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Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important inflammasome in mammals, which is of great significance to eliminate pathogens. However, the research of the NLRP3 inflammasome in teleost is limited. Tetraodon nigroviridis has the characteristics of small genome and easy feeding, which can be used as a model for the study of fish immune function. In present study, three NLRP3 inflammasome component genes (NLRP3, ASC and caspase-1) in T. nigroviridis has been cloned. Real-time fluorescence quantitative PCR showed that TnNLRP3 (T. nigroviridis NLRP3), TnASC (T. nigroviridis ASC) and Tncaspase-1 (T. nigroviridis caspase-1) mRNA in various tissues from health T. nigroviridis were highly expressed in immune-related tissues, such as spleen, gill, head kidney and intestine. After Vibrio parahemolyticus infection, the expression of TnNLRP3, TnASC and Tncaspase-1 mRNA in spleen, gill, head kidney reached a peak at 24 h, and the expression levels of these genes in intestine were the highest at 48 h. After the transfection of TnASC-pAcGFP-N1 monomer GFP plasmid into cos-7 cells, ASC specks, the activation marker of NLRP3 inflammasome, were observed. Bimolecular fluorescence complementarity and fluorescence colocation experiment showed that TnASC and Tncaspase-1 of TnNLRP3 inflammasome were co-located near the cell nucleus, and potentially interacted with each other. NLRP3 inflammasome inducer nigericin and agonist ATP could significantly induce the expression of TnNLRP3, TnASC and Tncaspase-1 mRNA, and activation of NLRP3 inflammasome could promote the generation of mature TnIL-1β (T. nigroviridis IL-1β). These results uncover that T. nigroviridis NLRP3 inflammasome could participate in the antibacterial immune response and the generation of mature TnIL-1β after activation.

Genes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3β/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.

When performing endoluminal surgery inside the colon using a flexible endoscopic robot, there is a problem of losing visualization and task space due to the collapsing of the surrounding wall. This happens mainly because of the intra-abdominal pressure and peristalsis of the colon. Although insufflation is commonly used for expanding the colon, it does not function when a full-thickness incision is created on the colon wall. To support the collapsing colon and ensure sufficient visualization and task space even with a hole, we developed a deployable colon support structure (CSS) that can be seamlessly adapted to the existing procedures. While the CSS is designed to be small and flexible enough to pass through an endoscopic channel that can be tortuous, it becomes steady enough to hold the collapsing/squeezing colon after being deployed. Also, the CSS is collapsible after task completion, for retraction through an endoscopic channel. Through the ex-vivo and in-vivo studies with a swine, we have successfully demonstrated the feasibility of supporting the colon wall during endoluminal interventions with the CSS. We confirmed that the CSS was easily deliverable and deployable and the created space was large enough to perform surgical tasks using robotic arms. National Research Foundation (NRF) Published version This work was supported by the National Research Foundation (NRF) Singapore under Grant NRFI2016-07

Breast cancer is the most prevalent malignancy and the first leading cause of cancer-related mortality among the female population worldwide. Approaches for precise and reliable detection of breast cancer cells, particularly in the nascent state, are desperately needed for elevating the survival rate of patients bearing the breast tumor. In this work, we successfully performed the sensitive, precise, and reliable breast cancer cell detection using facilely fabricated bovine serum albumin-gold nanocluster (BSA-AuNCs) protein corona stabilized, epithelial cell adhesion molecule (EpCAM) aptamer linked fluorescent polystyrene nanoparticle (PS NP), termed as PS-BSA-AuNCs-Apt. The rapidly adsorbed BSA-AuNCs hard protein corona without complicated covalent conjugation not only imparted excellent colloidal stability to the PS nanoparticles, but also offered numerous active anchors for the targeted EpCAM aptamers to locate. With the remarkable aid of the aptamers specifically targeting the EpCAM-positive breast cancer cells, the PS-BSA-AuNCs-Apt emitted strong and photostable dual-color fluorescent signals for precise and reliable cancer cell detection by overcoming the false signals. The specific identification potency of the PS-BSA-AuNCs-Apt system was further verified by successfully detecting the xenografted breast tumor tissue. Notably, to the best of our knowledge, the protein corona formed nanoprobes was exploited for direct tumor cell and tissue detection with high efficacy for the first time, demonstrating their promising potential in clinical tumor detection.

