Vagal-α7 nicotinic acetylcholine receptor signaling exacerbates influenza severity by promoting lung epithelial cell infection.

The vagus nerve circuit, operating through the alpha-7 nicotinic acetylcholine receptor (α7 nAChR), regulates the inflammatory response by influencing immune cells. However, the role of vagal-α7 nAChR signaling in influenza virus infection is unclear. In particular, does vagal-α7 nAChR signaling impact the infection of alveolar epithelial cells (AECs), the primary target cells of influenza virus? Here, we demonstrated a distinct role of α7 nAChR in type II AECs compared to its role in immune cells during influenza infection. We found that deletion of Chrna7 (encoding gene of α7 nAChR) in type II AECs or disruption of vagal circuits reduced lung influenza infection and protected mice from influenza-induced lung injury. We further unveiled that activation of α7 nAChR enhanced influenza infection through PTP1B-NEDD4L-ASK1-p38MAPK pathway. Mechanistically, activation of α7 nAChR signaling decreased p38MAPK phosphorylation during infection, facilitating the nuclear export of influenza viral ribonucleoproteins and thereby promoting infection. Taken together, our findings reveal a mechanism mediated by vagal-α7 nAChR signaling that promotes influenza viral infection and exacerbates disease severity. Targeting vagal-α7 nAChR signaling may offer novel strategies for combating influenza virus infections.

Covalent Triazine Based Frameworks with Donor-Donor-π-Acceptor Structures for Dendrite-Free Lithium Metal Batteries.

The appearance of disordered lithium dendrites and fragile solid electrolyte interfaces (SEI) significantly hinder the serviceability of lithium metal batteries. Herein, guided by theoretical predictions, a multi-component covalent triazine framework with partially electronegative channels (4C-TA0.5TF0.5-CTF) is incorporated as a protective layer to modulate the interface stability of the lithium metal batteries. Notably, the 4C-TA0.5TF0.5-CTF with optimized electronic structure at the molecular level by fine-tuning the local acceptor-donor functionalities not only enhances the intermolecular interaction thereby providing larger dipole moment and improved crystallinity and mechanical stress, but also facilitates the beneficial effect of lithiophilic sites (C-F bonds, triazine cores, C=N linkages and aromatic rings) to further regulate the migration of Li+ and achieve a uniform lithium deposition behavior as determined by various in-depth in/ex situ characterizations. Due to the synergistic effect of multi-component organic functionalities, the 4C-TA0.5TF0.5-CTF modified full cells perform significantly better than the common two/three-component 2C-TA-CTF and 3C-TF-CTF electrodes, delivering an excellent capacity of 116.3 mAh g-1 (capacity retention ratio: 86.8%) after 1000 cycles at 5 C and improved rate capability. This work lays a platform for the prospective molecular design of improved organic framework relative artificial SEI for highly stable lithium metal batteries.

Sorption of Iodine on Biochar Derived from the Processing of Urban Sludge and Garden Waste at Different Pyrolysis Temperatures.

The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g-1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.

Preparation of Quaternary Ammonium Separation Material based on Coupling Agent Chloromethyl Trimethoxysilane (KH-150) and Its Adsorption and Separation Properties in Studies of Th(IV).

In this research, the authors studied the synthesis of a silicon-based quaternary ammonium material based on the coupling agent chloromethyl trimethoxysilane (KH-150) as well as its adsorption and separation properties for Th(IV). Using FTIR and NMR methods, the silicon-based materials before and after grafting were characterized to determine the spatial structure of functional groups in the silicon-based quaternary ammonium material SG-CTSQ. Based on this, the functional group grafting amount (0.537 mmol·g-1) and quaternization rate (83.6%) of the material were accurately calculated using TGA weight loss and XPS. In the adsorption experiment, the four materials with different grafting amounts showed different degrees of variation in their adsorption of Th(IV) with changes in HNO3 concentration and NO3- concentration but all exhibited a tendency toward anion exchange. The thermodynamic and kinetic experimental results demonstrated that materials with low grafting amounts (SG-CTSQ1 and SG-CTSQ2) tended to physical adsorption of Th(IV), while the other two tended toward chemical adsorption. The adsorption mechanism experiment further proved that the functional groups achieve the adsorption of Th(IV) through an anion-exchange reaction. Chromatographic column separation experiments showed that SG-CTSQ has a good performance in U-Th separation, with a decontamination factor for uranium in Th(IV) of up to 385.1, and a uranium removal rate that can reach 99.75%.

