(UP+NP), model 6(CMP+NP), and model 7(UP+CMP+NP). The radiomics model demonstrating the highest discrimination performance was utilized to construct the combined model (model 8) with clinical factors. A nomogram based on the model 8 was established. To evaluate the diagnostic performance of the different models, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used. Delong's test was utilized to assess the statistical significance of the AUC improvement across the models. RESULTS: Among the seven radiomics models, model 7 exhibited the highest AUC of 0.84 (95% CI 0.69, 0.99), and model 7 demonstrated a significantly superior AUC compared to the other radiomics models (all P < 0.05). The AUC values of radiomics models based on two phases (model4, mode5, mode6) were greater than the models based on single phase (model1, mode2, mode3) (all P < 0.05). Model 3 illustrated the best performance of the three radiomics models based on single phase with an AUC of 0.76 (95% CI 0.57, 099). Model 6 illustrated the best performance of the three radiomics models based on two-phases combination with an AUC of 0.83 (0.66, 0.99). Model 8 achieved an AUC of 0.93 (95% CI 0.83, 1.00) which is higher than those all radiomics models. CONCLUSION: Radiomics models based on combination of radiomics features from UP, CMP, and NP can be a useful and promising technique to differentiate RO from chRCC. Moreover, the model combining clinical factors and radiomics features showed better classification performance to distinguish them.

Safety of daratumumab in the real-world: a pharmacovigilance study based on FAERS database.

BACKGROUND: Daratumumab is widely used in multiple myeloma (MM) and light chain amyloidosis (AL amyloidosis). The purpose of this study was to identify adverse event (AE) signals for daratumumab through the FDA Adverse Event Reporting System (FAERS) database to assess its safety in a large sample of people. METHODS: Based on data from the FAERS database, three disproportionality analysis methods were used to mine AE signals for daratumumab, including reporting odd ratio (ROR), proportional reporting ratio (PRR), and bayesian configuration promotion neural network (BCPNN). RESULTS: A total of 9220 AE reports with daratumumab as the primary suspect drug were collected, containing 23,946 AEs. Within these reports, 252 preferred terms (PT) levels, 73 high level term (HLT) levels and 11 system organ class (SOC) levels of AE signals were detected, along with some new AEs. Most AEs occurred within the first month after drug administration. CONCLUSION: Our findings were consistent with the results of established studies that daratumumab has a good safety profile. The newly identified AEs are of concern and prospective clinical studies are needed to confirm whether they are causally related to daratumumab. This study provided an early warning for the safe use of daratumumab and also provided guidance for further safety studies.

Efficacy of continuous positive airway pressure on TNF-α in obstructive sleep apnea patients: A meta-analysis.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is an important mediator of the immune response. At present, the improvement of TNF-α after continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is still controversial. METHODS: We conducted a systematic review of the present evidence based on a meta-analysis to elucidate the effects of TNF-α on OSAHS after CPAP treatment. RESULTS: To measure TNF-α, ten studies used enzyme-linked immunosorbent assay (ELISA), and one used radioimmunoassay. The forest plot outcome indicated that CPAP therapy would lower the TNF-α levels in OSAHS patients, with a weighted mean difference (WMD) of 1.08 (95% CI: 0.62-1.55; P < 0.001) based on the REM since there is highly significant heterogeneity (I2 = 90%) among the studies. Therefore, we used the subgroup and sensitivity analyses to investigate the source of heterogeneity. The findings of the sensitivity analysis revealed that the pooled WMD ranged from 0.91 (95% CI: 0.52-1.31; P < 0.001) to 1.18 (95% CI: 0.74-1.63; P < 0.001). The findings were not influenced by any single study. Notably, there was homogeneity in the Asia subgroup and publication year: 2019, implying that these subgroups could be the source of heterogeneity. CONCLUSION: Our meta-analysis recommends that CPAP therapy will decrease the TNF-α level in OSAHS patients, but more related research should be conducted.

Multilineage-differentiating stress-enduring cells alleviate atopic dermatitis-associated behaviors in mice.