If a perforation occurs as a result of a flexible endoscopic procedure, suturing through urgent laparoscopy or open surgery may be required to repair the perforation because suturing is normally stronger than closure using existing endoscopic devices. Suturing with stitches and knots, widely adopted in open or laparoscopic surgery, is still not possible in flexible endoscopy. This is because of the confined space of the natural orifice and target area, high levels of motion dexterity and force needed for stitching and knot-tying, and critical size and strength requirements of wound closure. We present a novel flexible endoscopic robotic suturing system that is able to suture gastrointestinal defects without opening up the patient’s body like in open or laparoscopic surgery. This system features a robotic needle driver and a robotic grasper, both of which are flexible, through-the-scope (small in sizes), and dexterous with five degrees of freedom. The needle driver, facilitated by the grasper, enables the surgeon to control a needle through teleoperation to make stitches and knots in flexible endoscopy. Successful in vivo trials were conducted in the rectum of a live pig to confirm the feasibility of endoscopic suturing and knot-tying using the system in a realistic surgical scenario (not possible with existing devices which are all manually driven). This new technology will change the way how surgeons close gastrointestinal defects. NRF (Natl Research Foundation, S’pore) Accepted version

Haptic feedback is absent in flexible endoscopic surgical robots due to the size constraint of installing sensors on the small robotic arms. Besides, inherent hysteresis caused by the nonlinear friction between tendons and sheaths makes it hard to estimate the distal force by modeling. In this work, we addressed this challenge by proposing a new three-axial force sensor. This standalone device can be seamlessly integrated into the endoscopic robotic arm. Three optical fibers with Fiber Bragg Gratings (FBGs) are embedded in the sensing structure, where one is located at the center hole of the structure (⌀ 1.4 mm), and the other two are eccentrically placed around the structure at 90° apart from each other. This device can measure the pulling force and lateral forces of an articulated surgical instrument. Mechanics analysis has been studied to reveal the link between FBGs’ wavelength shifts and forces caused by the elongation and the bending, with a temperature-compensation feature. The sensor has a lateral force sensitivity of 838.386 pm/N, with a measurement resolution of 1.19 mN. Performance comparison with a commercial force sensor Nano17 was made, with measurement errors from 4.50% to 6.18%. In the ex-vivo tests, we teleoperated the sensorized grasper to pull, steer and lift a piece of pig colon tissue. The tool-tissue interaction forces measured by the force sensor were displayed on the computer screen in real-time. In addition to the endoscopic robots, the force sensor can also be integrated with other surgical robots such as laparoscopic robots and catheters. National Research Foundation (NRF) This work was supported by National Research Foundation (NRF) Singapore (NRFI2016-07).

Flexible endoscopy requires a lot of skill to manipulate both the endoscope and the associated instruments. In most robotic flexible endoscopic systems, the endoscope and instruments are controlled separately by two operators, which may result in communication errors and inefficient operation. Our solution is to enable the surgeon to control both the endoscope and the instruments. Here, we present a novel tele-operation robotic endoscopic system commanded by one operator using the continuous and simultaneous movements of their two hands and one foot. This 13-degree-of-freedom (DoF) system integrates a foot-controlled robotic flexible endoscope and two hand-controlled robotic endoscopic instruments, a robotic grasper and a robotic cauterizing hook. A dedicated foot-interface transfers the natural foot movements to the 4-DoF movements of the endoscope while two other commercial hand interfaces map the movements of the two hands to the two instruments individually. An ex-vivo experiment was carried out by six subjects without surgical experience, where the simultaneous control with foot and hands was compared with a sequential clutch-based hand control. The participants could successfully teleoperate the endoscope and the two instruments to cut the tissues at scattered target areas in a porcine stomach. Foot control yielded 43.7% faster task completion and required less mental effort as compared to the clutch-based hand control scheme, which proves the concept of three-limb tele-operation surgery and the developed flexible endoscopic system.

