Good Internal Stability Research Articles

A Novel Scale for Diagnosis of Pulmonary Ground-Glass Nodules: A Multicenter and Ambispective Cohort Study.

A screening tool was devised to aid the diagnosis and treatment of ground-glass nodules (GGNs). The current ambispective cohort study included retrospective collation of 20 variables synthesizing a patient's clinical characteristics, serum tumor markers, and CT results, which allowed division into noninvasive (benign, atypical adenomatous hyperplasia, and adenocarcinoma insitu) and invasive (minimally invasive and invasive adenocarcinomas) tumors to build a prediction nomogram and GGN screening scale. The model was verified internally. A prospective cohort of patients was randomly divided by envelope method into those assessed by the GGN screening scale and those assessed via CT values. The diagnostic efficiencies were compared to allow external verification of the model. A total of 223 patients with 225 GGNs were recruited into the retrospective cohort between January 2021 and December 2022. Multivariable analysis showed sex, diameter, air bronchogram, and vessel convergence sign to be independent factors for prediction of noninvasive and invasive GGNs. Internal verification showed the model had a sensitivity of 70.7% and specificity of 75.0% with the Youden index at 0.457 and area under the curve (AUC) of 0.793 (95% CI: 0.734-0.852). Calibration curves indicated good internal stability (p = 0.357). Between January 2023 and March 2023, 147 patients with 148 GGNs were recruited into the prospective cohort. External verification showed the model had a sensitivity of 92.4% and specificity of 40.0% with the Youden index at 0.324 and AUC of 0.678 (95% CI: 0.509-0.847). Calibration curves indicated good external stability (p = 0.088). The scale was shown to have a sensitivity of 75.00%, specificity of 37.50%, positive predictive value of 91.53%, negative predictive value of 14.29%, and accuracy of 71.25%. The GGN screening scale has high sensitivity and accuracy, making it suitable for diagnosis of GGNs.

Preparation of pH-sensitive alginate-based hydrogel by microfluidic technology for intestinal targeting drug delivery

Hydrogel microspheres stand out in drug delivery due to their small particle size, biocompatibility and good internal stability. In this paper, pH-sensitive hydrogels are prepared by microfluidic technology for targeted drug delivery in the small intestine. A coaxial dual-channel microfluidic chip is constructed. By analyzing the effects of flow rates and three fracture stages (Rayleigh-Plateau instability crushing stage, pressure difference crushing stage and shear force crushing stage) on the size of hydrogel microspheres, the optimal control stage of the microsphere size is determined (shear force crushing stage). Based on this, the accurate control model of the hydrogel microsphere size is proposed. In addition, based on the coaxial dual channel microfluidic chip, a monolayer hydrogel microcapsule loaded with Indometacin is prepared. The core-shell hydrogel microcapsules loaded with Indometacin are prepared by an improved coaxial three channel microfluidic chip. The swelling rates of both microcapsules in simulated intestinal fluid are significantly higher than those in simulated gastric fluid. The results of in vitro simulated release experiments show that the two hydrogel microcapsules basically do not release in simulated gastric juice. In simulated intestinal fluid, single-layer hydrogel microcapsules show rapid release, while core-shell hydrogel microcapsules showed slow release. In conclusion, the alginate-based hydrogel microcapsules have good stability and pH sensitivity, and are suitable for targeted drug delivery in the small intestine.

Design of novel DABO derivatives as HIV-1 RT inhibitors using molecular docking, molecular dynamics simulations and ADMET properties

HIV-1 reverse transcriptase is an important target for developing effective anti-HIV-1 inhibitors. Different types of small molecules have been designed based on this target, showing different levels of inhibitory activity against various types of HIV-1 strains. The relationship between structure and activity of DABO derivatives was investigated by means of 3D-QSAR molecular model, molecular docking, molecular dynamics and ADMET properties. The statistical results of molecular models show that the CoMFA and CoMSIA models have good internal stability (CoMFA: q2 = 0.623, r2 = 0.946; CoMSIA: q2 = 0.668, r2 = 0.983) and external prediction ability (CoMFA: rpred 2 = 0.961; CoMSIA: rpred 2 = 0.961). In addition, molecular docking has explored the mechanism of action between small molecules and receptor proteins, and the results show that hydrogen bonding between amino acid Lys101 and small molecules can improve the affinity of ligands to receptor binding. A total of 12 novel molecules were designed and their activities were predicted based on the 3D-QSAR model and molecular docking results. The results showed that the designed molecules had higher predictive activity. Subsequently, 100 ns MD simulation and binding free energy verified the stability of molecular docking results. Finally, the pharmacokinetic properties of the novel designed molecule were verified by using ADMET to predict its properties. These results can provide reference for the design and development of novel and effective HIV-1 RT inhibitors, and provide new ideas for the design of subsequent drugs. Communicated by Ramaswamy H. Sarma

Graphite Disk UO2Fuel Elements Designed for Extended Burnups at High Powers

Zircaloy-clad fuel elements containing UO/sub 2/ pellets separated by thin graphite disks have been irradiated to maximum burnups of 800 MWh/kg U (33 000 MWd/tonne U) at a linear power range of 30 to 70 kW/m. Fission gas release and sheath strains were lower than experienced for conventional fuel under comparable conditions because of the lower bulk average fuel temperatures in disk elements. The irradiated disk elements also showed good internal stability, tolerance to power ramping, and acceptable defect behavior.