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Journal of Environmental Management Nov 2022As the most abundant greenhouse gas, atmospheric carbon dioxide (CO) is considered one of the main attributors to climate change. Atmospheric CO concentrations can be... (Review)
Review
As the most abundant greenhouse gas, atmospheric carbon dioxide (CO) is considered one of the main attributors to climate change. Atmospheric CO concentrations can be measured by ground-based monitoring networks, mobile monitoring campaigns, and carbon-observing satellites. However, the worldwide ground-based monitoring networks are composed of sparsely distributed sites and are inadequate to represent the spatiotemporal distributions of CO. Satellite-based remote sensing features repeated, long-term, and large-scale measurements, so it plays a crucial role in monitoring the global distributions of atmospheric CO. However, due to the presence of heavy clouds (or aerosols) and the limitation of satellite orbiting tracks, there exist large amounts of missing data in satellite retrievals. Various methods, including chemical transport models (CTMs), geostatistical methods, and regression-based models, have been employed to derive full-coverage spatiotemporal distributions of CO based on the limited CO measurements. This review summarizes the strengths and limitations of these methods. However, CTMs simulation results can have high uncertainty due to imperfect knowledge of the real world, and the interpolation accuracy of all geostatistical methods is limited by the large amount of data gaps in current satellite retrieved CO products. To overcome these limitations, regression-based methods (especially machine learning models) have the ability to predict CO with superior predictive performance, so this review also summarizes the framework of the machine learning approach. Leveraging the ongoing advancements of satellite instrumentation, the satellite-based CO products have been improving dramatically in recent decades, and this review will describe and critically assess the advantages and disadvantages of the currently used systems in detail. For future improvements, we recommend the fusion of data from multiple satellite retrievals and CTMs by using machine learning algorithms in order to obtain even longer-term, larger-scale, finer-resolution, and higher-accuracy CO datasets.
Topics: Aerosols; Carbon Dioxide; Cyclohexanes; Environmental Monitoring; Greenhouse Gases; Mesylates
PubMed: 36055102
DOI: 10.1016/j.jenvman.2022.116101 -
Journal of Labelled Compounds &... May 2022Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and...
Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and neuropsychiatric disorders. [ C]Martinostat allows in vivo quantification of class I/IIb HDACs and may be useful for the quantification of drug-occupancy relationship, facilitating drug development for disease modifying therapies. The present study reports a radiosynthesis of [ C]martinostat using [ C]methyl triflate in ethanol, as opposed to the originally described synthesis using [ C]methyl iodide and DMSO. [ C]Methyl triflate is trapped in a solution of 2 mg of precursor 1 dissolved in anhydrous ethanol (400 μl), reacted at ambient temperature for 5 min and purified by high-performance liquid chromatography; 1.5-1.8 GBq (41-48 mCi; n = 3) of formulated [ C]martinostat was obtained from solid-phase extraction using a hydrophilic-lipophilic cartridge in a radiochemical yield of 11.4% ± 1.1% (nondecay corrected to trapped [ C]MeI), with a molar activity of 369 ± 53 GBq/μmol (9.97 ± 1.3 Ci/μmol) at the end of synthesis (40 min) and validated for human use. This methodology was used at our production site to produce [ C]martinostat in sufficient quantities of activity to scan humans, including losses incurred from decay during pre-release quality control testing.
Topics: Adamantane; Carbon Radioisotopes; Ethanol; Humans; Hydroxamic Acids; Mesylates; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 35218059
DOI: 10.1002/jlcr.3968 -
Angewandte Chemie (International Ed. in... Dec 2018Analysing protein complexes by chemical crosslinking-mass spectrometry (XL-MS) is limited by the side-chain reactivities and sizes of available crosslinkers, their slow...
