Discovery of LLC355 as an Autophagy-Tethering Compound for the Degradation of Discoidin Domain Receptor 1.

Discoidin domain receptor 1 (DDR1) is a potential target for cancer drug discovery. Although several DDR1 kinase inhibitors have been developed, recent studies have revealed the critical roles of the noncatalytic functions of DDR1 in tumor progression, metastasis, and immune exclusion. Degradation of DDR1 presents an opportunity to block its noncatalytic functions. Here, we report the discovery of the DDR1 degrader LLC355 by employing autophagosome-tethering compound technology. Compound LLC355 efficiently degraded DDR1 protein with a DC50 value of 150.8 nM in non-small cell lung cancer NCI-H23 cells. Mechanistic studies revealed compound LLC355 to induce DDR1 degradation via lysosome-mediated autophagy. Importantly, compound LLC355 potently suppressed cancer cell tumorigenicity, migration, and invasion and significantly outperformed the corresponding inhibitor 1. These results underline the therapeutic advantage of targeting the noncatalytic function of DDR1 over inhibition of its kinase activity.

An intelligent grasper to provide real-time force feedback to shorten the learning curve in laparoscopic training.

BACKGROUND: A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices. METHODS: Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared. RESULTS: In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons' performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p < 0.005). During the training period, the Group B2 takes 6 trails to achieve gripping force of 0.635 N, which is lower than the threshold line, whereas the Group A2 needs 11 trails, meaning that the learning curve of Group B2 was significantly shorter than that of Group A2. Additionally, during the follow-up period, there was no significant decline in force learning, and Group B2 demonstrated better control of gripping operations. The training with force feedback received positive evaluations. CONCLUSION: Our study shows that using a grasper providing force feedback in laparoscopic training can help to control the gripping force and shorten the learning curve. It is anticipated that the laparoscopic grasper equipped with FBG sensor is promising to provide force feedback during laparoscopic training, which ultimately shows great potential in laparoscopic surgery.

Convolutional-neural-network-based versus vision-transformer-based SNR estimation for visible light communication networks.

Visible light communication (VLC) has emerged as a promising technology for future sixth-generation (6 G) communications. Estimating and predicting the impairments, such as turbulence and free space signal scattering, can help to construct flexible and adaptive VLC networks. However, the monitoring of impairments of VLC is still in its infancy. In this Letter, we experimentally demonstrate a deep-neural-network-based signal-to-noise ratio (SNR) estimation scheme for VLC networks. A vision transformer (ViT) is first utilized and compared with the conventional scheme based on a convolutional neural network (CNN). Experimental results show that the ViT-based scheme exhibits robust performance in SNR estimation for VLC networks compared to the CNN-based scheme. Specifically, the ViT-based scheme can achieve accuracies of 76%, 63.33%, 45.33%, and 37.67% for 2-quadrature amplitude modulation (2QAM), 4QAM, 8QAM, and 16QAM, respectively, against 65%, 57.67%, 41.67%, and 34.33% for the CNN-based scheme. Additionally, data augmentation has been employed for achieving enhanced SNR estimation accuracies of 95%, 79.67%, 58.33%, and 50.33% for 2QAM, 4QAM, 8QAM, and 16QAM, respectively. The effect of the SNR step size of a contour stellar image dataset on the SNR estimation accuracy is also studied.

Polymeric fiber sensors for insertion forces and trajectory determination of cochlear implants in hearing preservation.

The level of hearing restoration in patients with severe to profound sensorineural hearing loss by means of cochlear implants (CIs) has drastically risen since the introduction of these neuroprosthetics. The proposed CI integrated with polymer optical fiber Bragg gratings (POFBGs) enables real-time evaluation of insertion forces and trajectory determination during implantation irrespective of the speed of insertion, as well as provides high signal quality, low stiffness levels, minimum induced stress even under forces of high magnitudes and exhibits significant reduction of the risk of fiber breakage inside the constricted cochlear geometry. As such, the proposed device opens new avenues towards atraumatic cochlear implantations and provides a direct route for the next generation of CIs with intraoperative insertion force assessment and path planning capacity crucial for surgical navigation. Hence, adaptation of this technology to clinical reality holds promising prospects for the hearing impaired.

Ultrasensitive cascaded in-line Fabry-Perot refractometers based on a C-shaped fiber and the Vernier effect.

