3D-Printed Origami Actuators for a Multianimal-Inspired Soft Robot with Amphibious Locomotion and Tongue Hunting.

The field of soft robotics is rapidly evolving, and there is a growing interest in developing soft robots with bioinspired features for use in various applications. This research presented the design and development of 3D-printed origami actuators for a soft robot with amphibious locomotion and tongue hunting capabilities. Two different types of programmable origami actuators were designed and manufactured, namely Z-shaped and twist tower actuators. In addition, two actuator variations were developed based on the Z-shaped actuator, including the pelvic fin and the coiling/uncoiling types. The Z-shaped actuators were used for the rear legs to facilitate the locomotion of the water-like frogs. Meanwhile, the twisted tower actuators were used for the rotation joints in the forelegs and for locomotion on land. The pelvic fin actuator was developed to imitate the land locomotion of the mudskipper, and the coiling/uncoiling actuator was designed for tongue hunting motion. The origami actuators and soft robot prototype were tested through a series of experiments, which showed that the robot was capable of efficiently moving in water and on land and performing tongue hunting motions. Our results demonstrate the effectiveness of these actuators in producing the desired motions and provide insights into the potential of applying 3D-printed origami actuators in the development of soft robots with bioinspired features.

An Untethered Soft Robotic Dog Standing and Fast Trotting with Jointless and Resilient Soft Legs.

Soft robots are compliant, impact resistant, and relatively safe in comparison to hard robots. However, the development of untethered soft robots is still a major challenge because soft legs cannot effectively support the power and control systems. Most untethered soft robots apply a crawling or walking gait, which limits their locomotion speed and mobility. This paper presents an untethered soft robot that can move with a bioinspired dynamic trotting gait. The robot is driven by inflatable soft legs designed on the basis of the pre-charged pneumatic (PCP) actuation principle. Experimental results demonstrate that the developed robot can trot stably with the fastest speed of 23 cm/s (0.97 body length per second) and can trot over different terrains (slope, step, rough terrain, and natural terrains). The robotic dog can hold up to a 5.5 kg load in the static state and can carry up to 1.5 kg in the trotting state. Without any rigid components inside the legs, the developed robotic dog exhibits resistance to large impacts, i.e., after withstanding a 73 kg adult (46 times its body mass), the robotic dog can stand up and continue its trotting gait. This innovative robotic system has great potential in equipment inspection, field exploration, and disaster rescue.

Investigation of Fluidic Universal Gripper for Delicate Object Manipulation.

The compliance of conventional granular jamming universal grippers is limited due to the increasing friction among particles when enveloping an object. This property limits the applications of such grippers. In this paper, we propose a fluidic-based approach for universal gripper which has a much higher compliance compared to conventional granular jamming universal grippers. The fluid is made of micro-particles suspended in liquid. Jamming transition of the dense granular suspension fluid from a fluid (hydrodynamic interactions) to solid-like state (frictional contacts) in the gripper is achieved by external pressure from the inflation of an airbag. The basic jamming mechanism and theoretical analysis of the proposed fluid is investigated, and a prototype universal gripper based on the fluid is developed. The proposed universal gripper exhibits advantageous compliance and grasping robustness in sample grasping of delicate objects, such as plants and sponge objects, where the traditional granular jamming universal gripper fails.

PCSK9 Knockdown Can Improve Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy.

This study investigates the effect and mechanism of proprotein convertase subtilisin/Kexin type 9 (PCSK9) on myocardial ischemia-reperfusion injury (MIRI) and provides a reference for clinical prevention and treatment of acute myocardial infarction (AMI). We established a rat model of myocardial ischemia/reperfusion (I/R) and AC16 hypoxia/reoxygenation (H/R) model. A total of 48 adult 7-week-old male Sprague-Dawley rats were randomly assigned to three groups (n = 16): control, I/R, and I/R + SiRNA. In I/R and I/R + siRNA groups, myocardial ischemia was induced via occlusion of the left anterior descending branch (LAD) of the coronary artery in rats in I/R group for 30 min and reperfused for 3 days. To assess the myocardial injury, the rats were subjected to an electrocardiogram (ECG), cardiac function tests, cardiac enzymes analysis, and 2,3,5-triphenyl tetrazolium chloride (TTC)/Evan Blue (EB) staining. Meanwhile, differences in the expression of autophagy-level proteins and Bcl-2/adenovirus E1B 19-kDa interacting protein (Bnip3) signaling-related proteins were determined by protein blotting. In vitro and in vivo experimental studies revealed that siRNA knockdown of PCSK9 reduced the expression of autophagic protein Beclin-1, light chain 3 (LC3) compared to normal control-treated cells and control-operated groups. Simultaneously, the expression of Bnip3 pathway protein was downregulated. Furthermore, the PCSK9-mediated small interfering RNA (siRNA) group injected into the left ventricular wall significantly improved cardiac function and myocardial infarct size. In ischemic/hypoxic circumstances, PCSK9 expression was dramatically increased. PCSK9 knockdown alleviated MIRI via Bnip3-mediated autophagic pathway, inhibited inflammatory response, reduced myocardial infarct size, and protected cardiac function.

