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In recent years, there has been an increase in accidents involving vessels colliding with bridge piers. These ship–bridge collisions can result in tragic loss of life and severe damage to the bridge structure. To address this issue, a type of fender pile made of winding-formed glass fiber-reinforced polymer (GFRP) was proposed as a solution. In this article, three- and four-point bending tests were performed to compare and analyze the damage modes and load-carrying capacity of the fender piles at two different winding angles, namely 45° and 75°. Vertical impact test was simulated using ANSYS/LS-DYNA to verify finite element models. The results revealed variations in damage patterns and bending performance of GFRP piles under the two fiber winding angles. The simulation results suggest that GFRP fender piles can effectively increase the impact time of ship–bridge collisions and reduce the collision forces, thereby significantly improving the protection of bridge piers.

Objective To explore the regulative effect and mechanism of cytochrome P450 1A1 (CYP1A1) on regulating lipopolysaccharide (LPS)-induced arginase-1 (Arg-1) expression in macrophages. Methods After mouse macrophage-like cell line RAW264.7 (RAW) was treated with 10 mg/L LPS for 0, 12 and 24 h, respectively (n=3 for each time point), the expression of CYP1A1 and Arg-1 at mRNA and protein levels were measured by RT-PCR and Western blotting. Negative control RAW(NC/RAW) cells, CYP1A1-overexpression RAW (CYP1A1/RAW) cells, CYP1A1-knockout RAW (CYP1A1 KO/RAW) cells and CYP1A1 hydroxylase-activity mutant RAW (CYP1A1m/RAW) cells were constructed, respectively, and then the cells were treated with LPS and further detected with RT-PCR and Western blotting for the expression and activation levels of Arg-1 and signal transducer and activators of transcription-6 (STAT6). Then STAT 6 inhibitor AS1517499 was added to treat the CYP1A1 KO/RAW cells and NC/RAW cells, and the mRNA and protein expression of Arg-1 was measured again after LPS or PBS treatment. CYP1A1 epoxidase inhibitor, nordihydroguaiaretic acid (NDGA) and 12 (S)-HETE were introduced to treat normal RAW cells, the mRNA and protein levels of Arg-1 and activity of STAT6 were detected after LPS or PBS treatment. Results LPS-induced CYP1A1 and Arg-1 were highly expressed in staggering peaks in RAW cells (P < 0.05). Overexpression of CYP1A1 inhibited LPS-induced Arg-1 expression and STAT6 activation in RAW cells, while CYP1A1 knockout enhanced above effects (P < 0.05). STAT6 inhibitor AS1517499 abolished the enhancement of CYP1A1 knockout (P < 0.05). CYP1A1 hydroxylase-activity mutation or 12(S)-HETE simulation had no effect on the expression of Arg-1 (P>0.05), while CYP1A1 epoxidase-activity inhibitor NDGA enhanced Arg-1 expression and STAT6 activation (P < 0.05). Conclusion CYP1A1 can inhibit Arg-1 expression by reducing STAT6 activation in LPS-induced macrophages, and CYP1A1 hydroxylase-activity or its proinflammatory metabolism 12(S)-HETE has no effect on this regulation, while CYP1A1 epoxidase-activity may be involved in this effect.

Solid state amplifier (SSA) has been increasingly applicated in accelerators facilities in recent years. However, with the improvement of the power level, equipment failure caused by reflected power becomes the main risk in long-term operation of SSA. A high-power SSA is usually composed of multiple power amplifier modules through power combiner nets. When the power amplifier modules with unequal amplitudes and SSA operate under a full reflection caused by arcing of the cavity, the modules may be easily damaged due to excessive reflected power. The optimization of the power combiners is an effective means for improving the stability of SSAs under high power reflection. In this paper, the mechanisms and conditions under which reflection power arises were analyzed by using the scattering parameter of the combiner, and the optimization scheme of the combiner to reduce the maximum reflected power was proposed. In addition, a set of 500 MHz 8-way power combiner experimental facility was designed to verify the result of theoretical calculation under various working conditions. Simulation and experimental results show that the reflected power of the power amplifier module not only is related to the matching state of SSA, but also is related to the output state of the power amplifier module itself and parameters of combiner. The total reflected power of the power amplifier module is the sum of the reflected power from the mismatched load and the combined power from the other modules. When all the power amplifier modules of the SSA working perfectly, the reflected power of its own signal of a module is exactly compensated by the sum of the power with opposite phase from all other modules. In this case, the reflected power of the module is only related to the matching state of the SSA, and its maximum value is equivalent to the rated output power of the module. In another case, when one of the SSA’s power amplifier modules is switched off, the reflected power received by some of the modules may be as high as nearly 4 times the rated power of a single module, which will lead to severe overloading of the circulator loads and risk of damage to the modules. Eventually, by optimizing the parameters of the combiner, the maximum reflection power is effectively reduced due to suppress in-phase superposition of the reflected power coupled form other modules. The experimental results are in good agreement with the theoretical calculations, which proves the effectiveness of the optimization scheme. Therefore, this research can provide some valuable references for the subsequent development of higher power SSA for CSNS, SAPS and other accelerator facilities.