We propose and experimentally demonstrate a fiber refractometer based on a C-shaped fiber and the Vernier effect. The sensor is fabricated by cascading a single mode fiber (SMF) pigtail together with a C-shaped fiber segment and another SMF segment. Thus, the C-shaped fiber would constitute an open cavity (sensing cavity) in which test analytes could be filled, while the SMF segment would constitute another reference cavity. Due to the similar optical path length of these two cavities, the Vernier effect would be activated, thus forming spectral envelops in the reflection spectrum of the sensor. Variations in the refractive index (RI) of analytes would result in the shifts of the spectral envelops. Both theoretical calculations and experiments are carried out in the characterization of the sensor measuring liquid and gaseous analytes. The experimental sensitivity of the sensor is found to be ∼37238 nm/RIU for gas RI measurement. The proposed sensor features the advantages such as ease of fabrication, extremely high sensitivity, capability of sensing of both gaseous and liquid analytes, small footprint, and good mechanical strength. Compared to other existing Vernier effect-based fiber refractometers typically fabricated using PCFs, the proposed sensor would allow analytes to have much easier and quicker access to the sensor probe.

Simultaneous Measurement of Temperature and Pressure Based on Fabry-Perot Interferometry for Marine Monitoring.

The temperature and pressure of seawater are of great importance to investigate the environmental evolution for the research of ocean science. With this regard, we proposed and experimentally demonstrated a seawater temperature and pressure sensor realized by a polyimide (PI) tube-based Fabry-Perot interferometer (FPI) together with a fiber Bragg grating (FBG). Benefiting from the higher thermo-optical coefficient and larger elasticity of polymer than the fused silica fiber, the sensitivity of the sensor is largely improved. The FBG is used to compensate the cross effect of the temperature. The measured temperature and pressure sensitivities of the sensor are 18.910 nm/°C and -35.605 nm/MPa, respectively. Furthermore, the temperature and pressure information measured by the sensor can be achieved simultaneously using the sensitivity matrix method. In addition, the proposed sensor has advantages of easy fabrication, compact size, as well as capability of multiplexing and long-distance measurement, making it competitive and promising during the marine monitoring.

Simultaneous measurement of axial strain and lateral stress based on cascaded interference structure.

To solve the cross-sensitivity problem in the dual-parameter optical fiber system, a new type of sensor based on cascaded interference structure is proposed without cross-sensitivity. The design consists of a Michelson interferometer and a Sagnac interferometer based on a high-birefringence suspended core fiber segment. After calculating by the analogous Fast Fourier Transformation (FFT) and filtering by FFT filter, the spectrum of the sensor responds linearly to the change of axial strain and lateral stress. The sensitivity to lateral stress is 3.13 nm/(kPa) in the range from 0 to 1200 Pa and the axial strain is 1.846e-4 (nm·µÉ›)-1 from 0 to 4000 µÉ›. The capability of the proposed sensor for dual-parameter sensing is also experimentally demonstrated. The precision rate for dual-parameter sensing is as high as 66.7%, reflecting the sensor's usability for simultaneous measurement of axial strain and lateral stress.

Smart laparoscopic grasper integrated with fiber Bragg grating based tactile sensor for real-time force feedback.

Minimally invasive surgery, such as laparoscopic surgery, has developed rapidly due to its small wound, less bleeding and quick recovery. However, a lack of force feedback, which leads to tissue damage, is still unsolved. Many sensors have been used to offer force feedback but still limited by their large size, low security and high complexity. Based on the advantages of small size, high sensitivity and immunity to electromagnetic interferences, we propose a tactile sensor integrated with fiber Bragg gratings (FBGs) at the tip of laparoscopic grasper to offer real-time force feedback in the laparoscopic surgery. The tactile sensor shows a force sensitivity of 0.076 nm/N with a repeatable accuracy of 0.118 N. A bench test is conducted in a laparoscopic training box to verify its feasibility. Test results illustrate that gripping force exerted on the laparoscopic grasper in terms of peak and standard deviation values reduce significantly for the novice subjects with force feedback compared to those without force feedback. The proposed sensor integrated at the tip of the laparoscopic grasper demonstrates a better control of the gripping force among the novice surgeons and indicates that the smart grasper can help surgeons achieve precise gripping force to reduce unnecessary tissue trauma.

Simultaneous measurement of salinity and temperature using a Sagnac interferometer based on concatenated polarization-maintaining fiber tapers.

A Sagnac loop interferometer based on concatenated polarization-maintaining fiber (PMF) tapers is proposed for simultaneous measurement of seawater salinity and temperature. The influences of the distance between the PMF tapers as well as fiber taper diameter on sensor performance have been investigated. Experimental results indicate that the fabricated sensor with a distance of 3 cm between adjacent fiber tapers possesses the salinity and temperature sensitivities of 0.367 nm/% and -0.728nm/∘C, respectively, and the taper waist diameter of 20 µm would help to improve salinity sensitivity in comparison with a sensor of 30 µm in diameter. The proposed Sagnac loop interferometer based on concatenated PMF tapers is expected to find potential applications in the measurement of seawater salinity.

Vernier effect assisted sucrose sensor based on a cascaded Sagnac interferometer with no-core fiber.