BACKGROUND: Pruritus is a recurring, long-lasting skin disease with few effective treatments. Many patients have unsatisfactory responses to currently available antipruritic treatments, and effective therapeutics are urgently needed to relieve symptoms. A previous study reported that mesenchymal stem cell (MSC)-mediated immune regulation could be used to treat skin inflammatory diseases. Multilineage-differentiating stress-enduring (Muse) cells are a new type of pluripotent stem cell that may also have the potential to treat inflammatory skin diseases. METHODS: Muse cells were isolated from human bone marrow-derived MSCs (BMSCs) via the 8-h longterm trypsin incubation (LTT) method. Repeated use of 2,4-dinitrofluorobenzene (DNFB) induced atopic dermatitis (AD) in a mouse model. Immunofluorescence, behavior recording, and image analysis were used to evaluate the therapeutic effect of subcutaneous Muse cell injection. Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of inflammatory factors. In vitro, wound healing and cell proliferation experiments were used to examine the effect of Muse cell supernatant on keratinocytes. RESULTS: Our results showed that subcutaneous injection of Muse cells after AD model induction significantly alleviated scratching behavior in mice. The evaluation of dermatitis and photos of damaged skin on the back of the neck revealed that Muse cells reduced dermatitis, playing an active role in healing the damaged skin. The activation of spinal glial cells and scratching behavior were also reduced by Muse cell injection. In addition, we also showed that the expression levels of the inflammatory factors interleukin (IL)-6, IL-17α, and IL-33 in both the spinal cord and skin were suppressed by Muse cells. Furthermore, Muse cells not only exerted anti-inflammatory effects on lipopolysaccharide (LPS)-induced human HaCat cells but also promoted wound healing and keratinocyte proliferation. CONCLUSIONS: In vivo, Muse cells could alleviate scratching symptoms, reduce epidermal inflammation, and promote wound healing. In vitro, Muse cells could also promote the migration and proliferation of keratinocytes. In summary, Muse cells may become a new therapeutic agent for the treatment of AD.

[Use of Iron-modified Calcite as an Active Capping Material to Control Phosphorus Release from Sediments in Surface Water Bodies].

The use of calcite (CA) as an active capping material has high potential for controlling the release of phosphorus (P) from sediments, but its efficiency still needs to be enhanced. To address this issue, an iron-modified CA (Fe-CA) was prepared, the removal performance of phosphate from aqueous solution by Fe-CA was studied, and the efficiency of the use of Fe-CA as an active capping material to prevent the liberation of P from sediments was investigated. The results showed that Fe-CA exhibited much higher phosphate removal ability than CA. The phosphate removal efficiency of Fe-CA increased with an increase in the Fe-CA dosage. Increasing the initial phosphate concentration gave rise to an increase in the amount of phosphate removed by Fe-CA, and the maximum amount of phosphate removed by Fe-CZ reached 3.09 mg·g-1. Sediment capping with Fe-CA could effectively control the release of soluble reactive P (SRP) from the sediment into the overlying water, leading to a very low concentration of SRP in the overlying water. Additionally, the Fe-CA capping also resulted in the transformation of a small amount of redox-sensitive P (BD-P) and metal-oxide-bound P (NaOH-rP) in sediments to residual P (Res-P), leading to a slight increase in the stability of P in the sediment. The overwhelming majority (90.8%) of P bound by the Fe-CA capping layer existed in the form of NaOH-rP, calcium-bound P (HCl-P), and Res-P, which are relatively very stable. Furthermore, the percentage of bioavailable P (BAP) as a proportion of total extractable P in the P-bound Fe-CA capping layer was very low, and the bound P was re-released with difficulty into the water column for algae growth. Compared to CA capping, the efficiency for the control of sedimentary P release into the overlying water by Fe-CA capping was much higher, and the stability of P bound by the Fe-CA capping layer was also higher. The results of this work indicate that Fe-CA is a very promising active capping material for the interception of the release of P from sediments into the overlying water.

Environmental estrogen exposure converts lipid metabolism in male fish to a female pattern mediated by AMPK and mTOR signaling pathways.