Characterization of m6A-related lncRNA signature in neuroblastoma.

N6-methyladenosine (m6A) constitutes one of the most common modifications in mRNA, rRNA, tRNA, microRNA, and long-chain noncoding RNA. The influence of modifications of m6A on the stability of RNA depends upon the expression of methyltransferase ("writer") and demethylase ("eraser") and m6A binding protein ("reader"). In this study, we identified a set of m6A-related lncRNA expression profiles in neuroblastoma (NBL) based on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Thereupon, we identified two subgroups of neuroblastoma (high-risk group and low-risk group) by applying consensus clustering to m6A RNA methylation regulators ("Readers,", "Writer," and "Erase"). Relative to the low-risk group, the high-risk group correlates with a poorer prognosis. Moreover, the present study also revealed that the high-risk group proves to be significantly positively enriched in the tumor-related signaling pathways, including the P53 signaling pathway, cell cycle, and DNA repair. This finding indicates that these molecular prognostic markers may also be potentially valuable in early diagnosis, which provides a new research direction for the study of molecular mechanisms underlying the development of NBL. In conclusion, this study constructed a new model of NBL prognosis based on m6a-associated lncRNAs. Ultimately, this model is helpful for stratification of prognosis and development of treatment strategies.

Double-Acting Soft Actuator for Soft Robotic Hand: A Bellow Pumping and Contraction Approach.

When compressing a soft bellow, the bellow will contract and pump out the fluid inside the bellow. Utilizing this property, we propose a novel actuation method called compressing bellow actuation (CBA), which can output fluidic power and tendon-driven force simultaneously. Based on the CBA method, a double-acting soft actuator (DASA) combining fluidic elastomer actuator (FEA) and tendon-driven metacarpophalangeal (MCP) joint is proposed for robotic finger design. The proposed DASA exhibits both compliance and adaptiveness of FEAs, and controllability and large output force of the tendon-driven methods. The fluid in the bellow can be either air or water or even integration of the two, thus constituting three different actuation modes. Mathematical modeling of the relationship between bellow compression displacement and DASA's bending angle is developed. Furthermore, experimental characterizations of DASA's bending angle and blocking force are conducted at different actuation modes. The double-acting method can availably promote the bending angle of an FEA by up to 155%, and the blocking force by up to 132% when the FEA is water-filled. A soft robotic hand with a forearm prototype based on the DASA fingers is fabricated for the demonstration of finger motion and gripping applications.

Face Recognition Algorithm Based on Multiscale Feature Fusion Network.

A face recognition model based on a multiscale feature fusion network is constructed, aiming to make full use of the characteristics of face and to improve the accuracy of face recognition. In addition, three different scale networks are designed to extract global features of faces. Multiscale cross-layer bilinear features of multiple networks are integrated via introducing a hierarchical bilinear pooling layer. By capturing some of the feature relationships between different levels, the model's ability to extract and distinguish subtle facial features is enhanced. Simultaneously, this study uses layer-by-layer deconvolution to fuse multilayer feature information, to solve the problem of losing some key features when extracting features from multilayer convolutional layers and pooled layers. The experimental results show that compared with the recognition accuracy of traditional algorithms, the recognition accuracy of the algorithm on Yale, AR, and ORL face databases is significantly improved.

Comparing desorption properties of pollutants on bentonite particles and in compacted bentonite.