We propose a sucrose concentration sensor by utilizing a fiber Sagnac interferometer with no-core fiber (SI-NCF) based on the Vernier effect. The Vernier effect is realized by introducing a single Sagnac interferometer (SI) with a similar free spectral range of SI-NCF. When the NCF is exposed to the external sucrose solution, the cladding state of NCF is changed, which induces the wavelength shift of the SI-NCF. The measured sucrose concentration sensitivity of a single SI-NCF is 2.97 nm/M, and the sensitivity can be improved to -13.84 nm/M with the assistance of the Vernier effect, which is 4.66 times of the single SI-NCF. The sensor has the advantages of high sensitivity, easy-fabrication and cost-effectiveness which can be applied in the field of the food industry, chemistry and agriculture.

High-Speed Handling Robot with Bionic End-Effector for Large Glass Substrate in Clean Environment.

The development of "large display, high performance and low cost" in the FPD industry demands glass substrates to be "larger and thinner". Therefore, the requirements of handling robots are developing in the direction of large scale, high speed, and high precision. This paper presents a novel construction of a glass substrate handling robot, which has a 2.5 m/s travelling speed. It innovatively adopts bionic end-suction technology to grasp the glass substrate more firmly. The structure design is divided into the following three parts: a travel track, a robot body, and an end-effector. The manipulator can be smoothly and rapidly extended by adjusting the transmission ratio of the reducer to 1:2:1, using only one motor to drive two sections of the arm. This robot can transfer two pieces of glass substrate at one time, and improves the working efficiency. The kinematic and dynamic models of the robot are built based on the DH coordinate. Through the positioning accuracy experiment and vibration experiment of the end-effector, it is found that the robot has high precision during handling. The robots developed in this study can be used in large-scale glass substrate handling.

Two semicircular-hole fiber in a Sagnac loop for simultaneous discrimination of torsion, strain and temperature.

We report a highly sensitive twist sensor based on a Sagnac interferometer constructed with a new type of optical fiber which contains an elliptical core and two large semicircular-holes, where the slow axis of the core orthogonal to the air-holes has a large sensitivity towards twist-induced birefringent changes. The novel fiber structure results in a highest twist sensitivity of 5.01 nm/° at a chosen dip over the range from 370°-400°. The resonance dips in the interference pattern respond with different rates in the wavelength shifts in the presence of physical parameters permitting to experimentally distinguish directional torsion, axial strain and temperature.

All-optical fiber filter based on an FBG inscribed in a silica/silicone composite fiber.

An all-optical tunable filter based on a fiber Bragg grating (FBG) inscribed in a self-heated silica/silicone composite fiber is demonstrated. A thin silicone film is coated inside the suspended core fiber), which acts as the silicone cladding. A periodic refractive index modulation is inscribed in the silicone cladding by UV irradiation. Silicone is an organic material whose optical properties are different than silica, which leads to interesting applications. The high thermo-optic properties are studied and applied here. A 1550 nm pump laser is utilized to heat the silicone grating where a wavelength shift is observed for the gratings when subjected to different pump powers. Experimental results indicate a wavelength tuning coefficient of -0.128nm/mW with a response time of 0.5 s to obtain a wavelength shift of 1 nm under periodic pump light. The new design of this miniature all-optical filter is cost-effective and can potentially be adhered in optical fiber sensing and communication systems.

Sensitive Mach-Zehnder interferometric sensor based on a grapefruit microstructured fiber by lateral offset splicing.

A novel inline Mach-Zehnder interferometric (MZI) sensor based on a homemade grapefruit microstructured fiber (GMF) was proposed and experimentally demonstrated. The sensing unit consists of a short segment of a GMF sandwiched between two single mode fibers using lateral offset splicing. The fabrication of the GMF and the GMF-based MZI sensor was introduced. Mode analysis of the GMF and theoretical simulation of the proposed MZI sensor were investigated and matched well with experimental results. The sensing performance of the MZI sensor for temperature and strain was tested. The strain and temperature sensitivity are 1.97pm/µÉ› and 37pm/°C, respectively. The compact size, low cost and high sensitivity makes the MZI sensor a good candidate for sensing application.

Application of Fibre Bragg Grating Sensors in Strain Monitoring and Fracture Recovery of Human Femur Bone.

