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Dual-phase high entropy oxide (HEO) ceramics (FeCoNiZn) x V 2 O y were prepared using a simple sintering process. Vanadium oxide was selected due to the characteristics of reduction ability and multiphase transformation under different conditions. The crystal structure, microstructure, elemental chemical state, magnetic property and microwave absorption (MA) properties of HEO ceramics were studied. The results show that the two-phase structure is spinel phase and vanadate phase, and there are oxygen vacancies in the samples. Magnetic properties can be promoted with high content of spinel phase. Lots of oxygen vacancies were found in the sample sintered at 900 °C, which exhibited good MA ability. The minimum reflection loss (RL) of −36.5 dB was obtained at 10.72 GHz with a thickness of 2.2 mm, while the effective bandwidth reached 2.77 GHz. Large number of oxygen vacancies can speed up the migration of electrons or ions, thereby improving the dielectric loss capability. [ABSTRACT FROM AUTHOR]

Alumina-coated cubic boron nitride (c-BN) particles (c-BN@Al 2 O 3) were prepared using a heterogeneous nucleation method. Then, they were added to a (Ti,W)C-based cermet tool material after synthesis via vacuum hot-press sintering. The microstructure and mechanical properties of the (Ti,W)C-based cermet tool material with varying c-BN@Al 2 O 3 contents were recorded and analyzed. The results show that with increasing c-BN@Al2O3 concentration, the relative density, flexural strength, fracture toughness, and Vickers hardness all increase first and then decrease, and the average grain size first decreases and then increases. The introduction of Al 2 O 3 into the c-BN particles used for surface modification can improve the wettability and interfacial bonding strength between the c-BN and matrix particles, restrain the grain growth of the matrix particles, and improve the flexural strength of cermet tool materials. The addition of c-BN@Al 2 O 3 also alters the crack propagation mechanism of the cermet tool material and introduces multiple toughening mechanisms to improve the fracture toughness of the cermet tool material. The high hardness of c-BN and Al 2 O 3 is the main reason for the increase in hardness; however, excessive addition of such material reduces the relative density, resulting in a decrease in hardness. [ABSTRACT FROM AUTHOR]

Abstract Endometritis, an inflammatory response of the uterus tissue, is characterized by the production of inflammatory cytokines and migration of neutrophil (PMN) into the uterus tissue. Melatonin has been demonstrated to have anti-inflammatory and antioxidant effects. The purpose of this study was to investigate the protective effects of melatonin on lipopolysaccharide (LPS)-induced endometritis in mice. An endometritis model was induced by LPS and melatonin was given 1 h before LPS treatment. The results showed that melatonin inhibited LPS-induced pathologic changes, Myeloperoxidase (MPO) activity, and levels of interleukin-1 beta (IL-1β). Melatonin also inhibited LPS-induced thioredoxin-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) activation, reactive oxygen species (ROS) production, and endoplasmic reticulum (ER) stress. Furthermore, melatonin was found to increase AMPK activity. In conclusion, our results demonstrated that melatonin inhibited ER stress-associated TXNIP/NLRP3 inflammasome activation with a regulation of adenosine monophosphate activated protein kinase (AMPK) in LPS-induced endometritis. Melatonin may serve as a promising nutritional supplement for the treatment of endometritis. Graphical abstract Unlabelled Image Highlights • Melatonin protects LPS-induced endometritis through anti-inflammation and anti-oxidant pathways. • Melatonin inhibits TXNIP/NLRP3 inflammasome activation induced by LPS. • Melatonin increases AMPK activity induced by LPS. [ABSTRACT FROM AUTHOR]

We evaluated the potential relationship between miRNAs and Th17 cytokines in multiple myeloma (MM) patients. Twenty-seven newly diagnosed myeloma patients and eight normal donors were studied. We determined that the relative expression levels of miR-15a/16, miR-34a, miR-194 in MM patients were significantly lower than those in the healthy controls with exception for miR-181a/b, which showed significantly higher in MM patients ( P < 0.05). In contrast, the levels of IL-17, IL-21 and IL-27 were up-regulated in MM patients compared to healthy controls while IL-22 was down-regulated ( P < 0.05). The expression patterns of them were differentially present in various groups according to the International Staging System (ISS) criteria. Up-regulated IL-17, IL-21 and IL-27 may potentially down-regulate the expression of several miRNAs in MM patients. Establishment of the relationship may be useful for understanding the pathogenesis of MM and for clinical diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Emodin is an anthraquinone derivative from the Chinese herb Radix et Rhizoma Rhei. It has been reported that emodin possesses a number of biological properties, such as anti-inflammatory, anti-virus, anti-bacteria, anti-tumor, and immunosuppressive properties. However, the effect of emodin on mastitis is not yet known. The aim of this study was to investigate whether emodin has protective effect against lipopolysaccharide (LPS)-induced mastitis in a mouse model. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Emodin was administered intraperitoneally with the dose of 1, 2, and 4mg/kg respectively 1h before and 12h after induction of LPS. Emodin significantly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), concentration of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), mRNA expression levels of TNF-α, IL-1β and IL-6, which were increased in LPS-induced mouse mastitis. In addition, emodin influenced nuclear factor kappa-B signal transduction pathway by inhibiting activation of nuclear transcription factor-kappaB (NF-κB) p65 and degradation inhibitor of NF-κB α (IκBα), and emodin also influenced mitogen activated protein kinases signal transduction pathway by depression activation of p38, extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). In conclusion, these results indicated that emodin could exert beneficial effects on experimental mastitis induced by LPS and may represent a novel treatment strategy for mastitis. [Copyright &y& Elsevier]

