Search

As a major strategic technology, artificial intelligence is developing rapidly while bringing numerous security risks.Currently, security data for artificial intelligence is collected from disparate sources and lacks standardized description, making it difficult to integrate and analyze effectively.To address this issue, a method for constructing an artificial intelligence security knowledge graph was proposed.The knowledge graph was used to integrate the current multi-source heterogeneous data, scientifically represent complex relationships of the data, mine potential value and form a domain knowledge base.In view of the diversity and correlation of concepts in the field of artificial intelligence security, a hierarchical structure of artificial intelligence security ontology was proposed to make the ontology structure more diversified and extensible, provide rule constraints for the process of knowledge graph construction, and form an artificial intelligence security knowledge base.To effectively utilize feature information and reduce noise interference, named entity recognition algorithm based on BiLSTM-CRF and relationship extraction algorithm based on CNN-ATT were adopted for information extraction.The constructed artificial intelligence security dataset was then used to verify the performance of the algorithm.Based on the proposed ontology, the multi-level visualization results of the artificial intelligence security knowledge graph were presented in 3D effect, effectively connecting the multi-source security data information.The experimental results show that the constructed knowledge graph meets the multi-dimensional evaluation criteria of accuracy, consistency, completeness, and timeliness, providing knowledge support for artificial intelligence security research.Overall, the proposed method can help address the complexity and heterogeneity of security data in artificial intelligence and provide a more standardized, integrated approach to knowledge representation and analysis.

A fully automated method for identification and quantification of five polar pesticides in groundwater by isotope dilution‐online solid‐phase extraction (SPE) coupled with high‐performance liquid chromatography‐quadrupole Orbitrap high‐resolution mass spectrometry was developed. After one step of filtration, an aliquot of a 7.5‐ml water sample was automatedly preconcentrated and purified on a turbulent Cyclone SPE column. The analytes were eluted in backflush mode, then separated on an analytical column and acquired by full MS/dd‐MS2 scan in negative and positive ions mode. The major parameters for sample loading, cleanup, and elution were optimized in detail. Preconcentration and ionization efficiency were highly improved by using 0.1% acid solution in the mobile phase. The method provided good linearity of calibration coefficients (R2 > 0.995), sensitive method limits of detection (0.5–10.0 ng/L), accurate mass spectra (within 5 ppm error), satisfactory matrix spiking recoveries (98.4% to 109%), and high precision (intraday/interday relative standard deviations 1.57–8.90%). The method was successfully applied to analyze large batch groundwater of National Groundwater Monitoring Project and suspect screening of potential pesticides in groundwater. The study provided a practical alternative for a simple, robust, sensitive, and accurate identification and qualification of five polar pesticides in groundwater. [ABSTRACT FROM AUTHOR]

To support high speed transmission and traffic offloading from cellular networks, LTE-unlicensed (LTE-U) standard was proposed by 3GPP to enable cellular data transmission in unlicensed band. The primary challenge of LTE-U is to successfully coexist with the incumbent systems (e.g., WiFi networks) in the unlicensed bands, while still maintaining the quality-of-service (QoS) for LTE-A users. This paper proposes a new framework for implementing LTE-U standard based on deployed LTE-A infrastructure and cognitive radio (CR) technology to sense radio environment and construct a spectrum map, based on which the LTE-U system can perform joint power and channel allocation to maximize the overall system throughput. We introduce a spectrum map construction scheme and evaluate the Cramer-Rao bound of the scheme. It is shown that the original NP-hard joint power and channel allocation problem can be transformed into a linear programming problem for its solution. Simulation results verify that the proposed LTE-U scheme helps improve system throughput via access collision avoidance. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Two compounds [Cu(biim)] 2 (TEA) 2 [HPW 12 O 40 ]·H 2 O ( 1 ); [Cu(im) 2 ](im)[H 2 PMo 12 O 40 ] ( 2 ), (biim = 2,2′-biimidazole, im = imidazole, TEA = triethylamine) have been hydrothermally synthesized and characterized by IR, XPS, XRD, UV-Vis, fluorescent spectra analysis, elemental analysis, X-ray diffraction analysis, cyclic voltammetric measurement and single crystal X-ray diffraction analysis. Single crystal X-ray diffraction analysis reveals that compounds 1–2 represent new examples formed by polyoxoanions, transition metal coordination complexes (TMCs) and organic amines. Compound 1 exhibits a 3-D supermolecular structure of which layers A and C are stacked alternatively, while compound 2 first shows a 1-D chain structure with an –A↑–A↓–A↑–A↓ linking mode, then along a , b and c axis, respectively exhibits different beautiful 2-D supramolecular networks via hydrogen bond interactions.The photodegradation properties of compounds 1–2 have been investigated. [ABSTRACT FROM AUTHOR]