Analysing protein complexes by chemical crosslinking-mass spectrometry (XL-MS) is limited by the side-chain reactivities and sizes of available crosslinkers, their slow reaction rates, and difficulties in crosslink enrichment, especially for rare, transient or dynamic complexes. Here we describe two new XL reagents that incorporate a methanethiosulfonate (MTS) group to label a reactive cysteine introduced into the bait protein, and a residue-unbiased diazirine-based photoactivatable XL group to trap its interacting partner(s). Reductive removal of the bait transfers a thiol-containing fragment of the crosslinking reagent onto the target that can be alkylated and located by MS sequencing and exploited for enrichment, enabling the detection of low abundance crosslinks. Using these reagents and a bespoke UV LED irradiation platform, we show that maximum crosslinking yield is achieved within 10 seconds. The utility of this "tag and transfer" approach is demonstrated using a well-defined peptide/protein regulatory interaction (BID /MCL-1), and the dynamic interaction interface of a chaperone/substrate complex (Skp/OmpA).
Topics: Cross-Linking Reagents; Cysteine; Mass Spectrometry; Mesylates; Molecular Structure; Photochemical Processes; Protein Interaction Maps; Proteins
PubMed: 30393918
DOI: 10.1002/anie.201809149 -
Journal of the American Chemical Society Jun 2020While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate...
While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate esters is unknown. We report here a general solution to this challenge catalyzed by a combination of Ni and Pd with Zn reductant and LiBr as an additive. The reaction has broad scope, as demonstrated in 33 examples (65% ± 11% average yield). Mechanistic studies show that Pd strongly prefers the aryl triflate, the Ni catalyst has a small preference for the aryl tosylate, aryl transfer between catalysts is mediated by Zn, and Pd improves yields by consuming arylzinc intermediates.
Topics: Catalysis; Mesylates; Molecular Structure; Nickel; Palladium; Sulfonic Acids; Tosyl Compounds; Zinc
PubMed: 32486635
DOI: 10.1021/jacs.0c04670 -
Annals of Medicine Dec 2022Previous studies have proven that Purinostat Mesylate (PM) is a new HDAC inhibitor and exhibits significant antitumor efficacy. However, the clinical application of PM...
Previous studies have proven that Purinostat Mesylate (PM) is a new HDAC inhibitor and exhibits significant antitumor efficacy. However, the clinical application of PM was greatly limited by its poor solubility in water and low bioavailability.To increase the solubility of PM through pharmaceutical research, and prepare it into an injection that meets the needs of intravenous use to promote its clinical application.The prepared PM/HP-β-CD inclusion complex was studied by computer simulation, fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (1H-NMR spectroscopy), and scanning electron microscopy (SEM). Then, the antitumor effects of PM/HP-β-CD inclusion complex were studied by in vitro cytotoxicity assay, apoptosis assay, pharmacokinetic study and in vivo antitumor assay.Phase Solubility Analysis revealed that PM and HP-β-CD were compatible and the solubility of PM increased almost 220 times, to 2.02 mg/mL. The interaction mechanism studies revealed that PM could be embedded into the cavity of HP-β-CD through the side of the aminobenzene ring. Cell viability and apoptosis assays showed that PM/HP-β-CD complex maintained the good anti-cancer activity of PM, and PM/HP-β-CD complex has a better anti-tumor effect and lower toxicity than LBH589 and Hyper-CVAD/RTX in vivo. All the results suggest that HP-β-CD can solve the problem of PM administration and provide a way for clinical application of PM. In this study, an injectable formulation of PM in HP-β-CD (10% w/v) was prepared to improve its water solubility. Our research provides a way for clinical administration of PM, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related hematologic malignancies in China and the USA.KEY MESSAGESWe developed a preparation of Purinostat Mesylate that can be administered intravenously, reducing the toxicity associated with oral administration.This preparation has an outstanding therapeutic effect on SU-DHL-6 xenograft tumour, indicating its clinical value, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related haematologic malignancies in China and the USA.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Calorimetry, Differential Scanning; Computer Simulation; Humans; Mesylates; Spectroscopy, Fourier Transform Infrared
PubMed: 35243950
DOI: 10.1080/07853890.2022.2045347 -
Bioorganic & Medicinal Chemistry Nov 2022A convenient route for the preparation of l-gulose and its C-6 derivatives starting from commercially available 2,3:5,6-diisopropylidene-d-mannofuranose via C-5...
