ABSTRACT
The ability to map trafficking for thousands of endogenous proteins at once in living cells would reveal biology currently invisible to both microscopy and mass spectrometry. Here we report TransitID, a method for unbiased mapping of endogenous proteome trafficking with nanometer spatial resolution in living cells. Two proximity labeling (PL) enzymes, TurboID and APEX, are targeted to source and destination compartments, and PL with each enzyme is performed in tandem via sequential addition of their small-molecule substrates. Mass spectrometry identifies the proteins tagged by both enzymes. Using TransitID, we mapped proteome trafficking between cytosol and mitochondria, cytosol and nucleus, and nucleolus and stress granules, uncovering a role for stress granules in protecting the transcription factor JUN from oxidative stress. TransitID also identifies proteins that signal intercellularly between macrophages and cancer cells. TransitID introduces a powerful approach for distinguishing protein populations based on compartment or cell type of origin.
ABSTRACT
Two analogous M4 L4 -type tetrahedral cages (smaller: MOC-19; larger: MOC-22) were synthesized and investigated for their interactions with the anticancer drug 5-fluoracil (5-FU) by NMR spectroscopy, high-resolution electrospray-ionization mass spectrometry (HR-ESI-MS), and molecular simulation. The cage's size and window are of importance for the host-guest binding, and consequently the smaller MOC-19 with a more suitable size of cavity window was found to have much stronger hydrogen-bond interactions with 5-FU. The porous nanoparticles of MOC-19 exhibited outstanding behavior for the controlled release of 5-FU in a simulated human body with liquid phosphate-buffered saline solution.
Subject(s)
Antineoplastic Agents/administration & dosage , Delayed-Action Preparations/chemistry , Fluorouracil/administration & dosage , Metal-Organic Frameworks/chemistry , Antineoplastic Agents/chemistry , Fluorouracil/chemistry , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Models, Molecular , Nanoparticles/chemistry , Particle Size , Porosity , Spectrometry, Mass, Electrospray IonizationABSTRACT
This retrospective study recruited 150 patients with recurrent major depressive disorder (MDD) who received modified electroconvulsive therapy (MECT) and 150 cases treated with repetitive transcranial magnetic stimulation (rTMS), which aimed to compare the short- and long-term effectiveness, as well as economic outcomes, of MECT and rTMS with a large sample size in patients with recurrent MDD. The results showed that the response rate of patients in the rTMS group was lower than that in the MECT group (46.0% vs 58.7%, p < 0.05). Patients in the rTMS group had elevated rate of dizziness, but reduced rates of poor memory and headache, as well as lower costs compared with the MECT group (p < 0.05). Importantly, we found that the relapse-free survival of patients was similar between the rTMS and MECT groups in the long term. In conclusion, rTMS is an alternative method for MECT in the treatment of patients with recurrent MDD.
Subject(s)
Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/therapy , Electroconvulsive Therapy/methods , Transcranial Magnetic Stimulation/methods , Adult , Aged , Depressive Disorder, Major/psychology , Electroconvulsive Therapy/trends , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Time Factors , Transcranial Magnetic Stimulation/trends , Treatment Outcome , Young AdultABSTRACT
An M(4) L4 type metal-organic cage (MOC-19) has been synthesized from the one-pot reaction of tri(pyridinylmethylene)phenylbenzeneamine (TPBA) with hydrated Zn(ClO4 )2 under mild conditions and characterized by single-crystal X-Ray diffraction. Iodine capture studies show that the porous crystals of MOC-19 exhibit a versatile behavior to accumulate iodine species not only in vapor (for I2 ) but also in solution (for I2 and I3 (-) ), and anion-exchange experiments indicate the capacity to extract IO3 (-) anions from aqueous solution. Enrichment of iodine species from KI/I2 aqueous solution proceeds facilely, revealing a pseudo-second-order kinetics of I3 (-) adsorption. Furthermore, the electrical conductivity of MOC-19 single crystals could be significantly altered by I2 inclusion.
ABSTRACT
L-Ascorbyl oleate and L-ascorbyl linoleate were synthesized by an immobilized lipase from Candida antarctica with yields of 38% and 44%, respectively. L-Ascorbyl oleate was stable in sterile culture medium over 12 h at 37 degrees C but L-ascorbyl linoleate degraded by 17%. Ascorbyl oleate had a better protective effect on human umbilical cord vein endothelial cells treated with H2O2 than of L-ascorbic acid-2-phosphate-6-palmitate (Asc2P6P).