Environmental estrogens, including bisphenol A (BPA) and 17ß-estradiol (E2), which are widely used in industries and medicine, pose a severe ecological threat to fish due to feminization induction. However, the related metabolic basis for reproductive feminization in male fish has not been well addressed. We first found that female zebrafish exhibited higher lipid accumulation and lipogenesis activity than males. Next, we exposed male and female zebrafish to E2 (200 ng/L) or BPA (100 µg/L) for six weeks, and observed an early-phase reproductive feminization in males, accompanied with reduced spermatids, significant fat deposition and lipogenic gene expressions that mimicked female patterns. Cellular signaling assays revealed that, E2 or BPA modulated lipid metabolism in males mainly through lowering 5' AMP-activated protein kinase (AMPK) and upregulating the lipogenic mechanistic target of rapamycin (mTOR) pathways. For the first time, we show that environmental estrogens could alter lipid metabolism in male fish to a female pattern (metabolic feminization) prior to gonad feminization in male fish, to allows males to accumulate efficiently lipids to harmonize with the feminized gonads. This study suggests that negative effects of environmental estrogens, as hazardous materials, on vertebrate health are more complicated than originally thought.

A fluorescent probe for simultaneously sensing NTR and hNQO1 and distinguishing cancer cells.

Identifying cancer at the cellular level during an early stage offers the hope of greatly improved outcomes for cancer patients. As potential cancer biomarkers, nitroreductase (NTR) and human quinine oxidoreductase 1 (hNQO1) are overexpressed in many type of cancer cells. Simultaneous detection of these two biomarkers would benefit diagnostic precision in related cancers without yielding false positive results. Herein, based on a dye generated in situ strategy, a dual-enzyme-responsive probe, CNN, was rationally designed and synthesized by installing p-nitrobenzene and trimethyl-locked quinone propionic acid groups, which are specific for NTR and hNQO1, respectively, into a single fluorophore. This probe is only activated in the presence of both NTR and hNQO1 and produces a large fluorescence response, enabling the detection of both endogenous NTR and hNQO1 activity in living cells. The imaging results indicate that the CNN probe differentiates cancer cells (HeLa, MDA-MB-231 and HepG2 cells) from normal liver HL-7702 cells owing to the existence of relatively high endogenous levels of both biomarkers in these cancer cells.

Mesenchymal stem cells derived from induced pluripotent stem cells play a key role in immunomodulation during cardiopulmonary resuscitation.

BACKGROUND/AIMS: Previous in vitro experiments have demonstrated the immunomodulatory functions of mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs) in brain injury. We have tried to further understand these functions by investigating the neuroprotective effects of iPSC-MSCs in a rat model of cardiac arrest (CA). METHODS: CA was induced in adult Sprague-Dawley rats by transcutaneous electrical epicardium stimulation. The rats were divided into four groups. In a separate cohort of sham operation animals, iPSC-MSCs or PBS was infused via the femoral vein after restoration of spontaneous circulation. Survival was evaluated every 2 h until 24 h after CA. Markers of classically activated macrophages (M1) and alternatively activated (M2) macrophages were assessed by qPCR and western blot analysis, and the gene expression profiles of the macrophages were studied in order to identify differentially expressed proteins. RESULTS: The 24-h survival rate was significantly different between the CPR group and iPSC-MSC group (P = 0.033). Additionally, a significant number of mRNAs were differentially expressed between the iPSC-MSC and PBS group. Compared with the sham operation group, both M1 (27/29) and M2 (2/29) mRNAs showed a significant increase in expression in the CPR group, while only M2 (22) mRNAs showed a significant increase in expression in the iPSC-MSC group. Western blotting analysis showed that the expression of Arg-1 and CD14 (M2 macrophage markers) was increased in the iPSC-MSC group (P < 0.05), while CD86 and iNOS (M1 macrophage markers) expression was increased in the CPR group (P < 0.05). CONCLUSION: IPSC-MSCs, which play a key role in immunomodulation, downregulate the level of M1 macrophages and upregulate the level of M2 macrophages after CA.

Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This life-threatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26-year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 µg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.

IPSC­MSC inhibition assessment in Raw 264.7 cells following oxygen and glucose deprivation reveals a distinct function for cardiopulmonary resuscitation.