FAK inhibitors in cancer, a patent review - an update on progress.

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

Maternal nutrient metabolism in the liver during pregnancy.

The liver plays pivotal roles in nutrient metabolism, and correct hepatic adaptations are required in maternal nutrient metabolism during pregnancy. In this review, hepatic nutrient metabolism, including glucose metabolism, lipid and cholesterol metabolism, and protein and amino acid metabolism, is first addressed. In addition, recent progress on maternal hepatic adaptations in nutrient metabolism during pregnancy is discussed. Finally, the factors that regulate hepatic nutrient metabolism during pregnancy are highlighted, and the factors include follicle-stimulating hormone, estrogen, progesterone, insulin-like growth factor 1, prostaglandins fibroblast growth factor 21, serotonin, growth hormone, adrenocorticotropic hormone, prolactin, thyroid stimulating hormone, melatonin, adrenal hormone, leptin, glucagon-like peptide-1, insulin glucagon and thyroid hormone. Our vision is that more attention should be paid to liver nutrient metabolism during pregnancy, which will be helpful for utilizing nutrient appropriately and efficiently, and avoiding liver diseases during pregnancy.

Elevated Circulating Procathepsin L as a Potential Biomarker of Inflamm-aging.

Inflamm-aging is a condition of low-grade and chronic systemic inflammation characterized by a systemic increase in multiple inflammatory biomarkers such as tumor necrosis factor (TNF), interleukin 6 (IL-6), C-reactive protein (CRP), and CXCL9 (MIG) in experimental and clinical settings. However, despite the recent identification of extracellular procathepsin L (pCTS-L) as a novel mediator of inflammatory diseases such as sepsis, its possible role in inflamm-aging was previously not investigated. In the present study, we compared blood levels of pCTS-L and other 62 cytokines and chemokines between young and aged Balb/C mice by Western blotting and Cytokine Antibody Arrays. In light of the surprising finding of a marked increase in blood pCTS-L levels in aged mice, we propose that blood pCTS-L levels may serve as another biomarker of inflamm-aging. Given the capacity of pCTS-L in inducing various cytokines (e.g., TNF and IL-6), it will be important to test the hypothetic role of pCTS-L in inflamm-aging under experimental and clinical conditions.

Roles of photochemical consumption of VOCs on regional background O3 concentration and atmospheric reactivity over the pearl river estuary, Southern China.

Understanding of the photochemical ozone (O3) pollution over the Pearl River Estuary (PRE) of southern China remains limited. We performed an in-depth analysis of volatile organic compounds (VOCs) data collected on an island (i.e., the Da Wan Shan Island, DWS) located at the downwind of Pearl River Delta (PRD) from 26 November to 15 December 2021. Abundances of O3 and its precursors were measured when the air masses originated from the inland PRD. We observed that the VOCs levels at the DWS site were lower, while the mixing ratio of O3 was higher, compared to those reported at inland PRD, indicating the occurrence of photochemical consumption of VOCs during the air masses transport, which was further confirmed by the composition and diurnal variations of VOCs, as well as ratios of specific VOCs. The simulation results from a photochemical box model showed that the O3 level in the outflow air masses of inland PRD (O3(out-flow)) was the dominant factor leading to the intensification of O3 pollution and the enhancement of atmospheric radical concentrations (ARC) over PRE, which was mainly contributed by the O3 production via photochemical consumption of VOCs during air masses transport. Overall, our findings provided direct quantitative evidence for the roles of outflow O3 and its precursors from inland PRD on O3 abundance and ARC over the PRE area, highlighting that alleviation of O3 pollution over PRE should focus on the impact of photochemical loss of VOCs in the outflow air masses from inland PRD.

Therapeutic potential of procathepsin L-inhibiting and progesterone-entrapping dimethyl-ß-cyclodextrin nanoparticles in treating experimental sepsis.

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-ß-cyclodextrin (DM-ß-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-ß-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24 h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-ß-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.

Fecal microbiota related to postoperative endoscopic recurrence in patients with Crohn's disease.