The continuous decline in the birth rate can lead to a series of social and economic problems. Accurately predicting the birth rate of a region will help national and local governments to formulate more scientifically sound development policies. This paper proposes a discrete-aware model BRP-Net based on attention mechanism and LSTM, for effectively predicting the birth rate of prefecture-level cities. BRP-Net is trained using multiple variables related to comprehensive development of prefecture-level cities, covering factors such as economy, education and population structure that can influence the birth rate. Additionally, the comprehensive data of China's prefecture-level cities exhibits strong spatiotemporal specificity. Our model leverages the advantages of attention mechanism to identify the feature correlation and temporal relationships of these multi-variable time series input data. Extensive experimental results demonstrate that the proposed BRP-Net has higher accuracy and better generalization performance compared to other mainstream methods, while being able to adapt to the spatiotemporal specificity of variables between prefecture-level cities. Using BRP-Net to achieve precise and robust prediction estimates of the birth rate in prefecture-level cities can provide more effective decision-making references for local governments to formulate more accurate and reasonable fertility encouragement policies. [ABSTRACT FROM AUTHOR]

Objective. To explore the value of the injury severity score (ISS) and the new injury severity score (NISS) for evaluating injuries and predicting complications (pneumonia and respiratory failure) and poor prognoses (in‐hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death) in patients with thoracic trauma. Methods. The data of consecutive patients with thoracic trauma who were admitted to the department of cardiothoracic surgery of a tertiary hospital between January 2018 and December 2021 were retrospectively collected. ISS and NISS were calculated for each patient. The study outcomes were complications and poor prognoses. The differences in ISS and NISS between patients with complications and poor prognoses and patients without the abovementioned conditions were compared using the Mann‒Whitney U test. Discrimination and calibration of ISS and NISS in predicting outcomes were compared using the area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer‒Lemeshow (H‐L) statistic. Results. A total of 310 patients were included. ISS and NISS of patients with complications and poor prognoses were greater than those of patients without complications and poor prognoses, respectively. The discrimination of ISS in predicting pneumonia, respiratory failure, in‐hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death (AUCs: 0.609, 0.721, 0.848, 0.784, 0.763, 0.716, and 0.804, respectively) was not statistically significantly different from that of NISS in predicting the corresponding outcomes (AUCs: 0.628, 0.712, 0.795, 0.767, 0.750, 0.750, and 0.818, respectively). ISS showed better calibration than NISS for predicting pneumonia, respiratory failure, in‐hospital tracheal intubation, extended length of hospital stay, and ICU admission but worse calibration for predicting prolonged ICU stay and death. Conclusion. ISS and NISS are both suitable for injury evaluation. There was no statistically significant difference in discrimination between ISS and NISS, but they had different calibrations when predicting different outcomes. [ABSTRACT FROM AUTHOR]

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti‐inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based‐virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down‐regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE‐411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE‐411/41415610 play a role in regulating JAK–STAT and AKT–mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR‐targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages. [ABSTRACT FROM AUTHOR]