Two new hybrid compounds, [Cu(1)(phen)(H2O)][Cu(2)(phen)(H2O)]([Cu(3)]0.25(H2O)][P2Mo5O23]·3.75H2O (1) and [Cu(en)2]1.5[P2Mo5O23]2·(enH2)3·2H2O (2) (phen = 1,10-phenanthroline, en = ethylenediamine), have been hydrothermally synthesized and characterized by IR, UV–Vis spectroscopy, X-ray photoelectron spectroscopy (XPS), powder XRD analyses, TG analyses, cyclic voltammogram analyses, elemental analyses, and single crystal X-ray diffraction analyses. Single crystal X-ray diffraction analyses reveal that the two compounds have a 1-D chain structure formed by Strandberg-type POMs and TMCs with –A–B–C–B–A–B–C–B– linking mode, then further extend into a 2-D layer structure through π⋯π or hydrogen bond interactions. [ABSTRACT FROM AUTHOR]

Manganese dioxides (MnO2) were successfully deposited on carbon nanotubes (CNTs) surface by redox reaction between potassium permanganate and CNTs. The characterization results showed that the MnO2exhibited the rice-shaped nanostructure with about 5∼10 nm in width and 10∼30 nm in the length on CNTs. The solvothermal temperature of composite can greatly affected its morphology and structure to improve the thermal catalytic on ammonium perchlorate (AP) decomposition. Compared with other samples, the prepared composite at 120°C exhibited superior catalytic performance, as 3wt% of composite added in AP, the second exothermic peak temperature decreased by 160.2°C and the apparent release heat of the thermal decomposition of AP which is four times of that of pure AP. A possible mechanism for formation the rice shaped MnO2/CNTs composite is also presented. [ABSTRACT FROM AUTHOR]

Gram-negative bacterial lipopolysaccharide (LPS) activates macrophages by interacting with Toll-like receptor 4 (TLR4) and triggers the production of various pro-inflammatory Th1 type (type 1) cytokines such as IFNγ, TNFα, and IL8. Though some recent studies cited macrophages as potential sources for Th2 type (type 2) cytokines, little however is known about the intracellular events that lead to LPS-induced type 2 cytokines in macrophages. To understand the mechanisms by which LPS induces type 2 cytokine gene expression, macrophages were stimulated with LPS, and the expression of IL-4 and IL-S genes were examined. LPS, acting through TLR4, activates both type 1 and type 2 cytokine production both in vitro and in vivo by using macrophages from C3H/HeJ or C3H/HeOuJ mice. Although the baseline level of both TNFE and IL-4 protein was very low, TNFα was released rapidly after stimulation (within 4 h); however, IL-4 was released after 48 h LPS stimulation in secreted form. Silencing of myeloid differentiation protein (MyD88) and TRIF-related adaptor molecule (TRAM), using small interfering RNA abolished IL-4 induction induced by LPS whereas silencing of TRAM has no effect on TNFa induction, thereby indicating that LPS-induced TNFα is MyD88-dependent but IL-4 is required both MyD88 and TRAM. These findings suggest a novel function of LPS and the signaling pathways in the induction of IL-4 gene expression. [ABSTRACT FROM AUTHOR]