Desorption is one of the main factors causing groundwater and soil pollution. Therefore, the study of clay desorption characteristics is important for the prediction of groundwater and soil pollution. In previous studies, batch tests and column tests were used to study the desorption characteristics of pollutants on clay. However, the desorption parameters obtained via the two test methods were often quite different. To investigate differences in the desorption characteristics of different pollutants on clay particles and in compacted clay, batch and column desorption tests were conducted using cadmium chloride, fulvic acid, and sodium phosphate as the adsorbates and bentonite as the adsorbent. It was found that the unit particle surface area desorption distribution coefficients of pollutants on bentonite particles were approximately equal to the unit pore surface area distribution coefficients of pollutants in compacted bentonite. This indicates that the desorbed amount per unit of surface area is basically consistent, regardless of whether they are sorbed on particles or in compacted bentonite. A simple formula for determining the desorption retardation factor of pollutants in compacted bentonite is presented. The results of this study provide a reference for the prediction and evaluation of groundwater and soil pollution.

Effect of competitive adsorption on the transport of multiple pollutants through a compacted clay liner.

Leachate transport through municipal solid waste (MSW) landfill liners can be slowed considerably by adsorption. MSW landfill leachate contains a large variety of pollutants at very different concentrations, and there will be competitive adsorption as these pollutants are transported through the landfill's compacted clay liner (CCL). In this study, we used batch adsorption tests and geotechnical centrifuge modelling to examine how the adsorption of pollutants commonly found in leachate changed under competitive adsorption conditions and how competitive adsorption affected the CCL breakthrough of multiple pollutants. The results showed that the adsorption of the target pollutant on clay decreased by approximately 30% when competing pollutants were added. The speed at which the pollutants were transported through a 2-m-thick CCL increased, and the breakthrough times reduced by up to 24.8%, when the competing pollutants were mixed. Competitive adsorption significantly promoted the CCL breakthrough of pollutants at low concentrations, but it had limited effect on pollutants at high concentrations.

Untethered Multimode Fluidic Actuation: A New Approach to Soft and Compliant Robotics.

Fluid actuated soft robots, or fluidic elastomer actuators, have shown great potential in robotic applications where large compliance and safe interaction are dominant concerns. They have been widely studied in wearable robotics, prosthetics, and rehabilitations in recent years. However, such soft robots and actuators are tethered to a bulky pump and controlled by various valves, limiting their applications to a small confined space. In this study, we report a new and effective approach to fluidic power actuation that is untethered, easy to design, fabricate, control, and allows various modes of actuation. In the proposed approach, a sealed elastic tube filled with fluid (gas or liquid) is segmented by adaptors. When twisting a segment, two major effects could be observed: (1) the twisted segment exhibits a contraction force and (2) other segments inflate or deform according to their constraint patterns. Utilizing such effects, various actuation modes could be realized. In this research, four modes of actuation are illustrated: (1) soft actuator and pump actuation, (2) serial actuation, (3) parallel actuation, and (4) agonist and antagonist actuation. Theoretic analysis and experimental studies for the basic actuation principle have been conducted. A case study on an anthropomorphic forearm based on the proposed twisting tube actuation has been developed to showcase the effectiveness of the actuation modes. The studies suggest that the proposed approach has a great potential in both soft and compliant robotics.

Untethered-Bioinspired Quadrupedal Robot Based on Double-Chamber Pre-charged Pneumatic Soft Actuators with Highly Flexible Trunk.

Given that mobile soft robots are adaptable to the environment, they are always tethered with slow locomotion speed. Compared with other types of mobile robots, mobile soft robots may be more suitable for rescuing tasks, accompanying elderly people, and being used as a safe toy for children. However, the infinite freedom of soft robots increases the difficulty of precision control. In addition, the large volume and long tube of the conventional soft actuator structure limit the range of motion of current mobile soft robots. In this article, a newly designed innovative untethered-bioinspired quadrupedal robot based on double-chamber pre-charged pneumatic (DCPCP) soft actuators with highly flexible trunk is proposed. Asymmetrical cross-tendons actuated by servo motors are used to drive the DCPCP soft legs so that buckling can be avoided and mimic the gait of quadruped animals with the simplest drive and control strategy. In addition, the proposed design greatly improves energy efficiency and exhibits superior performance of variable stiffness. The bioinspired highly flexible trunk is designed with the supporting spine structure and tendon driven muscle to deform, which can constantly adjust to the contact situation between the foot and the ground to adjust the center of gravity of the soft quadruped robot and increase stability when walking and turning. The proposed soft quadruped robot does not require any air compressors, valves, and hoses. The characteristics of untethered, high-energy efficiency, linear control, and stability make the soft quadruped robot suitable for many applications.