In this study, a HfO2 coating was developed on an Ir matrix using a customized open-tube airflow, cold-wall chemical vapor deposition instrument. The preparation process and structure of the as-prepared coating were investigated to gain insights into its characteristics. The HfO2 coating effectively prevents direct contact between Ir and O, leading to a reduction in the oxidation rate of Ir. Furthermore, defects such as micropores and cracks generated during sealed oxidation erosion contribute to Ir's decelerated oxidation failure. The as-prepared HfO2 coating exhibits low thermal conductivity and a high heat radiation rate, reducing the coating's surface temperature. These characteristics significantly enhance adversity tolerance and increase the working temperature of the coating. Moreover, the as-prepared HfO2 coating can serve as a diffusion barrier, blocking both the direct contact of O with the Ir coating and the diffusion of other elements to the Ir coating. As a result, the rates of diffusion of other elements to the Ir coating are reduced. [ABSTRACT FROM AUTHOR]

The accurate voltage measurement of distribution networks is of great significance in power dispatching and fault diagnosis. Voltage sensors based on the spatial electric field effect do not require grounding, which provides the possibility for the distributed measurement of transmission line voltages. However, the divider ratio of suspension grounding voltage sensors is affected by the height between the sensor and the ground, as well as the distance between the sensor and the telegraph pole. In this paper, a self-calibration method based on internal capacitance transformation is proposed to realize the on-line calibration of suspension grounding voltage sensors. The calibration is accomplished by switching different parameters in the conditioning circuit, and the calibration process does not require power failure or known input excitation. In addition, the impact of electric fields in the other two phases of three-phase transmission lines on measurement through simulation research is quantified in this paper. In order to reduce the impact of interference electric fields, an equipotential shielding structure is designed. The circuit topology and probe prototype have been developed and testing has been conducted in laboratory conditions; the experimental results show that the maximum relative error of voltage amplitude is 1.65%, and the phase relative error is 0.94%. The measurement accuracy is not limited by the height to ground or the distance to the telegraph pole. In addition, in the application of an equipotential shielding probe, the maximum deviation of measured voltage is 0.7% with and without interference electric fields. [ABSTRACT FROM AUTHOR]

The corona-generated space charge may vary in different air pressures, and the quantitative law between the corona-generated space charge density and air pressure has never been investigated. This work utilised computational approaches to explore the role of air pressure in the variation of negative corona-generated space charge. A negative fluid model in which the air pressure could be varied was built up to calculate the charged-particle density and electric field under different applied voltages. The continuity equations were solved by flux corrected transport algorithm and the Poisson equation was computed by the successive over relaxation method. The variations of important parameters due to air pressure were analysed. The particles densities of electrons, positive ions and negative ions at standard and low atmosphere pressures were computed, which increased markedly due to the decrease of atmosphere pressure. At fixed applied voltages, the exponential decay law between the maximal values of electron/positive ion densities at the head of the streamer and air pressure could be obtained. The quantitative law between the maximal values of electron/positive ion densities at the head of the streamer and the applied voltage, relative air density was also achieved.

Here, we report our recent progress in the design, fluid thermodynamics simulation, and high-power test of the2nd harmonic cavity for the China Spallation Neutron Source Phase II. A high-performance and large-size magnetic alloy (MA) core was developed as the load material for the radiofrequency cavity to achieve a high gradient of 40 kV/m. The water-cooling structure and cooling efficiency were studied and improved through numerical analysis and thermal experiments. The long-term stability of the cavity, especially the waterproofness of the MA cores with high heat load, was verified by high power tests. [ABSTRACT FROM AUTHOR]

As one of the important parameters characterizing the cable's operation status, an accurate measurement of the current is particularly important for the cable's reliable operation and status monitoring. Aiming at the problem that the sum of the current phasors of multiphase cables is 0 when running in a steady state, and that the traditional mutual inductance current measurement method cannot be used for the phase current measurement of such cables, or that the insulation layer needs to be damaged, this paper proposes a non-contact measurement method of three-phase cable current, based on the magnetic field decoupling calculation. When combined with the actual parameters of the three-phase cable, the analytical calculation model of the magnetic field distribution of the three-phase cable is established. The relationship between the output ratio of the sensor and the deflection angle is obtained through theoretical derivation, the magnetic field coupling coefficient matrix is determined, and the transfer relationship between the output of the magnetic sensor and the current of each phase is clarified; an array magnetic field sensor is designed, which can sense the information of the adjacent magnetic field independently and is used for the reconstruction of three-phase currents. The effectiveness of the proposed method was tested on the built three-phase four-core cable current measurement test platform. The experimental results show that under the three-phase current balance, the measurement error of phase A, phase B and phase C is less than 2.8%, and the waveform and phase angle of the three-phase current can be well restored, which verifies the three-phase current measurement method proposed in this paper. [ABSTRACT FROM AUTHOR]