GTPase RhoA is required for fMet-Leu-Phe (fMLP)-stimulated NF-κB activation in human peripheral blood monocytes. Here we have investigated different members of the Rho family of GTPases Rac1, Cdc42, and RhoA in regulating the transcription factor nuclear factor-κB (NF-κB) in human peripheral blood monocytes. Stimulation of monocytes with fMLP rapidly activated Rac1, Cdc42, and RhoA and cotransfection of the monocytic THP1 cells with dominant negative forms of Rho GTPases, we found that Rac1 and RhoA, but not Cdc42, involved fMLP-stimulated κB reporter gene expression. These results indicate that fMLP stimulates three members of the Rho family of GTPases Rac1, Cdc42, and RhoA activity in monocytes, and that Rac1 and RhoA, but not Cdc42, is required for fMLP-induced NF-κB activation. Furthermore, our data also suggest that RhoA is mediated by signals independent of Rac1 in NF-κB activation in human peripheral blood monocytes stimulated with bacterial products. [Copyright &y& Elsevier]

The porous media theory is extensively used to simulate the porous structures due to the complexity of the shape and grain configuration. In this study, The open-source code OpenFOAM was firstly extended to solve the interaction between the sloshing flow and the random porous structure, and the accuracy of the extension was validated by comparing the numerical results with experimental data. In addition, the effect of porosity, average diameter of the porous structure was analyzed, and then the anti-sloshing performance of rectangular tank for different excitation frequencies and distances between the random porous structure and the nodal line of eigenmode (m = 1) was also discussed. After that, a comparison of the wave-damping performance between the random porous layer and the traditional perforated baffle was conducted. Results indicated that the random porous structure with porosity (n) of 0.2 and average diameter (d 50 / b) of 0.85 has the best anti-sloshing performance, and the anti-sloshing performance of random porous layer is generally decreased when the excitation frequency moves close to the first-order natural frequency, and it is decreased with the increasing distance. A better wave-damping performance of the present random porous structure can be observed when compared with traditional perforated baffle. • The anti-sloshing performance of the random porous layer in the water tank is numerically analyzed. • Porous media theory is adopted to simulate the random porous layer in the water tank. • The parameters of the porosity (n) and averaged diameter (d 50) are optimized, and the effects of excitation frequencies and distances between the random porous layer and nodal line of eigenmode m = 1 are analyzed. • A comparison of the wave-damping performance between the present porous layer and the traditional porous baffle is conducted. • The water surface elevation, flow field, pressure on bulkhead and global average velocity in the water tank are investigated. [ABSTRACT FROM AUTHOR]

Establishment of vegetable soybean (edamame) [ Glycine max (L.) Merr.] germplasms has been highly valued in Asia and the United States owing to the increasing market demand for edamame. The idea of core collection (CC) is to shorten the breeding program so as to improve the availability of germplasm resources. However, multidimensional phenotypes typically are highly correlated and have different levels of missing rate, often failing to capture the underlying pattern of germplasms and select CC precisely. These are commonly observed on correlated samples. To overcome such scenario, we introduced the "multiple imputation" (MI) method to iteratively impute missing phenotypes for 46 morphological traits and jointly analyzed high-dimensional imputed missing phenotypes (EC impu ) to explore population structure and relatedness among 200 Taiwanese vegetable soybean accessions. An advanced maximization strategy with a heuristic algorithm and PowerCore was used to evaluate the morphological diversity among the EC impu . In total, 36 accessions (denoted as CC impu ) were efficiently selected representing high diversity and the entire coverage of the EC impu . Only 4 (8.7%) traits showed slightly significant differences between the CC impu and EC impu . Compared to the EC impu , 96% traits retained all characteristics or had a slight diversity loss in the CC impu . The CC impu exhibited a small percentage of significant mean difference (4.51%), and large coincidence rate (98.1%), variable rate (138.76%), and coverage (close to 100%), indicating the representativeness of the EC impu . We noted that the CC impu outperformed the CC raw in evaluation properties, suggesting that the multiple phenotype imputation method has the potential to deal with missing phenotypes in correlated samples efficiently and reliably without re-phenotyping accessions. Our results illustrated a significant role of imputed missing phenotypes in support of the MI-based framework for plant-breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Ku, Wang, Chen, He, Chen, Liao, Juan and Kao.)