Colloidal PbS quantum dots (QDs) are promising candidates for various optoelectronic applications based on solution-processed thin-film techniques. In this work, a versatile layer-by-layer (LBL) spray deposition of the QDs is introduced aiming for a future large-scale fabrication process of optoelectronic devices. As compared to spin-coated QD solids, a smaller inter-dot distance and a better-ordered superlattice stacking behavior of the QDs are found in the spray-deposited QD solids as confirmed by grazing-incidence small-angle X-ray scattering (GISAXS). The spectral mapping combined time-resolved photoluminescence analysis indicates a longer charge carrier lifetime and better order of the energy state distribution of the spray-deposited QD solid comparing with the spin-coated one. Thus, photodetectors based on spray deposition of QD solids demonstrate an excellent device performance, with the responsivity achieving 365.1 A/W and the detectivity reaching up to 1.4 × 1012 Jones under an illumination power of 63.5 μW/cm2 at a wavelength of 1250 nm. The spray-deposited device performances indicate a great potential of spray deposition of large sized QDs in large-scale fabrications for optoelectronics using longer wavelengths. Image 1 • Layer-by-layer (LBL) spray deposition of colloidal PbS quantum dots (QDs) is introduced. • Comparison of spray-deposited QD solids with spin-coated QD solids. • In-depth structure analysis of spray-deposited QD solids. • Photodetectors based on spray deposition of QD solids demonstrate excellent device performance. [ABSTRACT FROM AUTHOR]

Core-shell particles are considered to be one of the primary strengthening and toughening methods of cermet. In this study, a (W,Ti,Ta)C based cermet was prepared by vacuum hot pressing sintering technology with the addition of c-BN@Al 2 O 3 (Al 2 O 3 coated c-BN). Localized high residual stress around the core-shell particles causes the strengthening and toughening mechanism at short distances behind the crack tip, such as crack deflection, secondary cracks, crack branching, and grain pull-out, even at a small volume fraction of 10 vol%. Compared with cermet without Al 2 O 3 and c-BN, the flexural strength and fracture toughness of the cermet with 10 vol% c-BN@Al 2 O 3 are increased by 35.62% and 28.45%, reaching 1462 ± 49 MPa and 13.68 ± 0.51 MPa m1/2, respectively. [ABSTRACT FROM AUTHOR]

Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy. Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy. Both groups of patients had similar duration of grade 3–4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 μg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell–treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non–G-CSF group. Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

During the past era, small molecules derived from various plants have attracted extensive attention for their versatile medicinal benefits. Among these, one organic molecule called mangiferin from certain plant species including mangoes and honey bush tea is widely used in treating inflammation. In this study, a LPS-induced mastitis model in mouse is established to investigate the anti-inflammatory effects and mechanism of mangiferin. The result shows that mangiferin significantly alleviates LPS-induced histopathology, meanwhile, also decreases LPS-induced MPO activity. Furthermore, mangiferin treatment remarkably impeded the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, mangiferin was found to inhibit LPS-induced NF-ĸB and NLRP3 inflammasome activation. In conclusion, these results suggested that LPS-induced mastitis can be abated by mangiferin through inhibiting NF-ĸB and NLRP3 signaling pathways. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy is a new and effective method in relapsed or refractory (R/R) multiple myeloma (MM). This study was aimed to explore the risk factors of infection events. We retrospectively analyzed 68 patients with R/R MM who received CAR T-cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to June 2021.35 patients received anti-CD19 combined with anti-BCMA CAR T-cell therapy and 33 patients received anti-BCMA CAR T-cell therapy alone. Infection events in patients who received ≥4 prior lines of treatment or with grade 3–5 cytokines released syndrome (CRS) mainly occurred within 4 months after CAR T-cell infusion(CTI). The duration of infection-free survival was positively correlated with progression-free survival of patients with R/R MM (R2 = 0.962, p < 0.001) and the first infection event was closely accompanied by the disease relapse or progression. Treatment lines (p = 0.05), duration of ANC<500 cells/mm3 after CTI (p = 0.036), CRS grade (p = 0.007) and treatment response (p < 0.001) were the independent risk factors associated with infection for a multivariable model. The infection incidence was higher in patients with dual CAR T-cell therapy than with mono CAR T-cell therapy18 months after CTI although no statistic differences were observed within 18 months. Infections after CTI were closely associated with more lines of prior treatment, longer duration of ANC<500 cells/mm3, higher grade CRS and poor treatment response. Infections tended to occur in the early stage after CTI in patients with more lines of prior treatment and higher grade CRS. [ABSTRACT FROM AUTHOR]