Background: Postoperative recurrence (POR) remains a major challenge for patients with Crohn's disease (CD). Gut microbial dysbiosis has been reported to be involved in the pathogenesis of POR. This study aims to investigate the relationship between fecal microbiome and endoscopic recurrence in patients with CD after ileocolonic resection. Methods: This is a cross-sectional study. Fecal samples were collected from 52 patients with CD after surgical intervention from 6 to 12 months before endoscopic examination. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. The microbiome was analyzed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Results: A total of 52 patients were included and classified into POR (n = 27) and non-POR (n = 25) groups. Compared with the non-POR group, the POR group had a significantly lower community richness (Chao1 index: 106.5 vs 124, P = 0.013) and separated microbial community (P = 0.007 for Adonis, P = 0.032 for Anosim), combined with different distribution of 16 gut microbiotas and decrease of 11 predicted metabolic pathways (P < 0.05). Lactobacillus and Streptococcus were identified to closely correlate to non-POR (P < 0.05) after controlling for confounding factors. Kaplan-Meier analysis indicated that the patients with higher abundance of Streptococcus experienced longer remission periods (P < 0.01), but this was not for Lactobacillus. The predicted ethylmalonyl-coA pathway related to increased amount of succinate was positively correlated with Streptococcus (r > 0.5, P < 0.05). Conclusions: The characteristic alterations of fecal microbiota are associated with postoperative endoscopic recurrence in patients with CD; particularly, high abundance of Streptococcus may be closely related to endoscopic remission.

MicroRNA miR-7-5p targets MARK2 to control metamorphosis in Galeruca daurica.

The MARK2 gene, coding microtubule affinity-regulating kinase or serine/threonine protein kinase, is an important modulator in organism microtubule generation and cell polarity. However, its role in the metamorphosis of insects remains unknown. In this study, we found a conserved miRNA, miR-7-5p, which targets MARK2 to participate in the regulation of the larval-pupal metamorphosis in Galeruca daurica. The dual luciferase reporter assay showed that miR-7-5p interacted with the 3' UTR of MARK2 and repressed its expression. The expression profiling of miR-7-5p and MARK2 displayed an opposite trend during the larval-adult development process. In in-vivo experiments, overexpression of miR-7-5p by injecting miR-7-5p agomir in the final instar larvae down-regulated MARK2 and up-regulated main ecdysone signaling pathway genes including E74, E75, ECR, FTZ-F1 and HR3, which was similar to the results from knockdown of MARK2 by RNAi. In contrast, repression of miR-7-5p by injecting miR-7-5p antagomir obtained opposite effects. Notably, both overexpression and repression of miR-7-5p in the final instar larvae caused abnormal molting and high mortality during the larval-pupal transition, and high mortality during the pupal-adult transition. The 20-hydroxyecdysone (20E) injection experiment showed that 20E up-regulated miR-7-5p whereas down-regulated MARK2. This study reveals that the accurate regulation of miRNAs and their target genes is indispensable for insect metamorphosis.

MicroRNA miR-285 modulates the metamorphosis in Galeruca daurica by targeting Br-C.

BACKGROUND: Galeruca daurica has become a new pest on the Inner Mongolia grasslands since an abrupt outbreak in 2009 caused serious damage. As a pupa indicator during insect metamorphosis, the early response gene of the ecdysone signaling pathway, Broad-Complex (Br-C), plays a vital role in the growth and development of insects. MicroRNAs (miRNAs) are small non-coding RNAs which mediate various biological activities, but it is unknown whether and how Br-C is regulated by miRNAs. RESULTS: Temporal expression profiles revealed that miR-285 and Br-C basically displayed an opposite trend during larval-adult development, and Br-C was sharply up-regulated on the last day of final-instar larvae while miR-285 was significantly down-regulated. Both dual-luciferase reporter assay and miRNA-mRNA interaction assay indicated that miR-285 interacts with the coding sequence of Br-C and represses its expression. Not only overexpression but also downexpression of miR-285 led to the failure of larval to pupal to adult metamorphosis. In addition, both overexpression of miR-285 and silence of Br-C inhibited the expression of Br-C and other ecdysone signaling pathway genes, including E74, E75, ECR, FTZ-F1, and HR3. On the contrary, suppressing miR-285 obtained opposite results. Further experiments showed that 20-hydroxyecdysone down-regulated miR-285 and up-regulated Br-C and above-mentioned genes, whereas juvenile hormone alalogue (JHA) resulted in opposite effects. CONCLUSION: Our results reveal that miR-285 is involved in mediating the metamorphosis in G. daurica by targeting Br-C in the ecdysone signaling pathway. miR-285 and its target Br-C could be as a potential target for G. daurica management. © 2024 Society of Chemical Industry.

sp-Carbon-Conjugated Organic Polymer as Multifunctional Interfacial Layers for Ultra-Long Dendrite-Free Lithium Metal Batteries.

