Danggui-Shaoyao-San (DSS) ameliorates the progression of osteoarthritis via suppressing the NF-κB signaling pathway: an in vitro and in vivo study combined with bioinformatics analysis.

BACKGROUND: Osteoarthritis (OA) is a common chronic age-related joint disease characterized primarily by inflammation of synovial membrane and degeneration of articular cartilage. Accumulating evidence has demonstrated that Danggui-Shaoyao-San (DSS) exerts significant anti-inflammatory effects, suggesting that it may play an important role in the treatment of knee osteoarthritis (KOA). METHODS: In the present study, DSS was prepared and analyzed by high-performance liquid chromatography (HPLC). Bioinformatics analyses were carried out to uncover the functions and possible molecular mechanisms by which DSS against KOA. Furthermore, the protective effects of DSS on lipopolysaccharide (LPS)-induced rat chondrocytes and cartilage degeneration in a rat OA model were investigated in vivo and in vitro. RESULTS: In total, 114 targets of DSS were identified, of which 60 candidate targets were related to KOA. The target enrichment analysis suggested that the NF-κB signaling pathway may be an effective mechanism of DSS. In vitro, we found that DSS significantly inhibited LPS-induced upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP3), and matrix metalloproteinase-13 (MMP13). Meanwhile, the degradation of collagen II was also reversed by DSS. Mechanistically, DSS dramatically suppressed LPS-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway. In vivo, DSS treatment prevented cartilage degeneration in a rat OA model. CONCLUSIONS: DSS could ameliorate the progression of OA through suppressing the NF-κB signaling pathway. Our findings indicate that DSS may be a promising therapeutic approach for the treatment of KOA.

Data-Driven Optimal Tracking Control for Discrete-Time Nonlinear Systems With Unknown Dynamics Using Deterministic ADP.

This article aims to solve the optimal tracking problem (OTP) for a class of discrete-time (DT) nonlinear systems with completely unknown dynamics. A novel data-driven deterministic approximate dynamic programming (ADP) algorithm is proposed to solve this kind of problem with only input-output (I/O) data. The proposed algorithm has two advantages compared to existing data-driven deterministic ADP algorithms for the OTP. First, our algorithm can guarantee optimality while achieving better performance in the aspects of time-saving and robustness to data. Second, the near-optimal control policy learned by our algorithm can be implemented without considering expected control and enable the system states to track the user-specified reference signals. Therefore, the tracking performance is guaranteed while simplifying the algorithm implementation. Furthermore, the convergence and stability of the proposed algorithm are strictly proved through theoretical analysis, in which the errors caused by neural networks (NNs) are considered. At the end of this article, the developed algorithm is compared with two representative deterministic ADP algorithms through a numerical example and applied to solve the tracking problem for a two-link robotic manipulator. The simulation results demonstrate the effectiveness and advantages of the developed algorithm.

Ru(II)-Catalyzed N-Methylation of Amines Using Methanol as the C1 Source.

Four ruthenium complexes were used as catalysts for the N-methylation of amines using methanol as the C1 source under weak base conditions. The (DPEPhos)RuCl2PPh3(1a) catalyst showed the best catalytic performance (0.5 mol %, 12 h). The deuterium labeling and control experiments suggested the reaction via the Ru-H mechanism. This study provides a new ruthenium catalyst system for N-methylation with methanol under weak base conditions.

Myricitrin promotes osteogenesis and prevents ovariectomy bone mass loss via the PI3K/AKT signalling pathway.

This study aimed to explore the effect of myricitrin on osteoblast differentiation in mice immortalised bone marrow mesenchymal stem cells (imBMSCs). Additionally, ovariectomy (OVX) mice were employed to examine the effect of myricitrin on bone trabecular loss in vivo. The effect of myricitrin on the proliferation of imBMSCs was evaluated using a cell counting kit-8 assay. Alizarin red staining, alkaline phosphatase staining were performed to elucidate osteogenesis. Furthermore, qRT-PCR and western blot determined the expression of osteo-specific genes and proteins. To screen for candidate targets, mRNA transcriptome genes were sequenced using bioinformatics analyses. Western blot and molecular docking analysis were used to examine target signalling markers. Moreover, rescue experiments were used to confirm the effect of myricitrin on the osteogenic differentiation of imBMSCs. OVX mice were also used to estimate the delay capability of myricitrin on bone trabecular loss in vivo using western blot, micro-CT, tartaric acid phosphatase (Trap) staining, haematoxylin and eosin staining, Masson staining and immunochemistry. In vitro, myricitrin significantly enhanced osteo-specific genes and protein expression and calcium deposition. Moreover, mRNA transcriptome gene sequencing and molecular docking analysis revealed that this enhancement was accompanied by an upregulation of the PI3K/AKT signalling pathway. Furthermore, copanlisib, a PI3K inhibitor, partially reversed the osteogenesis promotion induced by myricitrin. In vivo, western blot, micro-CT, hematoxylin and eosin staining, Masson staining, Trap staining and immunochemistry revealed that bone trabecular loss rate was significantly alleviated in the myricitrin low- and high-dose groups, with an increased expression of osteopontin, osteoprotegerin, p-PI3K and p-AKT compared to the OVX group. Myricitrin enhances imBMSC osteoblast differentiation and attenuate bone mass loss partly through the upregulation of the PI3K/AKT signalling pathway. Thus, myricitrin has therapeutic potential as an antiosteoporosis drug.