A convenient route for the preparation of l-gulose and its C-6 derivatives starting from commercially available 2,3:5,6-diisopropylidene-d-mannofuranose via C-5 epimerization as the key step was developed. 1-O-Benzylation followed by regioselective hydrolysis of the 5,6-isopropylidene group furnished benzyl 2,3-isopropylidene-α-d-mannofuranoside, which was subjected upon regioselective one-pot 6-O-benzoylation and 5-O-mesylation, providing the corresponding 5-OMs-6-OBz derivative in excellent selectivity. Treatment of this mesylate compound with potassium t-butoxide to remove the benzoyl group followed by intramolecular S2 inversion led to benzyl 5,6-anhydro-2,3-isopropylidene-β-l-gulofuranoside, which could undergo not only nucleophilic substitutions to open the epoxide ring to give various C-6 derivatives, but also acidic hydrolysis to yield 1,6-anhydro-β-l-gulopyranose for further transformation into l-gulopyranosyl pentaacetate.
Topics: Alkenes; Epoxy Compounds; Hexoses; Mesylates; Potassium
PubMed: 36174449
DOI: 10.1016/j.bmc.2022.117029 -
Toxins Jun 2020Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species To get the maximum yield of ergot alkaloids a statistical...
Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of was improved using physical (ultraviolet (UV) and chemical (ethyl methane sulfonate (EMS) treatments to get the maximum yield of ergot alkaloids through surface culture fermentation technique. After improving the strain, survival rate of colonies of treated with UV and EMS was observed. Only 2.04% living colonies were observed after 150 min of exposure of in UV light and 3.2% living colonies were observed after 20 min of the exposure in EMS. The mutated strains of were screened for their production of ergot alkaloids and after fermentation experiments, maximum yield was obtained from PCUV-4 and PCEMS-1 strains. After strain improvement, Plackett-Burman design (PBD) and Box-Behnken design (BBD) of RSM were employed and 10-fold yield enhancement (35.60 mg/100 mL) of ergot alkaloids was achieved. This enhancement in yield of ergot alkaloids proved the positive impacts of RSM and UV on the yield of ergot alkaloids. The study provides a cost effective, economical and sustainable process to produce medically important ergot alkaloids which can be used in various pharmaceutical formulations to treat human diseases.
Topics: Ergot Alkaloids; Ethyl Methanesulfonate; Fermentation; Industrial Microbiology; Models, Statistical; Penicillium; Time Factors; Ultraviolet Rays
PubMed: 32610508
DOI: 10.3390/toxins12070427 -
The Annals of Pharmacotherapy Oct 2014To review 2 recently approved therapies for vasomotor symptoms (VMSs) of menopause. (Review)
Review
OBJECTIVE
To review 2 recently approved therapies for vasomotor symptoms (VMSs) of menopause.
DATA SOURCES
PubMed searches (June 2003 to May 2014) were conducted using the keywords paroxetine vasomotor and bazedoxifene vasomotor. References from relevant articles were reviewed for pertinent citations that were not identified in the PubMed search.
STUDY SELECTION AND DATA EXTRACTION
Phase 3 clinical trials of recently approved hormonal and nonhormonal therapies for the treatment of VMSs of menopause were selected. Studies that evaluated the use of paroxetine mesylate or bazedoxifene (BZA)/conjugated estrogens (CEs) for VMSs were included.
DATA SYNTHESIS
Four studies for BZA/CEs were identified. One published report of low-dose paroxetine mesylate was identified that was a combined analysis of 2 phase 3 studies. Both agents significantly decrease the incidence of hot flushes compared with placebo and are approved for the treatment of moderate to severe VMSs associated with menopause. BZA/CEs is only approved for women with an intact uterus. In all circumstances, the use of BZA/CEs should be limited to the shortest duration possible. Paroxetine mesylate was not studied head-to-head against hormone therapy, but the magnitude of its effect on VMSs is less than expected with hormone therapy.