The interaction between 5-Bromo-4-thio-2′-deoxyuridine (4-SBrdU) and human serum albumin (HSA) was investigated by the methods of UV–vis absorbance, fluorescence and circular dichroism (CD) spectroscopy and molecular docking under simulative physiological conditions. The results showed that the quenching mechanism of HAS by 4-SBrdU was dynamic fluorescence quenching, hydrophobic interaction was the main intermolecular force based on thermodynamic data, the fluorescence experimental results were in agreement with results obtained by the molecular docking study. [ABSTRACT FROM AUTHOR]

Abstract: Mastitis is an inflammatory disease caused by microbial infection. Staphylococcus aureus is the major etiological microorganism responsible for both clinical and subclinical mastitis in dairy cows. A mouse model of S. aureus mastitis is available. Baicalin is isolated from Scutellaria and is known to have anti-inflammatory properties. This study was designed to evaluate the effects of baicalin in S. aureus mastitis. In the present study, the mouse model was infected with S. aureus to cause mammary gland inflammation. Baicalin treatment was administered from 6h until 24h after infection. Baicalin significantly attenuated inflammatory cell infiltration and decreased levels of TNF-α, IL-β, and IL-6. Further studies revealed that baicalin downregulated phosphorylation of NF-κB and p38 in the mammary gland with S. aureus mastitis. Our results demonstrated that baicalin reduced the expression of the proinflammatory cytokines TNF-α, IL-β, and IL-6 by inhibiting NF-κB and p38 phosphorylation and mRNA expression. [Copyright &y& Elsevier]

A novel ceramic coating-like (CCL) structure was proposed for preparing a potential ceramic cutting tool material. The influence of critical factors, including the material composition, composition content and surface layer thickness, on the residual stress was analyzed by the finite element method (FEM). Under the condition of the optimized parameters, the compressive stress generated on the surface layer of the CCL tool material ranged from −163 MPa to −248 MPa. Based on the obtained results, a (Ti,W)C/Al 2 O 3 +SiC CCL tool material was prepared by vacuum hot-pressing sintering, indicating the residual compressive stress (−122.3 MPa) of the surface layer. Compared with the performance of homogeneous cermet materials, the surface hardness and flexural strength of the CCL tool materials were increased by 46.58% and 37.76%, respectively. Moreover, the SEM imaging results of the sample surface and fracture morphology and the energy dispersive spectroscopy (EDS) analysis results showed that the dense ceramic surface and phase interfacial transition layer were formed with a uniform gradient distribution and without defects. [ABSTRACT FROM AUTHOR]

• A high incidence of coagulation disorders was observed after chimeric antigen receptor (CAR)-T cell therapy infusion. • The changes of coagulation parameters were associated with cytokine release syndrome (CRS). • Disseminated intravascular coagulation was found in patients with severe CRS and indicated a poor prognosis. • Coagulation disorders are manageable in most patients after CAR-T cell infusion. Chimeric antigen receptor (CAR)-T cell therapy, a new immunotherapy for relapsed and refractory (R/R) hematologic malignancies, can be accompanied by adverse events, including coagulation disorders. Here, we performed a comprehensive analysis of coagulation parameters in 100 patients with R/R hematologic malignancies after receiving CAR-T cell therapy to illuminate the profiles of coagulation disorders and to facilitate the management of coagulation disorders. A high incidence of coagulation disorders was observed, including elevated D-dimer (50/100, 50%), increased fibrinogen degradation product (45/100, 45%), decreased fibrinogen (23/100, 23%), prolonged activated partial thromboplastin time (16/100, 16%), and prolonged prothrombin time (10/100, 10%). Coagulation disorders occurred mainly during day 6 to day 20 after CAR-T cell infusion. The changes in coagulation parameters were associated with high tumor burden in acute lymphoblastic leukemia, more lines of prior therapies, lower baseline platelet count, and especially cytokine release syndrome (CRS). Disseminated intravascular coagulation (DIC) was found in 7 patients with grade ≥3 CRS and indicated a poor prognosis. Our study suggests that coagulation disorders are manageable in most patients after CAR-T cell therapy. Coexistence of DIC and severe CRS is closely related to nonrelapsed deaths during the acute toxicity phase, and effective and timely treatment is the key to reduce nonrelapse mortality for patients with DIC and severe CRS. [ABSTRACT FROM AUTHOR]