Ni(II)-Catalyzed Transfer Hydrogenation of Azoarenes with NH3BH3.

A nickel-catalyzed semihydrogenation of azoarenes to hydrazoarenes with NH3BH3 is developed. The catalytic system exhibits good functional group tolerance and a high turnover frequency at room temperature. Results of control and deuterium-labeling experiments indicate that the ethanol hydroxyl and BH3 groups each donated one hydrogen to this transfer hydrogenation, and the main byproducts were B(OEt)3 and H2. Moreover, density functional theory calculations indicated that the reaction proceeded via a ligand-to-ligand hydrogen transfer mechanism. This study presents a novel nickel catalytic system for the semihydrogenation of azoarenes.

ELABELA-APJ-Akt/YAP Signaling Axis: A Novel Mechanism of Aerobic Exercise in Cardioprotection of Myocardial Infarction Rats.

PURPOSE: The aim of this study was to investigate the function and mechanisms of ELABELA (ELA) in the aerobic exercise-induced antiapoptosis and angiogenesis of ischemic heart. METHODS: The myocardial infarction (MI) model of Sprague-Dawley rat was established by the ligation of the left anterior descending coronary artery. MI rats underwent 5 wk of Fc-ELA-21 subcutaneous injection and aerobic exercise training using a motorized rodent treadmill. Heart function was evaluated by hemodynamic measures. Cardiac pathological remodeling was evaluated by Masson's staining and the calculation of left ventricular weight index. Cell proliferation, angiogenesis, and Yes-associated protein (YAP) translocation were observed by immunofluorescence staining. Cell apoptosis was analyzed by TUNEL. Cell culture and treatment were used to elucidate the molecular mechanism of ELA. Protein expression was detected by Western blotting. Angiogenesis was observed by tubule formation test. One-way or two-way ANOVA and Student's t -test were used for statistical analysis. RESULTS: Aerobic exercise stimulated the endogenous ELA expression. Exercise and Fc-ELA-21 intervention significantly activated APJ-Akt-mTOR-P70S6K signaling pathway, kept more cardiomyocytes alive, and increased angiogenesis, so as to inhibit the cardiac pathological remodeling and improved the heart function of MI rats. Fc-ELA-32 also had the cellular and functional cardioprotective activities in vivo . In vitro , ELA-14 peptide regulated the phosphorylation and nucleoplasmic translocation of YAP and activated the APJ-Akt signaling pathway so as to increase the proliferation of H9C2 cells. Moreover, the antiapoptosis and the tubule formation of HUVECs were also enhanced by ELA-14, whereas the inhibition of Akt activity weakened such effects. CONCLUSIONS: ELA is a potential therapeutic member that plays a key role through APJ-Akt/YAP signaling axis in aerobic exercise-induced cardioprotection of MI rats.

Comparative Study of Elabela and Apelin on Apelin Receptor Activation Through ß-Arrestin Recruitment.