Fibre Bragg Grating (FBG) sensors are gaining popularity in biomedical engineering. However, specific standards for in vivo testing for their use are absolutely limited. In this study, in vitro experimental tests were performed to investigate the behaviors and applications of gratings attached to intact and fractured thighbone for a range of compression loading (<300 N) based around some usual daily activities. The wavelength shifts and the corresponding strain sensitivities of the FBG sensors were measured to determine their effectiveness in monitoring the femoral fracture healing process. Four different arrangements of FBG sensors were selected to measure strains at different critical locations on the femoral sawbones surface. Data obtained for intact and plated sawbones were compared using both embedded longitudinal and coiled FBG arrays. Strains were measured close to the fracture, posterior linea aspera and popliteal surface areas, as well as at the proximal and distal ends of the synthetic femur; their responses are discussed herein. The gratings on the longitudinally secured FBG arrays were found to provide high levels of sensitivity and precise measurements, even for relatively small loads (<100 N). Nevertheless, embedding angled FBG sensors is essential to measure the strain generated by applied torque on the femur bone. The maximum recorded strain of the plated femur was 503.97 µÎµ for longitudinal and -274.97 µÎµ for coiled FBG arrays, respectively. These project results are important to configure effective arrangements and orientations of FBG sensors with respect to fracture position and fixation implant for future in vivo experiments.

The impact of sedation on quality metrics of colonoscopy: a single-center experience of 48,838 procedures.

PURPOSE: Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. METHODS: Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. RESULTS: A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16-85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. CONCLUSIONS: The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.

Resurgent regenerated fiber Bragg gratings and thermal annealing techniques for ultra-high temperature sensing beyond 1400°C.

We report for the first time the resurgence of regenerated fiber Bragg gratings (RFBGs) useful for ultra-high temperature measurements exceeding 1400 °C. A detailed study of the dynamics associated with grating regeneration in six-hole microstructured optical fibers (SHMOFs) and single mode fibers (SMFs) was conducted. Rapid heating and rapid cooling techniques appeared to have a significant impact on the thermal sustainability of the RFBGs in both types of optical fibers reaching temperature regimes exceeding 1400 °C. The presence of air holes sheds new light in understanding the thermal response of RFBGs and the stresses associated with them, which governs the variation in the Bragg wavelength.

Microstructured optical fiber based Fabry-Pérot interferometer as a humidity sensor utilizing chitosan polymeric matrix for breath monitoring.

This study reports a method for humidity sensing based on a specialty microstructured optical fiber (MOF). A suspended tri-core MOF was fabricated using the stack and draw technique. A low finesse sensing head was prepared by depositing a chitosan polymer matrix within the holes of the MOF, forming a Fabry-Pérot interferometer as a sensing platform while the chitosan film acts as the sensing material. The use of the probe for real-time breath monitoring was also successfully demonstrated. The probe possessed a maximum sensitivity of 81.05 pm/(%RH) for 90-95%RH range while the linear region of the sensor ranged from 70-95%RH. The temperature cross correlation was also experimented, and a lower influence of external temperature was observed. The probe shows an ultrafast response during human breath monitoring with a rising time and recovery time of 80 ms and 70 ms, respectively.

Role of HSP27 in the multidrug sensitivity and resistance of colon cancer cells.

Multidrug resistance in cancer cells is a primary factor affecting therapeutic efficacy. Heat shock 27 kD protein 1 (HSP27) is associated with cell apoptosis and resistance to chemotherapy. However, the mechanisms underlying HSP27-associated pathways in colon cancer cells remain unclear. Therefore, the present study used short hairpin (sh) RNA to inhibit HSP27 expression in colon cancer cells in order to investigate the effects in vitro and in vivo. Flow cytometry was used to investigate cell apoptosis and a xenograft model was employed to examine the tumorigenesis. Protein expression was measured by Western blotting. The results revealed that suppression of HSP27 expression significantly increased cell apoptosis, inhibited tumor growth and enhanced sensitivity to the anti-cancer agents 5-fluorouracil (5-FU) and vincristine (VCR). shHSP27 significantly decreased the expression of notch receptor 1 and the phosphorylation level of Akt and mTOR, and enhanced the effect of 5-FU and VCR. In conclusion, HSP27 suppression enhanced the sensitivity of colon cancer cells to 5-FU and VCR, and increased colon cancer cell apoptosis with and without chemotherapy. Therefore, the development of novel therapeutic agents that inhibit the expression of HSP27 may offer a new treatment option for colon cancer.

Non-invasive human vital signs monitoring based on twin-core optical fiber sensors.

Twin-core fiber (TCF)-based sensor was proposed for non-invasive vital sign monitoring, including respiration and heartbeat. The TCF was homemade and the corresponding sensor was fabricated by sandwiching single-mode fiber (SMF) on both ends. The offset distance between SMF and TCF was optimized while the length of TCF was identified from preliminary vital sign measurement results. Then, the TCF-based sensor was attached under a mattress to realize non-invasive vital sign monitoring. Both respiration and heartbeat signal can be obtained simultaneously, which is consistent with the reference signals. For further application, post-exercise physiological activitity characterization were realized based on this vital sign monitoring system. In discussion, mode coupling in TCF was analyzed and utilized for curvature sensing with achieved sensitivity as high as 18 nm/m-1, which supported its excellent performance for vital signs monitoring. In conclusion, the TCF-based vital signs monitors can be a promising candidate for healthcare and biomedical applications.