Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma

PurposeAnlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS.Materials and MethodsIn this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC.ResultsWe found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis.ConclusionTocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS

Extracellular vesicles as a new frontier of diagnostic biomarkers in osteosarcoma diseases: a bibliometric and visualized study

The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R “Bibliometrix” package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis

An arc tangent function demodulation method of fiber-optic Fabry-Perot high-temperature pressure sensor

Abstract A new demodulation algorithm of the fiber-optic Fabry-Perot cavity length based on the phase generated carrier (PGC) is proposed in this paper, which can be applied in the high-temperature pressure sensor. This new algorithm based on arc tangent function outputs two orthogonal signals by utilizing an optical system, which is designed based on the field-programmable gate array (FPGA) to overcome the range limit of the original PGC arc tangent function demodulation algorithm. The simulation and analysis are also carried on. According to the analysis of demodulation speed and precision, the simulation of different numbers of sampling points, and measurement results of the pressure sensor, the arc tangent function demodulation method has good demodulation results: 1 MHz processing speed of single data and less than 1% error showing practical feasibility in the fiber-optic Fabry-Perot cavity length demodulation of the Fabry-Perot high-temperature pressure sensor

Effect of carbon addition on the microstructure and mechanical behavior of near equiatomic NiTi alloy wire

According to the phase diagram, 0.03 wt% (C0.03) and 0.05 wt% (C0.05) carbon were added to Ni50.2Ti49.8 alloy, and the alloy wires with a diameter of 1.2 mm were prepared by vacuum induction melting and drawing. The results show that during melting and solidification, C combines with Ti in C0.03 and C0.05 to form eutectic TiC and primary TiC, respectively. Compared with the NiTi alloy wire without C, the tensile fatigue life (22866 cycles under 700 MPa tensile stress) and tensile strength (1536 MPa) of the alloy were increased by 39 % and 22 % respectively when 0.03 wt% C was added. With the further increase of C content to 0.05 wt%, the two properties began to deteriorate. This is mainly related to the changes of matrix phase composition, second phase morphology and internal microstructure caused by the addition of different amounts of C. The research results show that on the premise of following the requirements for C content (C ≤ 0.04 wt%) in the international standard ASTM F2063-18 for medical NiTi alloy composition, adding a certain amount of C (such as 0.03 wt%) to NiTi alloy is beneficial to improving the tensile strength and tensile fatigue life of wire

An Accelerometer Based on All Silica In-Line Fiber Fabry-Perot Etalon for High Temperature up to 800 °C

High-temperature accelerometers have been widely used in aerospace, nuclear reactors, automobile technologies, etc. In this paper, a fiber-optic Fabry–Perot accelerometer (FOFPA) with a cantilever beam for high temperature is designed and experimentally demonstrated. The FOFPA is formed by bonding an all-silica in-line fiber Fabry–Perot etalon (ILFFPE) to one surface of the uniform cantilever beam with the lumped mass at the free end for acceleration measurement. The all silica in-line fiber FP etalon is made by welding two gold-coat single-mode fiber (GSMF) and a hollow silica glass tube (HST). The research results indicate that the sensitivity of the FOFPA is 0.02328rad/g, and the resonance frequency is 1146.6 Hz in the range of 1 g ~ 10 g. The high-temperature performance of the FOFPA was also evaluated. From 20 °C to 800 °C, the temperature drift is about 0.3178 nm/°C. The FOFPA has the potential of being applicable in higher temperatures compared to conventional accelerometers

An LC Wireless Passive Pressure Sensor Based on Single-Crystal MgO MEMS Processing Technique for High Temperature Applications

An LC wireless passive pressure sensor based on a single-crystalline magnesium oxide (MgO) MEMS processing technique is proposed and experimentally demonstrated for applications in environmental conditions of 900 °C. Compared to other high-temperature resistant materials, MgO was selected as the sensor substrate material for the first time in the field of wireless passive sensing because of its ultra-high melting point (2800 °C) and excellent mechanical properties at elevated temperatures. The sensor mainly consists of inductance coils and an embedded sealed cavity. The cavity length decreases with the applied pressure, leading to a monotonic variation in the resonant frequency of the sensor, which can be retrieved wirelessly via a readout antenna. The capacitor cavity was fabricated using a MgO MEMS technique. This MEMS processing technique, including the wet chemical etching and direct bonding process, can improve the operating temperature of the sensor. The experimental results indicate that the proposed sensor can stably operate at an ambient environment of 22–900 °C and 0–700 kPa, and the pressure sensitivity of this sensor at room temperature is 14.52 kHz/kPa. In addition, the sensor with a simple fabrication process shows high potential for practical engineering applications in harsh environments

Tunable Random Fiber Laser Based on Dual-Grating Structure

In order to reduce the pumping threshold and achieve a short-cavity single-mode transmission with a narrow-linewidth random fiber laser, we propose a tunable random fiber laser based on the combination of random grating and highly reflective fiber Bragg grating (FBG). Theoretical modeling of a random refractive index-modulated fiber grating was carried out. Random grating is regarded as a linear combination of uniform fiber gratings with different periods. Simulation calculations were performed using the transfer matrix method to determine the preparation parameters. Under the premise of satisfying light localization, a point-by-point method was used to write a random grating in a single-mode fiber using a femtosecond laser according to the simulated parameters. We constructed a random fiber laser with a linewidth of 1.68 kHz and a threshold of 29.2 mW using a random grating and a highly reflective FBG combined with an erbium-doped fiber. Due to the broad scattered wavelength range of the random grating, by changing the central wavelength of the high-reflection FBG, the tunable wavelength of the output laser was realized, and the tunable range was 0.847 nm (1549.110–1549.957 nm). Moreover, the laser’s central wavelength and output power are stable for a long time. Compared with other lasers, the proposed laser has the advantages of a lower threshold, shorter cavity length, narrower linewidth, and a relatively simple structure

Influence of Piloti Forms on Wind Comfort of Different Building Group Layouts by Large Eddy Simulation

This paper studies the influence of different piloti rates (0%, 20%, 40%, 60%, 80%, 100%) on outdoor wind comfort for three building groups, i.e., determinant type, point type, and enclosure type. LES (Large Eddy Simulation) is used to simulate the wind environment of three clusters at six different piloti rates. This paper mainly studies the effect of piloti rate on wind speed at pedestrian level (1.5 m). The outdoor wind environment was analyzed using the average wind speed ratio, and outdoor wind comfort was evaluated using the comfortable wind ratio. The following results were obtained: (1) The piloti setting has little influence on the overall wind speed in the target area, and even an inappropriate piloti rate setting may reduce the overall average wind speed in the target area. (2) A comprehensive comparison of the three building layouts shows that the comfortable wind ratio of the determinant layout is the highest when the piloti ratio is 80%. The results of this study can provide architects and urban planners with reference for piloti and urban layout settings

Deep Learning Optimizes Data-Driven Representation of Soil Organic Carbon in Earth System Model Over the Conterminous United States

International audiencegeographical biases. CLM5 with the spatially heterogeneous parameter values optimized from the neural networking method had the least estimation error and less geographical biases across the conterminous United States. Our study indicated that deep learning in combination with data assimilation can significantly improve the representation of SOC by complex land biogeochemical models