Apelin receptor (APJ) ligands elabela (ELA) and apelin have divergent distributions and function differently in vitro and in vivo. Whether differences exist in their capacity of recruitment of ß-arrestins (ARRBs) to APJ remains unknown. The aim of the current study was to investigate the different effects of ELA and apelin on the interaction between APJ and ARRBs in live cells by NanoBiT®. NanoBiT® system is a new technology for studying protein-protein interaction in real-time in live cells, based on the emission of luminescence when two split components of NanoLuc luciferase, large Bit (LgBit) and small Bit (SmBit), complement each other to form an enzymatically active entity. We tagged the APJ and ARRBs with LgBit or SmBit and then evaluated their interactions in transiently transfected HEK293T cells, and determined the signal strength yielded as a result of the interaction. We also investigated the concentration-dependent response of the APJ-ARRB interaction in response to ELA and apelin. Finally, we assessed the effect of F13A, an APJ antagonist which is structurally very similar to apelin-13, on ELA- and apelin-mediated APJ-ARRB interactions. The NanoLuc® luciferase signal was highest in the pair of APJ-LgBit with SmBit-ARRB1 or SmBit-ARRB2. NanoLuc® luciferase signal increased in a concentration-dependent manner from 0.1 nM to 10 µM in response to ELA or apelin. Interestingly, ELA elicited weaker APJ-ARRB interaction signals than apelin. Pre-treatment with F13A potently reduced the APJ-ARRB interaction in response to both ELA and apelin. Our results demonstrated that both ELA and apelin promoted the interaction of APJ and ARRBs in a concentration-dependent manner, and ELA is less efficacious than apelin in inducing the recruitment of ARRBs to APJ, providing a biased functional aspect of ELA vs. apelin at the receptor signaling level. Additionally, ELA and apelin may share the same binding site(s) or pocket(s) at the APJ level.

Parallel processing of radiation measurements and radiation video optimization.

In this study, we propose a parallel processing method for analyzing video-image radiation-response signals and suppressing radiation noise. We studied the linear-representation law of various image-information components on the radiation dose rate. Subsequently, the simulation images were used to examine the response-signal extract and radiation-noise suppression. The results indicate that the majority of response signals in the global image comprise forward superposition. The peak signal-to-noise ratio of the red channel was significantly improved when the noise signal-substitution algorithm and median filter were applied successively. Real-time radiation dose-rate measurements and clear images under irradiation can be obtained simultaneously.

Bidentate Ru(II)-NC Complex as a Catalyst for Semihydrogenation of Azoarenes to Hydrazoarenes with Ethanol.

The transfer hydrogenation of azoarenes to hydrazoarenes using ethanol as a hydrogen source by a bidentate Ru(II)-NC complex is developed. A weak base is crucial for this semihydrogenation that can efficiently avoid hydrazoarene dehydrogenation under strongly basic conditions. Control experiments and density functional theory calculations demonstrate the mechanism via a Meerwein-Ponndorf-Verley mechanism, and the only byproduct is ethyl acetate. This study offers a new and simple approach for the synthesis of hydrazoarenes.

Model-Free Optimal Tracking Control of Nonlinear Input-Affine Discrete-Time Systems via an Iterative Deterministic Q-Learning Algorithm.

In this article, a novel model-free dynamic inversion-based Q-learning (DIQL) algorithm is proposed to solve the optimal tracking control (OTC) problem of unknown nonlinear input-affine discrete-time (DT) systems. Compared with the existing DIQL algorithm and the discount factor-based Q-learning (DFQL) algorithm, the proposed algorithm can eliminate the tracking error while ensuring that it is model-free and off-policy. First, a new deterministic Q-learning iterative scheme is presented, and based on this scheme, a model-based off-policy DIQL algorithm is designed. The advantage of this new scheme is that it can avoid the training of unusual data and improve data utilization, thereby saving computing resources. Simultaneously, the convergence and stability of the designed algorithm are analyzed, and the proof that adding probing noise into the behavior policy does not affect the convergence is presented. Then, by introducing neural networks (NNs), the model-free version of the designed algorithm is further proposed so that the OTC problem can be solved without any knowledge about the system dynamics. Finally, three simulation examples are given to demonstrate the effectiveness of the proposed algorithm.

Does Individuals' Perception of Wastewater Pollution Decrease Their Self-Rated Health? Evidence from China.

Background: This study used original survey data to quantitatively investigate the associations between individuals' perception of locally present wastewater pollution and their self-rated health. Methods: This research used the data from large-scale surveys covering all the 31 provinces and equivalent administrative units in mainland China and interviewed 6112 participants. The ordered logit method was employed to estimate the models. Results: The results indicated that individuals' perceptions of local industrial and domestic wastewater pollution significantly decrease their self-rated health. If industrial wastewater pollution was reported, the possibility of the observers indicating lower levels of self-rated current health, comparing to the past year, and comparing with peers, all increased by 26% (p < 0.001), 23% (p = 0.005), and 18% (p = 0.006), respectively. Likewise, perceived domestic wastewater pollution led to the increase by 21% (p = 0.012), 17% (p = 0.034), and 33% (p = 0.000), respectively. Meanwhile, reported industrial wastewater pollution also has an obvious negative effect on individuals' health performance, such as being more fatigued and upset. Conclusions: The survey clearly shows that Chinese individuals who are aware of water pollution in their living environment tend to experience more negative health outcomes, which adds additional urgency to improving wastewater treatment.