Adaptive Variable Stiffness Particle Phalange for Robust and Durable Robotic Grasping.

Grasping is an important characteristic of robots in interacting with humans and the environment. Due to the inherent compliance of soft grippers, they can easily adapt to novel objects and operate safely in a human-centered environment. However, soft hands suffer from poor grasping robustness and operation durability, especially for heavy objects or objects with sharp spikes, mainly due to their fragile material and low structural stiffness of the soft actuators. Thus, the widespread use of soft hands in daily applications is still limited. Existing works have shown a promising direction to enhance grasping performance by solving the contradiction between inherent compliance/adaptability and loading capacity. It is known that the stiffness of the robotic phalange is highly related to the performance of robotic hands. In this article, we propose a novel variable stiffness particle phalange, called VSPP here. The proposed VSPP exhibits variable stiffness characteristics without the need for dedicated actuation by utilizing passive particle jamming resulted from forces in interacting with the environment. The VSPP can cooperate with any kind of actuators, soft or rigid, to function as a compliant and robust robotic hand. A prototype robotic hand based on VSPP could maintain reliable grasping even when pierced by sharp objects such as a needle, a cactus, and a durian. This durability is effective both in air and underwater, thus presents new possibilities for the soft robotic hand to work in a harsh environment. The inherent multidirectional compliance of the VSPP makes safety in human/robot interaction guaranteed. The design and modeling presented in this research will provide useful guidance in VSPP applications. A prototype gripper, VSPP-3, composed of three 2-segments VSPP fingers and pneumatic joints, has been built for demonstrations in reliable and robust grasping of daily objects. The sample grasping has shown that the proposed VSPP has great potential for a robust and durable soft robotic hand or gripper design.

A Novel Tendon-Driven Soft Actuator with Self-Pumping Property.

Soft actuators and robotics have been widely researched in recent years mainly due to their compliance to environments and safe interaction with humans. However, the need of tether and low energy efficiency of such actuators/robots has limited their practical applications. This article presents a novel tendon-driven soft actuator concept that has the property of self-pumping, called soft self-pumping actuator (SSPA) in this research. A SSPA is designed by assembling two soft pneumatic actuators (SPAs) face-to-face, whose air chambers are connected by two check valves. Actuation of the SSPA is achieved by tendons that allows precise and untethered control compared with traditional SPAs. The two chambers in the proposed actuators are precharged with air to a desired pressure to enlarge self-stiffness and to facilitate bending. When actuated, one chamber will be compressed and serve as a pump to inject its air into the other chamber, resulting in further bending of the actuator. The airflow involves energy transmission to help the intended actuation, thus improving energy efficiency. In experimental studies, differential chamber air pressure is found to reduce the force in initiating actuator bending. Experimental results have also shown that energy efficiency increase of up to 45% has been achieved compared with the same design but without air transmission. We believe that the proposed concept could lead to more novel designs of controllable and energy saving soft robots.

Bio-inspired robotic dog paddling: kinematic and hydro-dynamic analysis.

Research on quadrupedal robots inspired by canids or felids have been widely reported and demonstrated. However, none of these legged robots can deal with difficult environments that include water, such as small lakes, streams, rain, mud, flooded terrain, etc. In this paper, we present for the first time a kinematic analysis and a hydrodynamic model of dog paddling motion in a robotic system. The quadrupedal paddling gait of dogs was first analyzed based on underwater video recording. Hydrodynamic drag force analysis in a paddling gait cycle was conducted for a prototype robotic dog. The prototype robotic dog was developed using four pre-charged pneumatics soft actuators with consideration of relative positions of CG (center of gravity) and CB (center of buoyancy) and their dynamic variation in paddling. It was found that such soft actuators have great potential in developing amphibious legged robots, because they are inherently water-tight, anti-rusty, simple in structural design, and have large hydrodynamic advantage due to their mostly hemi-cylindrical shape design. Trotting and paddling of the prototype robotic dog was also demonstrated. It is believed that our findings reported in this research will provide useful guidance in future development of amphibious robotic dogs.

