This study described a successful application of the Quality by Design (QbD) approach to pseudorabies virus (PRV) production process development in a fixed-bed bioreactor using the serum-free medium (SFM). The innovated tube-fixed-bed bioreactor was used as a scale-down model of the fixed-bed bioreactor for process development. Risk analysis was performed using Ishikawa diagram combined with failure mode effects analysis (FMEA). The comparative experiment was performed to screen proper medium for adherent African green monkey kidney (Vero) cells from three commercially available SFMs (VP-SFM, ProVERO-1 and Vero-A). The Vero-A medium showed as an outstanding one for further study. The PRV titer in harvest medium was consider as Critical Quality Attribute (CQA) and the Critical Process Parameters (CPPs) [time of infection (TOI), multiplicity of infection (MOI) and initial inoculation cell density] ranked high with risk priority number (RPN) were taken into design of experiment (DoE) methodology. Then prediction model of PRV production process was established and a robust PRV production process was explored. Under the robust setpoint conditions, the Xcell 1 L laboratory-scale fixed-bed bioreactor yielded PRV titer up to 7.87 log10 TCID50/mL at 3 dpi, which was comparable with that in the tube-fixed-bed bioreactor. Combination of the tube-fixed-bed bioreactor and QbD approach could further accelerate the development of a robust virus production process.Short sleep duration is a known risk factor for suicidality in the general population, yet it is unclear how short sleep interacts with autism traits in predicting suicidality. In this cross-sectional online study, a general population sample (N = 650) completed measures assessing autism traits, suicidal ideation, and sleep duration. Moderated hierarchical regressions demonstrated that higher autism traits and shorter sleep were independent predictors of increased suicide ideation. However, sleep duration did not significantly moderate the autism trait to suicide ideation relationship. Future work should explore this relationship longitudinally using objective measures before considering intervention work to increase sleep duration in those with elevated autism traits.Since the interactions of anti-cancer agents with blood constituents, in particular with human serum albumin (HSA) may have a major impact on drug pharmacology, the present study designed to provide a fundamental understanding of the interaction of nanodiamonds (NDs) together with paclitaxel (PTX) with HSA in detail for the first time. The UV-Vis, steady-state fluorescence, far-UV CD and zeta potential results displayed that PTX + NDs could form a complex with HSA. Additionally, the values of binding constants and ΔG° showed that PTX + NDs interact strongly with HSA compared to PTX or NDs alone and the hydrophobic force plays a major role in this interaction. Moreover, the in vitro release behavior of PTX + NDs form HSA can be regulated at dissimilar pH levels. The anticancer property of 0.5 µM PTX + 20 µM NDs by MTT assay demonstrates that this combination can tremendously diminish the proliferation of MDA-MB-231cells compared to PTX or NDs alone. Altogether, the structure of HSA changed moderately in the presence of PTX + NDs and PTX + NDs can promote mortality of MDA-MB-231 cells besides those mortality effects induced via PTX or NDs alone. The results obtained from this study can help in understanding the pharmacokinetic properties of PTX + NDs.Therapeutic targeting of folate biosynthetic pathway has recently been explored as a viable strategy in the treatment of tuberculosis. The bioactive metabolite substrate of Para-amino salicyclic acid (PAS-M) reportedly dual-targets dihydrofolate reductase (DHFR) and flavin-dependent thymidylate synthase (FDTS), two essential enzymes in folate biosynthetic pathway. However, the molecular mechanisms and structural dynamics of this dual inhibitory activity of the PAS-M remain elusive. Molecular dynamics simulations revealed that binding of PAS-M towards DHFR is characterized by a recurrence of strong conventional hydrogen bond interactions between a peculiar DHFR binding site residue (Asp27) and the 2-amino-decahydropteridin-4-ol group of PAS-M. Similarly, the binding of PAS-M towards FDTS also involved consistent strong conventional hydrogen bond interactions between some specific residues (Tyr101, Arg172, Thr4, Gln103, Arg87 and Gln106) and, the 2-amino-decahydropteridin-4-ol group, thus establishing the cruciality of the group. Structural dynamics of the bound complexes of both enzymes revealed that, upon binding, PAS-M is anchored at the entrance of hydrophobic pockets by strong hydrogen bond interactions while the rest of the structure gains access to deeper hydrophobic residues to engage in favorable interactions. check details Further analysis of atomistic changes of both enzymes showed increased C-α atom deviations as well as an increase C-α atoms radius of gyration consistent with structural disorientations. These conformational changes possibly interfered with the biological functions of the enzymes and hence their inhibition as experimentally reported. Structural Insights provided could open up a novel paradigm of structure-based design of multi-targeting inhibitors of biological targets in the folate biosynthetic pathway toward tuberculosis therapy.Although endovascular or surgical treatment has been performed for preventing the rupture of saccular cerebral aneurysms (sCA), in some patients, the aneurysms may recur and require retreatment. We aimed to investigate the clinical and radiological outcomes of treating recurrent sCA. We retrospectively evaluated the data of 52 patients with 60 recurrent sCAs who were retreated and 1534 patients with 1817 sCAs who received initial treatment. The primary outcome was a recurrence of the aneurysm. Secondary outcomes were an additional treatment, rupture after treatment, and a neurological worsening, which was defined as an increase of 1 or more scores using the modified Rankin Scale at 12-month. Safety outcomes included postoperative ischemic and hemorrhagic complications. We compiled the 120 (60 each) propensity score-matched cohort based on a propensity score for the treatment of recurrent sCA. In the propensity score-matched cohort, recurrence after treatment was observed in 25% and 6.7% of cases in the retreatment and initial treatment groups, respectively.