12-Deoxyphorbol-13-Hexadecanoate Abrogates OVX-Induced Bone Loss in Mice and Osteoclastogenesis via Inhibiting ROS Level and Regulating RANKL-Mediated NFATc1 Activation.

Osteoporosis is a major health problem in the elderly. Almost every bone can fracture due to the increased bone fragility in osteoporosis, posing a major challenge to public health. 12-Deoxyphorbol-13-hexadecanoate (DHD), one of the main bioactive components of Stellera chamaejasme L. (Lang Du), is considered to have antitumor, antibacterial, and antifungal properties. However, the role of DHD in osteoporosis is still elusive. In this study, we demonstrated for the first time that DHD inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in a dose- and time-dependent manner without exhibiting cytotoxicity in vitro. Mechanistically, we found that DHD not only represses the expression of osteoclasts marker genes by suppressing RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways but also scavenges reactive oxygen species (ROS) through enhancing cytoprotective enzymes expression. Furthermore, DHD inhibits the activation of nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclasts formation. Preclinical studies revealed that DHD protects against bone loss in ovariectomy (OVX) mice. In sum, our data confirmed that DHD could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathways and promoting the expression of ROS scavenging enzymes, thereby preventing OVX-induced bone loss. Thus, DHD may act as a novel therapeutic agent to manage osteoporosis.

Parallel Image-Based Visual Servoing/Force Control of a Collaborative Delta Robot.

In this paper, a parallel Image-based visual servoing/force controller is developed in order to solve the interaction problem between the collaborative robot and the environment so that the robot can track the position trajectory and the desired force at the same time. This control methodology is based on the image-based visual servoing (IBVS) dynamic computed torque control and couples the force control feedback in parallel. Simulations are performed on a collaborative Delta robot and two types of image features are tested to determine which one is better for this parallel IBVS/force controller. The results show the efficiency of this controller.

Design of a Gough-Stewart Platform Based on Visual Servoing Controller.

Designing a robot with the best accuracy is always an attractive research direction in the robotics community. In order to create a Gough-Stewart platform with guaranteed accuracy performance for a dedicated controller, this paper describes a novel advanced optimal design methodology: control-based design methodology. This advanced optimal design method considers the controller positioning accuracy in the design process for getting the optimal geometric parameters of the robot. In this paper, three types of visual servoing controllers are applied to control the motions of the Gough-Stewart platform: leg-direction-based visual servoing, line-based visual servoing, and image moment visual servoing. Depending on these controllers, the positioning error models considering the camera observation error together with the controller singularities are analyzed. In the next step, the optimization problems are formulated in order to get the optimal geometric parameters of the robot and the placement of the camera for the Gough-Stewart platform for each type of controller. Then, we perform co-simulations on the three optimized Gough-Stewart platforms in order to test the positioning accuracy and the robustness with respect to the manufacturing errors. It turns out that the optimal control-based design methodology helps get both the optimum design parameters of the robot and the performance of the controller {robot + dedicated controller}.

Strong Radiation Field Online Detection and Monitoring System with Camera.

Herein, we report the γ-ray ionizing radiation response of a commercial monolithic active-pixel sensor (MAPS) camera under strong-dose-rate irradiation with an online detection and monitoring system for strong radiation conditions. We present the first results of the distribution of three types of MAPS camera and establish a linear relationship between the average response signal and radiation dose rate in the strong-dose-rate range. There is an obvious response signal in the video frames when the camera module parameters are set to automatic, but the linear response is very poor. However, the fixed image parameters are not good at adapting to the changes of the environment and affect the quality of the video frames. A dual module online radiation detection and monitoring probe was made to carry out effective video monitoring and radiation detection at the same time. The measurement results show that the dose rate detection error is less than 5% with a dose rate in the range of 60 to 425 Gy/h, and the visible light image does not have obvious distortion, deformation, or color shift due to the interference of the radiation response event and radiation damage. Hence, the system test results show that it can be used for online detection and monitoring in a strong radiation environment.

Effect of Fc-Elabela-21 on renal ischemia/reperfusion injury in mice: Mediation of anti-apoptotic effect via Akt phosphorylation.