Fatal issues in lithium metal anodes (LMA), such as detrimental lithium dendrites growth and fragile solid-electrolyte interphase (SEI) during the Li plating/stripping process, often hinder the practical application of Li metal batteries (LMBs). Herein, cobalt-coordinated sp-carbon-conjugated organic polymer (Co-spc-COP) is constructed as the protective layer for regulating the interface stability of LMA. The unique synergistic beneficial effect of organic functional groups (C≡C linkage, C=N units and aromatic rings) and Co sites not only regulate the Li+ coordination environment and rearrange Li+ concentration to facilitate its transport by optimizing the electronic density, enhancing the compatibility with electrolyte interface and supplying "external magnetic driving strategy", but also strengthens the interfacial stiffness with high Young's modulus to better withstand the mechanical stress. These beneficial effects and relative underlying working mode and mechanism of uniform Li plating and rapid Li+ migration on the Co-spc-COP are also revealed by various in situ/ex situ experimental technologies and theory calculation. The Co-spc-COP-based cell delivers an extraordinary lifespan of 6600 h and ultrahigh capacity retention of 78.3 % (111.9 mAh g-1) after 1000 cycles at 1 C. This demonstrated synergistic strategy in Co-coordinated organic polymer may gain new insights to regulate the uniform and non-dendritic deposition/dissolution behaviors for highly stable LMBs.

Revisiting the Ultraviolet Absorption Cross Section of Gaseous Nitrous Acid (HONO): New Insights for Atmospheric HONO Budget.

Nitrous acid (HONO) is an important source of hydroxyl radicals (OH) in the atmosphere. Precise determination of the absolute ultraviolet (UV) absorption cross section of gaseous HONO lays the basis for the accurate measurement of its concentration by optical methods and the estimation of HONO loss rate through photolysis. In this study, we performed a series of laboratory and field intercomparison experiments for HONO measurement between striping coil-liquid waveguide capillary cell (SC-LWCC) photometry and incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS). Specified HONO concentrations prepared by an ultrapure standard HONO source were utilized for laboratory intercomparisons. Results show a consistent ∼22% negative bias in measurements of the IBBCEAS compared with a SC-LWCC photometer. It is confirmed that the discrepancies occurring between these techniques are associated with the overestimation of the absolute UV absorption cross sections through careful analysis of possible uncertainties. We quantified the absorption cross section of gaseous HONO (360-390 nm) utilizing a custom-built IBBCEAS instrument, and the results were found to be 22-34% lower than the previously published absorption cross sections widely used in HONO concentration retrieval and atmospheric chemical transport models (CTMs). This suggests that the HONO concentrations retrieved by optical methods based on absolute absorption cross sections may have been underestimated by over 20%. Plus, the daytime loss rate and unidentified sources of HONO may also have evidently been overestimated in pre-existing studies. In summary, our findings underscore the significance of revisiting the absolute absorption cross section of HONO and the re-evaluation of the previously reported HONO budgets.

Reactive aldehyde chemistry explains the missing source of hydroxyl radicals.

Hydroxyl radicals (OH) determine the tropospheric self-cleansing capacity, thus regulating air quality and climate. However, the state-of-the-art mechanisms still underestimate OH at low nitrogen oxide and high volatile organic compound regimes even considering the latest isoprene chemistry. Here we propose that the reactive aldehyde chemistry, especially the autoxidation of carbonyl organic peroxy radicals (R(CO)O2) derived from higher aldehydes, is a noteworthy OH regeneration mechanism that overwhelms the contribution of the isoprene autoxidation, the latter has been proved to largely contribute to the missing OH source under high isoprene condition. As diagnosed by the quantum chemical calculations, the R(CO)O2 radicals undergo fast H-migration to produce unsaturated hydroperoxyl-carbonyls that generate OH through rapid photolysis. This chemistry could explain almost all unknown OH sources in areas rich in both natural and anthropogenic emissions in the warm seasons, and may increasingly impact the global self-cleansing capacity in a future low nitrogen oxide society under carbon neutrality scenarios.

