These authors contributed equally to this work.Keywords: autophagy, BECN1, ovarian cancer, paclitaxel resistance, TXNDC17Abbreviations: 95% CI, 95% confidence interval; ALDOC, aldolase C, fructose-bisphosphate; ATG5, autophagy-related 5; BafA1, bafilomycin A 1 ; BECN1, Beclin 1, autophagy-related; CNN3, calponin 3, acidic; DAPI, 4', 6-diamidino-2-phenylindole; FLNA, filamin A, a; GenMAPP, gene microarray pathway profiler; GO, gene ontology; HBSS, Hank's balanced salt solution; HR, hazard ratio; KEGG, Kyoto encyclopedia of genes and genome; LC-MS/MS, liquid chromatography-mass spectrometry/ mass spectrometry; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 b; OS, overall survival; PFS, progression-free survival; PGAM1, phosphoglycerate mutase 1 (brain); siRNA, short interfering RNA; SQSTM1, sequestosome 1; TNF, tumor necrosis factor; TXN, thioredoxin; TXNDC17, thioredoxin domain containing 17; UTP23, small subunit (SSU) processome component, homolog (yeast).Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients. Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1 expression, increase of autophagosome formation, and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17 inhibition by siRNA or enforced overexpression by a pcDNA3.1(C)-TXNDC17 plasmid correspondingly decreased or increased the autophagy response and paclitaxel resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17 overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17, through participation of BECN1, induces autophagy and consequently results in paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or target in ovarian cancer therapeutics.
Vibrationally inelastic scattering is a fundamental collision process that converts some of the kinetic energy of the colliding partners into vibrational excitation(,). The conventional wisdom is that collisions with high impact parameters (where the partners only 'graze' each other) are forward scattered and essentially elastic, whereas collisions with low impact parameters transfer a large amount of energy into vibrations and are mainly back scattered. Here we report experimental observations of exactly the opposite behaviour for the simplest and most studied of all neutral-neutral collisions: we find that the inelastic scattering process H + D(2)(v = 0, j = 0, 2) --> H + D(2)(v' = 3, j' = 0, 2, 4, 6, 8) leads dominantly to forward scattering (v and j respectively refer to the vibrational and rotational quantum numbers of the D(2) molecule). Quasi-classical trajectory calculations show that the vibrational excitation is caused by extension, not compression, of the D-D bond through interaction with the passing H atom. However, the H-D interaction never becomes strong enough for capture of the H atom before it departs with diminished kinetic energy; that is, the inelastic scattering process is essentially a frustrated reaction in which the collision typically excites the outward-going half of the H-D-D symmetric stretch before the H-D(2) complex dissociates. We suggest that this 'tug of war' between H and D(2) is a new mechanism for vibrational excitation that should play a role in all neutral-neutral collisions where strong attraction can develop between the collision partners.
Background Distracting interference cognitive tasks place undeniable pressure on the minds of people who need high precision and attention during the tasks, such as those tasks performed during surgery; these tasks might affect current surgical procedures. We measured the effect of additional cognitive tasks on the mental load of the physician by measuring the mean change in pupil size, blink rate, and subjective assessment during surgery. Material/Methods We recruited 24 participants with different levels of laparoscopic surgery to perform a complete appendectomy using a standardized virtual reality laparoscopic surgery simulator. The participants then performed the cognitive task (arithmetic problem), after that they performed an appendectomy surgery task while completing the cognitive task on the simulator. All participants wore trackers to monitor pupil size and blink rate during surgery and the cognitive task. The National Aeronautics and Space Administration (NASA) Task Load Index (TLX) score also recorded performance parameters during the surgical mission. Results The double-task pupil size and the blink rate were significantly increased compared to the single-task observation, and the associated increase in psychological load might have been affected by surgical performance, and the performance parameters were also statistically significant. However, for the aforementioned parameters, experienced surgeons had some differences compared with inexperienced surgeons, but these differences did not reach statistical significance. Conclusions Distracted cognitive task stimulation in the operating room can increase the surgeon’s psychological burden while also affecting their operational skills, thereby threatening patient safety; reduced cognitive costs might be obtained by improving or managing cognitive deficits.
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