INTRODUCTION: Renal ischemia/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI), and patients with AKI have a high rate of mortality. Apelin is a therapeutic candidate for treatment of IRI and Elabela (ELA) is a recently discovered hormone that also activates the apelin receptor (APJ). We examined the use of ELA as a preventive treatment for IRI using in vitro and in vivo models. METHODS: Male mice were subjected to renal IRI, with or without administration of a stabilized form of ELA (Fc-ELA-21) for 4 days. Renal tubular lesions were measured using H&E staining, reactive oxygen species (ROS) were measured using a dihydroethidium stain assay, and renal cell apoptosis was measured using the TUNEL assay and flow cytometry. Immortalized human proximal tubular epithelial (HK-2) cells were pretreated with or without LY294002 and/or ELA-32, maintained at normoxic or hypoxic conditions, and then returned to normal culture conditions to mimic IRI. Cell apoptosis was determined using the TUNEL assay and cell proliferation was determined using the MTT assay. The levels of Akt, p-Akt, ERK1/2, p- ERK1/2, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blotting. RESULTS: Fc-ELA-21 administration reduced renal tissue damage, ROS production, and apoptosis in mice that had renal IRI. ELA-32 reduced HK-2 cell apoptosis and restored the proliferation of cells subjected to IRI. Akt phosphorylation had a role in the anti-apoptotic effect of ELA. CONCLUSION: This study of in vitro and in vivo models of IRI indicated that the preventive and anti-apoptotic effects of ELA were mediated via the PI3K/Akt signaling pathway.

Low dose rate γ-ray detection using a MAPS camera under a neutron radiation environment.

We present γ-ray radiation detection in a neutron radiation environment using a monolithic active pixel sensor (MAPS) camera without conversion or shielding layers. The measured output signal is the sum of the pedestal value, noise, and real radiation response signal. The sensor response shows that the MAPS camera is sensitive to neutrons and can capture a single photon. The number of pixels with a signal exceeding 100 exhibits a strong dependence on the dose rate and is the best indicator of this value. Therefore, a MAPS camera can be efficiently used as a radiation detection sensor in a robotic system, further limiting human errors in performing radiation detection in complex nuclear radiation environments.

STK38 is a PPARγ-interacting protein promoting adipogenesis.

Peroxisome proliferator-activated receptor-γ (PPARγ) is the master regulator of adipogenesis, but knowledge about how PPARγ is regulated at the protein level is very limited. We aimed to identify PPARγ-interacting proteins which modulate PPARγ's protein levels and transactivating activities in human adipocytes. We expressed Flag-tagged PPARγ in human preadipocytes as bait to capture PPARγ-associated proteins, followed by mass spectroscopy and proteomics analysis, which identified serine/threonine kinase 38 (STK38) as a major PPARγ-associated protein. Protein pulldown studies confirmed this protein-protein interaction in transfected cells, and reporter assays demonstrated that STK38 enhanced PPARγ's transactivating activities without requiring STK38's kinase activity. In cell-based assays, STK38 increased PPARγ protein stability, extending PPARγ's half-life from ~1.08 to 1.95 h. Notably, in human preadipocytes, the overexpression of STK38 enhanced adipogenesis, whereas knockdown impaired the process in a PPARγ-dependent manner. Thus, we discovered that STK38 is a novel PPARγ-cofactor promoting adipogenesis, likely through stabilization of PPARγ.

Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A-Smad2/3 in rats following myocardial infarction.

PURPOSE: The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1 (FSTL1), which may induce cardioprotection in rats following myocardial infarction (MI) by inducing angiogenesis. METHODS: Male, adult Sprague-Dawley rats were randomly divided into 5 groups (n = 12 in each group): sham group (S), sedentary MI group (MI), MI + resistance exercise group (MR), MI + adeno-associated virus (AAV)-FSTL1 injection group (MA), and MI + AAV-FSTL1 injection + resistance exercise group (MAR). The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle. The MI model was established by ligation of the left anterior descending coronary artery. Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder. Heart function was evaluated by hemodynamic measures. Collagen volume fraction of myocardium was observed and analyzed by Masson's staining. Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-ß receptor 1 (TGFßR1) inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1. Angiogenesis, cell proliferation, and disco interacting protein 2 homolog A (DIP2A) location were observed by immunofluorescence staining. The expression of FSTL1, DIP2A, and the activation of signaling pathways were detected by Western blotting. Angiogenesis of endothelial cells was observed by tubule experiment. One-way analysis of variance and Student's t test were used for statistical analysis. RESULTS: Resistance exercise stimulated the secretion of skeletal muscle FSTL1, which promoted myocardial angiogenesis, inhibited pathological remodeling, and protected cardiac function in MI rats. Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart. Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A, while TGFßR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A, which was not conducive to angiogenesis. FSTL1 bound to the receptor, DIP2A, to regulate angiogenesis mainly through the Smad2/3 signaling pathway. FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFßR1. CONCLUSION: Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1, which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.

Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice.

Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition that lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In the present study, we evaluated the potential renoprotective effects of a long-acting constant fragment (Fc)-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for 5 days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced reactive oxygen species (ROS) production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found that ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.