Although multiple-protease based shotgun proteomics method was shown to improve coverage for phosphosite identification, this traditional pipeline is time-consuming and can be of low reproducibility. Here, we demonstrated a multi-in-one strategy to saturate the phosphosite coverage by combining the multiple-proteases based digestion, one-step enrichment, and one-shot data-independent acquisition (DIA) as short as one hour. In the "three-in-one" workflow, more than 19,700 and 13,500 phosphosites could be identified in the trypsin-like and non-trypsin-like mixture, respectively. By combining and applying our "three-in-one" strategy, nearly 30,000 phosphosites could be successfully quantified with high reproducibility across samples. Meanwhile, we developed a faster and more robust method, in which over a single 66-min chromatographic method by "six-in-one" strategy, 19,445 phosphosites could be successfully localized, drastically reducing the database search time required in the traditional method. Inspiringly, this strategy further enabled us to discover 2,675 phosphorylation events on the low abundant transcription factors (TFs) in living cells with high coverage. More broadly, the multi-in-one strategy makes the multiple-protease digestion in large-scale analysis applicable, with low time-consuming, high sensitivity, improved coverage, and high reproducibility.Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H2 gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.Nonclassical fullerene is a new member of the fullerene family. In the present work, a systematic investigation on LaxSc3-xN@C80 (x = 0-3) covering both classical and nonclassical C80 cages was performed utilizing density functional theory combined with statistical mechanics. At absolute zero, LaSc2N@Hept(6)-Cs(2)-C80 with a heptagon-containing nonclassical carbon is the second most stable isomer, whereas at the temperature range of endohedral metallofullerene (EMF) formation, due to the large vibrational frequencies, LaSc2N@Hept(6)-Cs(2)-C80 is the third most abundant isomer, and its mole fraction is very low, accounting for the low experimental yield of LaSc2N@Hept(6)-Cs(2)-C80; La2ScN@Hept(6)-Cs(2)-C80, and La3N@Hept(6)-Cs(2)-C80 are the overwhelming isomers of the corresponding series, but compared with the cases of Sc3N@C80 and LaSc2N@C80, La2ScN and La3N clusters suffer much larger constraints from the C80 cages, perhaps preventing the synthesis of La2ScN@C80 and La3N@C80 species. Because of the large mole fractions and large electron donation and back-donation of La2ScN@Hept(6)-Cs(2)-C80 and La3N@Hept(6)-Cs(2)-C80, it can be inferred that La2ScN and La3N clusters may be used to stabilize some other larger nonclassical fullerene cages. This work will provide useful insights into the origins of stabilization of nonclassical fullerene cages by endohedral derivation and guidelines for synthesis EMF with nonclassical cages.This paper describes, in detail, the development of a novel, low-cost, and flexible drift tube (DT) along with an associated ion mobility spectrometer system. The DT is constructed from a flexible printed circuit board (PCB), with a bespoke "dog-leg" track design, that can be rolled up for ease of assembly. This approach incorporates a shielding layer, as part of the flexible PCB design, and represents the minimum dimensional footprint conceivable for a DT. The low thermal mass of the polyimide substrate and overlapping electrodes, as afforded by the dog-leg design, allow for efficient heat management and high field linearity within the tube-achieved from a single PCB. This is further enhanced by a novel double-glazing configuration which provides a simple and effective means for gas management, minimizing thermal variation within the assembly. Herein, we provide a full experimental characterization of the flexible DT ion mobility spectrometer (Flex-DT-IMS) with corresponding electrodynamic (Simion 8.1) and fluid dynamic (SolidWorks) simulations. The Flex-DT-IMS is shown to have a resolution >80 and a detection limit of low nanograms for the analysis of common explosives (RDX, PETN, HMX, and TNT).Light absorption and emission have their origins in fast atomic-scale phenomena. To characterize these basic steps (e.g., in photosynthesis, luminescence, and quantum optics), it is necessary to access picosecond temporal and picometer spatial scales simultaneously. In this Perspective, we describe how state-of-the-art picosecond photon correlation spectroscopy combined with luminescence induced at the atomic scale with a scanning tunneling microscope (STM) enables such studies. We outline recent STM-induced luminescence work on single-photon emitters and the dynamics of excitons, charges, molecules, and atoms as well as several prospective experiments concerning light-matter interactions at the nanoscale. We also describe future strategies for measuring and rationalizing ultrafast phenomena at the nanoscale.We developed a focused set of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant and antinociceptive properties. These hybrid compounds demonstrated broad-spectrum protective activity in a range of mouse models, such as the maximal electroshock (MES) test, the pentylenetetrazole-induced seizures (scPTZ), and the 6 Hz (32 mA) seizures. https://www.selleckchem.com/products/sodium-l-ascorbyl-2-phosphate.html Compound 22 showed the most potent anticonvulsant activity (ED50 MES = 23.7 mg/kg, ED50 6 Hz (32 mA) = 22.4 mg/kg, ED50 scPTZ = 59.4 mg/kg). In addition, 22 revealed potent efficacy in the formalin-induced tonic pain. These in vivo activities of 22 are likely mediated by several targets and may result from the inhibition of central sodium/calcium currents and transient receptor potential vanilloid 1 (TRPV1) receptor antagonism. Finally, the lead compound 22 revealed drug-like absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) properties in the in vitro assays, making it a potential candidate for further development in epilepsy and neuropathic pain indications.