Flexible endoscopy requires high skills to manipulate both the endoscope and associated instruments. In most robotic flexible endoscopic systems, the endoscope and instruments are controlled separately by two operators, which may result in communication errors and inefficient operation. We present a novel teleoperation robotic endoscopic system that can be commanded by a surgeon alone. This 13 degrees-of-freedom (DoF) system integrates a foot-controlled robotic flexible endoscope and two hand-controlled robotic endoscopic instruments (a robotic grasper and a robotic cauterizing hook). A foot-controlled human-machine interface maps the natural foot gestures to the 4-DoF movements of the endoscope, and two hand-controlled interfaces map the movements of the two hands to the two instruments individually. The proposed robotic system was validated in an ex-vivo experiment carried out by six subjects, where foot control was also compared with a sequential clutch-based hand control scheme. The participants could successfully teleoperate the endoscope and the two instruments to cut the tissues at scattered target areas in a porcine stomach. Foot control yielded 43.7% faster task completion and required less mental effort as compared to the clutch-based hand control scheme. The system introduced in this paper is intuitive for three-limb manipulation even for operators without experience of handling the endoscope and robotic instruments. This three-limb teleoperated robotic system enables one surgeon to intuitively control three endoscopic tools which normally require two operators, leading to reduced manpower, less communication errors, and improved efficiency., 9 pages, 11 figures

G2 and S phase-expressed-1 (GTSE1) has been implicated in the pathogenesis of several malignant tumors. However, its specific role in prostate cancer (PCa) remains unclear. In this study, RNA-Seq data from patients with PCa and controls were downloaded from the FIREBROWSE database, and it was found that the GTSE1 mRNA level was significantly upregulated in PCa. Moreover, patients with higher GTSE1 mRNA levels had higher Gleason scores (P

Accurate motion control of surgical robots is critical for the efficiency and safety of both state-of-the-art teleoperated robotic surgery and the ultimate autonomous robotic surgery. However, fine motion control for a flexible endoscopic surgical robot is highly challenging because of the shape-dependent and speed-dependent motion hysteresis of tendon-sheath mechanisms (TSMs) in the long, tortuous, and dynamically shape-changing robot body. Aiming to achieve precise closed-loop motion control, we propose a small and flexible sensor to directly sense the large and sharp rotations of the articulated joints of a flexible endoscopic surgical robot. The sensor - a Fiber Bragg Grating (FBG) eccentrically embedded in a thin and flexible epoxy substrate - can be significantly bent with a large bending angle range of [-62.9°, 75.5°] and small bending radius of 6.9 mm. Mounted in-between the two pivot-connected links of a joint, the sensor will bend once the joint is actuated, resulting in the wavelength shift of the FBG. In this study, the relationship between the wavelength shift and the rotation angle of the joint was theoretically modeled and then experimentally verified before and after the installation of the sensor in a robotic endoscopic grasper. The sensor, with the calibrated model, can track the rotation of the robotic joint with an RMSE of 3.34°. This small and flexible sensor has good repeatability, high sensitivity (around 147.5 pm/degree), and low hysteresis (7.72%). It is suitable for surgical robots and manipulators whose articulated joints have a large rotation angle and small bending radius. National Research Foundation (NRF) Accepted version This work was supported by National Research Foundation (NRF) Singapore (NRFI2016-07).

Mycobacterium tuberculosis infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different. Therefore, the rapid and accurate identification of M. tuberculosis and NTM species is very important for the control of tuberculosis and NTM infections. In the present study, a Cas12a/guide RNA (gRNA)-based platform was developed to identify M. tuberculosis and most NTM species. By designing species-specific gRNA probes targeting the rpoB sequence, a Cas12a/gRNA-based platform successfully identified M. tuberculosis and six major NTM species (Mycobacterium abscessus, Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium gordonae, and Mycobacterium fortuitum) without cross-reactivity. In a blind assessment, a total of 72 out of 73 clinical Mycobacterium isolates were correctly identified, which is consistent with previous rpoB sequencing results. These results suggest that the Cas12a/gRNA-based platform is a promising tool for the rapid, accurate, and cost-effective identification of both M. tuberculosis and NTM species.

In traditional endoscopic surgery, the surgeon manipulating the endoscopic instruments is supported by an assistant controlling the endoscope, where their coordination may be affected by communication errors. To address this issue, we introduce a foot interface controlled robotic endoscopic system, enabling the surgeon to simultaneously operate the endoscope and instruments. The system consists of a foot interface using four degrees of freedom (DoFs) foot gestures and a robotic driving system for a commercial flexible endoscope. The proposed robotic system was validated in teleoperation experiments performed by ten subjects, where foot teleoperation was compared with hand teleoperation and direct control of the endoscope with two hands. The participants could successfully teleoperate the endoscope with foot teleoperation and exhibited 40% faster task completion as with direct control. They found both foot and hand teleoperations comfortable and intuitive. Although hand teleoperation enabled the best performance, only foot teleoperation allows simultaneous control of three instruments. Accepted version

