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A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).
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BACKGROUND: This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). METHODS: PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. RESULTS: The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. CONCLUSIONS: PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC.
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Carcinoma/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Carcinoma/secundario , Modelos Animales de Enfermedad , Doxorrubicina/síntesis química , Doxorrubicina/farmacología , Masculino , Neoplasias Peritoneales/secundario , Profármacos/farmacología , Conejos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
In recent years, the centrifugal casting material Cr35Ni45Nb has been widely used in cracking furnace tubes. The common failure forms in the service process are carburizing cracking, bending, bulging, creep cracking, thermal fatigue cracking, thermal shock cracking, and oxidation, among which the inner wall oxidation and carburization of cracking furnace tubes cause the largest proportion of material failure. In this paper, we will discuss the inner wall oxidation behavior of cracking furnace tubes and its influence on the lasting strength of the furnace tubes. Several groups of endurance tests were designed for service furnace tubes, and the oxidation characteristics, oxide film rupture damage, and its influence on the endurance life of furnace tubes in different service times were analyzed by means of XRD, SEM, and so on. The results show that the oxide layer of the furnace tube is divided into two layers, the outer layer is repeatedly destroyed and rebuilt. With the continuous evolution of material structure, its properties also deteriorate, and its tensile strength, yield strength, elongation, and durable life all decrease significantly.
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Cracking furnaces, operating under high temperatures and in a hydrocarbon medium, subject their tubes to complex stresses such as internal pressure, self-weight, fatigue, and thermal shock during start-up and shutdown. As a result, these furnace tubes frequently experience failures characterized by cracks and corrosion perforation. The high-temperature environment, constantly evolving structure of the tubes, and the close arrangement of the cracks within the tube box hinder detecting the cracks using conventional single-detection methods is challenging. This paper breaks through the limitations of the traditional single detection method and studies the effectiveness of the combination of ultrasonic-guided wave and low-frequency electromagnetic detection methods. The experiment was carried out by deliberately making cracks and thinning defects caused by corrosion on the cracking furnace tube of Cr35Ni45Nb after two years of service. The experimental results show that the ultrasonic guided wave detection technology can quickly detect the defects running through the whole furnace tube and effectively identify the manufacturing defects. On the other hand, low-frequency electromagnetic detection makes it possible to scan suspicious local defects and make qualitative and quantitative analyses of defect signals. The combination of ultrasonic guided wave and low-frequency electromagnetic detection can realize the rapid location and comprehensive qualitative and quantitative analysis of furnace tube defects, thus making up for the defects missed detection caused by the lack of effectiveness of single detection and the resulting safety problems. The research results have great popularization value in practical engineering applications.
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In the domestic petrochemical industry, mounded storage tanks (MSTs) are widely used to store hazardous chemicals. The shell of the mounded storage tank is completely covered by soil to effectively mitigate the effect of the external environment and prevent thermal-expansion-induced explosion of the stored material. Because mounded storage tanks are mostly underground, they are highly safe, provide effective land utilization, and are highly energy efficient. Furthermore, the impact radius in case of an explosion is less than that of aboveground tanks. However, adequate regulations and standards for safety management are yet to be established. This study established a novel method for the integrity management of mounded storage tanks through database construction, risk assessment, applicability monitoring, and testing. At the same time, the risk assessment method for mounded storage tank characteristics is constructed for the first time.
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PURPOSE: Glioma is an aggressive tumor from the nervous system, which causes more than 70% of primary malignant brain tumors. Considering its severe malignancy, there is an urgent need to investigate more practical markers to understand the pathogenesis of glioma, and potential treatment methods for glioma patients. In the paper, we are focused on examining the roles of LINC01140, miR-199a-3p, and ZHX1 in the progression of gliomas, as well as their inner associations and modulation mechanisms. METHODS: qRT-PCR was employed to examine the expression levels of LINC01140 and miR-199a-3p. We measured the expressions of ZHX1 via qRT-PCR and Western blotting. CCK8 assays, migration assays, and invasion assays were carried out to determine the cell viabilities and abilities of migration and invasion. We also conducted in vivo tumor growth experiments to investigate the roles of LINC01140 in glioma developments. RESULTS: The expressions of LINC01140 were promoted in glioma. Silencing LINC01140 could inhibit glioma cell viabilities, migration, and invasion. In our experiments, miR-199a-3p was inhibited in glioma. LINC01140 negatively regulated the expressions of miR-199a-3p in glioma. MiR-199a-3p could target ZHX1 to inhibit its expression in glioma cells. CONCLUSION: LINC01140 could promote glioma developments by modulating the miR-199a-3p/ZHX1 axis.
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BACKGROUND: To compare the efficacy and toxicity of peptide-doxorubicin (PDOX) and doxorubicin (DOX) on nude mice models of human gastric cancer. RESULTS: Both PDOX and DOX could significantly inhibit tumor growth compared with Control (P < 0.05) in both subcutaneous and orthotopic models. Animal survival was much better in PDOX group than DOX group. In peripheral blood test, PDOX group had significantly higher levels of platelets than the Control (P < 0.05), and lymphocyte lower than Control (P < 0.05). There were no significant differences on liver, kidney and cardiac function parameters among three groups (P > 0.05). Immunohistochemistry showed that treatment groups had much higher Tunel than Control (P < 0.05), and PDOX had significantly lower Ki-67 than doxorubicin and Control group (P < 0.01). Western blotting showed that PDOX caused much higher expressions of P53, P21, Aparf-1, pro- and cleaved-caspase 3, compared with DOX. CONCLUSION: Compared with DOX, PDOX has increased effects but much decreased toxicity in treating animal model of gastric cancer. MATERIALS AND METHODS: Animals in subcutaneous model were randomized into Control, doxorubicin, PDOX-L, PDOX-M, and PDOX-H groups. Animals in surgical orthotopic implantation model were randomized into Control, doxorubicin and, peptide-doxorubicin groups. The animals were treated, monitored and examined following a set protocol.