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The utilization of the spiral tube heat exchanger (SHE) has become increasingly prevalent in large-scale liquefaction processes. However, the flow pattern and frictional pressure drop of two-phase flow in the spiral tube have been scarcely studied, particularly under offshore sloshing conditions. An experimental system had been developed to explore the flow pattern and frictional pressure drop characteristics of mixed hydrocarbon fluid in a spiral tube. Moreover, these have been developed in order to examine the effects of sloshing style (roll, pitch, heave), sloshing period (5–15 s), sloshing amplitude (5–15° or 50–150 mm), mass flux (200–800 kg/(m2·s)), vapor quality (0–1), and saturation pressure (2–4 MPa) on the frictional pressure drop of methane/ethane mixture in the spiral tube. The results indicated that sloshing conditions reduce the frictional pressure drop, thereby enhancing fluid flow. A correlation was established to predict the sloshing factor of frictional pressure drop, and the MARD under verification conditions was 6.04%. Furthermore, three flow pattern boundaries were proposed based on We* as an indicator. [ABSTRACT FROM AUTHOR]

Spiral wound tube heat exchanger (SWHE) was confirmed as the core equipment of natural gas liquefaction (LNG). However, there was rare experimental research on large-scale SWHE for LNG, and the theory of heat transfer is not perfect. To investigate the tube-side flow and heat transfer characteristics in spiral tubes, an experimental system was proposed. To ensure the accuracy of the experimental data, the heat transfer coefficients of liquid propane under different conditions were measured, and the data acquired through the experiment were compared with two classical heat transfer correlation (Dittus–Boelter and Geielinski) under the identical working conditions. The applicability of the existing correlation was analyzed using the experimental data, and a novel heat transfer correlation was developed. As indicated by the results, the deviation between the experimental system and the classical correlation under the identical working condition was lower than ±10%. Furthermore, the error comparison between the novel correlation prediction value and the experimental data was less than ±15%. [ABSTRACT FROM AUTHOR]

Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (Papp AP-BL) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10−6 cm/s and (2.48 ± 0.18) × 10−6 cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins. [ABSTRACT FROM AUTHOR]

Molecular glue (MG) compounds are a type of unique small molecule that can change the protein–protein interactions (PPIs) and interactomes by degrading, stabilizing, or activating the target protein after their binging. These small-molecule MGs are gradually being recognized for their potential application in treating human diseases, including cancer. Evidence suggests that small-molecule MG compounds could essentially target any proteins, which play critical roles in human disease etiology, where many of these protein targets were previously considered undruggable. Intriguingly, most MG compounds with high efficacy for cancer treatment can glue on and control multiple key protein targets. On the other hand, a single key protein target can also be glued by multiple MG compounds with distinct chemical structures. The high flexibility of MG–protein interaction profiles provides rich soil for the growth and development of small-molecule MG compounds that can be used as molecular tools to assist in unraveling disease mechanisms, and they can also facilitate drug development for the treatment of human disease, especially human cancer. In this review, we elucidate this concept by using various types of small-molecule MG compounds and their corresponding protein targets that have been documented in the literature. [ABSTRACT FROM AUTHOR]

Simple Summary: FL118 is a novel orally available small molecule anticancer drug. We found that bladder cancer cells with a mutant Kras is highly sensitive to FL118-induced cell growth inhibition and cell death induction through inhibiting the anti-cancer cell death and drug resistance factors (survivin, Mcl-1, XIAP). In the Kras-mutation bladder cancer cells, FL118 can stimulate the reactive oxygen species (ROS) over-production for killing bladder cancer cells and inhibiting bladder cancer cell-established tumor growth. Elimination of mutant Kras by Kras-specific shRNA technology in mutant Kras-containing bladder cancer cell-established tumor decreased FL118 effectiveness to inhibit bladder cancer tumor growth. In this regard, mutant Kras is a potential favorable biomarker for FL118. This finding is significant because mutant Kras is known to be a formidable challenge treatment resistant factor in various types of cancer. Thus, FL118 could use mutant Kras as favorable biomarker for patient selection to carry out precision medicine. Tumor heterogeneity in key gene mutations in bladder cancer (BC) is a major hurdle for the development of effective treatments. Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively. In contrast, HT1376 BC cells with wild-type Ras are insensitive to FL118. This concept was further demonstrated in additional BC and colorectal cancer cells with mutant Kras versus those with wild-type Kras. FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells. Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy. FL118 increased reactive oxygen species (ROS) production in T24 and UMUC3 cells, but not in HT1376 cells. Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation. Proteomics analysis revealed that a profound and opposing Kras-relevant signaling protein is changed in UMUC3 cells and not in HT1376 cells. Consistently, in vivo studies indicated that UMUC3 tumors are highly sensitive to FL118 treatment, while HT1376 tumors are highly resistant to this agent. Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment. Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment. [ABSTRACT FROM AUTHOR]