Mycobacterium tuberculosis infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different. Therefore, the rapid and accurate identification of M. tuberculosis and NTM species is very important for the control of tuberculosis and NTM infections. In the present study, a Cas12a/guide RNA (gRNA)-based platform was developed to identify M. tuberculosis and most NTM species. By designing species-specific gRNA probes targeting the rpoB sequence, a Cas12a/gRNA-based platform successfully identified M. tuberculosis and six major NTM species (Mycobacterium abscessus, Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium gordonae, and Mycobacterium fortuitum) without cross-reactivity. In a blind assessment, a total of 72 out of 73 clinical Mycobacterium isolates were correctly identified, which is consistent with previous rpoB sequencing results. These results suggest that the Cas12a/gRNA-based platform is a promising tool for the rapid, accurate, and cost-effective identification of both M. tuberculosis and NTM species.

Haptic feedback for flexible endoscopic surgical robots is challenging due to space constraints for sensors and shape-dependent force hysteresis of tendon-sheath mechanisms (TSMs). This paper proposes (1) a single-axis fiber Bragg grating (FBG)-based force sensor for a TSM of a robotic arm and (2) an integrated sensor-model approach to estimate forces on other TSMs of that arm. With a robust and simple structure, a temperature-compensated sensor can be mounted on the distal sheath to measure forces applied by the TSM. This proposed sensor was integrated with a Ø4.2 mm articulated robotic arm driven by six TSMs, with a measurement error of 0.37 N in this work. The measurement from the single sensor was used to identify parameters in the force-transmission models of all other TSMs in the robot, realizing a one-sensor-for-all-distal-forces measurement method. The sensor-model approach could accurately estimate the distal force with an RMSE of 0.65 N. An animal study was carried out to demonstrate the sensor's feasibility in real-life surgery. The sensor-model approach presented a robust, space-saving, and cost-effective solution for haptic feedback of endoscopic robots without any assumption on the shapes of the robot. NRF (Natl Research Foundation, S’pore) Accepted version

This article presents a novel force sensor to detect the distal force of tendon-sheath mechanisms (TSMs) in flexible endoscopic surgical robots. We propose to measure the compression force on the sheath at the distal end so that the tension force on the tendon, which equals the compression force on the sheath, can be obtained. With this approach, a new force sensor made up of a 1 mm fiber Bragg grating attached to a 3 mm long nitinol tube was developed to measure the compression force exerted on the sheath. Mechanics analysis and verification tests were conducted to characterize the relationship between tension and compression on a TSM. Force calibrations, hysteresis study, and temperature compensation verification tests on the sensor were carried out. The force sensor has a measurement error of 0.178 N and a sensitivity of 34.14 pm/N. Applications of the sensor in a TSM-driven robotic grasper and a tendon-driven continuum robot were demonstrated. This force sensor has salient advantages: it is small, structurally simple, electrically passive, temperature-compensated, easy to assemble and disassemble, flexible, and biocompatible. This proposed approach with the new force sensor can also be applied to both TSM-driven systems and tendon-driven systems such as robotic fingers/hands, wearable devices, surgical catheters, and rehabilitation devices. NRF (Natl Research Foundation, S’pore) Accepted version

Distal-end force information is usually missing in flexible endoscopic robots due to the difficulties of mounting miniature force sensors on their end-effectors. This hurdle creates big challenges in providing a sense of touch for the operating surgeons. Many existing studies have developed models to calculate the distal-end forces based on the measured proximal-end forces of Tendon-Sheath Mechanisms (TSMs), but these models assume known sheath bending configuration which is unknown during real-life surgeries. This paper presents a two-stage data-driven method that makes dynamic distal-end force prediction of a flexible endoscopic robot without this assumption. In stage one, a convolutional neural network is used to estimate the sheath cumulative bending angle based on the proximal-end force responses of the robot to a probing signal; in stage two, a combination of two long-short-term-memory models pre-trained for the bending angles nearest to the estimated angle (obtained in stage one) makes dynamic estimations of the distal-end force of the robot. The proposed approach overcomes the challenges due to unknown TSM configurations and can robustly identify the correct force hysteresis phases of TSMs. The force prediction is continuous, accurate, and has a mean RMSE of 0.1711 N. This method was validated on an actual flexible surgical robot. In addition, since the proposed approach provides an estimation of the current system cumulative bending angle, it can also be used to facilitate the mathematical modeling methods which require information on the cumulative bending angle. Accepted version

