Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro

<p>Abstract</p> <p>Background</p> <p>Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells.</p> <p>Methods</p> <p>After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP.</p> <p>Results</p> <p>Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined.</p> <p>Conclusions</p> <p>The mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro.</p

Design of a novel crack-free precipitation-strengthened nickel-based superalloy and composites for laser powder bed fusion

Avoiding cracking defects is crucial to ensuring processability in the laser powder bed fusion (LPBF) of metallic materials. In this study, a crack-free Ni-based superalloy with a high volume fraction of the γ′ phase was designed for the LPBF process using the thermodynamic approach. The results indicate that the designed SD01 Ni-based alloy was crack-free and over 21% of the spherical γ′ phase was uniformly distributed in the matrix after heat treatment. In addition, 1 wt.% TiB2 particles were introduced into the SD01 alloy to further enhance high-temperature mechanical performance. It was found that the morphology of the γ′ phase was altered from spherical to cubic structures, and its volume fraction increased from 21% to 40% after the TiB2 addition. The SD01-TiB2 composite exhibited an excellent combination of tensile strength (437.43 MPa) and elongation (7.71%) at 900 °C compared with the SD01 alloy (252.03 MPa, 3.02%). These findings provide a new metallic material design method for the LPBF of crack-free high-performance Ni-based materials

The safety and efficacy of carbon nanoparticle suspension injection versus indocyanine green tracer-guided lymph node dissection during radical gastrectomy (FUTURE-01): A single-center randomized controlled trial protocol

BackgroundThe use of lymph node (LN) tracers can help obtain a complete dissection of the lymph nodes and increase the detection rate of LNs and metastatic LNs. Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have been widely used in radical gastrectomy in recent years. Nevertheless, the comparison of their clinical effects has not been studied.Method/designThe FUTURE-01 trial will be the first randomized, open-label, single-center trial to compare CNSI and ICG. The study started in 2021 and enrolled 96 patients according to a prior sample size calculation. The primary outcome is the number of LNs retrieved. The secondary outcomes are LN staining rate, LN metastasis rate, stained LN metastasis rate, perioperative recovery and survival.ConclusionBy comparing the safety and efficacy of CNSI and ICG tracer-guided LN dissection in patients with gastric cancer, we can determine the most appropriate LN tracer at present. With the help of LN tracers, the operation is simplified, and the prognosis of these patients is improved. Our study is a prospective exploration of the safety, efficacy, and prognosis of CNSI and ICG.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05229874?cond=NCT05229874&amp;draw=2&amp;rank=1, identifier NCT05229874

cDNA Cloning and Expression Analysis of Gustavus Gene in the Oriental River Prawn Macrobrachium nipponense

The gustavus gene is required for localizing pole plasm and specifying germ cells. Research on gustavus gene expression will advance our understanding of the biological function of gustavus in animals. A cDNA encoding gustavus protein was identified and termed MnGus in the oriental river prawn Macrobrachium nipponense. Bioinformatic analyses showed that this gene encoded a protein of 262 amino acids and the protein belongs to the Spsb1 family. Real-time quantitative PCR analyses revealed that the expression level of MnGus in prawn embryos was slightly higher at the cleavage stage than at the blastula stage, and reached the maximum level during the zoea stage of embryos. The minimum level of MnGus expression occurred during the perinucleolus stage in the ovary, while the maximum was at the oil globule stage, and then the level of MnGus expression gradually decreased with the advancement of ovarian development. The expression level of MnGus in muscle was much higher than that in other tissues in mature prawn. The gustavus cDNA sequence was firstly cloned from the oriental river prawn and the pattern of gene expression was described during oocyte maturation, embryonic development, and in other tissues. The differential expression patterns of MnGus in the embryo, ovary and other somatic tissues suggest that the gustavus gene performs multiple physiological functions in the oriental river prawn

Effects of TiC content on microstructure and mechanical properties of nickel-based hastelloy X nanocomposites manufactured by selective laser melting