The application of high-power solid state amplifiers (SSAs) in accelerator facilities is increasing, and equipment failure caused by reflected power is the main risk to their long-term operation. High-power SSAs often comprise multiple power amplifier modules. Full power reflection is more likely to damage the modules in SSAs if the amplitudes of the modules are unequal. Optimization of the power combiners is an effective means for improving the stability of SSAs under high power reflection. This study analyzes the mechanisms and conditions of reflected power generation using the scattering parameters of the combiner and proposes an optimization scheme for the combiner. The simulation and experimental results show that some modules may receive reflected power as high as nearly four times the rated power of one module when the SSA meets certain conditions, which could damage the modules. The maximum reflected power can be effectively reduced and the anti-reflection ability of SSAs can be improved by optimizing the combiner parameters to suppress the maximum reflected power. [ABSTRACT FROM AUTHOR]

Three-phase four-wire power cables are a primary kind of power transmission method in low-voltage distribution networks. This paper addresses the problem that calibration currents are not easily electrified during the transporting of three-phase four-wire power cable measurements, and proposes a method for obtaining the magnetic field strength distribution in the tangential direction around the cable, finally enabling online self-calibration. The simulation and experimental results show that this method can self-calibrate the sensor arrays and reconstruct the phase current waveforms in three-phase four-wire power cables without calibration currents, and this method is not affected by disturbances such as wire diameter, current amplitudes, and high-frequency harmonics. This study reduces the time and equipment costs required to calibrate the sensing module compared to related studies using calibration currents. This research offers the possibility of fusing sensing modules directly with running primary equipment, and the development of hand-held measurement devices. [ABSTRACT FROM AUTHOR]

In order to study the influence of initial installation deformation of floating oil seal 0-ring,based on the An-sys Workbench platform,a two-dimensional axisymmetric finite element model of the floating oil seal was established,and the nonlinear contact analysis during the installation process was carried out by considering initial installation deformation of floating oil seal 0-ring. The effects of different oil pressure, installation clearance, and hardness on the stress, contact pressure,contact friction force of the 0-ring and the supporting reaction force of the floating seal ring end cover were studied.The results show that when considering the installation process,the 0-ring is not located in the relatively central position in the floating oil seal, but in the upper position in the middle of the floating oil seal, and the maximum von Mises stress of the 0-ring is greater than that without considering the installation process,so considering the installation process of the 0-ring is more in line with the actual situation.The maximum von Mises area will become smaller and narrower with the increase of oil pressure,which will increase the risk of crack failure.The maximum contact friction is concentrated on the end face of the floating seal ring,and the contact length increases continuously with the increase of oil pressure.The increase rate of the force in the y direction of the floating seal ring end cover far exceeds the increase rate of the force in the x direction.Under the condition of constant oil pressure,the stress increases with the decrease of installation clearance,and the stress increases with the increase of hardness. The maximum contact pressure of the floating oil seal is greater than the oil pressure within the oil pressure range of 2 MPa,which can ensure the self-sealing of the floating oil seal. [ABSTRACT FROM AUTHOR]

A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21 Cip1 (p21 high) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21 high cells improves physical function at all remaining stages of life, suggesting healthspan extension. Mechanistically, p21 high cells encompass several cell types with a relatively conserved proinflammatory signature. Clearance of p21 high cells reduces inflammation and alleviates age-related transcriptomic signatures of various tissues. These findings demonstrate the feasibility of healthspan extension in mice and indicate p21 high cells as a therapeutic target for healthy aging. [Display omitted] • p21 high cells, distinct from p16 high cells, accumulate in various tissues with aging • Intermittent p21 high cell clearance extends both median and maximum lifespans in mice • Intermittent p21 high cell clearance results in sustained health improvement • Intermittent p21 high cell clearance alleviates age-related transcriptomic signatures Wang et al. identify a distinct senescent cell population (p21 high cells) in various tissues with aging. p21 high cells encompass numerous cell types with a conserved proinflammatory signature. Intermittent clearance of p21 high cells reduces inflammation, extends lifespan, and results in sustained benefits to health and physical function in old mice. [ABSTRACT FROM AUTHOR]