Hypoxia is a serious stress state. The nervous system is less tolerant to hypoxia, and cell death due to hypoxia is irreversible. With the incidence of cardiovascular disease gradually increasing, the sudden cardiac death rate is additionally increasing. Although cardiopulmonary resuscitation (CPR) is an important development, recovery is frequently poor. In a successful recovery population, ~40% of the population was in a vegetative state or subsequently succumbed to their condition, and ~20% had brain damage. Therefore, the recovery of the brain is of particular importance in CPR. Immune disorders are one of the major mechanisms of cerebral resuscitation following CPR. Studies have demonstrated that induced pluripotent stem cell­derived mesenchymal stem cells (IPSC­MSCs) have a strong immune regulatory effect during tissue repair and anti­inflammatory effects. IPSC­MSCs may inhibit the inflammatory response by means of the inflammatory reaction network to improve brain function following CPR, although the cellular and molecular mechanisms remain unclear. Macrophages are a bridge between innate immune and specific immune responses in the body; therefore, it was hypothesized that macrophages may be the important effector cell of the role of IPSC­MSCs in improving brain function following recovery of spontaneous respiration and circulation subsequent to cardiopulmonary resuscitation. In the present study, IPSC­MSCs were applied to the oxygen and glucose deprivation (OGD) model. It was observed that intervention with IPSC­MSCs was able to alter the polarization direction of macrophages. The difference in the proportions of M1 and M2 macrophages was statistically significant at 6, 12, 24 and 48 h (P=0.037, P<0.05) in the OGD + IPSC­MSCs group (M1, 33.48±5.6%; M2, 50.84±6.9%) and in the OGD group (M1, 83.55±7.3%; M2, 11.41±3.2%), and over time this trend was more obvious. The polarization direction of macrophages is associated with the neurogenic locus notch homolog protein 1 (Notch­1) signaling pathway. In conclusion, it was observed that IPSC­MSCs may be associated with altered macrophage polarization, which may be accomplished by inhibiting the Notch­1 signaling pathway.

Influence of Endogenous and Exogenous Estrogenic Endocrine on Intestinal Microbiota in Zebrafish.

Gender is one of the factors influencing the intestinal microbial composition in mammals, but whether fish also have gender-specific intestinal microbial patterns remains unknown. In this decade, endocrine disrupting chemicals in surface and ground water of many areas and increasing observation of freshwater male fish displaying female sexual characteristics have been reported. Here we identified the difference in intestinal microbiota between male and female zebrafish, and revealed the influence of endocrine disrupting chemicals on zebrafish intestinal microbiota by using high-throughput sequencing. The results indicated that Fusobacteria, Bacteroidetes and Proteobacteria were dominant in the gut of zebrafish and there were no obvious gender-specific intestinal microbial patterns. Two endocrine disrupting chemicals, Estradiol (E2) and Bisphenol A (BPA), were selected to treat male zebrafish for 5 weeks. E2 and BPA increased vitellogenin expression in the liver of male zebrafish and altered the intestinal microbial composition with the abundance of the phylum CKC4 increased significantly. Our results suggested that because of the developmental character and living environment, gender did not influence the assembly of intestinal microbiota in zebrafish as it does in mammals, but exposure extra to endocrine disrupting chemicals disturbed the intestinal microbial composition, which may be related to changes in host physiological metabolism.

[Factors associated with retention in a community-based methadone maintenance treatment among heroin addicts].

OBJECTIVE: To explore factors associated with retention in a community-based methadone maintenance treatment (MMT) among heroin addicts in Xichang of Sichuan province. METHODS: All 206 heroin addicts were first admitted to MMT community-based program between March to September 2004. Baseline data of patients characteristics, social function, drug using behaviors, sexual behaviors, dose of methadone and retention were collected. RESULTS: Up to Oct, 2005, all 206 patients contributed 8.98 +/- 5.74 person-months of following-up. The retention rates were 58.7% after 6 months and 34.6% after 12 months respectively. Cox proportional hazard regression model indicated that the employed (HR, 0.60; 95% CI, 0.39 - 0.92), helping family to do housework in past 30 days more than once a day (HR, 0.59; 95% CI, 0.42 - 0.82) and previous self-detoxification > or = 3 times (HR, 0.65; 95% CI, 0.47 - 0.91) were independently associated with retention. CONCLUSION: We should give individual counseling to help heroin addicts increasing compliance.