A fully automated method for identification and quantification of five polar pesticides in groundwater by isotope dilution-online solid-phase extraction (SPE) coupled with high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry was developed. After one step of filtration, an aliquot of a 7.5-ml water sample was automatedly preconcentrated and purified on a turbulent Cyclone SPE column. The analytes were eluted in backflush mode, then separated on an analytical column and acquired by full MS/dd-MS 2 scan in negative and positive ions mode. The major parameters for sample loading, cleanup, and elution were optimized in detail. Preconcentration and ionization efficiency were highly improved by using 0.1% acid solution in the mobile phase. The method provided good linearity of calibration coefficients (R 2 > 0.995), sensitive method limits of detection (0.5-10.0 ng/L), accurate mass spectra (within 5 ppm error), satisfactory matrix spiking recoveries (98.4% to 109%), and high precision (intraday/interday relative standard deviations 1.57-8.90%). The method was successfully applied to analyze large batch groundwater of National Groundwater Monitoring Project and suspect screening of potential pesticides in groundwater. The study provided a practical alternative for a simple, robust, sensitive, and accurate identification and qualification of five polar pesticides in groundwater., (© 2020 John Wiley & Sons, Ltd.)

Surface properties and structures of materials are essential for their adsorption of pollutants in water. Humic acids (HA)-supported CeO₂ nanosheet composites are synthesised by solvothermal method. The size of CeO₂ nanosheets are approximately 100-500 nm. The obtained composite exhibits superior adsorption ability for Congo Red (CR) in water, which can be attributed to its unique structure and highly dispersed CeO₂ nanosheet. The composite's adsorption behaviour of CR follows a pseudo-second-order mode and Langmuir adsorption model well, and the maximum adsorptive capacity for CR achieves 260 mg g -1 . The presence of CeO₂ nanosheets enhances surface area and enriches the mesoporous structure of the composites, thereby promoting CR adsorption capacity.

Stimulation of phagocytic leukocytes with bacterial chemoattractant resulted in the release of matrix metal-loproteinases (MMPs). Little is known about the mechanisms of bacterial chemoattractant regulation of MMP in phagocytic leukocytes. We report here that the mechanisms of the bacterial chemotactic peptidefMLP-induced MMP -9 release in monocytes appeared to be different from fMLP-stimulated MMP-9 release in neutrophils. In freshly prepared peripheral blood monocytes, fMLP induces MMP-9 release, starting at 8 h after stimulation. These functions of fMLP is accompanied by an increase in TNFα expression, and mediated through the phosphorylation of ERK1/2 in monocytes. However, neutrophil preparations that responded to fMLP with MMP-9 release did not require activation of ERK1/2 and TNFα expression. These results suggest a different role of fMLP in MMP-9 expression in neutrophils and monocytes, and the signal molecules involved in mediating this effect in human blood monocytes stimulated by bacterial chemoattractant.

In the host immune system, leukocytes are often exposed to multiple inflammation inducers. NF-κB is of considerable importance in leukocyte function because of its ability to activate the transcription of many proinflammatory immediate-early genes. Tremendous efforts have been made toward understanding how NF-κB is activated by various inducers. However, most research on NF-κB regulation has been focused on understanding how NF-κB is activated by a single inducer. This is unlike the situation in the human immune system where multiple inflammation inducers, including both exogenous and endogenous mediators, are present concurrently. We now present evidence that the formylated peptide f-Met-Leu-Phe (fMLP), a bacterial chemoattractant, synergizes with TNFα to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. The mechanism of synergistic activation of NF-κB by bacterial fMLP and TNFα may be involved in the induction of RelA acetylation, which is regulated by p38 MAPK. Thus, this study provides direct evidence for the synergistic induction of NF-κB-dependent inflammatory responses by both exogenous and endogenous inducers. The ability of fMLP to synergize with TNFα and activate NF-κB represents a novel and potentially important mechanism through which bacterial fMLP not only attracts leukocytes but also directly contributes to inflammation by synergizing with the endogenous mediator TNFα.

Accumulating evidence demonstrates that bacterial chemoattractants not only attract leukocytes (chemotaxis) but also contribute directly to inflammation by activation of leukocytes to produce a variety of pro-inflammatory cytokines. Recent studies have shown that mixtures of the bacterial chemoattractant fMLP (N-formyl-Met-Leu-Phe) and other bacterial products/components such as LPS (lipopolysaccharide) behave synergistically in activating leukocytes. These results suggest that inflammatory responses are induced by multiple inducers that operate synergistically through multiple signaling pathways. This synergy is likely to play a significant role in the induction of host defense to bacterial infections and in the pathogenesis of inflammatory disorders. These results also demonstrate that the control of inflammation is likely best understood at the level of synergistic regulation of intracellular signaling. The use of pharmacological inhibitors to modulate synergistic molecules is therefore an attractive possibility for the treatment of inflammatory disease. In this review, we will provide a brief summary of recent studies on the regulation of leukocyte functioning by bacterial chemoattractants.