This paper presents an optimized design and preliminary test result of a high-power input coupler. The design is motivated by five-cell Petra-type cavities operating in the Southern Advanced Photon Sources booster. We optimize the design of the high-power input coupler from the prototype, including the window geometry redesign and multipacting analysis to meet a 250 kW operation power upgrade plan. The cooling system of the coupler is redesigned to achieve a low temperature in high-power operation. Design results fulfill the five-cell cavity operation requirement. The corresponding waveguide and coaxial transition structures are developed and tested. We also describe the coupler's coupling coefficient tests and high-power test plans. [ABSTRACT FROM AUTHOR]

Background: Host-microbiota crosstalk has been implicated in multiple host metabolic pathway axes that regulate intestinal barrier function. Although constitutive cytochrome P4501A1 (CYP1A1) expression perturbs the microbiome-derived autoregulatory loop following enteric infection, little is known about the role of host CYP1A1 in modulating gut microbiome-mediated signaling during methicillin-resistant Staphylococcus aureus (MRSA)-induced abdominal sepsis and its effects on intestinal barrier integrity. Methods: Abdominal sepsis was induced by the intraperitoneal injection of MRSA in mice. The effect of CYP1A1 deficiency on gut barrier integrity was investigated using RNA sequencing, microbiome analyses, and targeted metabolomics. The microbiota-produced metabolites were validated in patients with sepsis and persistent MRSA infection. Results: Mice lacking CYP1A1 exhibited an altered gut microbiome, a reduced metabolic shift from lysine to cadaverine in the caecal contents and antimicrobial molecule production (Retnlb, Gbp7, and Gbp3), and they were protected against gut barrier disruption when subjected to MRSA challenge. These beneficial effects were validated in aryl hydrocarbon receptor (AHR) knockout (KO) mice by cohousing with CYP1A1 KO mice and abrogated after supplementation with cadaverine or Enterococcus faecalis , the primary microbiota genus for cadaverine synthesis. Antibiotic-driven gut dysbacteriosis impaired the survival benefit and disrupted the intestinal barrier integrity in CYP1A1 KO mice after MRSA infection. Furthermore, increased cadaverine levels in feces and serum were detected in critically ill patients with gut leakiness during persistent MRSA infection, whereas cadaverine was not detected in healthy controls. Additionally, microbiota-derived cadaverine induced enterocyte junction disruption by activating the histamine H4 receptor/nuclear factor-κB/myosin light-chain kinase signaling pathway. Conclusion: This study revealed the unexpected function of host CYP1A1 in microbiota-mediated cadaverine metabolism, with crucial consequences for dysbacteriosis following MRSA-induced abdominal sepsis, indicating that inhibiting CYP1A1 or blocking cadaverine-histamine H4 receptor signaling could be a potential therapeutic target against abdominal sepsis. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018646]. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effect of different probe placements on the ventral and dorsal sides of the same finger using pulse oxygen saturation monitoring. Methods: This clinical trial used a convenience sampling method in patients admitted to the Second Hospital of Hebei Medical University. We enrolled 1330 patients from March to July 2018, including patients who were hospitalized in the intensive care unit (n = 258) and in the general ward (n = 1072). Pulse oxygen saturation measurements obtained from the ventral and dorsal sides of the same finger were compared. This work adhered to the STROBE checklist requirements. Results: We found that pulse oxygen saturation measurements between the dorsal and ventral sides of a finger were not affected by different fingers, disease types, the application of a ventilator, vasoactive drugs, the conscious state of the patient or the instrument model. Conclusion: Our findings suggested no significant difference in saturation measurements with variation in the placement of the pulse oxygen saturation measurement instrument between the dorsal and ventral sides of a finger, regardless of illness severity. We believe that these results could simplify the monitoring procedures performed by nurses and eliminate worries concerning the inaccuracy of data because of varied probe positions. SUMMARY STATEMENT: What is already known about this topic? Early application of digital pulse oxygen measurement in patients with early hypoxia can continuously display their blood oxygen status and can promptly detect hypoxaemia development.Some details may have an impact on clinical comprehension of pulse oximetry values, such as the signal averaging time, data sampling rates and sensor position.In clinical practice, although various medical units adopt different pulse oximeter monitoring instruments, the use of different brands of pulse oximeters requires the placement of the fingernail bed and probe on the same side during finger insertion. What is already known about this topic? In our study, we investigated whether the oxygen saturation measurements obtained from the ventral and dorsal sides of the same fingers in either hand were credible.Factors that affected the perfusion status of the fingertip (i.e. ventilator use, vasoactive drugs and coma) had no effect on the consistency of the oxygen saturation measurements obtained from the ventral and dorsal sides of the same fingers of either hand.Even when monitoring patients in, for example, fixed position, with fingers absent and with a range of different disease states, there is no difference between oxygen saturation measurements on the ventral and dorsal sides of fingers of either hand. The oxygen saturation measurements were found to be reliable. The implications of this paper: Placement of the probe on the dorsal or ventral sides of the fingers does not affect the pulse oxygen saturation measurement in patients with a range of different disease states.In clinical practice, the oxygen saturation measurement results from the ventral and dorsal sides of the same finger from either hand are credible. This finding would simplify daily nursing work. [ABSTRACT FROM AUTHOR]