Nonfatal overdose among heroin users in southwestern China.

OBJECTIVE: To evaluate the prevalence of and risk factors for nonfatal overdose among heroin users in southwestern China. METHODS: In 2005, 731 heroin users in Sichuan Province, China were interviewed for overdose experiences in the past 12 months. Factors hypothesized to be associated with overdose were evaluated with logistic regression models. RESULTS: Eighty-eight (12%) drug users experienced at least one overdose, with a range from 1 to 20; 45 (51%) experienced 2 or more overdoses. Over half of participants with experience of overdose were recently released from prison (52%), and 56% used benzodiazepines before overdose. Longer methadone treatment in the past year (>or=180 vs. 0 days; OR, .3; 95% CI, .1-.8; P = .02), longer duration of using drugs (>or=7 vs. <7 years; OR, 2.2; 95% CI, 1.3-3.6; P = .002), and more frequency of injecting drugs in the past 3 months (>or=7 vs. <7 times/week; OR, 5.4; 95% CI, 3.2-9.0; P < .001) were independently associated with increased risk of nonfatal heroin overdose. CONCLUSIONS: Nonfatal heroin overdoses are common among Chinese heroin users. Drug users should be encouraged to participate and remain in methadone treatment to prevent overdose and be educated about proper response to overdose to reduce risk of overdose death.

ird1 is a Vps15 homologue important for antibacterial immune responses in Drosophila.

The immune response-deficient 1 (ird1) gene was identified in a forward genetic screen as a novel regulator for the activation of Imd NFkappaB immune signalling pathway in Drosophila. ird1 animals are also more susceptible to Escherichia coli and Micrococcus luteus bacterial infection. ird1 encodes the Drosophila homologue of the Vps15/p150 serine/threonine kinase that regulates a class III phosphoinositide 3-kinase and is necessary for phagosome maturation and starvation-induced autophagy in yeast and mammalian cells. To gain insight into the role of ird1 in the immune response, we examine how amino acid starvation affects the immune signalling pathways in Drosophila. Starvation, in the absence of infection, leads to expression of antimicrobial peptide (AMP) genes and this response is dependent on ird1 and the Imd immune signalling pathway. Starvation, in addition to bacterial infection, suppresses the AMP response in wild-type animals and reduces the ability to survive M. luteus infection. Our results suggest that starvation and innate immune signalling may be intimately linked processes.

The peptidoglycan recognition protein PGRP-SC1a is essential for Toll signaling and phagocytosis of Staphylococcus aureus in Drosophila.

From a forward genetic screen for phagocytosis mutants in Drosophila melanogaster, we identified a mutation that affects peptidoglycan recognition protein (PGRP) SC1a and impairs the ability to phagocytose the bacteria Staphylococcus aureus, but not Escherichia coli and Bacillus subtilis. Because of the differences in peptidoglycan peptide linkages in these bacteria, our data suggest that PGRP-SC1a is necessary for recognition of the Lys-type peptidoglycan typical of most Gram(+) bacteria. PGRP-SC1a mutants also fail to activate the Toll/NF-kappaB signaling pathway and are compromised for survival after S. aureus infection. This mutant phenotype is the first found for an N-acetylmuramoyl-l-alanine amidase PGRP that cleaves peptidoglycan at the lactylamide bond between the glycan backbone and the crosslinking stem peptides. By generating transgenic rescue flies that express either wild-type or a noncatalytic cysteine-serine mutant PGRP-SC1a, we find that PGRP-SC1a amidase activity is not necessary for Toll signaling, but is essential for uptake of S. aureus into the host phagocytes and for survival after S. aureus infection. Furthermore, we find that the PGRP-SC1a amidase activity can be substituted by exogenous addition of free peptidoglycan, suggesting that the presence of peptidoglycan cleavage products is more important than the generation of cleaved peptidoglycan on the bacterial surface for PGRP-SC1a mediated phagocytosis.