We have reported that the bacterial LPS induces the activation of NF-kappaB and inflammatory cytokine gene expression and that this requires the activity of small GTPase, RhoA. In this study, we show that an atypical protein kinase C isozyme, PKCzeta, associates functionally with RhoA and that PKCzeta acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCzeta activation and that inhibition of PKCzeta activity blocks both LPS-stimulated activation of NF-kappaB and IL-1beta gene expression. Our results also indicate that transforming growth factor beta-activated kinase 1 acts as a signaling component downstream of PKCzeta in cytokine gene transcription stimulated by LPS in human peripheral blood monocytes and macrophages. The specificity of this response suggests an important role for the Rho GTPase/PKCzeta/transforming growth factor beta-activated kinase 1/NF-kappaB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.

A wide variety of stimuli have been shown to induce inflammation, but bacteria products/components are considered the major inducers during bacterial infections. We previously demonstrated that bacterial products/components such as LPS, a glycolipid component of the bacterial outer membrane, and formylated peptides (fMLP), a bacterial-derived peptide, induced proinflammatory cytokine gene expression in human peripheral blood monocytes. We now present evidence that mixtures of bacterial products/components LPS and fMLP behave synergistically in the induction of inflammation in vitro and in vivo. Furthermore, our results indicate that the TLR4 and the IKKbeta-IkappaBalpha signaling pathways are involved in the synergistic induction of inflammatory cytokines. The mechanism of synergistic activation of NF-kappaB is depended on nuclear translocation of p65 and phosphorylation of p65 at both Ser536 and Ser276 sites. These results demonstrate an important role for bacterial products/components from lysed bacteria in the pathogenesis of infectious diseases. We believe that this synergistic induction of inflammation by bacterial products LPS and fMLP represents an important pathogenic mechanism during bacterial infection, which may suggest novel therapeutic strategies or targets to minimize host injury following bacterial infection.

We have reported that the chemoattractant, fMet-Leu-Phe (fMLP), induces the activation of NF-kappaB in human peripheral blood monocytes and that this requires the activity of small GTPase, RhoA (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we showed that the novel protein kinase C isozyme, PKCepsilon, associates functionally with RhoA in fMLP-stimulated monocytes and that PKCepsilon acted as a signaling component downstream of the GTPase RhoA during fMLP-induced activation of NF-kappaB. Stimulation of monocytes with fMLP resulted in activation of both PKCepsilon and NF-kappaB. This latter activation was largely blocked by specific inhibitors of PKCepsilon by transient expression of a dominant-negative form of PKCepsilon and by PKCepsilon-specific short interfering RNA. These findings demonstrate, for the first time, that fMLP-induced activation of NF-kappaB utilizes a signaling pathway, which requires activity of PKCepsilon, and that PKCepsilon acts as a signaling component downstream of RhoA in cytokine gene transcription stimulated by a chemoattractant. The specificity of this response suggests an important role for the Rho GTPase-PKCepsilon-NF-kappaB pathway in host defense and represents a novel and potentially important mechanism through which fMLP not only attracts leukocytes but may also contribute directly to inflammation.

We reported previously that fMLP stimulates NF-kappaB activation, and this function of fMLP requires small GTPase RhoA in human peripheral blood monocytes (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we present evidence that RhoA associates specifically with the guanine nucleotide exchange factor Lbc in human peripheral blood monocytes stimulated with fMLP and that Lbc specifically catalyzes the guanine nucleotide exchange activity of RhoA in human peripheral blood monocytes. Cotransfection of the monocytic THP1 cells with lbc with a kappaB promoter reporter plasmid results in a marked increase in NF-kappaB-mediated reporter gene expression. Finally, Lbc-enhanced NF-kappaB activation is inhibited by a RhoA inhibitor, C3 transferase from Clostridium botulinum. A dominant-negative form of RhoA (T19N) also inhibited Lbc-enhanced reporter gene expression in a kappaB-dependent manner. These results indicate that guanine nucleotide exchange factor Lbc is a novel signal transducer for RhoA-mediated NF-kappaB activation in human peripheral blood monocytes stimulated with bacterial products.