Collision on reinforced concrete (RC) piers by moving vessels or vehicles is a significant issue. This paper presents the static and impact behavior of RC piers with different hollow ratios. Three specimens were statically tested to obtain the load-displacement response. Low-velocity collision on eleven RC piers was conducted under the same velocity of 2.42 m/s. The damage process, failure mode, and force response were comprehensively analyzed. The experimental results indicate that the hollow ratio plays a significant role in the failure mode and ultimate load of RC piers under static and impact loadings. For RC piers with a hollow ratio of 0 and 0.4, the global failure dominated the damage process. However, failure of piers with a hollow ratio of 0.6 was governed by the local damage near the loading point. The static load capacities of the RC piers with a hollow ratio of 0.4 and 0.6 were 1.27% and 60.5% smaller than that of the solid pier, respectively. RC piers with a higher hollow ratio or lighter drop weight suffer smaller peak impact force. The increase of the longitudinal reinforcements leads to a promotion of the peak and mean impact force. Furthermore, the numerically predicted failure modes and impact load response show satisfactory agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Objectives: The knowledge that agmatine is found in the human body has existed for several years; however, its role in sepsis has not yet been studied. In the present study, we investigate the role of agmatine in the progression and treatment of sepsis.Design: Clinical/laboratory investigations.Setting: Medical centers/University-based research laboratory.Subjects: Elective ICU patients with severe sepsis and healthy volunteers; C57BL/6 mice weighing 18-22 g.Interventions: Serum agmatine level and its associations with inflammatory markers were assessed in patients with sepsis. Agmatine was administered intraperitoneally to mice before a lipopolysaccharide challenge. Human peripheral blood mononuclear cells and murine macrophages were pretreated with agmatine followed by lipopolysaccharide stimulation.Measurements and Main Results: Serum agmatine levels were significantly decreased in patients with sepsis and lipopolysaccharide-induced mice, and correlated with Acute Physiology and Chronic Health Evaluation II score, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels. In a therapeutic experiment, exogenous agmatine attenuated the cytokine production of peripheral blood mononuclear cells from patients with sepsis and healthy controls. Agmatine also exerted a significant beneficial effect in the inflammatory response and organ damage and reduced the death rate in lipopolysaccharide-induced mice. Imidazoline I2 receptor agonist 2-benzofuran-2-yl blocked the pharmacological action of agmatine; whereas, other imidazoline receptor ligands did not. Furthermore, agmatine significantly impaired the inflammatory response by inactivating nuclear factor-κB, but not protein 38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and inducible nitric oxide synthase signaling in macrophages. Activation of imidazoline I2 receptor or knockdown of ribosomal S6 kinase 2 counteracted the effects of agmatine on phosphorylation and degradation of inhibitor of nuclear factor-κBα.Conclusions: Endogenous agmatine metabolism correlated with the progression of sepsis. Supplemental exogenous agmatine could ameliorate the lipopolysaccharide-induced systemic inflammatory responses and multiple organ injuries through the imidazoline I2 receptor-ribosomal S6 kinase 2-nuclear factor-κB pathway. Agmatine could be used as both a clinical biomarker and a promising pharmaconutrient in patients with severe sepsis. [ABSTRACT FROM AUTHOR]