CONCLUSIONS
BZA/CEs is an effective hormonal therapy for treating VMSs in women with an intact uterus. Paroxetine mesylate is the first nonhormonal therapy that the FDA has approved for VMSs, making both viable options for the treatment of VMSs of menopause.
Topics: Clinical Trials as Topic; Drug Combinations; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Indoles; Menopause; Mesylates; Paroxetine; Vasomotor System
PubMed: 25028744
DOI: 10.1177/1060028014543099 -
Bioconjugate Chemistry Aug 20215-(Alkynyl)dibenzothiophenium triflates are introduced as new reagents to prepare different protein conjugates through site-selective cysteine alkynylation. The protocol...
5-(Alkynyl)dibenzothiophenium triflates are introduced as new reagents to prepare different protein conjugates through site-selective cysteine alkynylation. The protocol developed allows a highly efficient label of free cysteine-containing proteins with relevant biological roles, such as ubiquitin, the C2A domain of Synaptotagmin-I, or HER2 targeting nanobodies. An electrophilic bis-alkynylating reagent was also designed. The second alkynylating handle thus introduced in the desired protein enables access to protein-thiol, protein-peptide, and protein-protein conjugates, and even diubiquitin dimers can be prepared through this approach. The low excess of reagent needed, mild reaction conditions used, short reaction times, and stability of the S-C(alkyne) bonds at physiological conditions make this approach an interesting addition to the toolbox of classical, site-selective cysteine-conjugation methods.
Topics: Alkynes; Animals; Chemistry Techniques, Synthetic; Cysteine; Humans; Indicators and Reagents; Mesylates; Models, Molecular; Proteins; Sulfhydryl Compounds; Thiophenes
PubMed: 34232618
DOI: 10.1021/acs.bioconjchem.1c00317 -
Chemosphere Nov 2023The rapid and efficient mineralization of the chemotherapeutic drug busulfan (BSF) as the target pollutant has been investigated for the first time by three different...
The rapid and efficient mineralization of the chemotherapeutic drug busulfan (BSF) as the target pollutant has been investigated for the first time by three different heterogeneous EF systems that were constructed to ensure the continuous electro-generation of HO and OH consisting of: i) a multifunctional carbon felt (CF) based cathode composed of reduced graphene oxide (rGO), iron oxide nanoparticles and carbon black (CB) (rGO-FeO/CB@CF), ii) rGO modified cathode (rGO/CB@CF) and rGO supported FeO (rGO-FeO) catalyst and iii) rGO modified cathode (rGO/CB@CF) and multi walled carbon nanotube supported FeO (MWCNT-FeO) catalyst. The effects of main variables, including the catalyst amount, applied current and initial pH were investigated. Based on the results, HO was produced by oxygen reduction reaction (ORR) on the liquid-solid interface of both fabricated cathodes. OH was generated by the reaction of HO with the active site of ≡Fe on the surface of the multifunctional cathode and heterogeneous EF catalysts. Utilizing carbon materials with high conductivity, the redox cycling between ≡Fe and ≡Fe was effectively facilitated and therefore promoted the performance of the process. The results demonstrated almost complete mineralization of BSF through the heterogeneous systems over a wide applicable pH range. According to the reusability and stability tests, multifunctional cathode exhibited outstanding performance after five consecutive cycles which is promising for the efficient mineralization of refractory organic pollutants. Moreover, intermediates products of BSF oxidation were identified and a plausible oxidation pathway was proposed. Therefore, this study demonstrates efficient and stable cathodes and catalysts for the efficient treatment of an anticancer active substance.
Topics: Busulfan; Ferric Compounds; Hydrogen Peroxide; Electric Conductivity; Environmental Pollutants; Nanocomposites; Soot; Ferrous Compounds
PubMed: 37690550
DOI: 10.1016/j.chemosphere.2023.140129