The surface of the bridge pier is divided into upstream surface and downstream surface. The tsunami force characteristics and generation mechanisms for regular piers, i.e. square, circular and diamond piers, as well as pressure distribution and flow field around piers are discussed. Results show that the upstream surface of the diamond pier is most beneficial to reduce water blocking effect and to lower runup at the stagnation point, which ultimately reduces the tsunami force on the upstream surface before tsunami bore reaches the downstream surface. Downstream surface of the circular pier is most beneficial for two branches of tsunami bore flow back and run up on the downstream surface, which generates larger negative tsunami force on downstream surface larger earlier, and ultimately makes entire tsunami force on circular pier smaller after tsunami bore reaches the downstream surface. Based on which, a new type pier is invented by combining the upstream surface of diamond pier and downstream surface of circular pier together. Further, the mitigation effect of new type pier is validated and the mitigation mechanism is explored. Among circular pier and the three piers of new type, N60 is proven to the best to reduce tsunami force.

The generation mechanism and characteristics of peak values of tsunami bore vertical force are investigated comprehensively and thoroughly. A scaled down two-dimensional T-girder model, whose surface is divided into a series of panels, is tested in the cases with fixed initial downstream water depth, different incoming wave height and different initial clearance. Time history of vertical force is divided into four stages, in which the impinging stage is further divided into four sub-stages. Then the contribution rates of panels to the vertical force are discussed. Results show each peak value of vertical force in the impinging stage is composed of at least one peak value of vertical force on bottom panels of the girder, the continue increase of vertical force peak value is the result of more and more panels suffering static pressure of entrapped air when the chambers are successively closed by tsunami bore. The vertical force peak values on top panels of the chambers are mainly generated by the static pressure peak values of entrapped air. The entrapped air decreases the vertical velocity of tsunami bore under already closed chambers, resulting the simultaneous occurrences of pressure peaks of entrapped air in previous closed chambers.

Accurate haptic feedback is a critical challenge for surgical robots, especially for flexible endoscopic surgical robots whose transmission systems are Tendon-Sheath Mechanisms (TSMs) with highly nonlinear friction profiles and force hysteresis. For distal end haptic sensing of TSMs, this paper, for the first time, proposes to measure the compression force on the sheath at the distal end so that the tension force on the tendon, which equals the compression force on the sheath, can be obtained. A new force sensor, i.e., a nitinol tube attached with an optical Fiber Bragg Grating (FBG) fiber, is proposed to measure the compression force on the sheath. This sensor, with similar diameter and configuration (hollow) as the sheath, can be compactly integrated with TSMs and surgical end-effectors. In this paper, mechanics analysis and verification tests are presented to reveal the relationship between the tension force on the tendon and the compression force on the sheath. The proposed force sensor was calibrated in tests with a sensitivity of 24.28 pm/N and integrated with a tendon-sheath driven grasper to demonstrate the effectiveness of the proposed approach and sensor. The proposed approach and sensor can also be applied for a variety of TSMs-driven systems, such as robotic fingers/hands, wearable devices, and rehabilitation devices. NRF (Natl Research Foundation, S’pore) Accepted version

While angiomyolipoma (AML) is a fairly common urological tumor, malignant AMLs rarely appear in clinical practice. As such, currently there exists little knowledge of malignant AMLs. This article discusses the differences between benign and malignant AMLs. Besides, we report two cases of AML with opposite nature in Nan Fang Hospital from 2010 to 2016 and discuss the key features based on clinical manifestation, pathogenesis, radiology, and pathology. Case 1 was a 44-year-old, asymptomatic female presenting with a mass measuring 4 cm in diameter in the inferior pole of the left kidney. Case 2 was a 23-year-old female presenting with abdominal pain for 1 month, a mass measuring 5.5 cm in diameter in the superior pole of the right kidney, regional infiltration, and enlarged retroperitoneal lymph nodes. Based on Folpe's grading scheme, the Case 1 tumor was benign due to the absence of criteria mentioned in the grade and the Case 2 tumor was malignant due to a tumor size >5 cm, infiltrative growth pattern, necrosis, high nuclear grade, and subsequent aggressive clinical behavior. Each patient underwent surgical resection: Case 1 demonstrated no evidence of recurrence at the 9-month follow-up; however, Case 2 died 3 years postoperation due to tumor recurrence. These results demonstrate that malignant AML has aggressive biological activities and almost always associates with unfavorable prognoses. Therefore, a strict follow-up should be given to “uncertain malignant potential” patients, and surgical resection should be performed.