Precharged Pneumatic Soft Actuators and Their Applications to Untethered Soft Robots.

The past decade has witnessed tremendous progress in soft robotics. Unlike most pneumatic-based methods, we present a new approach to soft robot design based on precharged pneumatics (PCP). We propose a PCP soft bending actuator, which is actuated by precharged air pressure and retracted by inextensible tendons. By pulling or releasing the tendons, the air pressure in the soft actuator is modulated, and hence, its bending angle. The tendons serve in a way similar to pressure-regulating valves that are used in typical pneumatic systems. The linear motion of tendons is transduced into complex motion via the prepressurized bent soft actuator. Furthermore, since a PCP actuator does not need any gas supply, complicated pneumatic control systems used in traditional soft robotics are eliminated. This facilitates the development of compact untethered autonomous soft robots for various applications. Both theoretical modeling and experimental validation have been conducted on a sample PCP soft actuator design. A fully untethered autonomous quadrupedal soft robot and a soft gripper have been developed to demonstrate the superiority of the proposed approach over traditional pneumatic-driven soft robots.

Novel Variable-Stiffness Robotic Fingers with Built-In Position Feedback.

Despite the increasing popularity of soft robotic research, the application of soft robots is hindered by their limited ability to change compliance and acquire force and position feedback. In this article, both the controllability of compliance and the acquisition of position feedback are achieved in soft robotic fingers in the novel design of a three-dimensional (3D)-printed multismart material substrate. The substrate is composed of shape memory polymer (SMP) and conductive elastomer thermoplastic polyurethane (TPU). The SMP material is utilized to modulate the finger stiffness through its elastic modulus change around glass transition temperature (Tg). The conductive TPU has two functions: one is to tune SMP temperature by producing Joule heat when electrical power is supplied and the other is to provide position feedback of the finger by utilizing the piezoresistive effect of the conductive TPU. Theoretical modeling of finger position feedback and stiffness modulation are conducted. The theoretical analysis has been experimentally validated by a prototype robotic finger built from the proposed concept.

Left Ventricular Mechanics Assessed by 2-dimensional Speckle Tracking Echocardiography in Children and Adolescents With Idiopathic Scoliosis.

STUDY DESIGN: A retrospective review of data collected prospectively. OBJECTIVE: The study aimed to assess the possible effects of idiopathic scoliosis on left ventricular (LV) myocardial performance in children and adolescent patients. SUMMARY OF BACKGROUND DATA: Spine anomaly may impair cardiorespiratory function. It has been confirmed that respiratory function decreased in patients with scoliosis. However, limited study of the effect of scoliosis on heart function has been published, and no assessment of myocardial deformation of these patients has been reported to our knowledge. METHODS: Forty-one patients with a median age of 16 years and a median Cobb's angle of 75 degrees were studied. LV myocardial deformation was evaluated using 2-dimensional speckle-tracking echocardiography. The results were compared with those of 33 controls. The correlations between Cobb's angle and echocardiographic parameters in patients were also explored. RESULTS: Compared with controls, patients had significantly lower global LV longitudinal systolic strain in all 3 views (4 chamber, 2 chamber, and 3 chamber views), lower global radial and circumferential strains in mitral valve (MV) level and papillary muscle (PM) level; reduced LV longitudinal early diastolic strain rate (SRe) in all 3 longitudinal views and reduced radial SRe in MV level and reduced circumferential SRe in apical (AP) level; decreased LV longitudinal late diastolic strain rate in 4-chamber view and decreased radial ones in all 3 short-axis levels. Among patients, Cobb's angle correlated negatively with LV global radial strain of MV level (r=-0.37, P=0.02), global circumferential strain of MV level (r=-0.35, P=0.03), and global circumferential strain of PM level (r=-0.49, P=0.001), whereas positively with LV longitudinal SRa of 4-chamber view (r=0.46, P=0.003), longitudinal SRa of 2-chamber view (r=0.49, P=0.001), and circumferential SRa of AP level (r=0.35, P=0.02). CONCLUSIONS: LV mechanics are impaired in patients with idiopathic scoliosis, which correlate with the severity of scoliosis. Our findings suggest the need and provide a mechanical basis for further studies in these patients.