Garlic-derived compounds: Epigenetic modulators and their antitumor effects.

Cancer is a highly heterogeneous disease that poses a serious threat to human health worldwide. Despite significant advances in the diagnosis and treatment of cancer, the prognosis and survival rate of cancer remain poor due to late diagnosis, drug resistance, and adverse reactions. Therefore, it is very necessary to study the development mechanism of cancer and formulate effective therapeutic interventions. As widely available bioactive substances, natural products have shown obvious anticancer potential, especially by targeting abnormal epigenetic changes. The main active part of garlic is organic sulfur compounds, of which diallyl trisulfide (DATS) content is the highest, accounting for more than 40% of the total composition. The garlic-derived compounds have been recognized as an antioxidant for cancer prevention and treatment. However, the molecular mechanism of the antitumor effect of garlic-derived compounds remains unclear. Recent studies have identified garlic-derived compound DATS that plays critical roles in enhancing CpG demethylation or promoting histone acetylation as an epigenetic inhibitor. Here, we review the therapeutic progress of garlic-derived compounds against cancer through epigenetic pathways.

MRI-visible enlarged perivascular spaces in basal ganglia rather than centrum semiovale was associated with aneurysmal subarachnoid hemorrhage.

Background: The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS in basal ganglia (BG-EPVS) are more closely associated with aneurysmal subarachnoid hemorrhage (aSAH) than other SAH without aneurysm. Methods: Magnetic resonance imaging (MRI) scans of 271 consecutive SAH survivors with and without aneurysm were analyzed for EPVS and other markers of imaging data. In the subgroup analysis, we compared the clinical characteristics and EPVS of SAH participants with and without pre-existing known risk factors (hypertension, diabetes, and smoking history) using multivariable logistic regression. Results: Patients with aSAH (n = 195) had a higher severity of BG-EPVS and centrum semiovale EPVS (CSO-EPVS) than those without aneurysm (n = 76). Importantly, BG-EPVS predominance pattern (BG-EPVS>CSO-EPVS) only existed in aSAH survivors rather than other SAH without aneurysm. In the subgroup analysis, interestingly, we also found that a high degree of BG-EPVS showed an independent relationship with aSAH in patients without pre-existing risk factors (e.g., hypertension). Conclusion: In this cohort study, BG-EPVS predominance pattern was associated with aSAH patients compared with those without aneurysm. Moreover, BG-EPVS still showed a strong association with aSAH survivors without pre-existing vascular risk factors. Our present study suggested the BG-EPVS as a potential MRI-visible characteristic would shed light on the pathogenesis of glymphatic function at the skull base for aSAH.

A novel opsonic eCIRP inhibitor for lethal sepsis.

Sepsis is a life-threatening inflammatory condition partly orchestrated by the release of various damage-associated molecular patterns such as extracellular cold-inducible RNA-binding protein (eCIRP). Despite advances in understanding the pathogenic role of eCIRP in inflammatory diseases, novel therapeutic strategies to prevent its excessive inflammatory response are lacking. Milk fat globule-epidermal growth factor-VIII (MFG-E8) is critical for the opsonic clearance of apoptotic cells, but its potential involvement in the removal of eCIRP was previously unknown. Here, we report that MFG-E8 can strongly bind eCIRP to facilitate αvß3-integrin-dependent internalization and lysosome-dependent degradation of MFG-E8/eCIRP complexes, thereby attenuating excessive inflammation. Genetic disruption of MFG-E8 expression exaggerated sepsis-induced systemic accumulation of eCIRP and other cytokines, and consequently exacerbated sepsis-associated acute lung injury. In contrast, MFG-E8-derived oligopeptide recapitulated its eCIRP binding properties, and significantly attenuated eCIRP-induced inflammation to confer protection against sepsis. Our findings suggest a novel therapeutic approach to attenuate eCIRP-induced inflammation to improve outcomes of lethal sepsis.