The large ownership of direct-expansion (DX) air-conditioning (A/C) systems in small and medium-sized buildings brings with it the need to reduce their energy consumption without damaging the thermal comfort of the occupants. Model predictive control (MPC) is an effective method to optimally control the operation of air-conditioners. However, most existing MPC methods require the investment of additional equipment and labor-intensive work, which greatly increases the cost of MPC and hinders its practical application. To solve the problem, this paper presents an economical and practical MPC algorithm for DX A/C systems, capable of achieving a balance between thermal comfort and energy saving. The proposed algorithm was experimentally validated on both an experimental DX A/C system and a market available split-type air-conditioner. Experimental results on the experimental DX A/C system show that temperature and humidity set-points selected at α = 1 saved 23.3% of energy consumption compared to those selected at α = 0, while keeping indoor thermal comfort within acceptable range. And results on the split-type air-conditioner demonstrate energy savings of up to more than 32% compared to the baseline and proved that the algorithm can be practically applied on market available D/X air-conditioners. • A practical application-oriented model predictive control algorithm is developed for DX A/C systems. • A cooling capacity prediction ANN model of the DX A/C system is used to predict the cooling load. • An ANN model for predicting the operational status of the DX A/C system is developed without increasing the training data. • A cost function is used to balance indoor thermal comfort levels and energy consumption. • The algorithm has been validated in both an experimental DX A/C system and a market available split-type air-conditioner. [ABSTRACT FROM AUTHOR]

As a nonspecific alkylating antineoplastic agent, busulfan has been widely used in the treatment of patients with chronic myeloid leukemia. In vitro and in vivo studies demonstrated busulfan-induced cell apoptosis. Whether busulfan triggers platelet apoptosis remains unclear. This study aimed to evaluate the role of busulfan in platelet apoptosis. Isolated human platelets were incubated with busulfan followed by analysis of platelet apoptosis by flow cytometry or western blot, including mitochondrial depolarization, expression of Bcl-2, and Bax and caspase 3 activation. Meanwhile, platelet activation, expression of glycoprotein Ibα (GPIbα), glycoprotein VI (GPVI), and IIb3 and platelet aggregation in response to collagen and adenosine diphosphate (ADP) were measured. Additionally, busulfan was injected into mice with or without administration of caspase inhibitor QVD-Oph to investigate its effect on platelet lifespan. Our results showed that busulfan-treated platelets displayed increased mitochondrial membrane depolarization, decreased expression of Bcl-2, increased expression of Bax and caspase 3 activation in dose-dependent manner, which were inhibited by QVD-Oph. Platelet activation was not observed in busulfan-treated platelets as showed by no increased P-selectin expression and PAC-1 binding. However, busulfan reduced collagen- or ADP-induced platelet aggregation without affecting expression of GPIbα, GPVI, and IIb3. Furthermore, busulfan reduced circulating platelet lifespan which was ameliorated by QVD-Oph in mice. In conclusion, busulfan triggers mitochondrial-dependent platelet apoptosis and reduces platelet lifespan in mice. These data suggest targeting caspase activation might be beneficial in the prophylaxis of platelet apoptosis-associated thrombocytopenia after administration of busulfan. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, characterized by dysregulation of cellular immunity. Th17 and associated IL-17 were involved in the pathogenesis of ITP. Runt-related transcription factor 1 (RUNX1), a member of the runt domain-containing family of transcription factors, is required for Th17 differentiation. Whether RUNX1 was involved in the pathogenesis of ITP remains poorly understood. In this study, 30 active ITP patients, 20 ITP in remission and 20 age and gender matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated to measure mRNA level of RUNX1 and retinoic acid receptor-related orphan receptor-γt (RORγt) by quantitative real-time PCR and Th17 cells by flow cytometry. Meanwhile, plasma was extracted for measurement of IL-17 level by ELISA. Our results showed a significantly higher expression of RUNX1, RORγt, Th17 cells and plasma level of IL-17 in active ITP patients than that in healthy controls. No differences of expression of RUNX1, RORγt and Th17 cells were observed between remission patients and controls. Furthermore, a significantly positive correlation of RUNX1 with RORγt was found in active ITP patients. In conclusion, RUNX1 was associated with the pathogenesis of ITP possibly through regulation of Th17 cell differentiation and therapeutically targeting it might be a novel approach in ITP treatment. [ABSTRACT FROM AUTHOR]