Bacterial lipopolysaccharide (LPS) is a powerful activator of the innate immune system. Exposure to LPS induces an inflammatory reaction in the lung mediated primarily by human blood monocytes and alveolar macrophages, which release an array of inflammatory chemokines and cytokines including IL-8, TNF-alpha, IL-1beta, and IL-6. The signaling mechanisms utilized by LPS to stimulate the release of cytokines and chemokines are still incompletely understood. Pretreatment with the protein tyrosine kinase-specific inhibitors genistein and herbimycin A effectively blocked LPS-induced NF-kappaB activation as well as IL-8 gene expression in human peripheral blood monocytes. However, when genistein was added 2 min after the addition of LPS, no inhibition was observed. Utilizing a coimmunoprecipitation assay, we further showed that LPS-stimulated tyrosine phosphorylation of Toll-like receptor 4 (TLR4) may be involved in downstream signaling events induced by LPS. These findings provide evidence that LPS-induced NF-kappaB activation and IL-8 gene expression use a signaling pathway requiring protein tyrosine kinase and that such regulation may occur through tyrosine phosphorylation of TLR4.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma and B-cell neoplasms. The genomic organization of KSHV is similar to that of Epstein-Barr virus (EBV). EBV encodes two transcriptional factors, Rta and Zta, which functionally interact to transactivate EBV genes during replication and reactivation from latency. KSHV encodes a basic leucine zipper protein (K-bZIP), a homologue of EBV Zta, and K-Rta, the homologue of EBV Rta. EBV Rta and Zta are strong transcriptional transactivators. Although there is ample evidence that K-Rta is a potent transactivator, the role of K-bZIP as a transcriptional factor is much less clear. In this study, we report that K-bZIP modulates K-Rta function. We show that K-bZIP directly interacts with K-Rta in vivo and in vitro. This association is specific, requiring the basic domain (amino acids 122 to 189) of K-bZIP and a specific region (amino acids 499 to 550) of K-Rta, and can be detected with K-bZIP and K-Rta endogenously expressed in BCBL-1 cells treated with tetradecanoyl phorbol acetate. The functional relevance of this association was revealed by the observation that K-bZIP represses the transactivation of the ORF57 promoter by K-Rta in a dose-dependent manner. K-bZIP lacking the interaction domain fails to repress K-Rta-mediated transactivation; this finding attests to the specificity of the repression. Interestingly, this repression is not observed for the promoter of polyadenylated nuclear (PAN) RNA, another target of K-Rta; thus, repression is promoter dependent. Finally, we provide evidence that the modulation of K-Rta by K-bZIP also occurs in vivo during reactivation of the viral genome in BCBL-1 cells. When K-bZIP is overexpressed in BCBL-1 cells, the level of expression of ORF57 but not PAN RNA is repressed. These data support the model that one function of K-bZIP is to modulate the activity of the transcriptional transactivator K-Rta.

Proinflammatory cytokines such as IL-1, TNF, IL-6, and IL-8 are produced by leukocytes in response to bacteria or bacterial components. A great deal has been learned during the past few years about the synthesis and release of proinflammatory cytokines by leukocytes; however, relatively little is known about the intracellular events that lead to leukocyte proinflammatory cytokine gene transcription. This study examined the signal transduction pathway of IL-8 induction by bacterial LPS. Stimulation of monocytes with LPS rapidly activated RhoA, and pretreatment of monocytes with a RhoA inhibitor, C3 transferase exoenzyme, effectively blocked LPS-induced IL-8 gene expression. Overexpression of dominant negative RhoA (T19N) or IL-1R-associated kinase completely inhibited LPS-stimulated reporter gene expression. Induction of IL-8 was also inhibited by dominant negative IkappaB kinase and myeloid differentiation protein (MyD88). These results indicate that RhoA and IL-1R-associated kinase are novel signal transducers for LPS-induced Toll-like receptor 4-mediated proinflammatory cytokine synthesis in human monocytes.