The nickel-based Hastelloy X (HX) superalloy is widely applied in the aerospace industry because of its exceptional oxidation resistance and various beneficial properties at high temperatures. HX-based nanocomposites manufactured by additive-manufacturing processes based on powder-bed fusion, such as selective laser melting (SLM), are expected to further enhance the material's mechanical and thermophysical performance. This paper systematically studies the effects of TiC nanoparticle content on the microstructure and tensile performance of SLM-fabricated HX nanocomposites. The results reveal that the microcracking that formed in pure HX was successfully eliminated in the fabricated nanocomposites when 1 wt% and 3 wt% TiC nanoparticles were introduced. The fabricated HX-3 wt.% (HX-3) TiC nanocomposite showed several TiC clusters and a much higher pore-volume percentage (0.15%) compared to the HX-1 wt.% (HX-1) TiC nanocomposite, in which this percentage was determined to be 0.026%. Compared to SLM-fabricated pure HX alloy, the HX-1 nanocomposite exhibited over 19% and 10% improvements in ultimate tensile strength and elongation to failure, respectively. A further increase in TiC content to 3 wt% was not found to further enhance the tensile strength but did result in a 10% loss in elongation to failure in HX-3 nanocomposite. These findings offer a promising pathway to employ SLM to manufacture both high-strength and high-ductility materials through the careful selection of nanoparticle materials and their content

Characteristics and changes of streamflow on the Tibetan Plateau: A review

Study region: The Tibetan Plateau (TP). Study focus: The TP exerts great influence on regional and global climate through thermal and mechanical forcings. The TP is also the headwater of large Asian rivers that provide water for billions of people and numerous ecosystems. Understanding the characteristics and changes of streamflow on the TP will help manage water resources under changing environment. Three categories of rivers (the Pacific Ocean, the Indian Ocean, and the interior) on the TP were examined for their seasonal and long term change patterns. Outstanding research issues were also identified. New hydrological insights for the region: Streamflow follows the monthly patterns of precipitation and temperature in that all peak in May–September. Streamflow changes are affected by climate change and human activities depending on the basins. Streamflow is precipitation dominated in the northern, eastern and southeastern basins. In the central and western basin either melt water or groundwater, or both contributes significantly to streamflow. Human activities have altered streamflow in the lower reaches of the eastern, northern and western basins. Long-term trends in streamflow vary with basins. Outstanding research issues include: (1) What are the linkages between streamflow and climate systems? (2) What are the basin-wide hydrological processes? And (3) What are the cryospheric change impacts on hydrological processes and water balance

Quantitative gaseous temperature and mole concentration measurements in spray generated mixture by p-xylene-PLIF imaging

The current study originally presents a detailed approach to implement the p-xylene based two-color PLIF for measuring gaseous mixture temperature and mole concentration field simultaneously. An 80 * 0.8mm(2) laser sheet at 266nm is employed to excite homogenous p-xylene/nitrogen steady mixture flow in a calibration cell, where the known p-xylene mole concentration and temperature are adjustable. Doing so, the full band/spectral (centered at 289nm) fluorescence intensity are respectively captured by ICCD camera that allows establishments of temperature-fluorescence ratio database. Concomitantly, the full band fluorescence intensity correlation with temperature and mole concentration is rightly created as well. Utilizing the identical laser sheet and detection channel, the quantitative temperature and mole concentration field in a far-field developed-spray region could be inferred by terms of full band/spectral fluorescence imaging through previous calibration database. The error propagation issue of temperature and mole concentration measurement by this approach are discussed. As a result, it is found that the relative temperature and mole concentration uncertainties are in the range of 5.4 similar to 7.3% and 8 similar to 9.3% (or 12.3 similar to 18.7% by bottom-up approach), respectively, within studied temperature range of 423 similar to 573K. Therefore, the suitability and capability of p-xylene as the tracer for spatio-temporal temperature and mole concentration measurements are preliminarily validated, which offers an alternative tracer option for gasoline/its surrogate spray studies. It is noted that replacing the p-xylene by other suitable fluorescence tracer, i.e.,1-methylnaphthalene, this approach could be rightly performed for studies of Diesel engine, or even gas turbine