Concentrations of 16 polybrominated diphenyl ether (PBDE) congeners were measured in river sediments, paddy soils and three species of paddy-field organisms (crab, loach and carp) collected from the Liaohe River Basin, northeastern China. The total contents of PBDEs (∑ 16 PBDEs) in sediments and paddy soils were in the ranges of 273.4–3246.3 pg/g dry weight (dw), and 192.1–1783.8 pg/g dw, respectively. BDE 209 was the dominant congener both in sediments and paddy soils. The concentrations of ∑ 16 PBDEs in sediments were significantly higher than those in the adjacent paddy soils, indicating a potential transport of PBDEs from river to paddy ecosystems via river water irrigation. The biota–soil accumulation factor (BSAF) was calculated as the ratio between the lipid-normalized concentration in paddy-field organisms and the total organic carbon-normalized concentration in paddy soil. The average BSAF values of ∑ 15 PBDEs followed the sequence of crab (3.6) > loach (3.3) > carp (2.1). BDE 154 had the highest BSAF value, and a parabolic trend between BSAF values of individual PBDE congeners and their log K OW values was observed. In view of the fact that crab had the larger BSAF value and higher lipid content, the ecological risk and health risk for crab cultivation in paddy fields should be of particular concern. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune disease, characterized by dysregulation of cellular immunity. Previous studies demonstrated that immune imbalance between Th1 and Th2 was associated with the pathogenesis of ITP. Runt-related transcription factor 3 (RUNX3) is a member of the runt domain-containing family of transcription factors and plays an important role in the regulation of T cell differentiation into Th1 cells. Whether RUNX3 was involved in the pathogenesis of ITP remains unclear. In this study, 47 active ITP patients, 18 ITP with remission and 26 age and gender matched healthy control were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma which were used to measure mRNA level of RUNX3 and T-box transcription factor (T-bet) by quantitative real-time PCR and interferon γ (IFN-γ) plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of RUNX3 expression. Our results showed a significantly higher expression of RUNX3, T-bet and plasma level of IFN-γ in active ITP patients compared to control. No differences were observed between ITP with remission and control. Furthermore, a positive correlation of RUNX3 with T-bet was found in active ITP patients. In conclusion, aberrant expression of RUNX3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a novel approach in ITP treatment. [ABSTRACT FROM AUTHOR]

Abstract: Mastitis is a prevalent and economic disease around the world and defined as infection and inflammation of the mammary gland. Astragalin, a bioactive component isolated from persimmon or Rosa agrestis, has been reported to have anti-inflammatory properties. To investigate the potential therapeutic effect of astragalin in mastitis, a murine model of mastitis was induced by administration of LPS in mammary gland. Astragalin was applied 1h before and 12h after LPS treatment. The results showed that astragalin attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO) and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, Western blotting results showed that astragalin efficiently blunt decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα and the nuclear translocation of p65. These results suggested that astragalin exerts anti-inflammatory properties in LPS-mediated mastitis, possibly through inhibiting inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. Astragalin may be a potential therapeutic agent against mastitis. [Copyright &y& Elsevier]

Abstract: Geniposide, a main iridoid glucoside component of gardenia fruit, has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The objective of this study was to investigate the protective effects of geniposide on inflammation in lipopolysaccharide (LPS) stimulated primary mouse macrophages in vitro and LPS induced lung injury model in vivo. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by Western blot. Further analysis was carried out in mTLR4 and mMD-2 co-transfected HEK293 cells. The results showed that geniposide markedly inhibited the LPS-induced TNF-α, IL-6 and IL-1β production both in vitro and in vivo. Geniposide blocked the phosphorylation of IκBα, p65, p38, ERK and JNK in LPS stimulated primary mouse macrophages. Furthermore, geniposide inhibited the expression of TLR4 in LPS stimulated primary mouse macrophages and inhibited the LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells. In vivo study, it was also observed that geniposide attenuated lung histopathologic changes in the mouse models. These results suggest that geniposide exerts an anti-inflammatory property by down-regulating the expression of TLR4 up-regulated by LPS. Geniposide is highly effective in inhibiting acute lung injury and may be a promising potential therapeutic reagent for acute lung injury treatment. [Copyright &y& Elsevier]