Pentoxifylline Prevents Driamycin-Induced Myocardial Fibrosis and Apoptosis in Rats.

Adriamycin (ADR) is a potent antineoplastic agent, but long-term treatment is limited by its cumulative, life-threatening cardiomyopathy. Recently, a few reports have shown that pentoxifylline (PTX) might produce cardioprotection in cardiac dysfunction. Here, we investigated the protective effects of PTX on ADR-induced cardiomyopathy in rats. Male rats were randomly assigned either to saline, ADR (adriamycin, 5 mg/kg/week), or A (adriamycin, 5 mg/kg/week) + PTX (pentoxifylline, 50 mg/kg/day) groups. After 3 weeks, these animals were sacrificed and the heart tissue was harvested for histological analysis and assessment of hepatocyte growth factor (HGF) and caspase-3 expression. Histopathological findings showed that PTX can alleviate myocardial damage caused by ADR. Cardiac fibrosis was significantly suppressed in the A+PTX group compared to that in the ADR group. The HGF gene expression was decreased significantly in the ADR group compared with the control group, but was increased in the A+PTX group. Caspase-3 was up-regulated in the ADR group, and down-regulated in the A+PTX group. These results show that treatment with PTX exerts a protective effect against ADR-induced myocardial fibrosis via regulation of HGF and caspase-3 gene expression. PTX may thus represent a useful new clinical tool for the treatment of ADR-induced cardiomyopathy.

Ventricular and atrial mechanics and their interaction in patients with congenital scoliosis without clinical heart failure.

OBJECTIVES: This study sought to evaluate left ventricular, right ventricular, and left atrial mechanics and their interactions in patients with congenital scoliosis without clinical heart failure. METHODS: A total of 23 patients with a median age of 14 years and a median Cobb's angle of 61° were studied. Ventricular and atrial myocardial deformation was measured using speckle tracking echocardiography. The results of the patients were compared with 22 controls. RESULTS: Compared with controls, the patients had a significantly greater annular a velocity (p=0.04) and lower e/a ratio (p=0.03); the left ventricular deformation significantly decreased in radial global (p=0.04) and segmental systolic strain and early diastolic strain rate (p=0.03); the left atrial deformation showed a significantly lower positive strain (p=0.02), greater negative strain (p=0.01), and active contractile strain rate (p=0.01). For the patients, the Cobb's angle was negatively correlated with the left ventricular global radial systolic strain (r=-0.65, p=0.001), left atrial positive strain (r=-0.68, p<0.001), and the left atrial negative strain was positively correlated with the left ventricular circumferential late diastolic strain rate (r=0.46, p=0.01). The left atrial conduit strain rate was positively correlated with the left ventricular circumferential early diastolic strain rate (r=0.42, p=0.03). The left atrial active contractile strain rate was positively correlated with the left ventricular longitudinal late diastolic strain rate (r=-0.4, p=0.03). CONCLUSIONS: Impaired left ventricular and altered left atrial mechanics occur relatively early in patients with congenital scoliosis, and are correlated with the severity of their scoliosis. Our findings provide evidence of preclinical heart dysfunction in patients with this disorder.

H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2.

The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H(2)S) all play an important role. In the present study, we aimed to examine the effects of H(2)S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl(2)), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl(2), the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H(2)S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI(2)) secretion and H(2)S levels were detected in the cells. The exposure of the HPASMCs to CoCl(2) markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI(2) secretion and H(2)S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H(2)O(2), triggered similar degrees of proliferation to CoCl(2), the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H(2)O(2)­induced cell proliferation, as opposed to the CoCl(2)-induced proliferation. The CoCl(2)-induced proliferation of HPASMCs was suppressed by exogenously applied PGI(2). The addition of H(2)S (NaHS) attenuated the CoCl(2)-induced cell proliferation through the increase in the intercellular content of H(2)S. Importantly, the exposure of the cells to H(2)S suppressed the CoCl(2)-induced downregulation in COX-2 expression and PGI(2) secretion from the HPASMCs. In conclusion, the results from the current study suggest that H(2)S enhances hypoxia-induced cell proliferation through the upregulation of COX-2/PGI(2), as opposed to ROS.